Akebia Therapeutics Annual Report 2023

Plain-text annual report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the ﬁscal year ended December 31, 2023 OR For the transion period from _to_ Commission File Number 001-36352 AKEBIA THERAPEUTICS, INC. (Exact name of registrant as speciﬁed in its charter) Delaware (State or other jurisdicon of incorporaon or organizaon) 245 First Street, Cambridge, MA (Address of principal execuve oﬃces) 20-8756903 (I.R.S. Employer Idenﬁcaon No.) 02142 (Zip Code) Registrant’s telephone number, including area code: (617) 871-2098 Securies registered pursuant to Secon 12(b) of the Act: Title of each class Common Stock, $0.00001 par value per share Trading Symbol(s) AKBA Name of each exchange on which registered The Nasdaq Capital Market Indicate by check mark if the registrant is a well-known seasoned issuer, as deﬁned in Rule 405 of the Securies Act. Yes ☐ No ☒ Indicate by check mark if the registrant is not required to ﬁle reports pursuant to Secon 13 or 15(d) of the Act. Yes ☐ No ☒ Securies registered pursuant to Secon 12(g) of the Act: None Indicate by check mark whether the registrant: (1) has ﬁled all reports required to be ﬁled by Secon 13 or 15(d) of the Securies Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to ﬁle such reports), and (2) has been subject to such ﬁling requirements for the past 90 days. Yes ☒ No ☐ Indicate by check mark whether the registrant has submied electronically every Interacve Data File required to be submied pursuant to Rule 405 of Regulaon S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such ﬁles). Yes ☒ No ☐ Indicate by check mark whether the registrant is a large accelerated ﬁler, an accelerated ﬁler, a non-accelerated ﬁler, a smaller reporng company, or an emerging growth company. See the deﬁnions of “large accelerated ﬁler,” “accelerated ﬁler,” “smaller reporng company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act. Large accelerated ﬁler Non-accelerated ﬁler ☐ ☐ Accelerated ﬁler Smaller reporng company Emerging growth company ☒ ☒ ☐ If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transion period for complying with any new or revised ﬁnancial accounng standards provided pursuant to Secon 13(a) of the Exchange Act. ☐ Indicate by check mark whether the registrant has ﬁled a report on and aestaon to its management’s assessment of the eﬀecveness of its internal control over ﬁnancial reporng under Secon 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounng ﬁrm that prepared or issued its audit report. ☒ If securies are registered pursuant to Secon 12(b) of the Act, indicate by check mark whether the ﬁnancial statements of the registrant included in the ﬁling reﬂect the correcon of an error to previously issued ﬁnancial statements. ☐ Indicate by check mark whether any of those error correcons are restatements that required a recovery analysis of incenve-based compensaon received by any of the registrant’s execuve oﬃcers during the relevant recovery period pursuant to § 240.10D-1(b). ☐ Indicate by check mark whether registrant is a shell company (as deﬁned in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒ The aggregate market value of the vong and non-vong common equity held by non-aﬃliates of the registrant, based on the closing price of the registrant’s Common Stock on The Nasdaq Global Market on June 30, 2023, was $169,721,714. The number of shares of registrant’s Common Stock outstanding as of March 13, 2024 was 209,372,275. The registrant intends to ﬁle a deﬁnive proxy statement pursuant to Regulaon 14A in connecon with its 2024 Annual Meeng of Stockholders within 120 days aer the end of the registrant’s ﬁscal year ended December 31, 2023. Porons of the proxy statement are incorporated by reference into Part III of this Annual Report on Form 10-K. DOCUMENTS INCORPORATED BY REFERENCE Table of Contents Akebia Therapeucs, Inc. Form 10-K For the Year Ended December 31, 2023 TABLE OF CONTENTS Cauonary Note Regarding Forward Looking Statements Risk Factors Summary PART I Business Risk Factors Unresolved Staﬀ Comments Cybersecurity Properes Legal Proceedings Mine Safety Disclosures PART II Market for Registrant’s Common Equity, Related Stockholder Maers and Issuer Purchases of Equity Securies [Reserved] Management’s Discussion and Analysis of Financial Condion and Results of Operaons Quantave and Qualitave Disclosures About Market Risk Financial Statements and Supplementary Data Changes in and Disagreements with Accountants on Accounng and Financial Disclosure Controls and Procedures Other Informaon Disclosure Regarding Foreign Jurisdicons that Prevent Inspecons PART III Directors, Execuve Oﬃcers and Corporate Governance Execuve Compensaon Security Ownership of Certain Beneﬁcial Owners and Management and Related Stockholder Maers Certain Relaonships and Related Transacons, and Director Independence Principal Accountant Fees and Services PART IV Exhibits and Financial Statement Schedules Form 10-K Summary SIGNATURES Item 1. Item 1A. Item 1B. Item 1C. Item 2. Item 3. Item 4. Item 5. Item 6. Item 7. Item 7A. Item 8. Item 9. Item 9A. Item 9B. Item 9C. Item 10. Item 11. Item 12. Item 13. Item 14. Item 15. Item 16. Page 2 4 7 50 105 105 106 106 109 110 110 110 124 125 166 166 169 170 170 170 170 170 170 171 171 180 181 In this Annual Report on Form 10-K, or Form 10-K, unless otherwise stated or the context otherwise requires, references to “Akebia,” “we,” “us,” “our,” “the Company,” "our Company" and similar references refer to Akebia Therapeucs, Inc. and, where appropriate, its consolidated subsidiaries. On December 12, 2018, in connecon with the consummaon of the merger, or Merger, with Keryx Biopharmaceucals, Inc., or Keryx, Keryx became a wholly owned subsidiary of the Company. AURYXIA®, AKEBIA Therapeucs®, Vafseo® and their associated logos are trademarks of Akebia and/or its aﬃliates. All other trademarks, trade names and service marks appearing in this Form 10-K are the property of their respecve owners. Solely for convenience, trademarks, trade names and service marks referred to in this Form 10-K may appear without the ® or symbols, but such references are not intended to indicate, in any way, that the applicable licensor will not assert, to the fullest extent under applicable law, its rights to these trademarks and trade names. We do not intend our use or display of other companies’ trade names, trademarks or service marks to imply a relaonship with, or endorsement or sponsorship of us by, any other company. TM Akebia Therapeucs, Inc. | Form 10-K | Page 1 Table of Contents CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K, or Form 10-K, contains forward-looking statements that are being made pursuant to the provisions of the U.S. Private Securies Ligaon Reform Act of 1995 with the intenon of obtaining the beneﬁts of the “safe harbor” provisions of that Act. All statements contained in this Form 10-K other than statements of historical fact are forward-looking statements. These forward-looking statements may be accompanied by words such as “ancipate,” “believe,” “build,” “can,” “contemplate,” “connue,” “could,” “should,” “designed,” “esmate,” “project,” “expect,” “forecast,” “future,” “goal,” “intend,” “likely,” “may,” “plan,” “possible,” “potenal,” “predict,” “strategy,” “seek,” “target,” “will,” “would,” and other words and terms of similar meaning, but the absence of these words does not necessarily mean that a statement is not forward-looking. These forward-looking statements include, but are not limited to, statements about: • • • • • • • • • • • • • • • • • • • the ming of or likelihood of regulatory ﬁlings and approvals, including with respect to labeling or other restricons, such as the ancipated ming of a response by the FDA to our resubmission of our new drug applicaon for vadadustat following our receipt of a complete response leer from the FDA, and potenal indicaons for vadadustat; the potenal therapeuc beneﬁts, safety proﬁle, and eﬀecveness of vadadustat; our pipeline and porolio, including its potenal, and our related research and development acvies; the ming, investment and associated acvies involved in connued commercializaon of Auryxia® (ferric citrate), its growth opportunies and our ability to execute thereon; the potenal indicaons, demand and market opportunity, potenal and acceptance of Auryxia and vadadustat, if approved, including the size of eligible paent populaons; the potenal therapeuc applicaons of the hypoxia inducible factor pathway; our compeve posion, including esmates, developments and projecons relang to our competors and their products and product candidates, and our industry; our expectaons, projecons and esmates regarding our capital requirements, need for addional capital, ﬁnancing our future cash needs, costs, expenses, revenues, capital resources, cash ﬂows, ﬁnancial performance, proﬁtability, tax obligaons, liquidity, growth, contractual obligaons and the period of me our cash resources will fund our current operang plan, esmates with respect to our ability to operate as a going concern, our internal control over ﬁnancial reporng and disclosure controls and procedures, and any future deﬁciencies or material weaknesses in our internal controls and procedures; delivering value broadly to the kidney community, as well as others who may beneﬁt from our medicines, will result in delivering value for stockholders; the direct or indirect impacts of the recent COVID-19 pandemic on our business, operaons and the markets and communies in which we and our partners, collaborators, vendors, and customers operate; our manufacturing, supply and quality maers and any recalls, write-downs, impairments or other related consequences or potenal consequences; esmates, beliefs and judgments related to the valuaon of intangible asset, goodwill, debt and other assets and liabilies, including classiﬁcaon of expenses, assets and liabilies, our impairment analyses and our methodology and assumpons regarding fair value measurements; the ming of the availability and disclosure of clinical trial data and results; the designs of our studies, and the type of informaon and data expected from our studies and the expected beneﬁts thereof; our and our collaborators’ strategy, plans and expectaons with respect to the development, manufacturing, supply, commercializaon, launch, markeng and sale of Auryxia, Vafseo and vadadustat, if approved, and the associated ming thereof; our ability to maintain any markeng authorizaons we currently hold or will obtain, including our markeng authorizaons for Auryxia and our ability to complete post-markeng requirements with respect thereto; our ability to negoate, secure and maintain adequate pricing, coverage and reimbursement terms and processes on a mely basis, or at all, with third-party payors for Auryxia and vadadustat, if approved; the ming of iniaon of our clinical trials and plans to conduct preclinical studies and clinical trials in the future; the ming and amounts of payments from or to our collaborators and licensees, and the ancipated arrangements and beneﬁts under our collaboraon and license agreements, including with respect to milestones and royales; Akebia Therapeucs, Inc. | Form 10-K | Page 2 Table of Contents • • • • • • • • • • • our intellectual property posion, including obtaining and maintaining patents, and the ming, outcome and impact of administrave, regulatory, legal and other proceedings relang to our patents and other proprietary and intellectual property rights, patent infringement suits that we have ﬁled or may ﬁle, or other acons that we may take against companies, and the ming and resoluon thereof; expected ongoing reliance on third pares, including with respect to the development, manufacturing, supply and commercializaon of Auryxia and vadadustat, if approved; accounng standards and esmates, their impact, and their expected ming of compleon; esmated periods of performance of key contracts; our facilies, lease commitments, and future availability of facilies; cybersecurity; insurance coverage; management of personnel, including our management team, and our employees, including employee compensaon, employee relaons, and our ability to aract, train and retain high quality employees; the implementaon of our business model, current operang plan, and strategic plans for our business, product candidates and technology, and business development opportunies including potenal collaboraons, alliances, mergers, acquisions or licensing of assets; addional costs we may incur due to events associated with or resulng from our prior workforce reducons or other operang expenses, including addional costs related to vadadustat and selling, general and administrave expenses; and the ming, outcome and impact of current and any future legal proceedings. Any or all of these forward-looking statements in this Form 10-K may turn out to be inaccurate. These forward-looking statements involve risks and uncertaines, including those that are discussed below under the heading "Risk Factors Summary", and the risk factors idenﬁed further in Part I, Item 1A. "Risk Factors" included in this Form 10-K and elsewhere in this Form 10-K and in our Securies and Exchange Commission reports ﬁled aer this report, that could cause our actual results, ﬁnancial condion, performance or achievements to be materially diﬀerent from those indicated in these forward-looking statements. Given these risks and uncertaines, you should not place undue reliance on these forward-looking statements. Forward-looking statements speak only as of the date of this Form 10-K. Except as required by law, we assume no obligaon to publicly update or revise these forward-looking statements for any reason. Unless otherwise stated, our forward-looking statements do not reﬂect the potenal impact of any future acquisions, mergers, disposions, joint ventures or investments we may make. This Form 10-K also contains esmates and other informaon concerning our industry and the markets for certain diseases, including data regarding the esmated size of those markets, and the incidence and prevalence of certain medical condions. Unless otherwise expressly stated, we obtained this industry, market and other data from reports, research surveys, studies and similar data prepared by market research ﬁrms and other third pares, industry, medical and general publicaons, government data and similar sources. Akebia Therapeucs, Inc. | Form 10-K | Page 3 Table of Contents RISK FACTORS SUMMARY Invesng in our common stock involves numerous risks, including the risks summarized below and described in further detail in “Part I, Item 1A. Risk Factors” of this Form 10-K, any one of which could materially adversely aﬀect our business, ﬁnancial condion, results of operaons, and prospects. These risks include, but are not limited to, the following. • We have incurred signiﬁcant losses since our incepon and ancipate that we will connue to incur losses and cannot guarantee when, if ever, we will become proﬁtable or aain posive cash ﬂows. • We may require substanal addional ﬁnancing to fund our business. A failure to obtain this necessary capital when needed, or on acceptable terms, could force us to delay, limit, reduce or terminate our product development or commercializaon eﬀorts. • • Raising addional capital may cause diluon to our exisng stockholders, restrict our operaons or require us to relinquish rights to our product and product candidates on unfavorable terms to us. If we fail to comply with the connued lisng requirements of Nasdaq, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negavely impacted. • We may not be successful in our eﬀorts to idenfy, acquire, in-license, discover, develop and commercialize addional products or product candidates or our decisions to priorize the development of certain product candidates over others may not be successful, which could impair our ability to grow. • We may engage in strategic transacons to acquire assets, businesses, or rights to products, product candidates or technologies or form collaboraons or make investments in other companies or technologies that could harm our operang results, dilute our stockholders’ ownership, increase our debt, or cause us to incur signiﬁcant expense. • Our obligaons in connecon with the Agreement for the Provision of a Loan Facility, or the BlackRock Credit Agreement, with Kreos Capital VII (UK) Limited, or Kreos, which are funds and accounts managed by BlackRock Inc., collecvely BlackRock, and requirements and restricons in the BlackRock Credit Agreement could adversely aﬀect our ﬁnancial condion and restrict our operaons. • Our Royalty Interest Acquision Agreement with HealthCare Royalty Partners IV, L.P. contains various covenants and other provisions, which, if violated, could materially adversely aﬀect our ﬁnancial condion. • Our business is substanally dependent on the commercial success of Auryxia and vadadustat, if approved. If we are unable to connue to successfully commercialize Auryxia or vadadustat, if approved and commercialized, our results of operaons and ﬁnancial condion will be materially harmed. • If we are unable to maintain or expand, or, if vadadustat is approved, iniate, sales and markeng capabilies or enter into addional agreements with third pares, we may not be successful in commercializing Auryxia, vadadustat, if approved, or any other product candidates that may be approved. • Our, or our partners', failure to obtain or maintain adequate coverage, pricing and reimbursement for Auryxia, vadadustat, if approved, or any other future approved products, could have a material adverse eﬀect on our or our collaboraon partners’ ability to sell such approved products proﬁtably and otherwise have a material adverse impact on our business. • We face substanal compeon, which may result in others discovering, developing or commercializing products before, or more successfully than, we do. • • The commercializaon of Riona and Vafseo in Japan, Vafseo in Europe and other territories where it is approved, and our current and potenal future eﬀorts with respect to the development and commercializaon of our products and product candidates outside of the United States, or U.S., subject us to a variety of risks associated with internaonal operaons, which could materially adversely aﬀect our business. Clinical drug development involves a lengthy and expensive process with an uncertain outcome, and we will incur addional costs in connecon with, and may experience delays in compleng, or ulmately be unable to complete, the development of vadadustat and any other product candidates. • We may ﬁnd it diﬃcult to enroll paents in our clinical trials, which could delay or prevent clinical trials of Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired. • • Conducng clinical trials outside of the U.S., as we have done historically and as we may decide to do in the future, presents addional risks and complexies and, if we decide to conduct a clinical trial outside of the U.S. in the future, we may not complete such trials successfully, in a mely manner, or at all, which could aﬀect our ability to obtain regulatory approvals. Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired, may cause undesirable side eﬀects or have other properes that may delay or prevent markeng approval or limit their commercial potenal. Akebia Therapeucs, Inc. | Form 10-K | Page 4 Table of Contents • We may not be able to obtain markeng approval for vadadustat or any other product candidate, or we may experience signiﬁcant delays in doing so, any of which would materially harm our business. • Products approved for markeng are subject to extensive post-markeng regulatory requirements and could be subject to post-markeng restricons or withdrawal from the market, and we may be subject to penales, including withdrawal of markeng approval, if we fail to comply with regulatory requirements or if we experience unancipated problems with our products, or product candidates, when and if any of them is approved. • We are subject to complex regulatory schemes that require signiﬁcant resources to ensure compliance and our failure to comply with applicable laws could subject us to government scruny or enforcement, potenally resulng in costly invesgaons, ﬁnes, penales or sancons, contractual damages, reputaonal harm, administrave burdens and diminished proﬁts and future earnings. • We will incur signiﬁcant liability if it is determined that we are promong any “oﬀ-label” use of Auryxia or any other product we may develop, in- license or acquire or if it is determined that any of our acvies violates the federal An-Kickback Statute. • • • Disrupons in the U.S. Food and Drug Administraon, regulatory authories outside the U.S. and other government agencies caused by global health concerns or funding shortages could prevent new products and services from being developed or commercialized in a mely manner, which could negavely impact our business. Compliance with privacy and data security requirements could result in addional costs and liabilies to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to signiﬁcant ﬁnes and penales, which may have a material adverse eﬀect on our business, ﬁnancial condion or results of operaons. Legislave and regulatory healthcare reform may increase the diﬃculty and cost for us to obtain markeng approval of and commercialize our product candidates and aﬀect the prices we may obtain for any products that are approved in the U.S. or foreign jurisdicons. • We depend on collaboraons with third pares for the development and commercializaon of Auryxia, Riona, Vafseo and vadadustat and if these collaboraons are not successful or if our collaborators terminate their agreements with us, we may not be able to capitalize on the market potenal of Auryxia, Riona, Vafseo and vadadustat, and our business could be materially harmed. • We may seek to establish addional collaboraons and, if we are not able to establish them on commercially reasonable terms, or at all, we may have to alter our development and commercializaon plans. • We rely upon third pares to conduct all aspects of our product manufacturing and commercial distribuon, and in many instances only have a single supplier or distributor, and the loss of these manufacturers or distributors, their failure to supply us on a mely basis, or at all, or their failure to successfully carry out their contractual dues or comply with regulatory requirements, cGMP requirements, or guidance could cause delays in or disrupons to our supply chain and substanally harm our business. • We rely upon third pares to conduct our clinical trials and certain of our preclinical studies. If they do not successfully carry out their contractual dues, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain or maintain markeng approval for Auryxia, vadadustat or any of our product candidates, and our business could be substanally harmed. • • If the licensor of certain intellectual property relang to Auryxia terminates, modiﬁes or threatens to terminate exisng contracts or relaonships with us, our business may be materially harmed. If we are unable to adequately protect our intellectual property, third pares may be able to use our intellectual property, which could adversely aﬀect our ability to compete in the market. • We may not be able to protect our intellectual property rights throughout the world. • • • The intellectual property that we own or have licensed and related non-patent exclusivity relang to our current and future products is, and may be, limited, which could adversely aﬀect our ability to compete in the market and adversely aﬀect the value of Auryxia, vadadustat, if approved, or future products. The market entry of one or more generic competors or any third party’s aempt to challenge our intellectual property rights will likely limit Auryxia sales and have an adverse impact on our business and results of operaon. Ligaon and administrave proceedings, including third party claims of intellectual property infringement and opposion/invalidaon proceedings against third party patents, may be costly and me consuming and may delay or harm our drug discovery, development and commercializaon eﬀorts. • We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed conﬁdenal informaon of third pares. Akebia Therapeucs, Inc. | Form 10-K | Page 5 Table of Contents • If we fail to aract, retain and movate senior management and qualiﬁed personnel, we may be unable to successfully develop, obtain and/or maintain markeng approval of and commercialize vadadustat or commercialize Auryxia. • Our cost savings plan and the associated workforce reducons implemented in April, May and November 2022 may not result in ancipated savings, could result in total costs and expenses that are greater than expected and could disrupt our business. • We may encounter diﬃcules in managing our growth, including with respect to our employee base, and managing our partnerships and operaons successfully. • We have idenﬁed a material weakness in our internal control over ﬁnancial reporng as of December 31, 2023 relang to our accounng for inventory and inventory related transacons. If we are not able to remediate this material weakness, or if we experience addional material weaknesses or other deﬁciencies in our internal control over ﬁnancial reporng in the future or otherwise fail to maintain an eﬀecve system of internal control over ﬁnancial reporng, we may not be able to accurately or mely report our ﬁnancial results or prevent fraud, and we may conclude that our internal control over ﬁnancial reporng is not eﬀecve, which may adversely aﬀect our business. • We are currently subject to legal proceedings that could result in substanal costs and divert management's aenon, and we could be subject to addional legal proceedings. • Our stock price has been and may connue to be volale, which could result in substanal losses for holders or future purchasers of our common stock and lawsuits against us and our oﬃcers and directors. Akebia Therapeucs, Inc. | Form 10-K | Page 6 Table of Contents Item 1. Business Overview PART I We are a fully integrated, commercial-stage biopharmaceucal company commied to addressing paents’ unmet needs. We have built a business focused on developing and commercializing innovave therapeucs that we believe serve as a foundaon for future growth. Our purpose is to beer the life of each person impacted by kidney disease, and we have established ourselves as a leader in the kidney community. We believe our demonstrated ability to deliver value broadly to the kidney community has enabled us to build a sustainable company. Upon this solid foundaon and our connued commitment to paents, we believe focusing on all paents who can realize a meaningful beneﬁt from our medicines will deliver value for our shareholders. Our current porolio and hypoxia-inducible factor (HIF)-based pipeline includes: Product Indicaon Region(s) Discovery Phase 1 Phase 2 Phase 3 Regulatory Review Commercial Approval In Market Auryxia® (ferric citrate) Hyperphosphatemia, IDA 2 United States , Japan 2 and Taiwan 1 Vafseo® Anemia DD-CKD, Anemia NDD-CKD 3 Japan Vafseo® Anemia DD-CKD 4 European Union , 4 United Kingdom , 4 Switzerland , Australia , Taiwan and 5 Korea 5 4 Vadadustat Anemia DD-CKD 1 United States Vadadustat Anemia NDD-CKD 6 Global AKB-9090 AKI, ARDS 1 Global AKB-10108 ROP 1 Global 1 Marketed by Akebia 2 Marketed by JT Torii 3 Marketed by MTPC 4 To be marketed by Medice 5 To be marketed by MTPC 6 To be marketed by Akebia; MTPC and Medice have certain rights in their territories Auryxia® (ferric citrate) is an orally administered medicine approved and marketed in the United States, or U.S., for two indicaons: (1) the control of serum phosphorus levels in adult paents with dialysis dependent chronic kidney disease, or DD-CKD, and (2) the treatment of iron deﬁciency anemia, or IDA, in adult paents with non-dialysis-dependent chronic kidney disease, or NDD-CKD. Today, we market Auryxia in the U.S. with our well-established, nephrology- focused commercial organizaon. Our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceucal Co., Ltd., collecvely, JT and Torii, commercialize ferric citrate hydrate as Riona in Japan. Averoa SAS, or Averoa, has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA, Turkey, Switzerland and the United Kingdom, or UK. We expect Averoa will apply for markeng authorizaon for ferric citrate in Europe. Vafseo® (vadadustat) is a HIF prolyl hydroxylase, or HIF-PH, inhibitor, approved in 36 countries as a treatment for anemia due to chronic kidney disease, or CKD. Akebia Therapeucs, Inc. | Form 10-K | Page 7 Table of Contents • • In the European Union, or EU, the UK, Switzerland and Australia, vadadustat is approved under the trade name Vafseo for the treatment of symptomac anemia associated with CKD in adults on chronic maintenance dialysis. In May 2023, we entered into a License Agreement with MEDICE Arzneimiel Püer GmbH & Co. KG, or Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with CKD in the EEA, the UK, Switzerland and Australia, or the Medice Territory. In Japan, vadadustat is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent paents under the trade name Vafseo, and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporaon, or MTPC. In Taiwan, vadadustat is approved for the treatment of symptomac anemia due to CKD in adult paents on chronic maintenance dialysis and in Korea as an anemia treatment for paents with CKD on hemodialysis. MTPC plans to commercialize vadadustat in Taiwan. We connue to pursue approval for vadadustat in the U.S. In September 2023, we completed our resubmission to our New Drug Applicaon, or NDA, for the treatment of anemia due to CKD in adult paents on dialysis to the U.S. Food and Drug Administraon, or FDA. In October 2023, the FDA acknowledged that the resubmission was complete, classiﬁed it as a Class 2 response and set a user fee goal date, or PDUFA Date, of March 27, 2024. We inially submied an NDA to the FDA for vadadustat in March of 2021. On March 29, 2022, the FDA issued a complete response leer, or CRL, to our NDA. The FDA concluded that the data in the NDA did not support a favorable beneﬁt-risk assessment of vadadustat for dialysis and non-dialysis paents. The FDA expressed safety concerns, nong failure to meet non-inferiority in Major Adverse Cardiovascular Events, or MACE, in the non-dialysis paent populaon, the increased risk of thromboembolic events driven by vascular access thrombosis in dialysis paents and the risk of drug-induced liver injury. We believe there are compelling data supporng a posive beneﬁt-risk proﬁle for the use of vadadustat broadly in paents with CKD. In October 2022, we submied a Formal Dispute Resoluon Request, or FDRR, with the FDA regarding the CRL focused on the favorable balance of the beneﬁts and risks of vadadustat for the treatment of adult paents with anemia due to CKD on dialysis. In May 2023, the Oﬃce of New Drugs, or OND, denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. This led to the NDA resubmission in September 2023. We own full rights to vadadustat in the U.S., subject to our licensing agreement with Vifor (Internaonal) Ltd. (now a part of CSL Limited), or CSL Vifor. If we obtain FDA approval for vadadustat as an oral treatment for anemia due to CKD in adult dialysis paents, we plan to commercialize vadadustat in the U.S. with CSL Vifor. Beyond seeking U.S. approval, we have several lifecycle management and indicaon expansion opportunies currently under evaluaon for vadadustat, including the potenal for alternave dosing and label expansion for treatment of anemia due to CKD in adult paents not on dialysis. Our HIF-based pipeline assets are molecules being evaluated to target areas of unmet needs in acute care sengs. The discovery of HIF laid the foundaon to explore the central role of oxygen sensing in many diseases. As we have seen through the development of vadadustat as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adapve, protecve responses during hypoxic or ischemic condions. We have selected two addional HIF molecules for preclinical development: AKB-9090, for use in an acute care seng, potenally for acute kidney disease, or AKI, or acute respiratory distress syndrome, or ARDS, and AKB-10108 for renopathy of prematurity, or ROP, in neonates. We connue to explore addional commercial and development opportunies to expand our pipeline and porolio of novel therapeucs through both internal research and external innovaon to leverage our fully integrated team. Strategy Our strategic focus and business operaons are driven by our commitment to paents. Our broad understanding of kidney disease helps us serve the unmet needs of kidney paents and others impacted by chronic and debilitang illness. Our team has extensive experience in developing and commercializing innovave products, a deep understanding of the renal space commercially as well as the biological pathways involved in kidney disease and business development experse. We are focused on execung on the following four key iniaves: • Maximize the Value of Auryxia: We connue to use our nephrology-focused commercial organizaon to increase awareness and the demand for and adopon of Auryxia for its approved indicaons with key stakeholders including nephrologists, third-party payors, dialysis organizaons and paents. Auryxia has contributed consistent, meaningful revenue to the business since it became part of our porolio in 2018. Our goals are to grow Auryxia net product revenue in 2024 and posion the brand to enable our team to leverage potenal tailwinds which could slow revenue decline upon loss of exclusivity, or LoE, for Auryxia in March 2025. • Unlock Signiﬁcant Value with Potenal U.S. Vadadustat Approval and Commercial Launch Globally: Our near-term goal is to secure approval for vadadustat as an oral treatment for anemia due to CKD in adult dialysis paents in the U.S., which is the largest market opportunity globally for this populaon. We will also connue to support our partners in preparaon to launch Vafseo in Europe, Taiwan and potenally other countries to pursue our goal of Akebia Therapeucs, Inc. | Form 10-K | Page 8 Table of Contents enabling broad access to vadadustat for paents globally. We own full rights to vadadustat in China, Lan America and certain other territories and U.S. rights subject to our license agreement with CSL Vifor, which could provide potenal long-term value. • • Advance pipeline, with focus on HIF-based molecules: As a leader in HIF biology, we aim to thoughully invest in our pipeline, including our decision to advance two HIF-based molecules for potenal use in acute care sengs to the clinic. Through pipeline advancement, our goal is to target new market opportunies in areas of high unmet need. Explore Strategic Growth: We connue to explore addional commercial and development opportunies to expand our pipeline and porolio of novel therapeucs through both internal research and external innovaon to leverage our fully integrated team. In addion to our work to maximize net product revenue, we plan to pursue iniaves to ensure strategic use of capital, most recently securing access to a term loan with a payback period beyond a potenal launch of vadadustat in the U.S., if approved. We will also connue on our path of ﬁnancial discipline, cross-organizaonal eﬃciency and operaonal eﬀecveness. Background on Chronic Kidney Disease There is a clear need to improve the quality of life outcomes for people living with kidney disease. CKD is a condion in which the kidneys are progressively damaged to the point that they cannot properly ﬁlter the blood circulang in the body. This damage causes waste products to build up in the paent’s blood, leading to other health problems, including anemia, cardiovascular disease and bone disease. In the U.S., CKD signiﬁcantly impacts the U.S. healthcare system, potenally aﬀecng about 37 million paents and cosng Medicare nearly $125.0 billion annually for treang Medicare beneﬁciaries with CKD or end-stage renal disease, or ESRD, according to the Centers for Disease Control and Prevenon. The prevalence and incidence of CKD is increasing in all segments of the U.S. populaon. Risk factors for the development of CKD include concomitant diseases such as obesity, hypertension, diabetes mellitus and cardiovascular disease, lifestyle factors such as tobacco use and inacvity, family history, aging and prenatal factors such as maternal diabetes mellitus, low birth weight and small-for-gestaonal-age status. The progression of CKD towards renal failure is complicated by mulple condions which further deteriorate kidney funcon and the general health of paents if le untreated. Typically the prevalence of these condions increases as CKD progresses. For instance, paents with CKD oen experience high phosphorus and develop hyperphosphatemia, which can result in bone disease, vascular calciﬁcaon and calciphylaxis (skin ulceraon). Addionally, anemia, characterized by low hemoglobin levels, is typically associated with fague, worsening quality of life, increased hospitalizaons and increased mortality. Anemia, or low hemoglobin/red blood count, in paents with CKD most commonly arises from two eologies: 1. Anemia due to CKD: results from inadequate levels of erythropoien, or EPO, a protein hormone synthesized by specialized cells in the kidney that smulates red blood cell, or RBC, producon in the bone marrow. As renal funcon declines, the body progressively loses the ability to produce endogenous EPO; and 2. IDA: results from low levels of iron due to abnormal iron absorpon and ulizaon in paents with CKD. Auryxia Auryxia is an iron-based, non-calcium, non-chewable, orally-administered tablet approved and marketed in the U.S., Japan and Taiwan for the treatment of hyperphosphatemia in adult paents with dialysis dependent CKD and for the treatment of IDA in adult paents with NDD-CKD. Market Opportunity – Hyperphosphatemia and Iron Deﬁciency Anemia Hyperphosphatemia is a metabolic disorder characterized by elevated serum phosphorus levels. Phosphorus is a vital element required for most cellular processes and, in individuals with normal kidney funcon, excess dietary phosphorus is removed by the kidneys and excreted in urine. In adults with funconing kidneys, normal serum phosphorus levels are 2.5 to 4.5 mg/dL. In adults with DD-CKD, elevated phosphorus levels, or hyperphosphatemia, can be associated with adverse eﬀects, including increased risk for cardiovascular disease, bone disease and death. Phosphate binders and phosphate inhibitors are the only intervenons marketed for the treatment of hyperphosphatemia. According to the U.S. Renal Data System 2022 Annual Data Report, there were nearly 558,000 paents in the U.S. on dialysis in 2020, of which approximately 80% were treated with a phosphate binder. Phosphate binders need to be taken with meals and snacks, and it is not uncommon for DD-CKD paents to be prescribed as many as 12 or more phosphate binder pills per day, among other medicaons. Paents taking phosphate binders also experience gastrointesnal tolerability issues. As a result of the pill burden and tolerability issues associated phosphate binders, prescribed phosphate binders are oen intolerable for many paents, leading to lack of treatment adherence. In addion, in 2020 approximately 44% of paents treated with a phosphate binder were treated solely with a calcium-based binder, which can lead to side eﬀects such as increased cardiovascular risk, hypercalcemia and gastrointesnal-related Akebia Therapeucs, Inc. | Form 10-K | Page 9 Table of Contents adverse events. Due to the risks associated with calcium-based binders, in 2017 Kidney Disease: Improving Global Outcomes, or KDIGO, recommended that clinicians limit the use of calcium-based binders. Anemia is a condion characterized by abnormally low levels of hemoglobin. Hemoglobin is contained within RBCs and carries oxygen to other parts of the body. If there are too few RBCs or if hemoglobin levels are low, the cells in the body will not get enough oxygen. IDA is a common form of anemia that is caused by paents not having enough iron to manufacture healthy RBCs. Although anyone can develop IDA, IDA is parcularly common in NDD-CKD paents. IDA is associated with fague, lethargy, decrease quality of life, cardiovascular complicaons, hospitalizaons and increased mortality. We esmate that there are more than 500,000 adult paents in the U.S. with NDD-CKD diagnosed with IDA and managed by a nephrologist. Currently, there are two forms of iron therapy used to treat IDA: oral iron supplements and iron delivered via intravenous infusion, or IV, iron. Oral iron is currently the ﬁrst- line iron replacement therapy for most physicians; however, oral iron supplements are poorly absorbed by many paents, which may adversely impact their eﬀecveness, and are associated with certain side eﬀects, such as conspaon, diarrhea and cramping, that may adversely aﬀect treatment adherence. IV iron is viewed as an eﬀecve treatment; however, like other intravenous medicines, it is logiscally diﬃcult to administer in an oﬃce seng, where NDD-CKD paents are more oen treated. Commercializaon We market Auryxia in the U.S. through our well-established, nephrology-focused sales force and commercial organizaon. Auryxia, as an oral drug, is covered by Medicare under Part D and commercial channels. Paents with hyperphosphatemia have access to Auryxia through the major Medicare Part D plans and the ten largest commercial plans and pharmacy beneﬁt managers in the U.S., which provide coverage for approximately 127 million people. In September 2018, the Centers for Medicare & Medicaid Services, or CMS, decided that Auryxia would no longer be covered by Medicare for the treatment of IDA. While this decision does not impact CMS coverage for the treatment of hyperphosphatemia, it requires all Auryxia prescripons for Medicare paents to undergo a prior authorizaon, or PA, to ensure their use in that indicaon. We decided beginning in 2022 to terminate certain Part D contracts, as paents no longer had the access beneﬁt given the PA requirement. Now, paents must go through a medical exempon process, which is very similar to a PA review. While we believe this had, and may connue to have, a negave impact on our overall sales volume, we believe it had a signiﬁcant posive impact on our net selling price. In recognion of the evoluon of chronic kidney care to value-based reimbursement and care delivery, in late 2022 we shied our commercial model to align to customer objecves. The team of key account managers are focused on high value individual prescribers that represent approximately 70% of Auryxia prescribing and 40% of the overall binder market potenal. The team also focuses on large group pracces that are part of the Comprehensive Kidney Care Contracng, or CKCC, program. These enes are focused on delivering coordinated, cost-eﬀecve care for advanced CKD paents, including those receiving dialysis. This customer group requires diﬀerent clinical and economic raonale for supporng product use in protocols and formularies. Therefore, we have aligned key account managers to these high-volume, value-based care organizaons. We believe this model is more aligned to our customers’ needs and recognion of our product’s value proposion. JT and Torii market Riona in Japan. We receive ered double-digit royales from JT and Torii based on their sales in Japan. Vadadustat Market Opportunity Anemia is common in paents with CKD, and its prevalence increases with disease progression. Anemia due to CKD results from inadequate EPO levels, negavely aﬀecng RBC producon. Le untreated, anemia accelerates the overall deterioraon of paent health with increased morbidity and mortality. Based on third-party prevalence data and company esmates, approximately 5.7 million people in the U.S. with CKD suﬀer from anemia. According to the U.S. Renal Data System 2022 Annual Data Report, there were nearly 558,000 paents in the U.S. on dialysis in 2020, of which 86% were on in-center hemodialysis and the remainder on home dialysis, which includes both peritoneal dialysis and home hemodialysis. The current standard of care for anemia due to CKD is treatment by injectable recombinant human erythropoiesis-smulang agents, or ESAs, such as Epogen® (epoen alfa), Aranesp® (darbepoen alfa) or Mircera® (methoxy polyethylene glycol-epoen beta), or blood transfusion. Based on publicly available informaon on ESA sales and market data compiled by a third-party vendor, global sales of injectable ESAs for all uses were esmated to be approximately $10.0 billion in 2022. The vast majority of these sales are believed to have been for the treatment of anemia due to CKD. In Europe, within the EU5, which refers to the ﬁve largest markets in Europe or France, Germany, Italy, Spain and England, more than 200,000 dialysis paents are diagnosed with anemia due to CKD and are treated with ESAs. When administered to a paent, injectable ESAs provide supraphysiological levels of exogenous EPO to smulate producon of RBCs. While injectable ESAs can be eﬀecve in raising hemoglobin levels, they have the potenal to cause signiﬁcant side Akebia Therapeucs, Inc. | Form 10-K | Page 10 Table of Contents eﬀects, and need to be injected subcutaneously or intravenously. In parcular, injectable ESAs may lead to thrombosis, stroke, myocardial infarcon and death. Also, controlled trials have demonstrated that paents experienced greater risk of death, serious adverse cardiovascular reacons, and stroke when administered ESAs to a target hemoglobin level of greater than 11g/dL. While these safety concerns, which became evident starng in 2006, have led to a signiﬁcant reducon in the use of injectable ESAs, and an increase in the use of injectable iron, injectable ESAs remain the current standard of care for the treatment of anemia due to CKD in paents on dialysis and not dialysis dependent. We believe there is a signiﬁcant opportunity for vadadustat to address limitaons of injectable ESAs and become a new oral opon for the treatment of anemia due to CKD in adult paents on dialysis, if approved. In addion, clinical data from our Phase 3 INNO VATE program showed vadadustat was non- inferior to darbepoen alfa with respect to hematological eﬃcacy (change in hemoglobin concentraon) and cardiovascular safety (MACE) in adult paents on dialysis. 2 Injectable ESAs are administered by dialysis center staﬀ to approximately 90% of in-center hemodialysis paents and 75% of home dialysis paents. Although the signiﬁcant majority of dialysis paents are cared for in-center, recently, several factors including the COVID-19 pandemic, changing paent preferences, government iniaves and reimbursement changes are supporng a shi toward home dialysis. We believe as an oral therapeuc, vadadustat has potenal to be a convenient treatment alternave to injectable ESAs not only for in-center dialysis paents, but also for the growing number of home dialysis paents and paents transioning to home dialysis. Given the concentraon of dialysis clinics in large networks, with DaVita, Inc., or DaVita, and Fresenius Kidney Care Group LLC, or Fresenius, accounng for a vast majority of the dialysis populaon in the U.S., treatment is usually driven by medical protocols that are implemented across the enre network of clinics. These protocols are informed by very large data sets and when updated, result in rapid change applicable to large segments of the paent populaon. This is parcularly true of medicaons covered under the ESRD Prospecve Payment System, or PPS, in Medicare, or the ESRD Bundle, a payment structure with a ﬂat base rate per dialysis session adjusted for individual paent and facility characteriscs. Dialysis-related drugs are included in the ESRD Bundle if they fall into funconal categories such as anemia management and bone and mineral metabolism, except that oral-only drugs are exempted from inclusion unl 2025. In a ﬁnal ESRD PPS rule published in November 2018, CMS conﬁrmed that it will expand the Transional Drug Add-on Payment Adjustment, or TDAPA, to all new dialysis drugs approved by the FDA aer January 1, 2020. The TDAPA will provide separate payment for new drugs for two years based on the drug’s Average Sales Price, or ASP, that will be in addion to the base rate in order to facilitate the adopon of innovave therapies. Although there are several details that need further clariﬁcaon, and the precise ming of when we could receive codes to allow for reimbursement under TDAPA is not known, the codes are assigned on a quarterly basis, and the rule provides support for our assumpon that new anemia treatments, including those in the HIF-PH inhibitor class, will be included in the ESRD Bundle and will be eligible for separate payment inially under TDAPA, and we expect to receive TDAPA designaon for vadadustat six months post-ﬁling acceptance if approved by the FDA. Commercializaon We are supporng MTPC's commercializaon of vadadustat in Japan and will support Medice's commercializaon of vadadustat in Europe. We are also preparing for a potenal commercial launch of vadadustat in the U.S., if approved. If we obtain FDA approval for vadadustat for the treatment of anemia due to CKD in adult paents, we plan to commercialize vadadustat in the U.S. with CSL Vifor. Today, we have an established and embedded commercial team with approximately 30 key account managers supported by our commercial operaons team. There is a more than 96% overlap in call points that exists between Auryxia and vadadustat. Enhancing the ability of our commercial team, we also have renal experse across our organizaon, including among our leadership team and Board of Directors, as well as exisng relaonships with dialysis organizaons that we believe will enhance our commercial eﬀecveness if vadadustat is approved. In February 2022, we entered into a Second Amended and Restated License Agreement, or the Vifor Agreement, with CSL Vifor, under which we granted CSL Vifor an exclusive license to sell vadadustat to Fresenius Medical Care North America and its aﬃliates, including Fresenius, to certain third-party dialysis organizaons approved by us, to independent dialysis organizaons that are members of certain group purchasing organizaons and to certain non-retail specialty pharmacies, collecvely, the Supply Group, in the U.S., or Vifor Territory. If approved, we plan to market vadadustat in the U.S., including to the Supply Group, and we plan to sell vadadustat directly to organizaons outside the Supply Group. During the term of the Vifor Agreement, CSL Vifor is not permied to sell any HIF product that competes with vadadustat in the Vifor Territory to the Supply Group. Akebia Therapeucs, Inc. | Form 10-K | Page 11 Table of Contents Clinical Development Program Below is a summary of the clinical development work undertaken for vadadustat. Vadadustat Global Phase 3 Clinical Program in Anemia Due To CKD We conducted a global Phase 3 clinical development program for vadadustat, which included two programs, INNO VATE and PRO TECT. INNO VATE evaluated vadadustat in adult DD-CKD paents with anemia due to CKD in two studies, and PRO TECT evaluated vadadustat in adult NDD-CKD paents with anemia due to CKD in two studies. Combined, we enrolled approximately 7,500 paents in these studies and evaluated a once daily oral dosing of vadadustat against an injectable ESA acve comparator, darbepoen alfa. 2 2 2 2 2 2 2 2 Both the INNO VATE and PRO TECT Phase 3 programs were global, mulcenter, open-label, sponsor-blind, acve-controlled non-inferiority programs. In both programs, paents were randomized 1:1 to receive either oral vadadustat or injectable darbepoen alfa. The primary eﬃcacy endpoint for each study in the INNO VATE and PRO TECT programs was the mean change in hemoglobin between baseline and the primary evaluaon period. Non-inferiority, or NI, for the primary eﬃcacy endpoint was achieved if the lower bound of the 95% conﬁdence interval for the between-group diﬀerence of the mean hemoglobin change did not fall below the pre-speciﬁed NI margin. Both the INNO VATE and PRO TECT programs included the primary safety endpoint of the assessment of MACE, with a comparison of vadadustat to darbepoen alfa. MACE is deﬁned as the composite endpoint of all-cause mortality, non-fatal myocardial infarcon, or non-fatal stroke. The primary safety analysis for each program was based on the combined MACE events from the two studies in each of INNO VATE and PRO TECT. NI for the primary safety analysis was achieved if the upper bound of the 95% conﬁdence interval for the hazard rao of vadadustat to darbepoen alfa did not exceed the pre-speciﬁed NI margin. We prospecvely deﬁned and agreed to non-inferiority margins with the U.S. and European regulatory authories and agreed with the U.S. regulatory authories on the key components of our stascal analysis plan. 2 2 2 2 Top-line Results from Global Phase 3 INNO VATE Program within DD-CKD Adult Paents 2 The two INNO VATE studies (Correcon/Conversion and Conversion), which collecvely enrolled 3,923 paents, evaluated the eﬃcacy and safety of vadadustat versus darbepoen alfa for the treatment of anemia due to CKD in DD-CKD adult paents. 2 Vadadustat achieved the primary and key secondary eﬃcacy endpoint in each of the two INNO VATE studies, demonstrang non-inferiority to darbepoen alfa as measured by a mean change in hemoglobin, or Hb, between baseline and the primary evaluaon period (weeks 24 to 36) and secondary evaluaon period (weeks 40 to 52). Vadadustat also achieved the primary safety endpoint of the INNO VATE program, deﬁned as non-inferiority of vadadustat versus darbepoen alfa in me to ﬁrst occurrence of MACE across both INNO VATE studies. 2 2 2 Primary and Key Secondary Eﬃcacy Endpoint Results Vadadustat achieved each of the INNO VATE studies’ primary eﬃcacy endpoints of mean change in Hb between baseline and the primary evaluaon period compared to darbepoen alfa, in DD-CKD adult paents, demonstrang non-inferiority to darbepoen alfa based on using a non-inferiority margin of -0.75 g/dL. 2 In INNO VATE’s Correcon/Conversion study of incident dialysis paents (n=369): 2 • • Primary Eﬃcacy Endpoint Result: Vadadustat was non-inferior to darbepoen alfa. The least square mean diﬀerence in Hb was -0.31 g/dL (95% CI: -0.53, -0.10), achieving the pre-speciﬁed non-inferiority criterion of -0.75 g/dL. The mean (SD) Hb level at week 24 to week 36 was 10.36 (1.13) g/dL for vadadustat-treated paents compared to 10.61 (0.94) g/dL for darbepoen alfa-treated paents. Key Secondary Eﬃcacy Endpoint Result: Vadadustat sustained the target Hb eﬃcacy response at weeks 40 to 52 achieving non-inferiority compared to darbepoen alfa. The least square mean diﬀerence in Hb was -0.07 g/dL (95% CI: -0.34, 0.19). The mean (SD) Hb level at week 40 to week 52 was 10.51 (1.19) g/dL for vadadustat treated-paents compared to 10.55 (1.14) g/dL for darbepoen alfa-treated paents. In INNO VATE’s Conversion study of prevalent dialysis paents (n=3,554): 2 • • Primary Eﬃcacy Endpoint Result: Vadadustat was non-inferior to darbepoen alfa. The least square mean diﬀerence in Hb was -0.17 g/dL (95% CI: -0.23, -0.10), achieving the pre-speciﬁed non-inferiority criterion of -0.75 g/dL. The mean (SD) Hb level at week 24 to week 36 was 10.36 (1.01) g/dL for vadadustat-treated paents compared to 10.53 (0.96) g/dL for darbepoen alfa-treated paents. Key Secondary Eﬃcacy Endpoint Result: Vadadustat sustained eﬃcacy in the Conversion study demonstrang non-inferiority to darbepoen with a least square mean diﬀerence in Hb of -0.18 g/dL (95% CI: -0.25, -0.12). The mean (SD) Hb level at week 40 to week 52 was 10.40 (1.04) g/dL in the vadadustat-treated paents compared to 10.58 (0.98) g/dL for darbepoen treated paents. Akebia Therapeucs, Inc. | Form 10-K | Page 12 Table of Contents Primary Safety Major Adverse Cardiovascular Events (MACE) Endpoint Result Vadadustat achieved the INNO VATE program’s primary safety endpoint of non-inferiority for MACE. In the primary analysis of me to ﬁrst MACE event, vadadustat demonstrated non-inferiority to darbepoen alfa using a non-inferiority margin of 1.25 based on discussion with the FDA and a non-inferiority margin of 1.3 based on discussion with the EMA. 2 The INNO VATE program (Correcon/Conversion and Conversion studies) of dialysis paents (n=3,902): 2 • Vadadustat was non-inferior to darbepoen alfa. The upper bound of the 95% conﬁdence interval (CI) of the Hazard Rao (HR) was below the pre-speciﬁed non-inferiority margin of 1.25 for primary MACE analysis (HR 0.96, 95% CI: 0.83, 1.11.). The incidence of treatment emergent adverse events, or TEAEs, during the Correcon/Conversion study in vadadustat treated paents was 83.8% and 85.5 % in darbepoen alfa treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa treated paents were hypertension (16.2%/ 12.9%) and diarrhea (10.1%/ 9.7%). Serious TEAEs were lower in vadadustat treated paents at 49.7% compared to 56.5% for darbepoen alfa treated paents. The incidence of TEAEs during the Conversion study in the vadadustat treated paents was 88.3%, and 89.3% in darbepoen alfa treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa treated paents were diarrhea (13.0%/ 10.1%), pneumonia (11.0%/ 9.7%), hypertension (10.6%/ 13.8%), and hyperkalemia (9.0%/ 10.8%). Serious TEAEs were slightly lower for vadadustat treated paents at 55.0% and 58.3% for darbepoen alfa-treated paents. Paents with DD-CKD experienced an increased risk of thromboembolic events compared to darbepoen alfa with a me to ﬁrst event HR of 1.20 (95% CI 0.96 –- 1.50) driven by thrombosis of vascular access. 2 INNO VATE results on key secondary safety endpoints showed that vadadustat also demonstrated non-inferiority to darbepoen alfa in analyses of expanded MACE, cardiovascular MACE, cardiovascular mortality, and all-cause mortality. Top-line Results from Global Phase 3 PRO TECT Program within NDD-CKD Adult Paents 2 The two PRO TECT studies (Correcon and Conversion), which collecvely enrolled 3,476 paents, evaluated the eﬃcacy and safety of vadadustat for the treatment of anemia due to CKD in NDD-CKD adult paents. 2 Vadadustat achieved the primary and key secondary eﬃcacy endpoint in each of the two PRO TECT studies, demonstrang non-inferiority to darbepoen alfa as measured by a mean change in Hb between baseline and the primary evaluaon period (weeks 24 to 36) and secondary evaluaon period (weeks 40 to 52). Vadadustat did not meet the primary safety endpoint of the PRO TECT program, deﬁned as non-inferiority of vadadustat versus darbepoen alfa in me to ﬁrst occurrence of MACE, across both PRO TECT studies. 2 2 2 Primary and Key Secondary Eﬃcacy Endpoint Results Vadadustat achieved each of the PRO TECT studies' primary eﬃcacy endpoints of mean change in Hb between baseline and the primary evaluaon period compared to darbepoen alfa, in adult paents on dialysis, demonstrang non-inferiority to darbepoen alfa using an NI margin of -0.75 g/dL. 2 In PRO TECT's Correcon study (n=1,751): 2 • • Primary Eﬃcacy Endpoint Result: Vadadustat was non-inferior to darbepoen alfa. The least square mean diﬀerence in Hb was 0.05 g/dL (95% CI: -0.04, 0.15), achieving the pre-speciﬁed NI criterion of -0.75 g/dL. The mean (SD) Hb level at week 24 to week 36 was 10.39 (0.99) g/dL for vadadustat-treated paents compared to 10.35 (1.03) g/dL for darbepoen alfa-treated paents. Key Secondary Eﬃcacy Endpoint Result: Vadadustat sustained the target Hb eﬃcacy response at weeks 40 to 52 achieving non-inferiority compared to darbepoen alfa. The least square mean diﬀerence in Hb was 0.04 g/dL (95% CI: -0.06, 0.14). The mean (SD) Hb level at week 40 to week 52 was 10.48 (1.05) g/dL for vadadustat-treated paents compared to 10.45 (1.01) g/dL for darbepoen alfa-treated paents. In PRO TECT's Conversion study (n=1,725): 2 • • Primary Eﬃcacy Endpoint Result: Vadadustat was non-inferior to darbepoen alfa. The least square mean diﬀerence in Hb was -0.01 g/dL (95% CI: -0.09, 0.07), achieving the pre-speciﬁed NI criterion of -0.75 g/dL. The mean (SD) Hb level at week 24 to week 36 was 10.77 (0.98) g/dL for vadadustat-treated paents compared to 10.77 (0.99) g/dL for darbepoen alfa-treated paents. Key Secondary Eﬃcacy Endpoint Result: Vadadustat sustained eﬃcacy in the Conversion study demonstrang non-inferiority to darbepoen with a least square mean diﬀerence in Hb of 0.00 g/dL (95% CI: -0.10, 0.09). The mean (SD) Hb level at week 40 to week 52 was 10.80 (1.04) g/dL in the vadadustat-treated paents compared to 10.79 (1.05) g/dL for darbepoen alpha-treated paents. Akebia Therapeucs, Inc. | Form 10-K | Page 13 Table of Contents Primary Safety Major Adverse Cardiovascular Events (MACE) Endpoint Result The PRO TECT program (Correcon and Conversion studies) (n=3,471): 2 • Primary Safety MACE Endpoint Result: Vadadustat did not meet the PRO2TECT program's primary safety endpoint of non-inferiority for MACE. The upper bound of the 95% conﬁdence interval of the Hazard Rao (HR) was above the pre-speciﬁed NI margin of 1.25 for primary MACE analysis (HR 1.17, 95% CI: 1.01, 1.36). Analysis of MACE events conducted by Akebia in the PRO TECT program revealed that the greater number of MACE events observed among vadadustat paents as compared to the acve comparator was primarily related to an excess of non-cardiovascular death and death-of-unknown-cause in regions outside of the U.S. where signiﬁcant diﬀerences in treatment paerns for NDD-CKD paents were observed. 2 2 The PRO TECT analysis plan was prospecvely designed to analyze the eﬀect of regional diﬀerences, most notably, well-known diﬀerences in Hb treatment targets. Within PRO TECT, U.S. paents were treated to a target Hb range of 10 to 11 g/dL and non-U.S. paents were treated to a target Hb range of 10 to 12 g/dL. In October of 2020, we presented a pre-speciﬁed regional analysis that showed vadadustat was not associated with a clinically meaningful increase in cardiovascular risk compared to darbepoen alfa in U.S. paents treated to a target Hb range of 10 to 11 g/dL, in an analysis of MACE (HR 1.06, 95% CI: 0.87, 1.29). 2 The incidence of TEAEs during the Correcon study in the vadadustat-treated paents was 90.9%, and 91.6% in darbepoen alfa-treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa-treated paents were end-stage renal disease (34.7%/ 35.2%), hypertension (17.7%/ 22.1.%), hyperkalemia (12.3.%/ 15.6%), urinary tract infecon (12.9%/ 12.0%), diarrhea (13.9%/ 10.0%), peripheral oedema (12.5%/ 10.5%), fall (9.6%/ 10%) and nausea (10%/ 8.2%). Serious TEAEs were 65.3% for vadadustat-treated paents and 64.5% for darbepoen alfa-treated paents. The incidence of TEAEs during the Conversion study in vadadustat treated paents was 89.1% and 87.7% in darbepoen alfa-treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa-treated paents were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract infecon (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%). Serious TEAEs were 58.5% for vadadustat-treated paents and 56.6% for darbepoen alfa-treated paents. Hepac Safety Proﬁle of Vadadustat in Clinical Studies During the conduct of our Phase 3 program our team and hepac experts analyzed hepac cases (unblinded to treatment). Further, following the compleon of our global Phase 3 clinical program for vadadustat, there was a review of hepac safety across the vadadustat clinical program, which included eight completed Phase 2 and 3 studies in NDD-CKD paents, 10 completed Phase 1, 2, and 3 studies, and two then-ongoing Phase 3b studies in DD-CKD paents, and 18 completed studies in healthy subjects (17 Phase 1 and one Phase 3). This review consisted of a blinded re-assessment of hepac events conducted by a separate panel of hepac experts. While hepatocellular injury aributed to vadadustat was reported in less than 1% of paents, there was one case of severe hepatocellular injury with jaundice, and we cannot guarantee that similar events will not happen in the future. Addionally, the FDA expressed safety concerns related to the risk of drug-induced liver injury in the CRL that it issued in March 2022. Modiﬁed Dosing Studies From May 2020 to January 2023, we also conducted addional studies of vadadustat evaluang a modiﬁed approach to a once-daily and three-mes weekly dosing, including assessment of a vadadustat starng dose based on an individual’s pre-conversion ESA dose prior to study entry and higher traon doses of vadadustat (up to 1200 mg). 2 The FO CUS study evaluated the eﬃcacy and safety of vadadustat in hemodialysis paents who were converted from a long-acng ESA to three-mes weekly oral vadadustat dosing for the maintenance treatment of anemia. FO CUS was an open-label, acve-controlled, sponsor-blinded study that evaluated 456 hemodialysis paents who were randomized (1:1:1) into a vadadustat 600mg starng dose, vadadustat 900mg starng dose, or a long-acng ESA (Mircera®) treatment arms. 2 The MO DIFY study evaluated the eﬃcacy and safety of vadadustat in hemodialysis paents using a modiﬁed once-daily dosing regimen diﬀerent from the INNO VATE program dosing and a three-mes-weekly dosing regimen of oral vadadustat compared to darbepoen alfa. 2 2 FO CUS Study 2 Primary and Secondary Eﬃcacy Endpoint Results 2 In the FO CUS study, each vadadustat starng dose regimen (600 mg, 900 mg) and the combined vadadustat-treated group achieved the primary eﬃcacy endpoint of the mean change in Hb between baseline and the primary evaluaon period (weeks 20-26) compared to Mircera in adult paents on hemodialysis, demonstrang non-inferiority to Mircera based on a non-inferiority margin of -0.75 g/dL. Similarly, each starng dose regimen of vadadustat and the combined vadadustat-treated Akebia Therapeucs, Inc. | Form 10-K | Page 14 Table of Contents group achieved the secondary eﬃcacy endpoint of the mean change in Hb between baseline and the secondary evaluaon period (weeks 46-52). In the FO CUS study in hemodialysis paents (n=456): 2 • • Primary Eﬃcacy Endpoint Results: Vadadustat demonstrated non-inferiority to Mircera. The least square mean diﬀerence in Hb was -0.43 g/dL (-0.67, -0.20) for the vadadustat 600 mg starng dose group, -0.23 g/dL (-0.46, 0.01) for the vadadustat 900 mg starng dose group, and -0.33 g/dL (-0.53, -0.13) for the combined vadadustat-treated group, achieving the pre-speciﬁed non-inferiority margin of -0.75 g/dL. The mean Hb level during the primary evaluaon period was 10.11 (0.061) g/dL for the combined vadadustat-treated group compared to 10.41 (0.068) g/dL for Mircera-treated group. Secondary Eﬃcacy Endpoint Results: Vadadustat demonstrated non-inferiority to Mircera. The least square mean diﬀerence in Hb was -0.27 g/dL (-0.54, -0.00) for the vadadustat 600 mg starng dose group, -0.38 g/dL (-0.67, -0.10) for the vadadustat 900 mg starng dose group, and -0.33 g/dL (-0.56, -0.09) for the combined vadadustat-treated group. The mean Hb level during the secondary evaluaon period was 10.03 (0.066) g/dL for the combined vadadustat-treated group compared to 10.28 (0.076) g/dL for the Mircera-treated group. Safety Results 2 In the FO CUS study, a total of 78.7% of paents experienced any TEAEs in the combined vadadustat-treated group, and 75.3% experienced any TEAEs in the Mircera-treated group. The data demonstrated that 44.5% of paents experienced any serious TEAEs in the combined vadadustat-treated group, and 44.7% of paents experienced any serious TEAEs in the Mircera-treated group. During the study, the most common TEAEs reported in vadadustat-/Mircera- treated paents were COVID-19 (14.6%/16.0%), diarrhea (12.3%/8.0%) and hyperkalaemia (9.0%/10.7%). MO DIFY Study 2 Primary and Secondary Eﬃcacy Endpoint Results 2 In the MO DIFY study, the vadadustat once-daily, or QD, treatment (starng dose: 300 or 450 mg) achieved the primary eﬃcacy endpoint of the mean change in Hb from baseline to the primary evaluaon period (weeks 20-26) compared to darbepoen alfa in adult paents on hemodialysis, demonstrang non- inferiority to darbepoen alfa based on a non-inferiority margin of -0.75 g/dL. Vadadustat three-mes-weekly, or TIW, treatment (starng dose: 600 or 750) did not demonstrate noninferiority to darbepoen alfa. Based on a sensivity analysis using the per protocol populaon, both vadadustat dosing regimens demonstrated noninferiority to darbepoen alfa of the mean change in Hb between baseline and the primary evaluaon period. Neither dosing regimen of vadadustat achieved the secondary eﬃcacy endpoint of the mean change in Hb between baseline and the secondary evaluaon period (weeks 46-52). In the MO DIFY study in hemodialysis paents (n=319): 2 • • • Primary Eﬃcacy Endpoint Results: Vadadustat QD treatment was non-inferior to darbepoen alfa. The least square mean diﬀerence in Hb was -0.27 g/dL (-0.55, 0.01) for the vadadustat QD-treated group, meeng the pre-speciﬁed non-inferiority margin of -0.75 g/dL. The least square mean diﬀerence in Hb was -0.53 g/dL (-0.80, -0.25) for the vadadustat TIW-treated group. The mean Hb level during the primary evaluaon period was 10.23 (1.07) g/dL and 10.02 (0.87) g/dL for the vadadustat QD and vadadustat TIW groups respecvely, compared to 10.45 (0.83) g/dL for the darbepoen alfa group. Secondary Eﬃcacy Endpoint Results: The secondary eﬃcacy endpoint was the change in average Hb between baseline and the secondary evaluaon period (Weeks 46 to 52). The least square mean diﬀerence in Hb was -0.40 g/dL (-0.79, -0.02) for the vadadustat QD-treated group and -0.42 g/dL (-0.81, -0.02) for the vadadustat TIW-treated group. Since noninferiority for the secondary eﬃcacy endpoint of vadadustat TIW to darbepoen alfa was not established, no claims of noninferiority were made for the secondary eﬃcacy endpoint. Other eﬃcacy Endpoint: The proporon of subjects with an average Hb value within the target range (US [10.0 to 11.0 g/dL] and Europe [10.0 to 12.0 g/dL]) was similar in the vadadustat QD, vadadustat TIW and darbepoen alfa treatment groups during the primary evaluaon period (weeks 20 to 26) (51.0%, 50.7%, and 54.5%, respecvely) and secondary evaluaon period (weeks 46 to 52) (50.4%, 48.3%, and 51.3%, respecvely). Safety Results Akebia Therapeucs, Inc. | Form 10-K | Page 15 Table of Contents Among all randomized paents who received at least one dose of the study medicaon (n=317), 84.8% and 84.6% of paents in the vadadustat QD and TIW groups, respecvely, experienced any TEAEs, compared to 80.6% in the darbepoen alfa group. The data showed that 44.8% of paents in the vadadustat QD group and 45.2% in the vadadustat TIW group experienced any treatment-emergent serious adverse events, compared to 43.5% of paents in the darbepoen alfa group. The most commonly reported TEAEs in paents treated with vadadustat QD, vadadustat TIW, and darbepoen alfa were COVID-19 (13.3%, 12.5%, and 13.0% respecvely), diarrhea (13.3%, 14.4%, and 5.6% respecvely), and anemia (7.6%, 10.6%, and 9.3% respecvely). Pipeline We connue to add to our pipeline and porolio of novel therapeucs through internal research, discovery and development. We have invested resources to build out a preclinical porolio and have selected two candidates for further preclinical development: AKB-9090, a drug targeng crical-care indicaons, and AKB-10108, a drug targeng condions related to premature birth. We intend to explore AKB-9090 for potenal use in AKI and ARDS, and AKB-10108 for potenal use in ROP. Acute Kidney Injury (AKI) AKI is a sudden decline in the ability of the kidneys to work and perform their normal funcons. AKI occurs in 20-30% of the approximately two million paents that undergo cardiac surgeries annually and there are no current treatments available for cardiovascular surgery-related AKI. Stabilizaon of HIF by prolyl hydroxylase inhibion leads to the release of erythropoien, a shi to anaerobic metabolism (glycolysis) and decreased inﬂammatory responses that collecvely lessen kidney ischemia-reperfusion injury and ameliorate the decline in kidney funcon. Data from our preclinical studies showed AKB-9090 to be highly acve in lessening the severity of AKI in an animal model of ischemia-reperfusion injury. Acute Respiratory Distress Syndrome (ARDS) ARDS is a life-threatening acute form of lung disease characterized by acute bilateral pulmonary edema and severe hypoxemia (low blood oxygen). Despite improvement in supporve care, a third-party study indicated high hospital mortality rates for paents with ARDS admied to parcipang intensive care units. The mortality rate among paents with ARDS in the study was: 34.9% with mild ARDS; 40.3% with moderate ARDS and 46.1% with severe ARDS. There are currently no treatments available for ARDS except for supporve care. Stabilizaon of HIF by prolyl hydroxylase inhibion leads to the release of erythropoien, increased extracellular adenosine signaling, increased glycolyc acvity and decreased inﬂammaon in lung epithelial cells that promote resoluon of the lung injury. Vadadustat lessened the severity of COVID-19 pneumonia in a clinical trial (NCT04478071) and improved outcomes in animal models of acute lung injury. We plan to conduct a trial with vadadustat for the treatment of ARDS due to suspected aspiraon, pathogen-associated pneumonia, or sepsis in hospitalized paents, which could further validate the therapeuc approach for HIF stabilizaon in ARDS and provide clinical data to support clinical development of an alternave HIF-based molecule such as AKB- 9090 for ARDS. Based on the data and our strategic business consideraons, we may not pursue vadadustat as a treatment for ARDS. Renopathy of Prematurity (ROP) ROP is the leading cause of blindness in preterm infants globally and occurs due to incomplete renal development and abnormal blood vessel growth in the rena. ROP is caused by the high oxygen therapy used to treat preterm babies, which prevents rena growth. Annually, there are approximately 100,000 new cases of infant blindness worldwide due to ROP and currently no preventave therapy. HIF-PH inhibitors can protect the rena by stabilizing HIF, which degrades during hyperoxia, allowing normal renal development and prevenng abnormal blood vessel growth that can lead to scarring, bleeding, renal detachment and blindness. Data from our preclinical studies of AKB-10108 in mouse and rat models of ROP showed signiﬁcant improvements in renal development under hyperoxic condions, as well as signiﬁcant reducons in abnormal blood vessel growth aer returning to normal oxygen levels. Manufacturing and Supply Overview We neither own nor operate, and currently have no plans to own or operate, any manufacturing or distribuon facilies. We rely on third-party contract manufacturing organizaons, or CMOs, to produce all of our preclinical, clinical and commercial supply, and third-party distributors to distribute Auryxia. We have established relaonships with several CMOs and expect to connue to rely on either exisng or alternave distributors and CMOs to distribute our products and supply our ongoing and planned preclinical studies and clinical trials and for commercial producon. Our CMOs have other clients and may have other priories that could aﬀect their ability to perform the work sasfactorily and/or on a mely basis. Both of these occurrences Akebia Therapeucs, Inc. | Form 10-K | Page 16 Table of Contents would be beyond our control. All clinical and commercial supplies are manufactured under current Good Manufacturing Pracces, or cGMPs, which is a regulatory standard for the producon of pharmaceucals that will be used in humans. Vadadustat We currently rely on a single-source supplier for the direct manufacture of our drug substance and drug product for clinical and commercial supply of vadadustat. We have entered into supply agreements with STA Pharmaceucal Hong Kong Limited, or STA, for the manufacture of vadadustat drug substance and drug product for commercial use. We plan to migate potenal commercial supply risks for vadadustat, if any, through inventory management and we may enter into addional manufacturing arrangements for both drug substance and drug product if vadadustat is approved in the U.S. Vadadustat is a small molecule. The synthesis of vadadustat is reliable and reproducible from starng materials available from mulple sources at commercially relevant scale using no unusual manufacturing equipment. Vadadustat can be formulated into compressed tablets using proprietary processes. As with any supply program, obtaining raw materials and ﬁnished drug product of the required quality and quanty cannot be guaranteed, and we cannot ensure that we will be successful in this endeavor. Auryxia The acve pharmaceucal ingredient of Auryxia, ferric citrate, is a small molecule. The synthesis of ferric citrate is reliable and reproducible from starng materials available from mulple sources at commercially relevant scale. Ferric citrate can be formulated into compressed tablets using proprietary manufacturing processes. As with any supply program, obtaining raw materials and ﬁnished drug product of the required quality and quanty cannot be guaranteed, and we cannot ensure that we will be successful in this endeavor. We ulize third pares for the commercial distribuon of Auryxia, including wholesale distributors and certain specialty pharmacy providers. We have also engaged Cardinal Health as the exclusive third-party logiscs distribuon agent for commercial sales of Auryxia. The third-party logiscs provides services to the Company that include storage, distribuon, processing product returns, customer service support, logiscs support, electronic data interface and system access support We have established CMO relaonships for the supply of Auryxia to help ensure that we will have suﬃcient material for ongoing commercial sales and clinical trials. We currently rely on a single-source supplier for the manufacture of our drug substance for clinical and commercial supply of Auryxia. The drug substance for Auryxia is supplied by Siegfried Evionnaz SA, pursuant to a supply agreement, as amended, with pricing structured on a per-kilogram basis. Auryxia drug product is supplied by Patheon Manufacturing Services LLC (Thermo Fisher) pursuant to a Master Manufacturing Service Agreement with per- bole pricing structured on a ered basis, with the price reduced as the product volume increases. These agreements require that we sasfy certain minimum purchase requirements, but we are not obligated to use them as our exclusive suppliers. For more informaon about our manufacturing agreements for Auryxia, see Part II, Item 7. Management’s Discussion and Analysis and Note 10, Commitments and Conngencies, to our consolidated ﬁnancial statements in Part II, Item 8. Financial Statements and Supplementary Data. License and Collaboraon Agreements Vadadustat License and Collaboraon Agreements Medice License Agreement On May 24, 2023, or the Medice Eﬀecve Date, we entered into the Medice License Agreement with Medice, under which we granted to Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in adult paents with chronic kidney disease in the Medice Territory. Under the Medice License Agreement, we received an up-front payment of $10.0 million and are eligible to receive the following payments: (i) commercial milestone payments up to an aggregate of $100.0 million, and (ii) ered royales ranging from 10% to 30% of Medice's annual net sales of vadadustat in the Medice Territory, subject to reducon in certain circumstances. The royales will expire on a country-by-country basis upon the latest to occur of (i) the date of expiraon of the last-to-expire valid claim of ours, Medice or joint patent that covers vadadustat in such country in the Medice Territory, (ii) the date of expiraon of data or regulatory exclusivity for vadadustat in such country in the Medice Territory and (iii) the date that is 12 years from ﬁrst commercial sale of vadadustat in such country in the Medice Territory. Under the Medice License Agreement, we retain the right to develop vadadustat for non-dialysis paents with anemia due to chronic kidney disease in the Medice Territory. If we develop vadadustat for non-dialysis paents and vadadustat receives markeng approval for non-dialysis paents in the Medice Territory, Medice will commercialize vadadustat for both Akebia Therapeucs, Inc. | Form 10-K | Page 17 Table of Contents indicaons in the Medice Territory. In this instance, we would receive 70% of the net product margin of any sales of vadadustat in the non-dialysis paent populaon, unless Medice requests to share the cost of the development necessary to gain approval to market vadadustat for non-dialysis paents in the Medice Territory and the pares agree on alternave ﬁnancial terms. We and Medice established a joint steering commiee to oversee the development and commercializaon of vadadustat in the Medice Territory. The Medice License Agreement expires on the date of expiraon of all payment obligaons due thereunder with respect to vadadustat in the last country in the Medice Territory, unless earlier terminated in accordance with the terms of the Medice License Agreement. Either party may, subject to a cure period, terminate the Medice License Agreement in the event of the other party's uncured material breach. Medice has the right to terminate the Medice License Agreement in its enrety for convenience upon twelve months' prior wrien noce delivered on or aer the date that is twelve months aer the Medice Eﬀecve Date. The Medice License Agreement includes customary terms relang to, among others, indemniﬁcaon, conﬁdenality, remedies, and representaons and warranes. The Medice License Agreement provides that we and Medice will enter into a supply agreement pursuant to which we will supply vadadustat to Medice for commercial use in the Medice Territory. We are currently negoang the terms of the supply agreement with Medice. MTPC Collaboraon Agreement In December 2015, we entered into a collaboraon agreement with MTPC, as amended, or the MTPC Agreement, providing MTPC with exclusive development and commercializaon rights to vadadustat in Japan and certain other Asian countries, or the MTPC Territory. In addion, we supply vadadustat to MTPC for both clinical and commercial use in the MTPC Territory, subject to MTPC’s opon to manufacture commercial drug product in the MTPC Territory. On July 15, 2020, we entered into a supply agreement with MTPC for the commercial supply of vadadustat for use in Japan and certain other Asian countries, as contemplated by the MTPC Agreement, which was amended eﬀecve as of December 5, 2022. Unless earlier terminated, the MTPC Agreement will connue in eﬀect on a country-by-country basis unl the later of the following: (i) expiraon of the last- to-expire patent covering vadadustat in such country in the MTPC Territory; (ii) expiraon of markeng or regulatory exclusivity in such country in the MTPC Territory; or (iii) ten years aer the ﬁrst commercial sale of vadadustat in such country in the MTPC Territory. MTPC may terminate the MTPC Agreement upon twelve months’ noce. Either party may terminate the MTPC Agreement upon the material breach of the other party that is not cured within a speciﬁed me period or upon the insolvency of the other party. Under the terms of the MTPC Agreement, we are eligible to receive payments from MTPC of up to approximately $225.0 million in the aggregate based on the achievement of certain development, regulatory and sales milestones, as well as ered royalty payments ranging from 13% to 20% on annual net sales of vadadustat in the MTPC Territory, subject to reducon upon launch of a generic product on a country-by-country basis. In February 2021, we entered into a royalty interest acquision agreement with HealthCare Royalty Partners IV, L.P., or HCR, whereby we sold our right to receive royales and sales milestones for vadadustat in Japan and certain other Asian countries in the MTPC territory under the MTPC Agreement, subject to certain caps and other terms and condions. For more informaon on our royalty interest acquision agreement with HCR, see Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, to our consolidated ﬁnancial statements in Part II, Item 8. Financial Statements and Supplementary Data of this Form 10-K. CSL Vifor License Agreement The Vifor Agreement grants CSL Vifor an exclusive license to sell vadadustat to the Supply Group in the Vifor Territory. We currently retain rights to commercialize vadadustat for use in the non-dialysis dependent CKD market, to market vadadustat to the Supply Group and to market and sell to dialysis organizaons outside of the Supply Group. During the term of the Vifor Agreement, CSL Vifor is not permied to sell any HIF product that competes with vadadustat in the Vifor Territory to the Supply Group. The Vifor Agreement provides that we will enter into a commercial supply agreement with CSL Vifor for vadadustat pursuant to which we will supply all of CSL Vifor’s requirements for vadadustat in the Vifor Territory. We have not yet entered into a supply agreement with CSL Vifor. The Vifor Agreement is structured as a proﬁt share arrangement between us and CSL Vifor in which we will receive approximately 66% of the proﬁt, net of certain pre-speciﬁed costs. In connecon with the amendment and restatement of the Vifor Agreement in February 2022, CSL Vifor made an upfront payment to us of $25.0 million. In addion, we entered into certain investment agreements with CSL Vifor, pursuant to which we sold CSL Vifor an aggregate of 7,571,429 shares of our common stock for a total of $70.0 million. The shares have not been registered pursuant to the Securies Act of 1933, as amended, or the Securies Act, and were issued and sold in reliance upon the exempon from registraon contained in Akebia Therapeucs, Inc. | Form 10-K | Page 18 Table of Contents Secon 4(a)(2) of the Securies Act and Rule 506 promulgated thereunder as the transacon did not involve any public oﬀering within the meaning of Secon 4(a)(2) of the Securies Act. Finally, CSL Vifor contributed $40.0 million to a working capital facility, or Working Capital Fund, established to parally fund our costs of purchasing vadadustat from our contract manufacturers. The amount available under the Working Capital Fund is reviewed at speciﬁed intervals and is adjusted based on a number of factors including outstanding supply commitments for vadadustat for the Vifor Territory and agreed upon vadadustat inventory levels held by us for the Vifor Territory. Addionally, upon terminaon or expiraon of the Vifor Agreement for any reason other than convenience by CSL Vifor (including following receipt of the CRL for vadadustat), we will be required to refund the outstanding balance of the Working Capital Fund on the date of terminaon or expiraon. Unless earlier terminated, the Vifor Agreement will expire upon the later of the expiraon of all patents that claim or cover vadadustat or the expiraon of markeng or regulatory exclusivity for vadadustat in the Vifor Territory. CSL Vifor may terminate the Vifor Agreement in its enrety upon 30 months’ prior wrien noce aer the ﬁrst anniversary of the receipt of regulatory approval, if approved, from the FDA for vadadustat for dialysis-dependent CKD paents. We may terminate the Vifor Agreement in its enrety for convenience, following the earlier of a certain period of me elapsing or following certain speciﬁed regulatory events, and upon six months’ prior wrien noce. If we terminate for convenience, subject to a speciﬁed excepon, we will pay a terminaon fee to CSL Vifor. In addion, either party may, subject to a cure period, terminate the Vifor Agreement in the event of the other party’s uncured material breach or bankruptcy. We may also terminate the Vifor Agreement upon the occurrence of certain other events. Auryxia License and Collaboraon Agreements Averoa License Agreement On December 22, 2022, we and Averoa entered into a license agreement, or Averoa License Agreement, pursuant to which we granted to Averoa an exclusive license to develop and commercialize ferric citrate, or Averoa Licensed Product, in the EEA, Turkey, Switzerland and the United Kingdom, or Averoa Territory. We and Averoa have established a joint steering commiee to oversee the development, manufacturing and commercializaon of the Averoa Licensed Product in the Averoa Territory. We expect Averoa will apply for markeng authorizaon for ferric citrate in Europe. Under the Averoa License Agreement, we are entled to receive ered, escalang royales ranging from a mid-single digit percentage to a low double-digit percentage of Averoa's annual net sales of the Averoa Licensed Product in the Averoa Territory, including certain minimum royalty amounts in certain years, and subject to reducon in certain circumstances. The royales will expire on a country-by-country basis upon the last to occur of (a) ten years following the date of ﬁrst commercial sale of the Licensed Product in such country; (b) expiraon of the last valid claim of our patent rights and joint patent rights in such country; and (c) the date of expiraon of the data, regulatory, or markeng exclusivity period conferred by the applicable regulatory authority in such country with respect to the Licensed Product. We have not received royales from Averoa. As of December 31, 2023, we have not received any consideraon under this agreement. The Averoa License Agreement expires on the date of expiraon of all royalty obligaons due thereunder with respect to the Averoa Licensed Product on a country-by-country basis in the Averoa Territory, unless earlier terminated in accordance with the Averoa License Agreement. The Averoa License Agreement provides that we and Averoa will enter into a supply agreement pursuant to which we will supply the Averoa Licensed Product to Averoa for commercial use in the Averoa Territory. We will have the right to terminate the supply agreement upon twenty-four months' noce. We have not yet entered into a supply agreement with Averoa. Sublicense Agreement with Japan Tobacco Inc. and Torii Pharmaceucal Co., Ltd. In September 2007, we entered into a Sublicense Agreement with JT and Torii, under which JT and Torii obtained the exclusive sublicense rights for the development and commercializaon of ferric citrate in Japan. Eﬀecve June 8, 2009, we entered into an Amended and Restated Sublicense Agreement, which was amended in June 2013, or the Revised Agreement, with JT and Torii. In January 2014, JT and Torii received manufacturing and markeng approval of ferric citrate from the Japanese Ministry of Health, Labour and Welfare. Ferric citrate hydrate, which launched in May 2014 and is being marketed in Japan by Torii under the brand name Riona, is indicated as an oral treatment for the improvement of hyperphosphatemia in paents with CKD, including NDD-CKD and DD-CKD. In July 2019, JT and Torii, reported posive top-line results from a pivotal Phase 3 comparave study evaluang Riona for the treatment of IDA in adult paents in Japan, which was approved in March 2021. In May 2020, JT and Torii ﬁled an applicaon for approval of IDA as an addional indicaon for Riona in Japan. Under the terms of the Revised Agreement with JT and Torii, we are eligible to receive royalty payments based on a ered low double-digit percentage of net sales of Riona in Japan inclusive of amounts that we must pay to Panion on JT and Torii’s net sales of Riona under the Panion Amended License Agreement, subject to certain reducons upon expiraon or terminaon of the Panion Amended License Agreement, and may also receive up to an addional $55.0 million upon the achievement of certain annual Akebia Therapeucs, Inc. | Form 10-K | Page 19 Table of Contents net sales milestones. We recorded $5.4 million in license revenue related to royales earned on net sales of Riona in Japan during the twelve months ended December 31, 2023. The sublicense under the Revised Agreement terminates upon the expiraon of all underlying patent rights. Also, JT and Torii may terminate the Revised Agreement with or without cause upon at least six months prior wrien noce to us. Addionally, either party may terminate the Revised Agreement for cause upon 60 days’ prior wrien noce aer the breach of any uncured material provision of the Revised Agreement, or aer certain insolvency events. License Agreement with Panion & BF Biotech, Inc. for Which We Currently Pay Royales On April 17, 2019, we and Panion & BF Biotech, Inc., or Panion, entered into a second amended and restated license agreement, or the Panion Amended License Agreement, which amended and restated in full the license agreement between us and Panion. The Panion Amended License Agreement provides us with an exclusive license under Panion-owned know-how and patents covering the rights to sublicense, develop, make, use, sell, oﬀer for sale, import and export ferric citrate worldwide, excluding certain Asian Paciﬁc counes, or the Licensor Territory. The Panion Amended License Agreement also provides Panion with an exclusive license under our patents covering the rights to sublicense (with our wrien consent), develop, make, use, sell, oﬀer for sale, import and export ferric citrate in certain countries in the Licensor Territory. Consistent with the Panion License Agreement, under the Panion Amended License Agreement, Panion is eligible to receive from us or any sublicensee royalty payments based on a mid-single digit percentage of net sales of ferric citrate in our licensed territories. We are eligible to receive from Panion or any sublicensee royalty payments based on a mid-single digit percentage of net sales of ferric citrate in Panion’s licensed territories. The Panion Amended License Agreement terminates upon the expiraon of each of our and Panion’s obligaons to pay royales thereunder. In addion, we may terminate the Panion Amended License Agreement (i) in its enrety or (ii) with respect to one or more countries in our licensed territory, in either case upon 90 days’ noce. We and Panion also each have the right to terminate the Panion Amended License Agreement upon the occurrence of a material breach of the Panion Amended License Agreement by the other party, subject to certain cure provisions, or certain insolvency events. The Panion Amended License Agreement also provides that, on a country-by-country basis, during the term and unl the second anniversary of the expiraon of our or Panion’s obligaon, as applicable, to pay royales in a country in which such party has ferric citrate for sale on the date of such expiraon, neither the other party nor its aﬃliates will, directly or indirectly, sell, distribute or otherwise commercialize or supply or cause to supply ferric citrate to a third party for sale or distribuon in such country. In addion, the Panion Amended License Agreement provides that each of us and Panion has the right, but not the obligaon, to conduct ligaon against any infringer of certain patent rights under the Panion Amended License Agreement in certain territories. During the year ended December 31, 2023, we recorded $10.0 million in royales due to Panion relang to the sales of Auryxia in the U.S. and JT and Torii net sales of Riona in Japan. Cyclerion Therapeucs License Agreement In June 2021, we entered into the Cyclerion Agreement with Cyclerion Therapeucs, Inc., or Cyclerion, under which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an invesgaonal oral soluble guanylate cyclase, or sGC, smulator. Under the terms of the Cyclerion Agreement, we paid $3.0 million in cash upfront to Cyclerion and expensed the amount to research and development, or R&D, expense in June 2021. In addion, Cyclerion is eligible to receive up to an aggregate of $222.0 million from us in speciﬁed development and regulatory milestone payments on a product-by-product basis. Cyclerion will also be eligible to receive speciﬁed commercial milestones as well as ered royales ranging from a mid-single-digit to mid-teen percentage of net sales, on a product-by-product basis, and subject to reducon upon expiraon of patent rights or the launch of a generic product in the territory. Unless earlier terminated, the Cyclerion Agreement will expire on a product-by-product and country-by-country basis upon the expiraon of the last royalty term, which ends upon the longest of (i) the expiraon of the patents licensed under the Cyclerion Agreement, (ii) the expiraon of regulatory exclusivity for such product and (iii) 10 years from ﬁrst commercial sale of such product. We may terminate the Cyclerion Agreement in its enrety or only with respect to a parcular licensed compound or product upon 180 days' prior wrien noce to Cyclerion. We and Cyclerion also have customary terminaon rights, subject to a cure period, in the event of the other party’s material breach of the Cyclerion Agreement or in the event of certain addional circumstances. Intellectual Property The proprietary nature of, and protecon for, our products, product candidates and our discovery programs, processes and know-how are important to our business. Our policy is to seek to protect our proprietary posion by, among other methods, ﬁling patent applicaons related to our proprietary technology, invenons and improvements that are important to the Akebia Therapeucs, Inc. | Form 10-K | Page 20 Table of Contents development and implementaon of our business. We also rely on know-how, connuing technological innovaon and potenal in-licensing opportunies to develop and maintain our proprietary posion. Addionally, we may beneﬁt from a variety of statutory frameworks in the U.S., Europe and other countries that provide periods of non-patent-based exclusivity for qualifying molecules. Our commercial success will depend in part on obtaining and maintaining patent protecon of our current products as well as current and future product candidates, methods of their use and the methods used to develop and manufacture them, as well as successfully defending these patents against third-party challenges. Our ability to stop third pares from making, using, selling, oﬀering to sell or imporng our products depends on the extent to which we have rights under valid and enforceable patents that cover these acvies. We cannot be sure that patents will be granted with respect to any of our pending patent applicaons or with respect to any patent applicaons ﬁled by us in the future, nor can we be sure that any of our exisng patents or any patents that may be granted to us in the future will be commercially useful in protecng our product candidates, discovery programs and processes. Even once patents successfully issue, third pares may challenge the validity, enforceability, inventorship, or scope thereof, which may result in such patents being narrowed, invalidated or held not infringed or unenforceable. For this and more comprehensive risks related to our intellectual property, please see “Risk Factors—Risks Related to our Intellectual Property” in Part I, Item 1A. Risk Factors. Individual patents extend for varying periods of me depending on the date of ﬁling of the patent applicaon or the date of patent issuance and the legal term of patents in the countries in which they are obtained. Generally, patents issued from applicaons ﬁled in the U.S. are eﬀecve for 20 years from the earliest ﬁling date of a U.S. non-provisional applicaon or an internaonal applicaon ﬁled under the Patent Cooperaon Treaty. In addion, in certain instances, a patent term can be extended to recapture a poron of the term eﬀecvely lost as a result of the FDA regulatory review period, however, the restoraon period cannot be longer than ﬁve years and the total patent term including the restoraon period must not exceed 14 years following FDA approval. The duraon of foreign patents varies in accordance with provisions of applicable local law, but typically is also 20 years from the earliest internaonal ﬁling date. Patent term recapture for loss of term as a result of the regulatory review period is available in some foreign jurisdicons. In the U.S., a patent’s term may also be lengthened by patent term adjustment, which compensates a patentee for administrave delays by the U.S. Patent and Trademark Oﬃce, or USPTO, in granng a patent, or may be shortened if a patent is terminally disclaimed over an earlier-ﬁled patent. Changes in either the patent laws or interpretaons of patent laws in the U.S. and other countries can diminish our ability to protect our invenons and enforce our intellectual property rights. Accordingly, we cannot predict the breadth or enforceability of claims that may be granted in our patents or in third- party patents. The biotechnology and pharmaceucal industries are characterized by extensive ligaon regarding patents and other intellectual property rights. Our ability to maintain and solidify our proprietary posion for our drugs and technology will depend on our success in obtaining eﬀecve claims and enforcing those claims once granted. We do not know whether any of the patent applicaons that we may ﬁle or license from third pares will result in the issuance of any patents. The issued patents that we own or license or may receive or acquire in the future may be challenged, invalidated or circumvented, and the rights granted under any issued patents may not provide us with suﬃcient protecon or compeve advantages against competors with similar technology. Furthermore, our competors may be able to independently develop and commercialize similar drugs or duplicate our technology, business model or strategy without infringing our patents. Because of the extensive me required for clinical development and regulatory review of a drug we may develop, it is possible that, before any of our drugs can be commercialized, any related patent may expire or remain in force for only a short period following commercializaon, thereby reducing any advantage of any such patent. The patent posions for vadadustat and Auryxia are summarized below. Vadadustat Patent Porolio We hold 19 issued patents covering the composion of maer, polymorph, method of treang anemia, pharmaceucal composions of vadadustat, and processes for manufacturing vadadustat in the U.S. and addional patents issued or pending in many other major jurisdicons worldwide, including Europe, Japan, China, South Korea, Brazil, Mexico, Russia, Israel and India. The expected expiraon dates for these patents are between 2027 and 2039 plus any extensions or adjustments of term available under naonal law. We also hold patents and patent applicaons directed to starng materials and intermediates in the processes for manufacturing vadadustat, dosing regimens, formulaons and various other aspects relang to the treatment of anemia using vadadustat that are expected to expire between 2032 and 2042 exclusive of possible patent term extensions or adjustments. We have ongoing opposion proceedings relang to vadadustat. See Part I, Item 3. Legal Proceedings for further informaon relang to these maers. Akebia Therapeucs, Inc. | Form 10-K | Page 21 Table of Contents Auryxia Patent Porolio Pursuant to the Panion Amended License Agreement, we have the exclusive rights under a series of patents and patent applicaons to commercialize Auryxia worldwide, excluding certain Asian-Paciﬁc countries. These patents and patent applicaons include claims directed to composions of maer, pharmaceucal composions, methods of treatment, as well as methods for the manufacture of Auryxia. Our patent rights include 14 issued U.S. patents listed in the Orange Book covering the composion of maer, method of treang hyperphosphatemia, and pharmaceucal composions of Auryxia. The expected expiraon dates for these patents are between 2024 and 2030 plus any addional patent term extensions that may be available. Pursuant to the sublicense with our Japanese partner, Japan Tobacco Inc., or JT, and its subsidiary, Torii Pharmaceucal Co. Ltd., or Torii, we have exclusively sublicensed certain Japanese patent rights to JT and Torii. These sublicensed rights include several Japanese patents and pending patent applicaons with composion of maer claims, methods of synthesizing claims, and methods of use claims covering Riona, the trade name under which JT and Torii market ferric citrate in Japan. The expected expiraon dates for these patents and pending patent applicaons are between 2025 and 2028. To date, to our knowledge, no contested proceedings or third-party claims have been lodged against any of these Japanese patents. Pursuant to the sublicense with our European partner, Averoa, we have exclusively sublicensed certain European patent rights to Averoa. These sublicensed rights include several European patents and pending patent applicaons with composion of maer claims and methods of use claims covering ferric citrate. The expected expiraon dates for these patents and pending patent applicaons are between 2024 and 2036. To date, to our knowledge, no contested proceedings or third-party claims have been lodged against any of these European patents. We received Paragraph IV cerﬁcaon noce leers regarding abbreviated new drug applicaons, or ANDAs, submied to the FDA by third pares requesng approval for generic versions of Auryxia tablets (210 mg ferric iron per tablet). In response we ﬁled certain complaints for patent infringement against six third pares, and have entered into selement and license agreements with each of the six ANDA ﬁlers. Each selement agreement granted the defendants a license to market a generic version of Auryxia in the U.S. beginning on March 20, 2025 (subject to FDA approval), or earlier under certain circumstances customary for selement agreements of this nature. Other Intellectual Property Rights We depend upon trademarks, trade secrets, know-how and connuing technological advances to develop and maintain our compeve posion. To maintain the conﬁdenality of trade secrets and proprietary informaon, we require our employees, scienﬁc advisors, consultants and collaborators, upon commencement of a relaonship with us, to execute conﬁdenality agreements and, in the case of pares other than our research and development collaborators, to agree to assign their invenons to us. These agreements are designed to protect our proprietary informaon and to grant us ownership of technologies that are developed in connecon with their relaonship with us. These agreements may not, however, provide protecon for our trade secrets in the event of unauthorized disclosure of such informaon. In addion to patent protecon, we may ulize orphan drug regulaons, pediatric exclusivity or other provisions of the Food, Drug and Cosmec Act of 1938, as amended, or FDCA, such as new chemical enty exclusivity or new formulaon exclusivity, to provide market exclusivity for a product candidate. In the U.S., the FDA has the authority to grant addional data protecon for approved drugs where the sponsor conducts speciﬁed tesng in pediatric or adolescent populaons. If granted, this pediatric exclusivity may provide an addional six months which are added to the term of data protecon as well as to the term of a relevant patent, to the extent these protecons have not already expired. We may also seek to ulize market exclusivies in other territories. We cannot assure you that our products or any product candidates we may acquire or in-license, will obtain such orphan drug designaon, pediatric exclusivity, new chemical enty exclusivity or any other market exclusivity in the U.S., European Union, or EU, or any other territory, or that we will be the ﬁrst to receive the respecve regulatory approval for such drugs so as to be eligible for any market exclusivity protecon. Know-How In addion to patents, we rely upon unpatented know-how and connuing technological innovaon to develop and maintain our compeve posion. We seek to protect our proprietary informaon, in part, using conﬁdenality agreements with our collaborators, employees and consultants and invenon assignment provisions in the conﬁdenality agreements with our employees. These agreements are designed to protect our proprietary informaon and, in the case of the invenon assignment provisions, to grant us ownership of technologies that are developed by our employees. These agreements may be breached, and we may not have adequate remedies for any breach. To the extent that our commercial partners, collaborators, employees and consultants use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulng know-how and invenons. Akebia Therapeucs, Inc. | Form 10-K | Page 22 Table of Contents The Hatch-Waxman Act Orange Book Lisng In seeking approval for a drug through an NDA, sponsors are required to list with the FDA each patent whose claims cover the sponsor’s product. Upon approval of a drug, each of the patents listed in the applicaon for the drug is then published in the FDA’s Approved Drug Products with Therapeuc Equivalence Evaluaons, commonly known as the Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potenal generic competors in support of approval of an ANDA. An ANDA provides for markeng of a drug product that has the same acve ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence tesng to be therapeucally equivalent to the listed drug. Other than the requirement for bioequivalence tesng, ANDA sponsors are usually not required to conduct, or submit results of, nonclinical or clinical tests to prove the safety or eﬀecveness of their drug product. Drugs approved in this way are commonly referred to as “generic equivalents” to the listed drug and can oen be substuted by pharmacists under prescripons wrien for the original listed drug. The ANDA sponsor is required to make certain cerﬁcaons to the FDA concerning any patents listed for the approved product in the FDA’s Orange Book. Speciﬁcally, the sponsor must cerfy that: (i) the required patent informaon has not been ﬁled; (ii) the listed patent has expired; (iii) the listed patent has not expired but will expire on a parcular date and approval is sought aer patent expiraon; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA sponsor may also elect to submit a Secon viii statement, cerfying that its proposed ANDA label does not contain or carve out any language regarding the patented method-of-use, rather than cerfy to a listed method-of-use patent. If the sponsor does not challenge the listed patents, the ANDA will not be approved unl all the listed patents claiming the referenced product have expired. A cerﬁcaon that the new product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV cerﬁcaon. If the ANDA sponsor has provided a Paragraph IV cerﬁcaon to the FDA, the sponsor must also send noce of the Paragraph IV cerﬁcaon to the NDA and patent holders once the ANDA has been accepted for ﬁling by the FDA. The NDA and patent holders may then iniate a patent infringement lawsuit in response to the noce of the Paragraph IV cerﬁcaon. The ﬁling of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV cerﬁcaon automacally prevents the FDA from approving the ANDA unl the earlier of 30 months from receiving the Paragraph IV cerﬁcaon, expiraon of the patent, selement of the lawsuit or a decision in the infringement case that is favorable to the ANDA sponsor. Also, the ANDA will not be approved unl any applicable non-patent exclusivity listed in the Orange Book for the referenced product has expired. Exclusivity Upon NDA approval of a new chemical enty, or NCE, which is a drug that contains an acve moiety that has not been approved by the FDA in any other NDA, that drug receives ﬁve years of markeng exclusivity during which me the FDA cannot accept any ANDA seeking approval of a generic version of that drug. Certain changes to a drug, such as the addion of a new indicaon to the package insert, are associated with a three-year period of exclusivity during which the FDA cannot approve an ANDA for a generic drug that includes such changes. An ANDA may be submied one year before NCE exclusivity expires if a Paragraph IV cerﬁcaon is ﬁled. If there is no listed patent in the Orange Book, there may not be a Paragraph IV cerﬁcaon, and, thus, no ANDA may be ﬁled before the expiraon of the exclusivity period. Patent Term Extension Aer NDA approval, owners of relevant drug patents or their agents may apply for up to a ﬁve-year patent extension for delays caused by FDA regulatory review. The allowable patent term extension is calculated as half of the drug’s tesng phase which is the me between Invesgaonal New Drug applicaon, or IND submission, and NDA submission, and all of the review phase, which is the me between NDA submission and approval, up to a maximum of ﬁve years. The me can be shortened if the FDA determines that the sponsor did not pursue approval with due diligence. The total patent term aer the extension may not exceed 14 years from the date of approval by virtue of the patent term extension. We have ﬁled applicaons under the patent term extension provisions of 35 U.S.C. § 156 for U.S. Patent Nos. 8,299,298, 8,093,423, 7,767,851 and 8,338,642 each of which covers Auryxia for delays caused by FDA regulatory review. If granted, we can ulize the patent term extension on one of these patents, however, we cannot assure you that we can obtain any extension of the term of these patents. Upon expiraon of these patents, competors who obtain the requisite regulatory approval may potenally oﬀer products with the same composion and/or method of use as our product, so long as the competors do not infringe any other patents that we may own or license. For patents that might expire before a determinaon regarding patent term extension, the patent owner or its agent may request an interim patent term extension. An interim patent extension increases the patent term by one year and may be renewed up to four mes. For each interim patent extension granted, the post-approval patent extension is reduced by one Akebia Therapeucs, Inc. | Form 10-K | Page 23 Table of Contents year. The director of the USPTO must determine that approval of the drug covered by the patent for which a patent extension is being sought is likely. In addion, certain jurisdicons outside of the U.S., including Japan, have provisions that provide for patent term extension. In October 2014, following the regulatory approval of Riona in Japan, the Japan Patent oﬃce granted the patent term extensions ﬁled by our sublicensee, JT, for Japanese Patents Nos. 4964585 and 4173553. As a result of the extension of patent term, Japanese Patent No. 4173553 expired in November 2022 and Japanese Patent No. 4964585 will expire in November 2025 for hyperphosphatemia and December 2028 for iron deﬁciency anemia. In the future, if and when our product candidates, including vadadustat, receive approval by the FDA or foreign regulatory authories, we expect to apply for patent term extensions on issued patents covering those drugs, depending upon the length of the clinical trials for each product candidate and other factors. There can be no assurance that any of our pending patent applicaons will issue or that we will beneﬁt from any patent term extension or favorable adjustment to the term of any of our patents. Compeon The pharmaceucal and biotechnology industries are highly compeve, with several key players oﬀering innovave soluons. The growing prevalence of CKD and the increasing demand for beer anemia management soluons connue to drive compeon innovaon in this market. Our competors include public and private pharmaceucal and biotechnology companies, academic instuons, and public and private research instuons. In addion, companies that are acve in diﬀerent but related ﬁelds represent substanal compeon for us. Mergers and acquisions in the pharmaceucal and biotechnology industries may result in a larger concentraon of resources among a smaller number of our competors. These organizaons, as well as others in the broader industries, compete with us to recruit qualiﬁed personnel, aract partners for joint ventures or other collaboraons and license compeve technologies to ours. While major pharmaceucal companies are connuously invesng in R&D and have signiﬁcantly greater capital resources, larger R&D teams and facilies and more experience in drug development, regulaon, manufacturing and markeng than we do; we believe our novel HIF-PH inhibitors have the potenal to revoluonize the treatment landscape in mulple areas, including anemia due to CKD. To compete successfully in these industries, we must connue to idenfy novel and unique drugs or treatment methods and complete the development of those drugs as treatments before our competors. Vadadustat Competors Drugs that may compete with vadadustat, if approved, include Epogen® (epoen alfa) and Aranesp® (darbepoen alfa), both commercialized by Amgen, Procrit® (epoen alfa) and Eprex® (epoen alfa), commercialized by Johnson & Johnson in the U.S. and Europe, respecvely, and Mircera® (methoxy PEG- epoen beta), commercialized by CSL Vifor in the U.S. and Roche Holding Ltd. outside of the U.S. and Evrenzo (roxadustat) in Europe commercialized by Astellas Pharma Inc. (R) In addion, in the U.S., the FDA approved Jesduvroq (daprodustat), an oral HIF-PH inhibitor from GSK, for the once-a-day treatment of anemia due to CKD in adults who have been receiving dialysis for at least four months. FibroGen Inc., or FibroGen, ﬁled an NDA with the FDA for its product candidate, roxadustat, to which the FDA issued a complete response leer indicang the FDA will not approve the NDA in its present form. We and our partners may also face compeon from potenal new anemia therapies. There are several other HIF-PH inhibitor product candidates in various stages of development for anemia indicaons that may be in direct compeon with vadadustat, if and when approved and launched commercially. These candidates are being developed by companies such as JT and Bayer HealthCare AG, or Bayer. Furthermore, certain companies are developing new therapies for renal-related diseases that potenally could reduce injectable ESA ulizaon and thus limit the market potenal for vadadustat if approved and launched commercially. Other new therapies are in development for treang condions, including renal anemia, that may impact the market for anemia-targeted treatment. In Japan, vadadustat is sold under the name Vafseo, which is approved for paents with CKD, including both DD-CKD and NDD-CKD, and competes with roxadustat, daprodustat and enarodustat. Roxadustat is approved for the treatment of anemia due to CKD, including DD-CKD and NDD-CKD paents. In addion, daprodustat, GSK’s product candidate, and enarodustat, JT’s product candidate, are approved in Japan for the treatment of anemia due to CKD. In addion, Bayer HealthCare AG has submied a new drug applicaon for its product candidate for the treatment of renal anemia in Japan. In China, FibroGen launched roxadustat for the treatment of anemia due to CKD in DD-CKD paents and for the treatment of anemia due to CKD in NDD-CKD paents. A biosimilar is a biologic product approved based on demonstrang that it is highly similar to an exisng, FDA-approved branded biologic product. The patents for the exisng, branded biologic product must expire in a given market before biosimilars may enter that market without the risk of being sued for patent infringement. In addion, an applicaon for a Akebia Therapeucs, Inc. | Form 10-K | Page 24 Table of Contents biosimilar product can only be approved by the FDA 12 years aer the exisng, branded product was approved under a Biologics License Applicaon, or BLA. The patents for epoen alfa, an injectable ESA, expired in 2004 in the EU, and the remaining patents expired between 2012 and 2016 in the U.S. Because injectable ESAs are biologic products, introducing biosimilars into the injectable ESA market in the U.S. will constute addional compeon for vadadustat if we are able to obtain approval for and commercially launch vadadustat. In the U.S., Pﬁzer’s biosimilar version of injectable ESAs, Retacrit® (epoen alfa-epbx), was approved by the FDA in May 2018 and launched in November 2018 and several biosimilar versions of injectable ESAs are available for sale in the EU. Furthermore, if approved, vadadustat’s commercial opportunies, may be reduced or eliminated if our competors develop and market products that are less expensive, more eﬀecve, safer or oﬀer greater paent convenience than vadadustat. Auryxia Competors Hyperphosphatemia Compeon Auryxia is compeng in the hyperphosphatemia market in the U.S. with other FDA-approved phosphate binders such as Renagel® (sevelamer hydrochloride) and Renvela® (sevelamer carbonate), both marketed by Sanoﬁ, PhosLo® and Phoslyra® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol® (lanthanum carbonate), marketed by Shire Pharmaceucals Group plc, and Velphoro® (sucroferric oxyhydroxide), marketed by Fresenius Medical Care North America, as well as over-the-counter calcium carbonate products such as TUMS® and metal-based opons such as aluminum, lanthanum and magnesium. Most of the phosphate binders listed above are now also available in generic forms. In addion, other agents are in development, including OPKO Health Inc.’s Alpharen™ Tablets (fermagate tablets) and Unicycive’s RENAZORB™ (lanthanum dioxycarbonate) or could otherwise enter the market that may impact the market for Auryxia. In October 2023, the FDA approved XPHOZAH® (tenapanor), a phosphate absorpon inhibitor that is marketed by Ardelyx, Inc. and indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in paents who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. Iron Deﬁciency Anemia Compeon Auryxia is compeng in the IDA market in the U.S. with over-the-counter oral iron, ferrous sulfate, other prescripon oral iron formulaons, including ferrous gluconate, ferrous fumerate, and polysaccharide iron complex, and intravenous iron formulaons, including Feraheme® (ferumoxytol injecon), Venofer® (iron sucrose injecon), Ferrlicit® (sodium ferric gluconate complex in sucrose injecon), Injectafer® (ferric carboxymaltose injecon), and Triferic® (ferric pyrophosphate citrate). In addion, other new therapies for the treatment of IDA may impact the market for Auryxia, such as Shield Therapeuc’ plc's Feraccru® (ferric maltol), which is available in Europe for the treatment of IDA, and Accrufer® (ferric maltol), which was launched in the U.S. for the treatment of IDA in July 2021. Furthermore, Auryxia’s commercial opportunies may be reduced or eliminated if our competors develop and market products that are less expensive, more eﬀecve, safer or oﬀer greater paent convenience than Auryxia. Other companies have product candidates in various stages of preclinical or clinical development to treat diseases and complicaons of the diseases for which we are markeng Auryxia. In addion, we entered into selement agreements with each of our ANDA ﬁlers pursuant to which we granted licenses to market a generic version of Auryxia in the U.S. beginning in March 2025 (subject to FDA approval), or earlier under certain circumstances customary for selement agreements of this nature, which may materially adversely impact our business and results of operaons. Government Regulaon and Product Approvals Government authories in the U.S., at the federal, state and local level, and in other countries and jurisdicons, including the EU, extensively regulate, among other things, the research, development, tesng, manufacture, quality control, approval, packaging, storage, recordkeeping, labeling, adversing, promoon, distribuon, markeng, sales, pricing, reimbursement, post-approval monitoring and reporng, and import and export of pharmaceucal products. The processes for obtaining regulatory approvals in the U.S. and in foreign countries and jurisdicons, along with subsequent compliance with applicable statutes and regulaons and other regulatory requirements, require the expenditure of substanal me and ﬁnancial resources. Review and Approval of Drug Products in the U.S. In the U.S., the FDA approves and regulates drugs under the FDCA and applicable implemenng regulaons and guidance. Our product candidates must be approved by the FDA for therapeuc indicaons before we or our partners are able to market them in the U.S. A company, instuon, or organizaon which takes responsibility for the iniaon and management of a clinical development program for such products is referred to as a sponsor. A sponsor seeking approval to market and distribute a new drug product in the U.S. must typically undertake the following: Akebia Therapeucs, Inc. | Form 10-K | Page 25 Table of Contents • • • • • • • • • • compleon of preclinical laboratory tests, animal studies and formulaon studies in compliance with the FDA’s good laboratory pracce, or GLP, regulaons and consistent with Internaonal Council for Harmonisaon of Technical Requirements for Pharmaceucals for Human Use, or ICH, requirements; design of a clinical protocol and submission to the FDA of an IND for human clinical tesng, which must be reviewed and acve by the FDA before human clinical trials may begin; approval by an independent local or central instuonal review board, or IRB, represenng each clinical site before each clinical trial may be iniated; performance of adequate and well-controlled human clinical trials in accordance with good clinical pracces, or GCP, to establish the safety and eﬃcacy of the proposed product candidate for each indicaon; preparaon and submission to the FDA of an NDA requesng markeng for one or more proposed indicaons; review of the product candidate by an FDA advisory commiee, where appropriate or if applicable; sasfactory compleon of one or more FDA inspecons of the manufacturing facility or facilies at which the product candidate, or components thereof, are produced to assess compliance with current Good Manufacturing Pracces, or cGMP, requirements and to assure that the facilies, methods and controls are adequate to preserve the product candidate’s identy, strength, quality and purity; sasfactory compleon of FDA audits of clinical trial sites and records to assure compliance with GCPs and good pracces, or GxPs, the integrity of the clinical data and that adequate controls and oversight are in place regarding manufacturing, clinical trials, pharmacovigilance, safety, data management, vendor oversight, collecon and reporng of serious adverse events and other acvies; payment of user fees and securing FDA approval of an NDA; and compliance with any post-approval requirements and/or commitments, including the potenal requirement to implement a risk evaluaon and migaon strategy, or REMS, and potenally post-market requirement, or PMR, and post-market commitment, or PMC, studies. Preclinical Tests Before a sponsor begins tesng a product candidate with potenal therapeuc value in humans, the product candidate enters the preclinical tesng stage. Preclinical tests include laboratory evaluaons of product chemistry, formulaon and stability, as well as other studies to evaluate, among other things, the toxicity of the product candidate. The conduct of the preclinical tests and formulaon of the compounds for tesng must comply with federal regulaons and requirements, including GLP regulaons and standards and the U.S. Department of Agriculture’s Animal Welfare Act, if applicable. The results of the preclinical tests, together with manufacturing informaon and analycal data, are submied to the FDA as part of an IND and are generally referred to as IND-enabling studies. Some long-term preclinical tesng, such as animal tests of reproducve adverse events and carcinogenicity, and long-term toxicity studies, may connue aer the IND is submied. The IND and IRB Processes Clinical trials involve the administraon of the invesgaonal product to human paents under the supervision of qualiﬁed invesgators in accordance with GCP requirements, which include, among other things, the requirement that all research paents provide their voluntary informed consent in wring before their parcipaon in any clinical trial. Clinical trials are conducted under wrien study protocols detailing, among other things, the inclusion and exclusion criteria, the objecves of the study, the parameters to be used in monitoring safety and the eﬀecveness criteria to be evaluated. In support of a request for an IND, sponsors must submit a protocol for each clinical trial and any subsequent protocol amendments must be submied to the FDA as part of the IND. An IND is an exempon from the FDCA that allows an unapproved drug to be shipped through interstate commerce for use in an invesgaonal clinical trial and a request for FDA authorizaon to administer an invesgaonal drug to humans. Such authorizaon must be obtained prior to interstate shipment and administraon of any new drug that is not the subject of an approved NDA. In addion to reviewing an IND to assure the safety and rights of paents, the FDA also focuses on the quality of the invesgaon and whether it will be adequate to permit an evaluaon of the drug’s safety and eﬃcacy. The results of the preclinical tests, together with manufacturing informaon, analycal data, any available clinical data or literature and plans for clinical trials, among other things, are submied to the FDA as part of an IND. The FDA requires a 30-day waing period aer the submission of each IND before clinical trials may begin. This waing period is designed to allow the FDA to review the IND to determine whether human research paents will be exposed to unreasonable health risks. At any me during this 30-day period, or thereaer, the FDA may raise concerns or quesons about the conduct of the trials as outlined in the IND and impose a clinical hold or paral clinical hold or require that the sponsor amend the clinical protocol to include addional safety measurements. In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin (or resume if the clinical trial had been ongoing at the me a clinical hold was imposed). Akebia Therapeucs, Inc. | Form 10-K | Page 26 Table of Contents In addion to the foregoing requirements related to the IND submission, an IRB represenng each instuon parcipang in the clinical trial must review and approve the plan for any clinical trial before it commences at that instuon, and the IRB must conduct a connuing review and reapprove the trial at least annually. The IRB must review and approve, among other things, the trial protocol and informed consent informaon to be provided to study paents. An IRB must operate in compliance with FDA regulaons. An IRB can suspend or terminate approval of a clinical trial at its instuon, or an instuon it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the product candidate has been associated with unexpected serious harm to paents. A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND. When a foreign clinical study is conducted under an IND, all IND requirements must be met unless waived by the FDA. When a foreign clinical study is not conducted under an IND, the sponsor must ensure that the study complies with certain regulatory requirements of the FDA in order to use the study as support for an IND or applicaon for markeng approval. Speciﬁcally, the studies must be conducted in accordance with GCP, including undergoing review and receiving approval by an independent ethics commiee and seeking and receiving informed consent from subjects. GCP requirements encompass both ethical and data integrity standards for clinical trials. The FDA’s regulaons are intended to help ensure the protecon of human subjects enrolled in non-IND foreign clinical trials, as well as the quality and integrity of the resulng data. They further help ensure that non-IND foreign studies are conducted in a manner comparable to that required for IND studies. Reporng Clinical Trial Results Under the Public Health Service Act, or PHSA, sponsors of certain clinical trials of certain FDA-regulated products, including prescripon drugs and biologics, are required to register and disclose certain clinical trial informaon on a public registry (clinicaltrials.gov) maintained by the U.S. Naonal Instutes of Health, or NIH. In parcular, informaon related to the product, paent populaon, phase of invesgaon, study sites and invesgators and other aspects of the clinical trial is made public as part of the registraon of the clinical trial. Although sponsors are also obligated to disclose the results of their clinical trials aer compleon, disclosure of the results can be delayed in some cases for up to two years aer the date of compleon of the trial. The NIH’s Final Rule on registraon and reporng requirements for clinical trials became eﬀecve in 2017, and both NIH and the FDA have signaled the government’s willingness to begin enforcing those requirements against non-compliant clinical trial sponsors. Speciﬁcally, the PHSA grants the Secretary of the U.S. Department of Health and Human Services, or HHS, the authority to issue a noce of noncompliance to a responsible party for failure to submit clinical trial informaon as required. The responsible party, however, is allowed 30 days to correct the noncompliance and submit the required informaon. With the issuance of pre-noces for voluntary correcve acon and several noces of non-compliance during the past two years, the FDA has signaled the government’s willingness to enforce these requirements against non-compliant clinical trial sponsors. While these noces of non-compliance did not result in civil monetary penales, the failure to submit clinical trial informaon to clinicaltrials.gov, as required, is also a prohibited act under the FDCA with violaons subject to potenal civil monetary penales of up to $10,000 for each day the violaon connues. In addion to civil monetary penales, violaons may also result in other regulatory acon, such as injuncon and/or criminal prosecuon or disqualiﬁcaon from federal grants. Although the FDA has historically not enforced these reporng requirements due to HHS’s long delay in issuing ﬁnal implemenng regulaons, those regulaons have now been issued and the FDA has issued several Noces of Noncompliance to manufacturers during the past two years. Expanded Access to an Invesgaonal Drug for Treatment Use Expanded access, somemes called “compassionate use,” is the use of invesgaonal new drug products outside of clinical trials to treat paents with serious or immediately life-threatening diseases or condions when there are no comparable or sasfactory alternave treatment opons. The rules and regulaons related to expanded access are intended to improve access to invesgaonal drugs for paents who may beneﬁt from invesgaonal therapies. FDA regulaons allow access to invesgaonal drugs under an IND by the company or the treang physician for treatment purposes on a case-by-case basis for: individual paents (single-paent IND applicaons for treatment in emergency sengs and non-emergency sengs); intermediate-size paent populaons; and larger populaons for use of the drug under a treatment protocol or Treatment IND Applicaon. There is no obligaon for a sponsor to make its invesgaonal products available for expanded access; however, as required by amendments to the FDCA included in the 21st Century Cures Act passed in 2016, if a sponsor has a policy regarding how it responds to expanded access requests with respect to product candidates in development to treat serious diseases or condions, it must make that policy publicly available. Sponsors are required to make such policies publicly available upon the earlier of iniaon of a Phase 2 or Phase 3 trial for a covered invesgaonal product; or 15 days aer the invesgaonal product receives designaon from the FDA as a breakthrough therapy, fast track product, or regenerave medicine advanced therapy. Akebia Therapeucs, Inc. | Form 10-K | Page 27 Table of Contents On May 30, 2018, the Right to Try Act was signed into law. The law, among other things, provides a federal framework for certain paents to access certain invesgaonal new drug products that have completed a Phase I clinical trial and that are undergoing invesgaon for FDA approval. Under certain circumstances, eligible paents can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligaon for a drug manufacturer to make its product candidates available to eligible paents as a result of the Right to Try Act, but the manufacturer must develop an internal policy and respond to paent requests according to that policy. Human Clinical Trials in Support of an NDA Clinical trials involve the administraon of the invesgaonal product to human paents under the supervision of qualiﬁed invesgators in accordance with GCP requirements, which include, among other things, the requirement that all research paents provide their informed consent in wring before their parcipaon in any clinical trial. Clinical trials are conducted under wrien study protocols detailing, among other things, the inclusion and exclusion criteria, the objecves of the study, the parameters to be used in monitoring safety and the eﬀecveness criteria to be evaluated. Human clinical trials are typically conducted in four sequenal phases, which may overlap or be combined: • • • • Phase 1. The product candidate is inially introduced into a small number of healthy human paents or, in certain indicaons such as cancer, paents with the target disease or condion (e.g., cancer) and tested for safety, dosage tolerance, absorpon, metabolism, distribuon, excreon and, if possible, to gain an early indicaon of its eﬀecveness and to determine opmal dosage. Phase 2. The product candidate is administered to a limited paent populaon to idenfy possible adverse eﬀects and safety risks, to preliminarily evaluate the eﬃcacy of the product candidate for speciﬁc targeted diseases and to determine dosage tolerance and opmal dosage. Phase 3. These clinical trials are commonly referred to as “pivotal” studies, which denote a study that presents the data that the FDA or other relevant regulatory agency will use to determine whether or not to approve a product candidate. The product candidate is administered to an expanded paent populaon, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to stascally evaluate the eﬃcacy and safety of the product candidate for approval, idenfy adverse eﬀects, establish the overall risk-beneﬁt proﬁle of the product candidate and to provide adequate informaon for the labeling of the product candidate. Phase 4. Post-approval studies may be conducted aer inial markeng approval. These studies are used to gain addional experience from the treatment of paents in the intended therapeuc indicaon. A clinical trial may combine the elements of more than one phase and the FDA oen requires more than one Phase 3 trial to support markeng approval of a product candidate. Moreover, as noted above, a pivotal trial is a clinical trial that is believed to sasfy FDA requirements for the evaluaon of a product candidate’s safety and eﬃcacy such that it can be used, alone or with other pivotal or non-pivotal trials, to support regulatory approval. Generally, pivotal trials are Phase 3 trials, but they may be Phase 2 trials if the design provides a well-controlled and reliable assessment of clinical beneﬁt, parcularly in an area of unmet medical need. A company’s designaon of a clinical trial as being of a parcular phase is not necessarily indicave that the study will be suﬃcient to sasfy the FDA requirements of that phase because this determinaon cannot be made unl the protocol and data have been submied to and reviewed by the FDA. In December 2022, with the passage of the Food and Drug Omnibus Reform Act, or FDORA, Congress required sponsors to develop and submit a diversity acon plan for each phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse paent populaons in late-stage clinical trials of FDA-regulated products. Speciﬁcally, acons plans must include the sponsor’s goals for enrollment, the underlying raonale for those goals, and an explanaon of how the sponsor intends to meet them. In addion to these requirements, the legislaon directs the FDA to issue new guidance on diversity acon plans. Progress reports detailing the results of the clinical trials conducted under the IND must be submied at least annually to the FDA and, more frequently, if serious adverse events occur. In addion, IND safety reports must be submied to the FDA for any of the following: serious and unexpected suspected adverse reacons; ﬁndings from other studies or animal or in vitro tesng that suggest a signiﬁcant risk in humans exposed to the drug; and any clinically important increase in the case of a serious suspected adverse reacon over that listed in the protocol or invesgator brochure. The FDA, IRB or the sponsor or the data monitoring commiee may suspend or terminate a clinical trial at any me on various grounds, including a ﬁnding that the research paents are being exposed to an unacceptable health risk. The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submied. In June 2023, the FDA issued dra guidance with updated recommendaons for GCPs aimed at modernizing the design and conduct of clinical trials. The updates are intended to help pave the way for more eﬃcient clinical trials to facilitate the development of medical products. The dra guidance is adopted from the ICH’s recently updated E6(R3) dra guideline that Akebia Therapeucs, Inc. | Form 10-K | Page 28 Table of Contents was developed to enable the incorporaon of rapidly developing technological and methodological innovaons into the clinical trial enterprise. In addion, the FDA issued dra guidance outlining recommendaons for the implementaon of decentralized clinical trials. Interacons with the FDA During the Clinical Development Program Following the clearance of an IND and the commencement of clinical trials, a sponsor will connue to have interacons with the FDA and the sponsor may meet with the FDA at certain points in the clinical development program. Speciﬁcally, sponsors may meet with the FDA prior to the submission of an IND, or a pre-IND meeng, at the end of Phase 2 clinical trials and before an NDA is submied, or a pre-NDA meeng. Meengs at other mes may also be requested. These meengs provide an opportunity for the sponsor to share informaon about the data gathered to date with the FDA and for the FDA to provide advice on the next phase of development. There are ﬁve types of meengs that occur between sponsors and the FDA. Type A meengs are those that are necessary for an otherwise stalled product development program to proceed or to address an important safety issue. Type B meengs include pre-IND and pre-NDA meengs as well as end of phase meengs such as end-of-phase 2 meengs. A Type C meeng is any meeng other than a Type A or Type B meeng regarding the development and review of a product, including for example meengs to facilitate early consultaons on the use of a biomarker as a new surrogate endpoint that has never been previously used as the primary basis for product approval in the proposed context of use. A Type D meeng is focused on a narrow set of issues (typically limited to no more than two focused topics) and should not require input from more than three disciplines or divisions. Finally, INTERACT meengs are intended for novel products and development programs that present unique challenges in the early development of an invesgaonal product. Such meengs may be conducted in person, via teleconference/videoconference, or wrien response only with minutes reﬂecng the quesons that the sponsor posed to the FDA and the agency’s responses. The FDA has indicated that its responses, as conveyed in meeng minutes and advice leers, only constute mere recommendaons and/or advice made to a sponsor and, as such, sponsors are not bound by such recommendaons and/or advice. Nonetheless, from a praccal perspecve, a sponsor’s failure to follow the FDA’s recommendaons for design of a clinical program may put the program at signiﬁcant risk of failure. In September 2023, the FDA issued dra guidance outlining the terms of such meengs in more detail. Pediatric Studies Under the Pediatric Research Equity Act, or PREA, applicaons and certain types of supplements to applicaons must contain data that are adequate to assess the safety and eﬀecveness of the product for the claimed indicaons in all relevant pediatric subpopulaons, and to support dosing and administraon for each pediatric subpopulaon for which the product is safe and eﬀecve. The sponsor must submit an inial Pediatric Study Plan, or PSP, within 60 days of an end-of-phase 2 meeng or as may be agreed between the sponsor and the FDA. Those plans must contain an outline of the proposed pediatric study or studies the sponsor plans to conduct, including study objecves and design, age groups, relevant endpoints and stascal approach, or a jusﬁcaon for not including such detailed informaon, and any request for a deferral of pediatric assessments or a full or paral waiver of the requirement to provide data from pediatric studies along with supporng informaon. The sponsor and the FDA must reach agreement on a ﬁnal plan. A sponsor can submit amendments to an agreed-upon inial PSP at any me if changes to the pediatric plan need to be considered based on data collected from nonclinical trials, early phase clinical trials, and/or other clinical development programs. For invesgaonal products intended to treat a serious or life-threatening disease or condion, the FDA must, upon the request of a sponsor, meet to discuss preparaon of the inial pediatric study plan or to discuss deferral or waiver of pediatric assessments. In addion, the FDA will meet early in the development process to discuss pediatric study plans with sponsors, and the FDA must meet with sponsors by no later than the end-of-phase 1 meeng for serious or life- threatening diseases and by no later than ninety days aer the FDA’s receipt of the study plan. The FDA may, on its own iniave or at the request of the sponsor, grant deferrals for submission of some or all pediatric data unl aer approval of the product for use in adults, or full or paral waivers from the pediatric data requirements. A deferral may be granted for several reasons, including a ﬁnding that the product or therapeuc candidate is ready for approval for use in adults before pediatric trials are complete or that addional safety or eﬀecveness data needs to be collected before the pediatric trials begin. Pursuant to the Food and Drug Administraon Safety and Innovaon Act of 2012, or FDASIA, the FDA must send a PREA Non-Compliance leer to sponsors who have failed to submit their pediatric assessments required under PREA, have failed to seek or obtain a deferral or deferral extension or have failed to request approval for a required pediatric formulaon. FDASIA further requires the FDA to publicly post the PREA Non-Compliance leer and sponsor’s response. Unless otherwise required by regulaon, the pediatric data requirements do not apply to products with orphan designaon, although FDA has recently taken steps to limit what it considers abuse of this statutory exempon in PREA by announcing that it does not intend to grant any addional orphan drug designaons for rare pediatric subpopulaons of what is otherwise a common disease. The FDA also maintains a list of diseases that are exempt from PREA requirements due to low prevalence of disease Akebia Therapeucs, Inc. | Form 10-K | Page 29 Table of Contents in the pediatric populaon. In May 2023, the FDA issued new dra guidance that further describes the pediatric study requirements under PREA. Acceptance and Review of an NDA Assuming successful compleon of required clinical tesng and other requirements, the results of the preclinical studies and clinical trials, together with detailed informaon relang to the product’s chemistry, manufacture, controls and proposed labeling, among other things are submied to the FDA as part of an NDA requesng approval to market the product candidate for one or more indicaons. The fee required for the submission and review of an applicaon under the PDUFA is substanal (for example, for ﬁscal year 2024 this applicaon fee is a lile more than $4.0 million), and the sponsor of an approved applicaon is also subject to an annual program fee, currently approximately $0.4 million per eligible prescripon product. These fees are typically adjusted annually, and exempons and waivers may be available under certain circumstances, such as where a waiver is necessary to protect the public health, where the fee would present a signiﬁcant barrier to innovaon, or where the sponsor is a small business subming its ﬁrst human therapeuc applicaon for review. The FDA conducts a preliminary review of all applicaons within 60 days of receipt and must inform the sponsor at that me or before whether an applicaon is suﬃciently complete to permit substanve review. This is known as the ﬁling decision. In the event that FDA determines that an applicaon does not sasfy this standard, it will issue a Refuse to File determinaon to the sponsor. The FDA may request addional informaon rather than accept an NDA for ﬁling. In this event, the applicaon must be resubmied with the addional informaon. The resubmied applicaon is also subject to review before the FDA accepts it for ﬁling. Once the submission is accepted for ﬁling, the FDA begins an in-depth substanve review. The FDA has agreed to certain performance goals in the review process of NDAs. Most such applicaons are meant to be reviewed within ten months from the date of ﬁling, and most applicaons for “priority review” products are meant to be reviewed within six months of ﬁling. A product that has been designated as a breakthrough therapy may also be eligible for review within six months if supported by clinical data at the me of submission of the NDA. The review process may be extended by the FDA for three addional months to consider new informaon or clariﬁcaon provided by the sponsor to address an outstanding deﬁciency idenﬁed by the FDA following the original submission. Before approving an NDA, the FDA typically will inspect the facility or facilies where the product is or will be manufactured. These pre-approval inspecons may cover all facilies associated with an NDA submission, including drug component manufacturing such as acve pharmaceucal ingredients, ﬁnished drug product manufacturing, control tesng laboratories, as well as packaging and labeling facilies. The FDA will not approve an applicaon unless it determines that the manufacturing processes and facilies are in compliance with cGMP requirements and adequate to assure consistent producon of the product within required speciﬁcaons. The PREVENT Pandemics Act, which was enacted in December 2022, clariﬁes that foreign drug manufacturing establishments are subject to registraon and lisng requirements even if a drug or biologic undergoes further manufacture, preparaon, propagaon, compounding, or processing at a separate establishment outside the U.S. prior to being imported or oﬀered for import into the U.S. Addionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. The sponsor of the NDA may also have their records, processes, procedures, training, and other aspects reviewed during an inspecon. The FDA must implement a protocol to expedite review of responses to inspecon reports pertaining to certain drug applicaons, including applicaons for drugs in a shortage or drugs for which approval is dependent on remediaon of condions idenﬁed in the inspecon report. In addion, as a condion of approval, the FDA may require a sponsor to develop a REMS. REMS use risk minimizaon strategies beyond the professional labeling to ensure that the beneﬁts of the product outweigh the potenal risks. Finally, the FDA may refer an applicaon for a novel drug to an advisory commiee or explain why such referral was not made. Typically, an advisory commiee is a panel of independent experts, including clinicians and other scienﬁc experts, that reviews, evaluates and provides a recommendaon as to whether the applicaon should be approved and under what condions. The FDA is not bound by the recommendaons of an advisory commiee, but it considers such recommendaons carefully when making decisions. Fast Track, Breakthrough Therapy, Priority Review The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in the treatment of a serious or life-threatening disease or condion. These programs are referred to as fast track designaon, breakthrough therapy designaon, priority review designaon. Speciﬁcally, the FDA may designate a product for fast track review if it is intended, whether alone or in combinaon with one or more other drugs, for the treatment of a serious or life-threatening disease or condion, and it demonstrates the potenal to address unmet medical needs for such a disease or condion. The fast track designaon may be withdrawn by the FDA if the FDA believes that the designaon is no longer supported by data emerging in the clinical trial process. Akebia Therapeucs, Inc. | Form 10-K | Page 30 Table of Contents Second, in 2012, Congress enacted the Food and Drug Administraon Safety and Improvement Act. This law established a new regulatory scheme allowing for expedited review of products designated as “breakthrough therapies.” A product may be designated as a breakthrough therapy if it is intended, either alone or in combinaon with one or more other drugs, to treat a serious or life-threatening disease or condion and preliminary clinical evidence indicates that the product may demonstrate substanal improvement over exisng therapies on one or more clinically signiﬁcant endpoints, such as substanal treatment eﬀects observed early in clinical development. The FDA may take certain acons with respect to breakthrough therapies, including holding meengs with the sponsor throughout the development process; providing mely advice to the product sponsor regarding development and approval; involving more senior staﬀ in the review process; assigning a cross-disciplinary project lead for the review team; and taking other steps to design the clinical trials in an eﬃcient manner. Third, the FDA may designate a product for priority review if it is a drug that treats a serious condion and, if approved, would provide a signiﬁcant improvement in safety or eﬀecveness. The FDA determines, on a case-by-case basis, whether the proposed drug represents a signiﬁcant improvement when compared with other available therapies. A priority designaon is intended to direct overall aenon and resources to the evaluaon of such applicaons, and to shorten the FDA’s review clock goal for taking acon on a markeng applicaon from ten months to six months. Priority Review Vouchers A priority review voucher, or PRV, is a voucher that the FDA issues to a sponsor of a rare pediatric disease or tropical disease product applicaon at the me of the markeng applicaon approval. Vouchers are transferable to other sponsors that may apply it to their NDAs or biologics license applicaon, or BLAs. A PRV entles the holder to designate a single human drug applicaon submied under Secon 505(b)(1) of the U.S. Federal Food, Drug, and Cosmec Act or Secon 351 of the Public Health Service Act as qualifying for a priority review. An FDA priority review may expedite the review process of a markeng applicaon reducing the review me from ten months aer formal acceptance of the ﬁle to six months aer formal acceptance of the ﬁle. Applying the PRV to a markeng applicaon does not ensure the FDA’s approval of the markeng applicaon and all requirements supporng the safety and eﬃcacy of the product must be met. Our NDA submission for vadadustat did not include a PRV. Accelerated Approval Pathway Drug or biologic products studied for their safety and eﬀecveness in treang serious or life-threatening illnesses and that provide meaningful therapeuc beneﬁt over exisng treatments may receive accelerated approval. Accelerated approval means that a product candidate may be approved on the basis of adequate and well controlled clinical trials establishing that the product candidate has an eﬀect on a surrogate endpoint that is reasonably likely to predict a clinical beneﬁt, or on the basis of an eﬀect on a clinical endpoint other than survival or irreversible morbidity or mortality or other clinical beneﬁt, taking into account the severity, rarity and prevalence of the condion and the availability or lack of alternave treatments. As a condion of approval, the FDA may require that a sponsor of a drug or biologic product candidate receiving accelerated approval perform adequate and well controlled post-markeng clinical trials. In addion, the FDA currently requires as a condion for accelerated approval pre-approval of promoonal materials. With the passage of FDORA in December 2022, Congress modiﬁed certain provisions governing accelerated approval of drug and biologic products. Speciﬁcally, the new legislaon authorized the FDA to: require a sponsor to have its conﬁrmatory clinical trial underway before accelerated approval is awarded, require a sponsor of a product granted accelerated approval to submit progress reports on its post-approval studies to the FDA every six months (unl the study is completed); and use expedited procedures to withdraw accelerated approval of an NDA or BLA aer the conﬁrmatory trial fails to verify the product’s clinical beneﬁt. Further, FDORA requires the FDA to publish on its website “the raonale for why a post-approval study is not appropriate or necessary” whenever it decides not to require such a study upon granng accelerated approval. In March 2023, the FDA issued dra guidance that outlines its current thinking and approach to accelerated approval. The agency indicated that although single-arm trials have been commonly used to support accelerated approval, a randomized controlled trial is the preferred approach as it provides a more robust eﬃcacy and safety assessment and allows for direct comparisons to an available therapy. To that end, the FDA outlined consideraons for designing, conducng, and analyzing data for trials intended to support accelerated approvals of oncology therapeucs. While this guidance is currently only in dra form and generally applies to oncology products and will ulmately not be legally binding even when ﬁnalized, sponsors typically observe the FDA’s guidance closely to ensure that their invesgaonal products qualify for accelerated approval. The FDA’s Decision on an NDA The FDA reviews an applicaon to determine, among other things, whether the product is safe and whether it is eﬀecve for its intended use(s), with the laer determinaon being made on the basis of substanal evidence. The term “substanal evidence” is deﬁned under the FDCA as “evidence consisng of adequate and well-controlled invesgaons, including clinical invesgaons, by experts qualiﬁed by scienﬁc training and experience to evaluate the eﬀecveness of the product involved, on the basis of which it could fairly and responsibly be concluded by such experts that the product will have the eﬀect it Akebia Therapeucs, Inc. | Form 10-K | Page 31 Table of Contents purports or is represented to have under the condions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.” The FDA has interpreted this evidenary standard to require at least two adequate and well-controlled clinical invesgaons to establish eﬀecveness of a new product. Under certain circumstances, however, FDA has indicated that a single trial with certain characteriscs and addional informaon may sasfy this standard. This approach was subsequently endorsed by Congress in 1998 with legislaon providing, in pernent part, that “If [FDA] determines, based on relevant science, that data from one adequate and well-controlled clinical invesgaon and conﬁrmatory evidence (obtained prior to or aer such invesgaon) are suﬃcient to establish eﬀecveness, FDA may consider such data and evidence to constute substanal evidence.” This modiﬁcaon to the law recognized the potenal for FDA to ﬁnd that one adequate and well controlled clinical invesgaon with conﬁrmatory evidence, including supporve data outside of a controlled trial, is suﬃcient to establish eﬀecveness. In December 2019, FDA issued dra guidance further explaining the studies that are needed to establish substanal evidence of eﬀecveness. Although the FDA has not yet ﬁnalized that guidance, it did issue addional dra guidance in September 2023 that outlines consideraons for relying on conﬁrmatory evidence in lieu of a second clinical study. Aer evaluang the applicaon and all related informaon, including the advisory commiee recommendaons, if any, and inspecon reports of manufacturing facilies and clinical trial sites, the FDA will issue either a CRL or an approval leer. To reach this determinaon, the FDA must determine that the drug is eﬀecve and that its expected beneﬁts outweigh its potenal risks to paents. This “beneﬁt-risk” assessment is informed by the extensive body of evidence about the product’s safety and eﬃcacy in the NDA or BLA. This assessment is also informed by other factors, including: the severity of the underlying condion and how well paents’ medical needs are addressed by currently available therapies; uncertainty about how the premarket clinical trial evidence will extrapolate to real-world use of the product in the post-market seng; and whether risk management tools are necessary to manage speciﬁc risks. In connecon with this assessment, the FDA review team will assemble all individual reviews and other documents into an “acon package,” which becomes the record for FDA review. The review team then issues a recommendaon, and a senior FDA oﬃcial makes a decision. A CRL indicates that the review cycle of the applicaon is complete, and the applicaon will not be approved in its present form. A CRL generally outlines the deﬁciencies in the submission and may require substanal addional tesng or informaon in order for the FDA to reconsider the applicaon. The CRL may require addional clinical or other data, addional pivotal Phase 3 clinical trial(s) and/or other signiﬁcant and me- consuming requirements related to clinical trials, preclinical studies or manufacturing. If a CRL is issued, the sponsor will have one year to respond to the deﬁciencies idenﬁed by the FDA, at which me the FDA can deem the applicaon withdrawn or, in its discreon, grant the sponsor an addional six month extension to respond. The FDA has commied to reviewing resubmissions in response to an issued CRL in either two or six months depending on the type of informaon included. Even with the submission of this addional informaon, however, the FDA ulmately may decide that the applicaon does not sasfy the regulatory criteria for approval. The FDA has taken the posion that a CRL is not ﬁnal agency acon making the determinaon subject to judicial review. Rather, for those seeking to challenge FDA’s CRL decision, the agency has indicated that sponsors may request a formal hearing on the CRL or they may ﬁle a request for reconsideraon or a request for a formal dispute resoluon. An approval leer, on the other hand, authorizes commercial markeng of the product with speciﬁc prescribing informaon for speciﬁc indicaons. That is, the approval will be limited to the condions of use (e.g., paent populaon, indicaon) described in the FDA-approved labeling. Further, depending on the speciﬁc risk(s) to be addressed, the FDA may require that contraindicaons, warnings or precauons be included in the product labeling, require that post- approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s safety aer approval, require tesng and surveillance programs to monitor the product aer commercializaon or impose other condions, including distribuon and use restricons or other risk management mechanisms under a REMS which can materially aﬀect the potenal market and proﬁtability of the product. The FDA may prevent or limit further markeng of a product based on the results of post-markeng trials or surveillance programs. Aer approval, some types of changes to the approved product, such as adding new indicaons, manufacturing changes and addional labeling claims, are subject to further tesng requirements and FDA review and approval. Under the Ensuring Innovaon Act, which was signed into law in April 2021, the FDA must publish acon packages summarizing its decisions to approve new drugs and biologics within 30 days of approval of such products. To date, CRLs are not publicly available documents. Post-Approval Requirements and Commitments If a product receives regulatory approval, the approval may be signiﬁcantly limited to speciﬁc diseases and dosages or the indicaons for use may otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain contraindicaons, warnings or precauons be included in the product labeling. In addion, condions of NDA approval may include sponsor agreement to PMR or PMC studies, which are designed to further assess drug safety and Akebia Therapeucs, Inc. | Form 10-K | Page 32 Table of Contents eﬀecveness and may require tesng and surveillance programs to monitor the safety of approved products that have been commercialized. These may include addional studies, registries, data collecon, analyses, and/or informaon. Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and connuing regulaon by the FDA, including, among other things, requirements relang to recordkeeping, periodic reporng, product sampling and distribuon, adversing and promoon and reporng of adverse experiences with the product. Aer approval, most changes to the approved product, such as adding new indicaons or other labeling claims, are subject to prior FDA review and approval. There also are connuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured, as well as new applicaon fees for supplemental applicaons with clinical data. In addion, drug manufacturers and other enes involved in the manufacture and distribuon of approved drugs are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced inspecons by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and oen require prior FDA approval before being implemented. FDA regulaons also require invesgaon and correcon of any deviaons from cGMP and impose reporng and documentaon requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must connue to expend me, money, and eﬀort in the area of producon and quality control to maintain cGMP compliance. Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not maintained or if problems occur aer the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unancipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety informaon; imposion of post-market studies or clinical trials to assess new safety risks; or imposion of distribuon or other restricons under a REMS program. Other potenal consequences include, among other things: • • • • • restricons on the markeng or manufacturing of the product, suspension of the approval, or complete withdrawal of the product from the market or product recalls; ﬁnes, warning leers or holds on post-approval clinical trials; refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocaon of product license approvals; product seizure or detenon, or refusal to permit the import or export of products; or injuncons or the imposion of civil or criminal penales. The FDA strictly regulates the markeng, labeling, adversing and promoon of prescripon drug products placed on the market. This regulaon includes, among other things, standards and regulaons for direct-to-consumer adversing, communicaons regarding unapproved uses, industry-sponsored scienﬁc and educaonal acvies, and promoonal acvies involving the Internet and social media. Promoonal claims about a product candidate’s safety or eﬀecveness are prohibited before the product candidate is approved. Aer approval, a drug product generally may not be promoted for uses that are not approved by the FDA or in a manner that is inconsistent with the product’s prescribing informaon. In September 2021, the FDA published ﬁnal regulaons which describe the types of evidence that the agency will consider in determining the intended use of a drug product. In addion, in October 2023, the FDA published dra guidance outlining the agency’s non-binding policies governing the distribuon of scienﬁc informaon on unapproved uses to healthcare providers. This dra guidance calls for such communicaons to be truthful, non-misleading, factual, and unbiased and include all informaon necessary for healthcare providers to interpret the strengths and weaknesses and validity and ulity of the informaon about the unapproved use. In the U.S., healthcare professionals are generally permied to prescribe drugs for such uses not described in the drug’s labeling, known as oﬀ-label uses, because the FDA does not regulate the pracce of medicine. However, FDA regulaons impose rigorous restricons on manufacturers’ communicaons, prohibing the promoon of oﬀ-label uses. It may be permissible, under very speciﬁc condions, for a manufacturer to engage in nonpromoonal, truthful and non-misleading communicaon regarding oﬀ-label informaon, such as distribung scienﬁc or medical journal informaon. In addion, companies may also promote informaon that it consistent with the prescribing informaon and have the ability to proacvely speak to formulary commiee members of payors regarding data for an unapproved drug or unapproved uses of an approved drug under some relavely recent guidance from the FDA. Moreover, with the passage of the Pre-Approval Informaon Exchange Act, or PIE Act, in December 2022, sponsors of products that have not been approved may proacvely communicate to payors certain informaon about products in development to help expedite paent access upon product approval. Previously, such communicaons were permied under FDA guidance but the new legislaon explicitly provides protecon to sponsors who convey certain informaon about products in development to payors, including unapproved uses of approved products. Akebia Therapeucs, Inc. | Form 10-K | Page 33 Table of Contents However, if a company is found to have promoted oﬀ-label uses, it may become subject to adverse public relaons and administrave and judicial enforcement by the FDA, the Department of Jusce, or the Oﬃce of the Inspector General of the Department of Health and Human Services, as well as state authories. This could subject a company to a range of penales that could have a signiﬁcant commercial impact, including civil and criminal ﬁnes and agreements that materially restrict the manner in which a company promotes or distributes drug products. The federal government has levied large civil and criminal ﬁnes against companies for alleged improper promoon and has also requested that companies enter into consent decrees or permanent injuncons under which speciﬁed promoonal conduct is changed or curtailed. In addion, the distribuon of prescripon pharmaceucal products is subject to a variety of federal and state laws, the most recent of which is sll in the process of being phased into the U.S. supply chain and regulatory framework. The Prescripon Drug Markeng Act, or PDMA, was the ﬁrst federal law to set minimum standards for the registraon and regulaon of drug distributors by the states and to regulate the distribuon of drug samples. Today, both the PDMA and state laws limit the distribuon of prescripon pharmaceucal product samples and impose requirements to ensure accountability in distribuon. Congress more recently enacted the Drug Supply Chain Security Act, or DSCSA, which made signiﬁcant amendments to the FDCA, including by replacing certain provisions from the PDMA pertaining to wholesale distribuon of prescripon drugs with a more comprehensive statutory scheme. The DSCSA now requires uniform naonal standards for wholesale distribuon and, for the ﬁrst me, for third-party logiscs providers; it also provides for preempon of certain state laws in the areas of licensure and prescripon drug traceability. Secon 505(b)(2) NDAs NDAs for most new drug products are based on two full clinical trials which must contain substanal evidence of the safety and eﬃcacy of the proposed new product for the proposed use. These applicaons are submied under Secon 505(b)(1) of the FDCA. The FDA is, however, authorized to approve an alternave type of NDA under Secon 505(b)(2) of the FDCA. This type of applicaon allows the sponsor to rely, in part, on the FDA’s previous ﬁndings of safety and eﬃcacy for a similar product, or published literature. Speciﬁcally, Secon 505(b)(2) applies to NDAs for a drug for which the invesgaons made to show whether or not the drug is safe for use and eﬀecve in use and relied upon by the sponsor for approval of the applicaon “were not conducted by or for the sponsor and for which the sponsor has not obtained a right of reference or use from the person by or for whom the invesgaons were conducted.” Secon 505(b)(2) authorizes the FDA to approve an NDA based on safety and eﬀecveness data that were not developed by the sponsor. NDAs ﬁled under Secon 505(b)(2) may provide an alternate and potenally more expedious pathway to FDA approval for new or improved formulaons or new uses of previously approved products. If the 505(b)(2) sponsor can establish that reliance on the FDA’s previous approval is scienﬁcally appropriate, the sponsor may eliminate the need to conduct certain preclinical studies or clinical trials of the new product. The FDA may also require companies to perform addional studies or measurements to support the change from the approved product. The FDA may then approve the new product candidate for all or some of the label indicaons for which the referenced product has been approved, as well as for any new indicaon sought by the Secon 505(b)(2) sponsor. Products approved under Secon 505(b)(2) are oen referred to as follow-on products. Abbreviated New Drug Applicaons for Generic Drugs In 1984, with the passage of the Hatch-Waxman Amendments to the FDCA, Congress established an abbreviated regulatory scheme authorizing the FDA to approve generic drugs that are shown to contain the same acve ingredients as, and to be bioequivalent to, drugs previously approved by the FDA pursuant to NDAs. To obtain approval of a generic drug, a sponsor must submit an ANDA to the agency. An ANDA is a comprehensive submission that contains, among other things, data and informaon pertaining to the acve pharmaceucal ingredient, bioequivalence, drug product formulaon, speciﬁcaons and stability of the generic drug, as well as analycal methods, manufacturing process validaon data and quality control procedures. ANDAs are “abbreviated” because they generally do not include preclinical and clinical data to demonstrate safety and eﬀecveness. Instead, in support of such applicaons, a generic manufacturer may rely on the preclinical and clinical tesng previously conducted for a drug product previously approved under an NDA, known as the reference-listed drug, or RLD. Under the Hatch-Waxman Act, the FDA may not approve an ANDA or 505(b)(2) applicaon unl any applicable period of non-patent exclusivity for the RLD has expired. The FDCA provides a period of ﬁve years of non-patent data exclusivity for a new drug containing a new chemical enty, or NCE. For the purposes of this provision, the FDA has consistently taken the posion that an NCE is a drug that contains no acve moiety that has previously been approved by the FDA in any other NDA. This interpretaon was conﬁrmed with enactment of the Ensuring Innovaon Act in April 2021. An acve moiety is the molecule or ion responsible for the physiological or pharmacological acon of the drug substance. In cases where such NCE exclusivity has been granted, a generic or follow- on drug applicaon may not be ﬁled with the FDA unl the expiraon of ﬁve years unless the submission is accompanied by a Paragraph IV cerﬁcaon, in which case the sponsor may submit its applicaon four years following the original product approval. Akebia Therapeucs, Inc. | Form 10-K | Page 34 Table of Contents The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical invesgaons, other than bioavailability or bioequivalence studies, that were conducted by or for the sponsor and are essenal to the approval of the applicaon. This three-year exclusivity period oen protects changes to a previously approved drug product, such as a new dosage form, route of administraon, combinaon or indicaon. Three-year exclusivity would be available for a drug product that contains a previously approved acve moiety, provided the statutory requirement for a new clinical invesgaon is sasﬁed. Unlike ﬁve-year NCE exclusivity, an award of three-year exclusivity does not block the FDA from accepng ANDAs or 505(b)(2) applicaons seeking approval for generic versions of the drug as of the date of approval of the original drug product. The FDA typically makes decisions about awards of data exclusivity shortly before a product is approved. The FDA must establish a priority review track for certain generic drugs, requiring the FDA to review a drug applicaon within eight months for a drug that has three or fewer approved drugs listed in the Orange Book and is no longer protected by any patent or regulatory exclusivies, or is on the FDA’s drug shortage list. The new legislaon also authorizes FDA to expedite review of ‘‘competor generic therapies’’ or drugs with inadequate generic compeon, including holding meengs with or providing advice to the drug sponsor prior to submission of the applicaon. Hatch-Waxman Patent Cerﬁcaon and the 30-Month Stay As part of the submission of an NDA or certain supplemental applicaons, NDA sponsors are required to list with the FDA each patent with claims that cover the sponsor’s product or an approved method of using the product. Upon approval of a new drug, each of the patents listed in the applicaon for the drug is then published in the Orange Book. The FDA’s regulaons governing patent lisngs were largely codiﬁed into law with enactment of the Orange Book Modernizaon Act in January 2021. When an ANDA sponsor ﬁles its applicaon with the FDA, the sponsor is required to cerfy to the FDA concerning any patents listed for the reference product in the Orange Book. Speciﬁcally, the ANDA sponsor must cerfy that: (i) the required patent informaon has not been ﬁled; (ii) the listed patent has expired; (iii) the listed patent has not expired, but will expire on a parcular date and approval is sought aer patent expiraon; or (iv) the listed patent is invalid or will not be infringed by the new product. Moreover, to the extent that the Secon 505(b)(2) NDA sponsor is relying on studies conducted for an already approved product, the sponsor also is required to cerfy to the FDA concerning any patents listed for the NDA-approved product in the Orange Book to the same extent that an ANDA sponsor would. If the generic drug or follow-on drug sponsor does not challenge the innovator’s listed patents, FDA will not approve the ANDA or 505(b)(2) applicaon unl all the listed patents claiming the referenced product have expired. A cerﬁcaon that the new generic product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable is called a Paragraph IV cerﬁcaon. If the ANDA sponsor has provided a Paragraph IV cerﬁcaon to the FDA, the sponsor must also send noce of the Paragraph IV cerﬁcaon to the NDA owner and patent holders once the ANDA has been accepted for ﬁling by the FDA. The NDA owner and patent holders may then iniate a patent infringement lawsuit in response to the noce of the Paragraph IV cerﬁcaon. The ﬁling of a patent infringement lawsuit within 45 days aer the receipt of a Paragraph IV cerﬁcaon automacally prevents the FDA from approving the ANDA or 505(b)(2) NDA unl the earliest of 30 months aer the receipt of the Paragraph IV noce, expiraon of the patent or a decision in the infringement case that is favorable to the ANDA or 505(b)(2) NDA applicaon. Pediatric Studies and Exclusivity Pediatric exclusivity is another type of non-patent markeng exclusivity in the U.S. and, if granted, for drug products, provides for the aachment of an addional six months of markeng protecon to the term of any exisng patent or regulatory exclusivity, including the non-patent and orphan exclusivity. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a wrien request from the FDA for such data. The data do not need to show the product is eﬀecve in the pediatric populaon studied, rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the addional protecon is granted. If reports of requested pediatric studies are submied to and accepted by the FDA within the statutory me limits, whatever statutory or regulatory periods of exclusivity or patent protecon cover the product are extended by six months. This is not a patent term extension, but it eﬀecvely extends the regulatory period during which the FDA cannot approve another applicaon. With regard to patents, the six-month pediatric exclusivity period will not aach to any patents for which an ANDA or 505(b)(2) sponsor submied a Paragraph IV patent cerﬁcaon, unless the NDA sponsor or patent owner ﬁrst obtains a court determinaon that the patent is valid and infringed by the proposed product. Patent Term Restoraon and Extension A patent claiming a new drug product may be eligible for a limited patent term extension under the Hatch-Waxman Act, which permits a patent restoraon of up to ﬁve years for patent term lost during product development and the FDA regulatory review. The restoraon period granted is typically one-half the me between the eﬀecve date of an IND and the submission date of an NDA, plus the me between the submission date of an NDA and the ulmate approval date. Patent term restoraon cannot be used to extend the remaining term of a patent past a total of 14 years from the product’s approval Akebia Therapeucs, Inc. | Form 10-K | Page 35 Table of Contents date. Only one patent applicable to an approved drug product is eligible for the extension, and the applicaon for the extension must be submied prior to the expiraon of the patent in queson. A patent that covers mulple drugs for which approval is sought can only be extended in connecon with one of the approvals. The U.S. Patent and Trademark Oﬃce reviews and approves the applicaon for any patent term extension or restoraon in consultaon with the FDA. Federal and State Data Privacy Laws There are mulple privacy and data security laws that may impact our business acvies, in the U.S. and in other countries where we conduct trials or where we may do business in the future. These laws are evolving and may increase both our obligaons and our regulatory risks in the future. In the health care industry generally, under the federal Health Insurance Portability and Accountability Act of 1996, as amended by the Health Informaon Technology for Economic and Clinical Health Act, or HIPAA, the HHS has issued regulaons to protect the privacy and security of protected health informaon, or PHI, used or disclosed by covered enes including certain healthcare providers, health plans and healthcare clearinghouses. HIPAA also regulates standardizaon of data content, codes and formats used in healthcare transacons and standardizaon of idenﬁers for health plans and providers. HIPAA also imposes certain obligaons on the business associates of covered enes that obtain protected health informaon in providing services to or on behalf of covered enes. While we are not a covered enty, as a business associate, we could be subject to penales, including criminal penales, and contractual damages if we knowingly obtain or further disclose PHI from a covered enty, such as a health care provider or clinical research site, and therefore we must ensure the proper authorizaons are in place before we, or our vendors or business partners, obtain access to any PHI. In addion to federal privacy regulaons, there are a number of state laws governing conﬁdenality and security of health informaon that may be applicable to our business. In addion to possible federal civil and criminal penales for HIPAA violaons, state aorneys general are authorized to ﬁle civil acons for damages or injuncons in federal courts to enforce HIPAA and seek aorney’s fees and costs associated with pursuing federal civil acons. In addion, state aorneys general (along with private plainﬀs) have brought civil acons seeking injuncons and damages resulng from alleged violaons of HIPAA’s privacy and security rules. State aorneys general also have authority to enforce state privacy and security laws. New laws and regulaons governing privacy and security may be adopted in the future as well. In November 2020, California enacted legislaon that has been dubbed the ﬁrst “GDPR-like” law in the U.S. Known as the California Consumer Privacy Act, or CCPA, it creates new individual privacy rights for consumers (as that word is broadly deﬁned in the law) and places increased privacy and security obligaons on enes handling personal data of consumers or households. The CCPA went into eﬀect on January 1, 2020 and requires covered companies to provide new disclosures to California consumers, provide such consumers rights as it relates to their personal informaon, and allow for a new cause of acon for data breaches. Addionally, starng on January 1, 2023, the California Privacy Rights Act, or CPRA, signiﬁcantly modiﬁed the CCPA, including by expanding consumers’ rights, parcularly with respect to certain sensive personal informaon and creang new principles, such as data minimizaon, purpose limitaon, and storage limitaon. The CPRA also created a new state agency that will be vested with authority to implement and enforce the CCPA and the CPRA. The CCPA and CPRA could impact our business acvies depending on how it is interpreted and exempliﬁes the vulnerability of our business to not only cyber threats but also the evolving regulatory environment related to personal data and individually idenﬁable health informaon. These provisions may apply to some of our business acvies. In addion to California, eleven other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in eﬀect or will go into eﬀect someme before the end of 2026. Like the CCPA and CPRA, these laws create obligaons related to the processing of personal informaon, as well as special obligaons for the processing of “sensive” data, which includes health data in some cases. Some of the provisions of these laws may apply to our business acvies. There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2024 legislave sessions that will go into eﬀect in 2025 and beyond, including New Hampshire and New Jersey. Other states will be considering similar laws in the future, and Congress has also been debang passing a federal privacy law. There are also states that are speciﬁcally regulang health informaon that may aﬀect our business. For example, Washington state passed a health privacy law in 2023 that will regulate the collecon and sharing of health informaon, and the law also has a private right of acon, which further increases the relevant compliance risk. Conneccut and Nevada have also passed similar laws regulang consumer health data, and more states (such as Vermont) are considering such legislaon in 2024. Other states will be considering these laws in the future, and Congress has also been debang a proposed federal privacy law. These laws may impact our business acvies, including our idenﬁcaon of research subjects, relaonships with business partners and ulmately the markeng and distribuon of our products, if and once approved. Because of the breadth of these laws and the narrowness of the statutory excepons and regulatory safe harbors available under such laws, it is possible that some of our current or future business acvies, including certain clinical research, sales and markeng pracces and the provision of certain items and services to our customers, could be subject to challenge under one or more of such privacy and data security laws. The heightening compliance environment and the need to build and maintain robust and secure systems to comply with diﬀerent privacy compliance and/or reporng requirements in mulple jurisdicons could increase the possibility that a healthcare company may fail to comply fully with one or more of these Akebia Therapeucs, Inc. | Form 10-K | Page 36 Table of Contents requirements. If our operaons are found to be in violaon of any of the privacy or data security laws or regulaons described above that are applicable to us, or any other laws that apply to us, we may be subject to penales, including potenally signiﬁcant criminal, civil and administrave penales, damages, ﬁnes, imprisonment, contractual damages, reputaonal harm, diminished proﬁts and future earnings, addional reporng requirements and/or oversight if we become subject to a consent decree or similar agreement to resolve allegaons of non-compliance with these laws, and the curtailment or restructuring of our operaons, any of which could adversely aﬀect our ability to operate our business and our results of operaons. To the extent that any product candidates we may develop, once approved, are sold in a foreign country, we may be subject to similar foreign laws. Review and Approval of Drug Products Outside the U.S. In order to market any product outside of the U.S., a sponsor must also comply with numerous and varying regulatory requirements of other countries and jurisdicons regarding quality, safety and eﬃcacy and governing, among other things, clinical trials, markeng authorizaon, commercial sales and distribuon of drug products. Whether or not it obtains FDA approval for a product, the company would need to obtain the necessary approvals by the comparable foreign regulatory authories before it can commence clinical trials or markeng of the product in those countries or jurisdicons. The approval process ulmately varies between countries and jurisdicons and can involve addional product tesng and addional administrave review periods. The me required to obtain approval in other countries and jurisdicons might diﬀer from and be longer than that required to obtain FDA approval. Regulatory approval in one country or jurisdicon does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdicon may negavely impact the regulatory process in others. Non-clinical Studies Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances. Non-clinical (pharmaco- toxicological) studies must be conducted in compliance with the principles of GLP as set forth in EU Direcve 2004/10/EC (unless otherwise jusﬁed for certain parcular medicinal products such as, for example, radio-pharmaceucal precursors for radio-labeling purposes). In parcular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which deﬁne a set of rules and criteria for a quality system for the organizaonal process and the condions for non-clinical studies. These GLP standards reﬂect the Organizaon for Economic Co-operaon and Development requirements. Clinical Trial Approval in the EU On January 31, 2022, the Clinical Trials Regulaon (EU) No 536/2014 became eﬀecve in the EU and replaced the prior Clinical Trials Direcve 2001/20/EC. The Clinical Trials Regulaon aims to simplify and streamline the authorizaon, conduct and transparency of clinical trials in the EU. Under the new coordinated procedure for the approval of clinical trials, the sponsor of a clinical trial to be conducted in more than one Member State of the EU, or an EU Member State, will only be required to submit a single applicaon for approval. The submission will be made through the Clinical Trials Informaon System, a new clinical trials portal overseen by the EMA and available to clinical trial sponsors, competent authories of the EU Member States and the public. Beyond streamlining the process, the new regulaon includes a single set of documents to be prepared and submied for the applicaon as well as simpliﬁed reporng procedures for clinical trial sponsors, and a harmonized procedure for the assessment of applicaons for clinical trials, which is divided in two parts. Part I is assessed by the competent authories of all EU Member States in which an applicaon for authorizaon of a clinical trial has been submied, or EU Member States concerned. Part II is assessed separately by each EU Member State concerned. Strict deadlines have been established for the assessment of clinical trial applicaons. The role of the relevant ethics commiees in the assessment procedure will connue to be governed by the naonal law of the EU Member State concerned. However, overall related melines will be deﬁned by the Clinical Trials Regulaon. The Clinical Trials Regulaon did not change the preexisng requirement that a sponsor must obtain prior approval from the competent naonal authority of the EU Member State in which the clinical trial is to be conducted. If the clinical trial is conducted in diﬀerent EU Member States, the competent authories in each of these EU Member States must provide their approval for the conduct of the clinical trial. Furthermore, the sponsor may only start a clinical trial at a speciﬁc clinical site aer the applicable ethics commiee has issued a favorable opinion. Pares conducng certain clinical trials must, as in the U.S., post clinical trial informaon in the EU at the EudraCT website: hps://eudract.ema.europa.eu. PRIME Designaon in the European Union In March 2016, the EMA launched an iniave, the PRIority MEdicines, or PRIME, scheme, to facilitate development of product candidates in indicaons, oen rare, for which few or no therapies currently exist. The PRIME scheme is intended to Akebia Therapeucs, Inc. | Form 10-K | Page 37 Table of Contents encourage drug development in areas of unmet medical need and provides accelerated assessment of products represenng substanal innovaon reviewed under the centralized procedure. Products from small- and medium-sized enterprises, or SMEs, may qualify for earlier entry into the PRIME scheme than larger companies. Many beneﬁts accrue to sponsors of product candidates with PRIME designaon, including but not limited to, early and proacve regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated markeng authorizaon applicaon, or MAA, assessment once a dossier has been submied. Importantly, a dedicated agency contact and rapporteur from the Commiee for Human Medicinal Products, or CHMP, or Commiee for Advanced Therapies are appointed early in the PRIME scheme, facilitang increased understanding of the product at the EMA’s commiee level. A kick-oﬀ meeng iniates these relaonships and includes a team of muldisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies. Pediatric Studies Prior to obtaining a markeng authorizaon in the EU, sponsors have to demonstrate compliance with all measures included in an EMA-approved Pediatric Invesgaon Plan, or PIP, covering all subsets of the pediatric populaon, unless the EMA has granted a product-speciﬁc waiver, a class waiver or a deferral for one or more of the measures included in the PIP. The respecve requirements for all markeng authorizaon procedures are set forth in Regulaon (EC) No 1901/2006, which is referred to as the Pediatric Regulaon. This requirement also applies when a company wants to add a new indicaon, pharmaceucal form or route of administraon for a medicine that is already authorized. The Pediatric Commiee of the EMA, or PDCO, may grant deferrals for some medicines, allowing a company to delay development of the medicine in children unl there is enough informaon to demonstrate its eﬀecveness and safety in adults. The PDCO may also grant waivers when development of a medicine in children is not needed or is not appropriate because (a) the product is likely to be ineﬀecve or unsafe in part or all of the pediatric populaon; (b) the disease or condion occurs only in adult populaon; or (c) the product does not represent a signiﬁcant therapeuc beneﬁt over exisng treatments for pediatric populaon. Before a markeng authorizaon applicaon can be ﬁled, or an exisng markeng authorizaon can be amended, the EMA determines that companies actually comply with the agreed studies and measures listed in each relevant PIP. Markeng Authorizaon To obtain markeng approval of a product under EU regulatory systems, a sponsor must submit an MAA either under a centralized or decentralized procedure. The centralized procedure provides for the grant of a single markeng authorizaon by the European Commission that is valid for all EU member states. The centralized procedure is compulsory for speciﬁc products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy products and products with a new acve substance indicated for the treatment of certain diseases. For products with a new acve substance indicated for the treatment of other diseases and products that are highly innovave or for which a centralized process is in the interest of paents, the centralized procedure may be oponal. Under the centralized procedure, the CHMP established at the EMA is responsible for conducng the inial assessment of a product. The CHMP is also responsible for several post-authorizaon and maintenance acvies, such as the assessment of modiﬁcaons or extensions to an exisng markeng authorizaon. Under the centralized procedure in the EU, the maximum meframe for the evaluaon of an MAA is 210 days, excluding clock stops, when addional informaon or wrien or oral explanaon is to be provided by the sponsor in response to quesons of the CHMP. Accelerated evaluaon might be granted by the CHMP in exceponal cases, when a medicinal product is of major interest from the point of view of public health and in parcular from the viewpoint of therapeuc innovaon. In this circumstance, the EMA ensures that the opinion of the CHMP is given within 150 days. The decentralized procedure is available to sponsors who wish to market a product in various EU Member States where such product has not received markeng approval in any EU Member State before. The decentralized procedure provides for approval by one or more other, or concerned, member states of an assessment of an applicaon performed by one member state designated by the sponsor, known as the reference member state. Under this procedure, a sponsor submits an applicaon based on idencal dossiers and related materials, including a dra summary of product characteriscs, and dra labeling and package leaﬂet, to the reference member state and concerned member states. The reference member state prepares a dra assessment report and dras of the related materials within 210 days aer receipt of a valid applicaon. Within 90 days of receiving the reference member state’s assessment report and related materials, each concerned member state must decide whether to approve the assessment report and related materials. If a member state cannot approve the assessment report and related materials on the grounds of potenal serious risk to public health, the disputed points are subject to a dispute resoluon mechanism and may eventually be referred to the European Commission, whose decision is binding on all member states. A markeng authorizaon may be granted only to a sponsor established in the EU. Once the markeng authorizaon is obtained in all member states of the EU and study results are included in the product informaon, even when negave, the Akebia Therapeucs, Inc. | Form 10-K | Page 38 Table of Contents product is eligible for six months’ supplementary protecon cerﬁcate extension. For orphan-designated medicinal products, the 10-year period of market exclusivity is extended to 12 years. Periods of Authorizaon and Renewals in the EU A markeng authorizaon is valid for ﬁve years, in principle, and it may be renewed aer ﬁve years on the basis of a reevaluaon of the risk-beneﬁt balance by the EMA or by the competent authority of the relevant EU Member State. To that end, the markeng authorizaon holder must provide the EMA or the relevant competent authority of the EU Member State with a consolidated version of the ﬁle in respect of quality, safety and eﬃcacy, including all variaons introduced since the markeng authorizaon was granted, at least six months before the markeng authorizaon ceases to be valid. Once renewed, the markeng authorizaon is valid for an unlimited period, unless the EC or the relevant competent authority of the EU Member State decides, on jusﬁed grounds relang to pharmacovigilance, to proceed with one addional ﬁve-year renewal period. Any markeng authorizaon that is not followed by the markeng of the medicinal product on the EU market (in the case of the centralized procedure) or on the market of the EU Member State which delivered the markeng authorizaon within three years aer authorizaon ceases to be valid. Post-Approval Requirements As in the U.S., both markeng authorizaon, or MA, holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the EC, and the competent authories of EU Member States. The MA holder must, for example, comply with EU pharmacovigilance legislaon and its related regulaons and guidelines which entail many requirements for conducng pharmacovigilance, or the assessment and monitoring of the safety of medicinal products. In parcular, the MA holder must establish and maintain a pharmacovigilance system and appoint an individual qualiﬁed person for pharmacovigilance who is responsible for the establishment and maintenance of that system, and oversees the safety proﬁles of medicinal products and any emerging safety concerns. Key obligaons include expedited reporng of suspected serious adverse reacons and submission of periodic safety update reports, or PSURs. All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenng measures to prevent or minimize the risks associated with the product. The regulatory authories may also impose speciﬁc obligaons as a condion of the MA. Such risk-minimizaon measures or post-authorizaon obligaons may include addional safety monitoring, more frequent submission of PSURs, or the conduct of addional clinical trials or post-authorizaon safety studies. The manufacturing process for medicinal products in the EU is also highly regulated and regulators may shut down manufacturing facilies that they believe do not comply with regulaons. Manufacturing requires a manufacturing authorizaon, and the manufacturing authorizaon holder must comply with various requirements set out in the applicable EU laws, including compliance with EU GMP standards when manufacturing medicinal products and API. In the EU, the adversing and promoon of approved products are subject to laws governing promoon of medicinal products, interacons with physicians, misleading and comparave adversing, and unfair commercial pracces. These laws require that promoonal materials and adversing in relaon to medicinal products comply with the product’s Summary of Product Characteriscs, or SmPC, as approved by the competent authories. Promoon of a medicinal product that does not comply with the SmPC is considered to constute oﬀ-label promoon, which is prohibited in the EU. Direct-to-consumer adversing of prescripon medicines is also prohibited in the EU. Although general requirements for adversing and promoon of medicinal products are established under EU direcves, the details are governed by regulaons in each EU Member State and can diﬀer from one country to another. The aforemenoned EU rules are generally applicable in the EEA. Failure to comply with EU and EU Member State laws that apply to the conduct of clinical trials, manufacturing approval, MA of medicinal products and markeng of such products, both before and aer grant of the MA, manufacturing of pharmaceucal products, statutory health insurance, bribery and an- corrupon or with other applicable regulatory requirements may result in administrave, civil or criminal penales. These penales could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variaon of the MA, total or paral suspension of producon, distribuon, manufacturing or clinical trials, operang restricons, injuncons, suspension of licenses, ﬁnes and criminal penales. Regulatory Data Exclusivity in the EU In the EU, innovave medicinal products authorized in the EU on the basis of a full markeng authorizaon applicaon (as opposed to an applicaon for markeng authorizaon that relies on data available in the markeng authorizaon dossier for another, previously approved, medicinal product) are entled to eight years of data exclusivity. During this period, sponsors for authorizaon of generics of these innovave products cannot rely on data contained in the markeng authorizaon dossier submied for the innovave medicinal product. Innovave medicinal products are also entled to a total of ten years’ Akebia Therapeucs, Inc. | Form 10-K | Page 39 Table of Contents market exclusivity. During this ten-year period no generic of this medicinal product can be placed on the EU market. The overall ten-year period will be extended to a maximum of eleven years if, during the ﬁrst eight years of those ten years, the markeng authorizaon holder obtains an authorizaon for one or more new therapeuc indicaons which, during the scienﬁc evaluaon prior to authorizaon, is held to bring a signiﬁcant clinical beneﬁt in comparison with exisng therapies. Even if a compound is considered to be a NCE so that the innovator gains the prescribed period of data exclusivity, another company may market another version of the product if such company obtained markeng authorizaon based on an MAA with a complete independent data package of pharmaceucal tests, preclinical tests and clinical trials. Pediatric Exclusivity If a sponsor obtains a markeng authorizaon in all EU Member States, or a markeng authorizaon granted in the centralized procedure by the EC, and the study results for the pediatric populaon are included in the product informaon, even when negave, the medicine is then eligible for an addional six- month period of qualifying patent protecon through extension of the term of the Supplementary Protecon Cerﬁcate, or SPC, or alternavely a one year extension of the regulatory market exclusivity from ten to eleven years, as selected by the markeng authorizaon holder. Access Consorum In October 2020, the Medicines and Healthcare products Regulatory Agency, or MHRA, joined the Access Consorum along with the Australian Therapeuc Goods Administraon of Australia, Health Canada, Health Sciences Authority of Singapore and Swissmedic. The consorum is a coalion of these regulatory authories that work together to promote greater regulatory collaboraon and alignment of regulatory requirements. The consorum’s goal is to maximize internaonal co-operaon between partners in the consorum, reduce duplicaon, and increase each agency’s capacity to ensure paents have mely access to high quality, safe and eﬀecve therapeuc products. The MHRA commenced work-sharing applicaons with Access partners on January 1, 2021. Access Consorum working group members have regular meengs to exchange informaon on regulatory issues and challenges faced by the parcipang regulatory agencies, including issues on clinical trials, markeng authorizaons, product manufacturing site inspecons, post-markeng surveillance, joint development of technical guidelines or regulatory standards, and collaboraon on informaon plaorms. The Access consorum has developed three authorizaon procedures: the New Acve Substance and Biosimilar Work Sharing Iniaves and the Generic Medicine Work Sharing Iniave. General Data Protecon Regulaon Many countries outside of the U.S. maintain rigorous laws governing the privacy and security of personal informaon. The collecon, use, disclosure, transfer, or other processing of personal data, including personal health data, regarding individuals who are located in the EEA, and the processing of personal data that takes place in the EEA, is subject to the European Union General Data Protecon Regulaon, or GDPR, which became eﬀecve on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, and it imposes heightened requirements on companies that process health and other sensive data, such as requiring in many situaons that a company obtain the consent of the individuals to whom the sensive personal data relate before processing such data. Examples of obligaons imposed by the GDPR on companies processing personal data that fall within the scope of the GDPR include providing informaon to individuals regarding data processing acvies, implemenng safeguards to protect the security and conﬁdenality of personal data, appoinng a data protecon oﬃcer, providing noﬁcaon of data breaches and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EEA, including the U.S., and permits data protecon authories to impose large penales for violaons of the GDPR, including potenal ﬁnes of up to €20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of acon on data subjects and consumer associaons to lodge complaints with supervisory authories, seek judicial remedies, and obtain compensaon for damages resulng from violaons of the GDPR. Compliance with the GDPR is a rigorous and me-intensive process that may increase the cost of doing business or require companies to change their business pracces to ensure full compliance. There are ongoing concerns about the ability of companies to transfer personal data from the EU to other countries. In July 2020, the Court of Jusce of the EU, or the CJEU, invalidated the EU-U.S. Privacy Shield framework, one of the mechanisms used to legimize the transfer of personal data from the EEA to the U.S. The CJEU decision also drew into queson the long-term viability of an alternave means of data transfer, the standard contractual clauses, for transfers of personal data from the EEA to the U.S. This CJEU decision may lead to increased scruny on data transfers from the EU to the U.S. generally and increase our costs of compliance with data privacy legislaon as well as our costs of negoang appropriate privacy and security agreements with our vendors and business partners. Addionally, in October 2022, U.S. President Biden signed an execuve order to implement a new EU-U.S. Data Privacy Framework, which would serve as a replacement to the EU-U.S. Privacy Shield. The EU iniated the process to adopt the EU- Akebia Therapeucs, Inc. | Form 10-K | Page 40 Table of Contents U.S. Data Privacy Framework in December 2022. It is unclear if and when the framework will be ﬁnalized and whether it will be challenged in court. The uncertainty around this issue may further impact our business operaons in the EU. As with other issues related to Brexit, there are open quesons about how personal data will be protected in the UK and whether personal informaon can transfer from the EU to the UK Following the withdrawal of the UK from the EU, the UK Data Protecon Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligaons to those set forth by GDPR. While the Data Protecon Act 2018 in the UK that “implements” and complements the GDPR has achieved Royal Assent on May 23, 2018 and is now eﬀecve in the UK, it is sll unclear whether transfer of data from the EEA to the UK will remain lawful under GDPR. The UK government has already determined that it considers all EU and EEA member states to be adequate for the purposes of data protecon, ensuring that data ﬂows from the UK to the EU/EEA remain unaﬀected. In addion, a recent decision from the EC appears to deem the UK as being “essenally adequate” for purposes of data transfer from the EU to the UK, although this decision may be re-evaluated in the future. Beyond GDPR, there are privacy and data security laws in a growing number of countries around the world. While many loosely follow GDPR as a model, other laws contain diﬀerent or conﬂicng provisions. These laws will impact our ability to conduct our business acvies, including both our clinical trials and any eventual sale and distribuon of commercial products. Brexit and the Regulatory Framework in the United Kingdom The UK’s withdrawal from the EU took place on January 31, 2020. The EU and the UK reached an agreement on their new partnership in the Trade and Cooperaon Agreement, or the Agreement, which was applied provisionally beginning on January 1, 2021, and which entered into force on May 1, 2021. The Agreement focuses primarily on free trade by ensuring no tariﬀs or quotas on trade in goods, including healthcare products such as medicinal products. Thereaer, the EU and the UK will form two separate markets governed by two disnct regulatory and legal regimes, except that Northern Ireland will connue to broadly follow EU laws as further described below. As such, the Agreement seeks to minimize barriers to trade in goods while accepng that border checks will become inevitable as a consequence that the UK is no longer part of the single market. As of January 1, 2021, the MHRA became responsible for supervising medicines and medical devices in Great Britain, comprising England, Scotland, and Wales under domesc law whereas Northern Ireland connues to be subject to EU rules under the Northern Ireland Protocol. On February 27, 2023, the UK government and the EC announced a polical agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”. This new framework fundamentally changes the exisng system under the Northern Ireland Protocol, including with respect to the regulaon of medicinal products in the UK In parcular, the MHRA will be responsible for approving all medicinal products desned for the UK market (i.e., Great Britain and Northern Ireland), and the EMA will no longer have any role in approving medicinal products desned for Northern Ireland. A single UK-wide MA will be granted by the MHRA for all medicinal products to be sold in the UK, enabling products to be sold in a single pack and under a single authorizaon throughout the UK. The Windsor Framework was approved by the EU-UK Joint Commiee on March 24, 2023, so the UK government and the EU will enact legislave measures to bring it into law. On June 9, 2023, the MHRA announced that the medicines aspects of the Windsor Framework will apply beginning on January 1, 2025. The Human Medicines Regulaons 2012 (SI 2012/1916) (as amended), or HMR, is the primary legal instrument for the regulaon of medicines in the UK. The HMR has incorporated into the domesc law the body of EU law instruments governing medicinal products that pre-existed prior to the UK’s withdrawal from the EU. EU laws which have been transposed into UK law through secondary legislaon connue to be applicable as “retained EU law.” However, new legislaon such as the (EU) Clinical Trials Regulaon will not be applicable in Great Britain. Since a signiﬁcant proporon of the regulatory framework for pharmaceucal products in the UK covering the quality, safety, and eﬃcacy of pharmaceucal products, clinical trials, MAs, commercial sales, and distribuon of pharmaceucal products is derived from EU direcves and regulaons, Brexit may have a material impact upon the regulatory regime with respect to the development, manufacture, importaon, approval, and commercializaon of our product candidates in the UK. For example, the UK is no longer covered by the centralized procedures for obtaining EU-wide MAs from the EMA, and a separate MA will be required to market our product candidates in the UK. A new internaonal recognion framework has been in place since January 1, 2024, whereby the MHRA will have regard to decisions on the approval of MAs made by the EMA and certain other regulators when determining an applicaon for a new Great Britain MA. Pharmaceucal Coverage, Pricing and Reimbursement In the U.S. and markets in other countries, paents who are prescribed treatments for their condions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Signiﬁcant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authories. Thus, even if a product candidate is approved, sales of the product will depend, in part, on the extent to which third-party payors, including government health programs in the U.S. such as Medicare and Medicaid, commercial health insurers and managed care organizaons, provide coverage, and establish adequate reimbursement levels for, the Akebia Therapeucs, Inc. | Form 10-K | Page 41 Table of Contents product. The process for determining whether a payor will provide coverage for a product may be separate from the process for seng the price or reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical necessity, and reviewing the cost-eﬀecveness of medical products and services and imposing controls to manage costs. Third-party payors may limit coverage to speciﬁc products on an approved list, also known as a formulary, which might not include all of the approved products for a parcular indicaon. In addion, third-party payors may impose prior authorizaon or step edit requirements requiring paents to have tried other therapies prior to our products for coverage. Payors may also decline to include our products or product candidates on their formulary, which means that unless healthcare providers seek a medical excepon for coverage, the payors will not pay for the product. In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-eﬀecveness of the product, in addion to the costs required to obtain FDA or other comparable markeng approvals. Nonetheless, product candidates may not be considered medically necessary or cost eﬀecve. A decision by a third-party payor not to cover a product candidate could reduce physician ulizaon once the product is approved and have a material adverse eﬀect on sales, results of operaons and ﬁnancial condion. Addionally, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s determinaon to provide coverage for a drug product does not assure that other payors will also provide coverage and reimbursement for the product, and the level of coverage and reimbursement can diﬀer signiﬁcantly from payor to payor. Dialysis-related drugs are included in the ESRD prospecve payment system, or PPS, bundled payment and are grouped into funconal categories such as anemia management and bone and mineral metabolism, except that oral-only drugs are exempted from inclusion unl 2025. In a ﬁnal ESRD PPS rule published in October 2019, CMS conﬁrmed that it will expand the TDAPA to most new dialysis drugs approved by the FDA aer January 1, 2020. The TDAPA provides separate payment for eligible new drugs for two years based on the drug’s Average Sales Price, or ASP, that will be in addion to the base rate in order to facilitate the adopon of innovave therapies. Although there are several details that need further clariﬁcaon, including precise ming related to receiving codes to allow for reimbursement under TDAPA, which are assigned on a quarterly basis, the rule provides support for our assumpon that new anemia treatments, including those in the HIF-PH inhibitor class, will be included in the ESRD PPS bundle and will be eligible for separate payment inially under TDAPA, and we expect to receive TDAPA designaon for vadadustat six months post-ﬁling acceptance if approved by the FDA. As an oral drug, Auryxia is covered by Medicare under Part D. Under the ESRD PPS, CMS generally makes a single bundled payment to the dialysis facility for each dialysis treatment that covers all items and services rounely required for dialysis treatments furnished to Medicare beneﬁciaries in Medicare-cerﬁed ESRD facilies or at their home. The inclusion of oral medicaons without injectable or intravenous equivalents such as Auryxia in the bundled payment was inially delayed by CMS unl January 1, 2014, and through several subsequent legislave acons has been delayed unl January 1, 2025. Absent further legislaon or regulaon on this maer, beginning in January 2025, oral ESRD-related drugs without injectable or intravenous equivalents, including Auryxia and all other phosphate lowering medicaons, will be included in the ESRD bundle and separate Medicare payment for these drugs will no longer be available, as is the case today under Medicare Part D. ESRD facilies may nonetheless receive a TDAPA for new renal dialysis drugs and biological products that meet certain criteria for a period of two years. The TDAPA will provide separate payment based on the drug’s ASP that will be in addion to the base rate in order to facilitate the adopon of innovave therapies. There can be no assurances that CMS will not again delay the inclusion of these oral ESRD-related drugs in the bundled payment. Even if Auryxia is deemed eligible by CMS, revenue for sales of Auryxia could be signiﬁcantly less in the TDAPA period than it would be if Auryxia is not bundled into the ESRD PPS. Moreover, in the post-TDAPA period, CMS currently expects to increase the single bundled payment base rate paid to the dialysis facility for each dialysis treatment to reﬂect that oral only phosphate lowering drugs will be reimbursed as part of the single bundled payment for Medicare paents. There can be no assurances that any increase in the single bundled payment base rate will be suﬃcient to adequately reimburse the dialysis facilies for Auryxia at a price that is proﬁtable for us. The containment of healthcare costs also has become a priority of federal, state and foreign governments and the prices of drugs have been a focus in this eﬀort. Governments have shown signiﬁcant interest in implemenng cost-containment programs, including price controls, restricons on reimbursement and requirements for substuon of generic products. Adopon of price controls and cost-containment measures, and adopon of more restricve policies in jurisdicons with exisng controls and measures, could further limit a company’s revenue generated from the sale of any approved products. Coverage policies and third-party reimbursement rates may change at any me. Even if favorable coverage and reimbursement status is aained for one or more products for which a company or its collaborators receive markeng approval, less favorable coverage policies and reimbursement rates may be implemented in the future. Outside the U.S., ensuring adequate coverage and payment for a product also involves challenges. Pricing of prescripon pharmaceucals is subject to governmental control in many countries. Pricing negoaons with governmental authories can extend well beyond the receipt of regulatory markeng approval for a product and may require a clinical trial that compares Akebia Therapeucs, Inc. | Form 10-K | Page 42 Table of Contents the cost eﬀecveness of a product to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in commercializaon. In the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only aer a reimbursement price has been agreed. Some countries may require the compleon of addional studies that compare the cost-eﬀecveness of a parcular product candidate to currently available therapies or so-called health technology assessments, in order to obtain reimbursement or pricing approval. For example, the EU provides opons for its EU Member States to restrict the range of products for which their naonal health insurance systems provide reimbursement and to control the prices of medicinal products for human use. EU Member States may approve a speciﬁc price for a product or it may instead adopt a system of direct or indirect controls on the proﬁtability of the company placing the product on the market. Other EU Member States allow companies to ﬁx their own prices for products but monitor and control prescripon volumes and issue guidance to physicians to limit prescripons. Recently, many countries in the EU have increased the amount of discounts required on pharmaceucals and these eﬀorts could connue as countries aempt to manage healthcare expenditures, especially in light of the severe ﬁscal and debt crises experienced by many countries in the EU. The downward pressure on health care costs in general, parcularly prescripon drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. Polical, economic and regulatory developments may further complicate pricing negoaons, and pricing negoaons may connue aer reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade, i.e., arbitrage between low-priced and high- priced EU Member States, can further reduce prices. There can be no assurance that any country that has price controls or reimbursement limitaons for pharmaceucal products will allow favorable reimbursement and pricing arrangements for any products, if approved in those countries. Dialysis Organizaons Protocols Dialysis organizaons have their own formularies that list primary or preferred therapeuc opons based on contracng status with drug manufacturers. While a prescriber may make their own independent decision to prescribe what they determine most appropriate for a given paent, any non-formulary therapeuc opons are only available through an excepon process based on clinical need. Similar to how payor coverage may aﬀect the sales of a product, formulary status within dialysis organizaons may aﬀect what products are prescribed within that speciﬁc organizaon. Therefore, if a product is not on a formulary, the prescribers within that organizaon may be less likely to prescribe that product or may have a diﬃcult me prescribing that product, resulng in less sales. Further, one dialysis organizaon’s determinaon to add a product to their formulary does not assure that other dialysis organizaons will also add the product to theirs. There is always a risk a dialysis organizaon will not contract with a drug manufacturer for a speciﬁc product, resulng in that product not being on that organizaon’s formulary. Addionally, dialysis organizaons typically assess a product’s eﬃcacy before adding it to their formulary. Their process for assessing a product may diﬀer among organizaons and the ming of such assessment could delay adding such treatment to formulary, further aﬀecng product sales. Healthcare Law and Regulaon Healthcare providers and third-party payors play a primary role in the recommendaon and prescripon of drug products that are granted markeng approval. Arrangements with providers, consultants, third-party payors and customers are subject to broadly applicable fraud and abuse, an-kickback, false claims laws, reporng of payments to physicians, teaching hospitals and other healthcare providers, paent privacy laws and regulaons, and other healthcare laws and regulaons that may constrain business and/or ﬁnancial arrangements. Restricons under applicable federal and state healthcare laws and regulaons include the following: • • • the federal An-Kickback Statute, which prohibits, among other things, persons and enes from knowingly and willfully solicing, oﬀering, paying, receiving or providing remuneraon, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendaon of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid; the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penales laws, which prohibit individuals or enes from, among other things, knowingly presenng, or causing to be presented, to the federal government, claims for payment that are false, ﬁcous or fraudulent or knowingly making, using or causing to be made or used a false record or statement to avoid, decrease or conceal an obligaon to pay money to the federal government HIPAA, which created addional federal criminal laws that prohibit, among other things, knowingly and willfully execung, or aempng to execute, a scheme to defraud any healthcare beneﬁt program or making false statements relang to healthcare maers; Akebia Therapeucs, Inc. | Form 10-K | Page 43 Table of Contents • • • • • • HIPAA, as amended by the Health Informaon Technology for Economic and Clinical Health Act, and their respecve implemenng regulaons, including the Final Omnibus Rule published in January 2013, which impose obligaons, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually idenﬁable health informaon; the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connecon with the delivery of or payment for healthcare beneﬁts, items or services; the U.S. Foreign Corrupt Pracces Act, or FCPA, which prohibits companies and their intermediaries from making, or oﬀering or promising to make improper payments to non-U.S. oﬃcials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; the federal transparency requirements, known as the federal Physician Payments Sunshine Act (renamed the Open Payments Act), under the Paent Protecon and Aﬀordable Care Act, as amended by the Health Care Educaon Reconciliaon Act, or ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the CMS within the U.S. Department of Health and Human Services, informaon related to payments and other transfers of value made by that enty to physicians, other healthcare providers and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; the PDMA and its implementaon regulaons, as well as the DSCSA, which regulate the distribuon and tracing of prescripon drugs and prescripon drug samples at the federal level, and set minimum standards for the regulaon of drug distributors by the states; and analogous state and foreign laws and regulaons, such as state an-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by third-party payors, including private insurers, and state gi ban and disclosure law requirements that diﬀer from the federal Physician Payments Sunshine Act in terms of the nature and type of transfers of value that are reportable and the types of covered recipients. Violaons of these laws are punishable by criminal and/or civil sancons, including, in some instances, exclusion from parcipaon in federal and state health care programs, such as Medicare and Medicaid. Ensuring compliance is me consuming and costly. Similar healthcare laws and regulaons exist in the EU and other jurisdicons, including reporng requirements detailing interacons with and payments to healthcare providers and laws governing the privacy and security of personal informaon. Some state laws require pharmaceucal companies to comply with the pharmaceucal industry’s voluntary compliance guidelines, such as the Pharmaceucal Research and Manufacturers of America Code on Interacons with Health Care Professionals, known as the PhRMA Code. State and foreign laws also govern the privacy and security of health informaon in some circumstances, many of which diﬀer from each other in signiﬁcant ways and oen are not preempted by HIPAA, thus complicang compliance eﬀorts. Healthcare Reform in the U.S. A primary trend in the U.S. healthcare industry and elsewhere is cost containment. There have been a number of federal and state proposals during the last few years regarding the pricing of pharmaceucal and biopharmaceucal products, liming coverage and reimbursement for drugs and other medical products, government control and other changes to the healthcare system in the U.S. By way of example, the U.S. and state governments connue to propose and pass legislaon designed to reduce the cost of healthcare. In March 2010, the U.S. Congress enacted the ACA, which, among other things, includes changes to the coverage and payment for products under government health care programs. Other legislave changes have been proposed and adopted since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, created measures for spending reducons by Congress. A Joint Select Commiee on Deﬁcit Reducon, tasked with recommending a targeted deﬁcit reducon of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislaon’s automac reducon to several government programs. This includes aggregate reducons of Medicare payments to providers of up to 2% per ﬁscal year, which will remain in eﬀect through 2031 pursuant to the Coronavirus Aid, Relief and Economic Security Act, or CARES Act. Under current legislaon, the actual reducons in Medicare payments may vary up to 4%. The Consolidated Appropriaons Act, which was signed into law by President Biden in December 2022, made several changes to sequestraon of the Medicare program. Secon 1001 of the Consolidated Appropriaons Act delays the 4% Statutory Pay-As-You-Go Act of 2010 sequester for two years, through the end of calendar year 2024. Triggered by enactment of the Akebia Therapeucs, Inc. | Form 10-K | Page 44 Table of Contents American Rescue Plan Act of 2021, the 4% cut to the Medicare program would have taken eﬀect in January 2023. The Consolidated Appropriaons Act’s health care oﬀset tle includes Secon 4163, which extends the 2% Budget Control Act of 2011 Medicare sequester for six months into ﬁscal year 2032 and lowers the payment reducon percentages in ﬁscal years 2030 and 2031. Since enactment of the ACA, there have been, and connue to be, numerous legal challenges and Congressional acons to repeal and replace provisions of the law. For example, with enactment of the Tax Cuts and Jobs Act of 2017, or the Tax Act, which was signed by the prior administraon on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became eﬀecve in 2019. On November 10, 2020, the U.S. Supreme Court heard oral arguments as to whether the individual mandate poron of the ACA is an essenal and inseverable feature of the ACA, and therefore because the mandate was repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well. On February 10, 2021, the Biden Administraon withdrew the federal government’s support for overturning the ACA. On June 17, 2021, the Supreme Court struck down the lower court rulings ﬁnding that the plainﬀs did not have standing to challenge the constuonality of the ACA. Ligaon and legislaon over the ACA are likely to connue, with unpredictable and uncertain results. The prior administraon also took execuve acons to undermine or delay implementaon of the ACA, including direcng federal agencies with authories and responsibilies under the ACA to waive, defer, grant exempons from, or delay the implementaon of any provision of the ACA that would impose a ﬁscal or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceucals or medical devices. On January 28, 2021, however, President Biden rescinded those orders and issued a new execuve order that directs federal agencies to reconsider rules and other policies that limit access to healthcare, and consider acons that will protect and strengthen that access. Under this order, federal agencies are directed to re- examine: policies that undermine protecons for people with pre-exisng condions, including complicaons related to COVID-19; demonstraons and waivers under Medicaid and the ACA that may reduce coverage or undermine the programs, including work requirements; policies that undermine the Health Insurance Marketplace or other markets for health insurance; policies that make it more diﬃcult to enroll in Medicaid and under the ACA; and policies that reduce aﬀordability of coverage or ﬁnancial assistance, including for dependents. Pharmaceucal Prices in the U.S. The prices of prescripon pharmaceucals have also been the subject of considerable discussion in the U.S. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal legislaon designed to, among other things, bring more transparency to pharmaceucal pricing, review the relaonship between pricing and manufacturer paent programs, and reduce the costs of pharmaceucals under Medicare and Medicaid. In 2020, the prior administraon issued several execuve orders intended to lower the costs of prescripon products and certain provisions in these orders have been incorporated into regulaons. These regulaons include an interim ﬁnal rule implemenng a most favored naon model for prices that would e Medicare Part B payments for certain physician-administered pharmaceucals to the lowest price paid in other economically advanced countries, eﬀecve January 1, 2021. That rule, however, has been subject to a naonwide preliminary injuncon and, on December 29, 2021, CMS issued a ﬁnal rule to rescind it. With issuance of this rule, CMS stated that it will explore all opons to incorporate value into payments for Medicare Part B pharmaceucals and improve beneﬁciaries' access to evidence-based care. In addion, in October 2020, HHS and the FDA published a ﬁnal rule allowing states and other enes to develop a Secon 804 Importaon Program, or SIP, to import certain prescripon drugs from Canada into the U.S. That regulaon was challenged in a lawsuit by the Pharmaceucal Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 aer the court found that PhRMA did not have standing to sue HHS. Nine states (Vermont, Colorado, Florida, Maine, New Mexico, New Hampshire, North Dakota, Texas and Wisconsin) have passed laws allowing for the importaon of drugs from Canada. Certain of these states have submied Secon 804 Importaon Program proposals and are awaing FDA approval. On January 5, 2023, the FDA approved Florida’s plan for Canadian drug importaon. Further, the HHS ﬁnalized a regulaon removing safe harbor protecon for price reducons from pharmaceucal manufacturers to plan sponsors under Part D, either directly or through pharmacy beneﬁt managers, unless the price reducon is required by law. The ﬁnal rule would also eliminate the current safe harbor for Medicare drug rebates and create new safe harbors for beneﬁciary point-of-sale discounts and pharmacy beneﬁt manager service fees. It originally was set to go into eﬀect on January 1, 2022, but with passage of the Inﬂaon Reducon Act of 2022, or IRA, has been delayed by Congress to January 1, 2032. On July 9, 2021, President Biden signed Execuve Order 14063, which focuses on, among other things, the price of pharmaceucals. The Order directs HHS to create a plan within 45 days to combat “excessive pricing of prescripon pharmaceucals and enhance domesc pharmaceucal supply chains, to reduce the prices paid by the federal government for such pharmaceucals, and to address the recurrent problem of price gouging.” On September 9, 2021, HHS released its plan to reduce pharmaceucal prices. The key features of that plan are to: (a) make pharmaceucal prices more aﬀordable Akebia Therapeucs, Inc. | Form 10-K | Page 45 Table of Contents and equitable for all consumers and throughout the health care system by supporng pharmaceucal price negoaons with manufacturers; (b) improve and promote compeon throughout the prescripon pharmaceucal industry by supporng market changes that strengthen supply chains, promote biosimilars and generic drugs, and increase transparency; and (c) foster scienﬁc innovaon to promote beer healthcare and improve health by supporng public and private research and making sure that market incenves promote discovery of valuable and accessible new treatments. The IRA has implicaons for Medicare Part D, which is a program available to individuals who are entled to Medicare Part A or enrolled in Medicare Part B to give them the opon of paying a monthly premium for outpaent prescripon drug coverage. Among other things, the IRA requires manufacturers of certain drugs to engage in price negoaons with Medicare (beginning in 2026), with prices that can be negoated subject to a cap; imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inﬂaon (ﬁrst due in 2023); and replaces the Part D coverage gap discount program with a new discounng program (beginning in 2025). The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulaon, for the inial years. Speciﬁcally, with respect to price negoaons, Congress authorized Medicare to negoate lower prices for certain costly single-source drug and biologic products that do not have compeng generics or biosimilars and are reimbursed under Medicare Part B and Part D. CMS may negoate prices for ten high- cost drugs paid for by Medicare Part D starng in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond. This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condion. Further, the legislaon subjects drug manufacturers to civil monetary penales and a potenal excise tax for failing to comply with the legislaon by oﬀering a price that is not equal to or less than the negoated “maximum fair price” under the law or for taking price increases that exceed inﬂaon. The legislaon also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inﬂaon. The new law also caps Medicare out-of-pocket drug costs at an esmated $4,000 a year in 2024 and, thereaer beginning in 2025, at $2,000 a year. On June 6, 2023, Merck ﬁled a lawsuit against HHS and CMS asserng that, among other things, the IRA’s Drug Price Negoaon Program for Medicare constutes an uncompensated taking in violaon of the Fih Amendment of the Constuon. Subsequently, a number of other pares, including the U.S. Chamber of Commerce, Bristol Myers Squibb Company, the Pharmaceucal Research and Manufacturers of America, Astellas, Novo Nordisk, Janssen Pharmaceucals, Novars, AstraZeneca and Boehringer Ingelheim, also ﬁled lawsuits in various courts with similar constuonal claims against HHS and CMS. Ligaon involving these and other provisions of the IRA will connue with unpredictable and uncertain results. At the state level, individual states are increasingly aggressive in passing legislaon and implemenng regulaons designed to control pharmaceucal and biological product pricing, including price or paent reimbursement constraints, discounts, restricons on certain product access and markeng cost disclosure and transparency measures, and, in some cases, designed to encourage importaon from other countries and bulk purchasing. A number of states, for example, require drug manufacturers and other enes in the drug supply chain, including health carriers, pharmacy beneﬁt managers, wholesale distributors, to disclose informaon about pricing of pharmaceucals. In addion, regional healthcare organizaons and individual hospitals are increasingly using bidding procedures to determine what pharmaceucal products and which suppliers will be included in their prescripon pharmaceucal and other healthcare programs. These measures could reduce the ulmate demand for our products, once approved, or put pressure on our product pricing. We expect that addional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for our product candidates or addional pricing pressures. Healthcare Reform and Pharmaceucal Prices in the EU In the EU, similar polical, economic, and regulatory developments to those in the U.S. may aﬀect our ability to proﬁtably commercialize our product candidates, if approved. In many countries, including those of the EU, the pricing of prescripon pharmaceucals is subject to governmental control and access. In these countries, pricing negoaons with governmental authories can take considerable me aer the receipt of an MA. To obtain reimbursement or pricing approval in some countries, pharmaceucal ﬁrms may be required to conduct a clinical trial that compares the cost-eﬀecveness of the product to other available therapies. In addion to connuing pressure on prices and cost containment measures, legislave developments at the EU or EU Member State level may result in signiﬁcant addional requirements or obstacles. The delivery of healthcare in the EU, including the establishment and operaon of health services and the pricing and reimbursement of medicines, is almost exclusively a maer for naonal, rather than EU, law and policy. Naonal governments and health service providers have diﬀerent priories and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most EU Member States have resulted in restricons on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-increasing EU and naonal regulatory burdens on those wishing to develop and market products, this could restrict or Akebia Therapeucs, Inc. | Form 10-K | Page 46 Table of Contents regulate post-approval acvies and aﬀect the ability of pharmaceucal companies to commercialize their products. In internaonal markets, reimbursement and healthcare payment systems vary signiﬁcantly by country, and many countries have instuted price ceilings on speciﬁc products and therapies. In the EU, potenal reducons in prices and changes in reimbursement levels could be the result of diﬀerent factors, including reference pricing used by various EU Member States, parallel distribuon and parallel trade can further reduce prices. It could also result from the applicaon of external reference pricing mechanisms, which consist of arbitrage between low-priced and high-priced EU Member States. There can be no assurance that any country that has price controls or reimbursement limitaons for pharmaceucal products will allow favorable reimbursement and pricing arrangements for any product candidates, if approved in those countries. Health technology assessment, or HTA, of medicinal products in the EU is an essenal element of the pricing and reimbursement decision-making process in a number of EU Member States. The outcome of HTA has a direct impact on the pricing and reimbursement status granted to the medicinal product. A negave HTA by a leading and recognized HTA body concerning a medicinal product could undermine the prospects to obtain reimbursement for such product not only in the EU Member State in which the negave assessment was issued, but also in other EU Member States. In 2011, Direcve 2011/24/EU was adopted at the EU level. This direcve establishes a voluntary network of naonal authories or bodies responsible for HTA in the individual EU Member States. The network facilitates and supports the exchange of scienﬁc informaon concerning HTAs. Further to this, on December 13, 2021, Regulaon No 2021/2282 on HTA, amending Direcve 2011/24/EU, was adopted. While the regulaon entered into force in January 2022, it will only begin to apply from January 2025 onwards, with preparatory and implementaon-related steps to take place in the interim. Once applicable, it will have a phased implementaon depending on the concerned products. The regulaon intends to boost cooperaon among EU Member States in assessing health technologies, including new medicinal products as well as certain high-risk medical devices, and provide the basis for cooperaon at the EU level for joint clinical assessments in these areas. It will permit EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovave health technologies with the highest potenal impact for paents, joint scienﬁc consultaons whereby developers can seek advice from HTA authories, idenﬁcaon of emerging health technologies to idenfy promising technologies early, and connuing voluntary cooperaon in other areas. Individual EU Member States will connue to be responsible for assessing non- clinical (e.g., economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement. Laws Relang to Foreign Trade We are subject to various federal and foreign laws that govern our internaonal business pracces. These laws include the FCPA, which prohibits U.S. companies and their representaves from paying, oﬀering to pay, promising, or authorizing the payment of anything of value to any foreign government oﬃcial, government staﬀ member, polical party, or polical candidate for the purposes of obtaining or retaining business, or to otherwise obtain favorable treatment or inﬂuence a person working in an oﬃcial capacity. In many countries, the health care professionals we regularly interact with may meet the FCPA’s deﬁnion of a foreign government oﬃcial. Addionally, interacons with or on the part of our partners, collaborators, contract research organizaons, vendors or other agents may also implicate the FCPA. The FCPA also requires public companies to make and keep books and records that accurately and fairly reﬂect their transacons and to devise and maintain an adequate system of internal accounng controls. Compliance with the FCPA is expensive and diﬃcult, parcularly in countries in which corrupon is a recognized problem. In addion, the FCPA presents unique challenges in the pharmaceucal industry because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign oﬃcials. Certain payments made by pharmaceucal companies to hospitals in connecon with clinical trials and other work have been deemed to be improper payments to government oﬃcials and have led to FCPA enforcement acons. Our internaonal operaons could also be subject to compliance with naonal laws of other countries, such as the United Kingdom Bribery Act. of 2010, or UK Bribery Act. The UK Bribery Act applies to any company “carrying on business” in the UK, irrespecve of where the oﬀending conduct occurs. The UK Bribery Act applies to bribery acvies both in the public and private sector and prohibits the provision of an “advantage” intended to induce or reward “improper performance” of the recipient’s funcon. The failure by a company to prevent third pares from providing a bribe on its behalf could also constute an oﬀense. Penales under the UK Bribery Act include potenally unlimited ﬁnes for companies and criminal sancons for corporate oﬃcers under certain circumstances. There are local anbribery and ancorrupon laws in countries where we are conducng clinical trials, such as Brazil and Russia, and many of these also carry the risk of signiﬁcant ﬁnancial or criminal penales. Our clinical trial operaons could also result in enforcement acons by U.S., UK, or other governmental authories. There are also trade laws within the U.S. and in other regions that regulate the sale, purchase, import, export, reexport, transfer and shipment of goods, currency, products, materials, services and technology. Violaons of these laws can lead to serious consequences, including substanal ﬁnes. Akebia Therapeucs, Inc. | Form 10-K | Page 47 Table of Contents Other Regulaons We are also subject to numerous federal, state and local laws relang to such maers as safe working condions, manufacturing pracces, environmental protecon, ﬁre hazard control, and disposal of hazardous or potenally hazardous substances. We may incur signiﬁcant costs to comply with such laws and regulaons now or in the future. Seasonality Fluctuaons in wholesaler inventory levels impact our product sales. In recent years, product revenues during the fourth quarter tend to be stronger than other quarters as our distributors increase their inventory levels, resulng in inventory draw-down by wholesalers in the subsequent ﬁrst quarter. In addion, in December 2022 and December 2023, we changed our contracng strategy which can further impact ﬁrst quarter sales. In general, our ﬁrst quarter usually has lower revenues than the preceding fourth quarter, the second and third quarters have higher revenues than the ﬁrst quarter, and the fourth quarter revenues are the highest in the year. While seasonality may aﬀect quarterly comparisons within a ﬁscal year, it generally is not material to our annual consolidated results. However, we expect Auryxia to be included in the ESRD bundle starng in January 2025, and coupled with Auryxia loss exclusivity in March 2025, may impact our customer buying paerns and therefore their buying paerns may be diﬀerent during 2024 than historical pracces. Employees and Human Capital Resources As of December 31, 2023, we had 167 employees. None of our employees are represented by any collecve bargaining unit. We believe that we maintain good relaons with our employees. We face compeon for our personnel from our competors and other companies throughout our industry. Over the last several years, the challenges in recruing and retaining employees across the pharmaceucal and biotechnology industries have increased substanally due to current industry job market dynamics. Retenon, growth, training and development of our employees are integral to our success. We oﬀer compeve compensaon, including base salary and incenve bonuses. We conduct bi-annual internal and external pay reviews to ensure fair and equitable pay for our employees, which includes an internal pay equity analysis, as well as a review of our employees' pay against external market data. To foster a stronger sense of ownership and align the interests of employees with shareholders, we grant restricted stock units and common stock opons to eligible employees under our broad-based stock incenve program, and employees may purchase stock pursuant to our employee stock purchase plan. Further, our beneﬁts packages are designed to aract, movate and reward talented individuals who possess the skills necessary to support our business objecves, assist in the achievement of our strategic goals and create value for our stockholders. Our compensaon program is designed to diﬀerenate us from our compeon, incenvize achievement of corporate goals and individual performance and demonstrate our corporate values. In addion, we are commied to developing our team members and provide development and leadership opportunies to our employees to culvate talent throughout the Company. We are commied to our employees’ health, safety and well-being. Our work paradigm is ﬂexible and designed to accommodate a range of work proﬁles. Our workforce is primarily hybrid and fully remote, including ﬁeld-based, with certain employees being oﬃce based. We oﬀer a wide variety of compeve beneﬁts to support our employees' physical, mental and ﬁnancial well-being. Our beneﬁts package is comprehensive in coverage and oﬀers opons to support all employees in staying healthy, planning for their future and developing their careers. Our management connues to assess and respond to the evolving needs of our workforce. Environmental, Social and Governance Our commitment to diversity, equality and inclusion starts with our execuve leadership. Two members of our Board of Directors are women, and women comprise approximately 50% of our senior management team. In addion, approximately 25% of our employees are ethnically diverse and one member of our Board of Directors is African American. With the goal of ensuring every employee is included, supported and treated equitably, we developed a team (IDEA – Inclusion, Diversity & Equity Alliance) to support and guide Akebia as a diverse, inclusive and culturally intelligent workplace. Over the past three years this team has worked with execuve leadership to idenfy areas for growth and educaon and move forward several iniaves that will enable us to connue to build an inclusive workplace and a diverse workforce. Our other iniaves include learning, coaching, cultural awareness acvies and development opportunies for all of our employees. Our Cambridge oﬃce has a Fitwel Cerﬁcaon, a healthy building cerﬁcaon system, and is level two cerﬁed. Addionally, we consolidated our oﬃce footprint to reduce our use of energy and other resources and have iniated recycling programs, including single stream recycling and recycling cans at every desk. Furthermore, we oﬀer a commuter beneﬁt to all of our Akebia Therapeucs, Inc. | Form 10-K | Page 48 Table of Contents hybrid and oﬃce-based employees to encourage employees to use public transportaon and oﬀer bicycle parking free of charge in the onsite garage. In addion, we support kidney paent communies where we live and work. In the U.S., we have a paent services program, Akebia Cares, designed to provide one-on-one support to help communicate individual beneﬁts and available resources for paents today facing ﬁnancial obstacles that keep them from accessing important medicaons. In 2023, we provided over $7.0 million worth of Auryxia for free to approximately 15,000 paents needing assistance. We also have a cross-funconal Sponsorship Review Commiee that reviews and approves sponsorships and donaons based on the relevance of each projects to our purpose, business objecves and the communies we serve. We support and work closely with mulple kidney paent advocacy organizaons. We believe our involvement with and support of paent advocacy programs demonstrates our commitment to our purpose of beering the life of each person impacted by kidney disease. Available Informaon Our website address is www.akebia.com. The informaon on our website or that may be accessed by links on our website is not incorporated by reference into this Form 10-K. We make available, free of charge and through our website, our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and any amendments to any such reports ﬁled or furnished pursuant to Secon 13(a) or 15(d) of the Securies Exchange Act of 1934, as amended, as soon as reasonably praccable aer they are electronically ﬁled with or furnished to the U.S. Securies and Exchange Commission, or SEC. Corporate Informaon Akebia was incorporated in Delaware in 2007 and became a public company in 2014. Our mailing address and principal execuve oﬃces and our laboratory are located at 245 First Street, Cambridge, Massachuses 02142. Our telephone number is (617) 871-2098. We are required to ﬁle annual, quarterly and current reports, proxy statements and other informaon with the SEC. The SEC maintains a website at www.sec.gov that contains reports, proxy and informaon statements, and other informaon regarding issuers that ﬁle electronically with the SEC. Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, proxy statements, and other informaon, including amendments and exhibits to such reports, ﬁled or furnished pursuant to the Securies Exchange Act of 1934 are also available free of charge in the “SEC Filings” secon of our website located at hp://www.akebia.com, as soon as reasonably praccable aer the reports are electronically ﬁled with or furnished to the SEC. The informaon on our website is not part of this Annual Report on Form 10-K. Akebia Therapeucs, Inc. | Form 10-K | Page 49 Table of Contents Item 1A. Risk Factors. We face a variety of risks and uncertaines in our business. Addional risks and uncertaines not presently known to us or that we currently believe to be immaterial may also become important factors that aﬀect our business, reputaon, results of operaons, ﬁnancial condion and stock price which can be materially and adversely aﬀected. If any of the following risks occurs, our business, ﬁnancial condion, ﬁnancial statements, results of operaons and future growth prospects could be materially and adversely aﬀected. Risks Related to our Financial Posion, Need for Addional Capital and Growth Strategy We have incurred signiﬁcant losses since our incepon and ancipate that we will connue to incur losses and cannot guarantee when, if ever, we will become proﬁtable or aain posive cash ﬂows. Investment in pharmaceucal product development and commercializaon is highly speculave because it may require upfront capital expenditures and signiﬁcant R&D expenses. Despite the investment in assets and R&D, there is signiﬁcant risk that a product candidate will fail to gain markeng approval or that an approved product will not be commercially viable. Since our incepon, we have devoted most of our resources to research and development, or R&D, including our preclinical and clinical development acvies, commercializing Auryxia and providing general and administrave support for these operaons. We have funded our operaons principally through product sales, payments received from our collaboraon and licensing partners, borrowings under term loans, sales of our common stock, including through our employee stock purchase plan, a working capital payment from Vifor (Internaonal) Ltd. (now a part of CSL Limited), or CSL Vifor, and a royalty transacon. Prior to our 2018 merger, or the Merger, with Keryx Biopharmaceucals, Inc., or Keryx, whereby Keryx became our wholly owned subsidiary, we had no products approved for commercial sale and had not generated any revenue from the sale of products. We are not currently proﬁtable and we have incurred net losses each year since our incepon, including a net loss of $51.9 million for the year ended December 31, 2023. As of December 31, 2023, we had an accumulated deﬁcit of $1.6 billion. We cannot guarantee when, if ever, we will become proﬁtable. In March 2022, we received a complete response leer, or CRL, from the United States, or U.S., Food and Drug Administraon, or FDA, regarding our new drug applicaon, or NDA, for vadadustat, our lead invesgaonal product candidate, for the treatment of anemia associated with CKD. The FDA concluded that the data in the NDA did not support a favorable beneﬁt-risk assessment of vadadustat for dialysis and non-dialysis paents. In October 2022, we submied a Formal Dispute Resoluon Request, or FDRR, to the FDA and focused on the favorable balance between the beneﬁts and risks of vadadustat for the treatment of anemia due to CKD in adult paents on dialysis in light of safety concerns expressed by the FDA in the CRL for dialysis paents related to the rate of adjudicated thromboembolic events driven by vascular access thrombosis for vadadustat compared to the acve comparator and the risk of drug- induced liver injury. In May 2023, the Oﬃce of New Drugs, or OND, denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. In September 2023, we ﬁled our resubmission to our NDA, and in October 2023, the FDA acknowledged that the resubmission was complete and set a user fee goal date, or PDUFA date, of March 27, 2024. There can be no assurances that we will obtain approval for vadadustat in a mely manner, on favorable terms, or at all. As a result, the regulatory approval process for vadadustat in the U.S. is highly uncertain. If we do not obtain approval of vadadustat in the U.S., or if the approval is delayed, it would have a material adverse impact on our business. Even if we are able to obtain approval, the expense and me to do so could adversely impact our ability to successfully commercialize vadadustat or conduct our other business operaons and our ﬁnancial condion could be materially harmed. Our ability to generate product revenue and achieve proﬁtability depends on our ability to manage expenses and the overall success of Auryxia, vadadustat, if approved, and any current or future product candidates, including those that may be in-licensed or acquired, which depends on several factors, including: • • • • • our ability to obtain approval for vadadustat in the U.S. in a mely manner or at all; obtaining adequate or favorable pricing and reimbursement from private and governmental payors for Auryxia, vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired; obtaining and maintaining market acceptance of Auryxia, vadadustat, if approved, and any other product candidate, including those that may be in- licensed or acquired; the size of any market in which Auryxia, vadadustat and any other product or product candidate, including those that may be in-licensed or acquired, receives approval and obtaining adequate market share in those markets; the ming and scope of markeng approvals for vadadustat, if approved, and any other product candidate, if approved, including those that may be in-licensed or acquired; • maintaining markeng approvals for Auryxia, vadadustat, if approved, and any other product, including those that may be in-licensed or acquired; Akebia Therapeucs, Inc. | Form 10-K | Page 50 Table of Contents • actual or perceived advantages or disadvantages of our products or product candidates as compared to alternave treatments, including their respecve safety, tolerability and eﬃcacy proﬁles, the potenal convenience and ease of administraon and cost; • maintaining an acceptable safety and tolerability proﬁle of our approved products, including the frequency and severity of any side eﬀects; • • • • • the willingness of the target paent populaon to try new therapies and of physicians to prescribe these therapies, based, in part, on their percepon of our clinical trial data and/or the actual or perceived safety, tolerability and eﬃcacy proﬁle; establishing and maintaining supply and manufacturing relaonships with third pares that can provide adequate supplies of products that are compliant with good manufacturing pracces, or GMPs, to support the clinical development and the market demand for Auryxia, vadadustat, if approved, and any other product and product candidate, including those that may be in-licensed or acquired; current and future restricons or limitaons on our approved or future indicaons and paent populaons or other adverse regulatory acons or in the event that the FDA requires Risk Evaluaon and Migaon Strategies, or REMS, or risk management plans that use restricve risk minimizaon strategies; the eﬀecveness of our collaborators' and our sales, markeng, manufacturing and distribuon strategies and operaons; compeng eﬀecvely with any products for the same or similar indicaons as our products; • maintaining, protecng and expanding our porolio of intellectual property rights, including patents and trade secrets; and • the adverse impact of the recent COVID-19 pandemic on CKD paents and the phosphate binder market in which we compete. Our collaboraon, license and other revenue also depends on our partners’ ability to successfully market and sell vadadustat and Auryxia in the territories in which they have licensed our products. For example, in May 2023, we entered into a license agreement with MEDICE Arzneimiel Püer GmbH & Co. KG, or Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with chronic kidney disease in the European Economic Area, or the EEA, the United Kingdom, Switzerland and Australia, or Medice Territory. If Medice’s launch of vadadustat in the Medice Territory is delayed or their sales are lower than ancipated, we may not receive the revenue that we expect from Medice on the ming ancipated, or at all. In addion, under the Second Amended and Restated License Agreement that we entered into with CSL Vifor, in February 2022, or the Vifor Agreement, we granted CSL Vifor an exclusive license to sell vadadustat to Fresenius Medical Care North America and its aﬃliates, including Fresenius Kidney Care Group LLC, to certain third-party dialysis organizaons approved by us, to independent dialysis organizaons that are members of group purchase organizaons, and to certain non-retail specialty pharmacies in the U.S., which represents a signiﬁcant poron of the potenal market for vadadustat. If vadadustat is approved, but CSL Vifor is not successful in commercializing vadadustat in a mely manner, or at all, our expected revenue related to vadadustat would be adversely impacted. In addion, pursuant to the Vifor Agreement, CSL Vifor contributed $40.0 million to a working capital facility, or Working Capital Fund, established to parally fund our costs of purchasing pre-launch vadadustat inventory from our contract manufacturers. The amount available under the Working Capital Fund is reviewed at speciﬁed intervals and is adjusted based on a number of factors including outstanding supply commitments for vadadustat for the U.S. and agreed upon vadadustat inventory levels held by us for the U.S. Addionally, upon terminaon or expiraon of the Vifor Agreement for any reason other than convenience by CSL Vifor (including following receipt of the CRL for vadadustat), we will be required to refund the outstanding balance of the Working Capital Fund on the date of terminaon or expiraon. If we are required to repay all or part of the Working Capital Fund sooner than ancipated, it could have a material adverse impact on our consolidated ﬁnancial statements. Our ability to achieve proﬁtability also depends on our ability to manage our expenses. We expect to connue to incur addional operang expenses, including addional R&D expenses related to our pipeline, addional costs related to vadadustat, and R&D and selling, general and administrave expenses for ongoing development and commercializaon of Auryxia, which could lead to operang losses for the foreseeable future. We will connue to incur substanal expenditures relang to connued commercializaon and post-markeng requirements for Auryxia and vadadustat, if we are able to obtain markeng approval for vadadustat, and any other products, including those that may be in-licensed or acquired, as well as costs relang to the R&D of any other product candidate, including those that may be in-licensed or acquired. Our prior losses have had, and expected future losses will connue to have, an adverse eﬀect on our stockholders’ (deﬁcit) equity and working capital. In addion to any further costs not currently contemplated in our operang plan, our ability to achieve proﬁtability and our ﬁnancial posion will depend, in part, on the rate of our future expenditures, our ability to obtain approval for vadadustat in Akebia Therapeucs, Inc. | Form 10-K | Page 51 Table of Contents the U.S., the ming of our product revenue, collaboraon, license and other revenue, the ming and amount of any repayment of the Working Capital Fund from CSL Vifor, our connued compliance with the terms of the BlackRock Credit Agreement and our ability to obtain addional funding, should it be needed. In addion, we expect to connue to incur signiﬁcant expenses if and as we: • • • connue our commercializaon acvies for Auryxia and vadadustat, if we are able to obtain markeng approval for vadadustat following our resubmission to our NDA, and any other product or product candidate, including those that may be in-licensed or acquired; conduct and enroll paents in any clinical trials, including post-markeng studies or any other clinical trials for Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired; seek markeng approvals for vadadustat and any other product candidate, including those that may be in-licensed or acquired; • maintain markeng approvals for Auryxia and vadadustat, if we are able to obtain markeng approval for vadadustat, and any other product, including those that may be in-licensed or acquired; • manufacture Auryxia, vadadustat and any other product or product candidate, including those that may be in-licensed or acquired, for commercial sale and clinical trials; • • • conduct discovery and development acvies for addional product candidates or plaorms that may lead to the discovery of addional product candidates; engage in transacons, including strategic, merger, collaboraon, acquision and licensing transacons, pursuant to which we would market and develop commercial products, or develop and commercialize other product candidates and technologies; repay, and pay any associated pre-payment penales, if applicable, the term loans in an aggregate principal amount of up to $55.0 million, or the Term Loans, as of January 29, 2024, that were made available to us pursuant to an Agreement for the Provision of a Loan Facility, or the BlackRock Credit Agreement, with Kreos Capital VII (UK) Limited, which are funds and accounts managed by BlackRock Inc., collecvely, BlackRock; • make royalty, milestone or other payments under our current and any future in-licensing agreements; • maintain, protect and expand our intellectual property porolio; • make decisions with respect to our personnel, including the retenon of key employees; • make decisions with respect to our infrastructure, including to support our operaons as a fully integrated, publicly traded biopharmaceucal company; and • experience any addional delays or encounter issues with any of the above. We have and will connue to expend signiﬁcant resources on our legal proceedings, as described below under Part I, Item 3. Legal Proceedings, or any other legal proceedings brought by or against us in the future. Our expenses could increase beyond expectaons if we are required by the FDA, the European Medicines Agency, or the EMA, or other regulatory authories, or if we otherwise believe it is necessary, to change our manufacturing processes or assays, to amend or replace our study protocols, to perform studies diﬀerent from or larger than those currently planned, to conduct any addional clinical trials, whether in order to obtain approval or as a post-approval study, including any addional clinical trial that we decide to conduct for vadadustat, if there are any delays in compleng our clinical trials or if there are further delays in or issues with obtaining markeng approval for vadadustat in the U.S. beyond our PDUFA date. Because of the numerous risks and uncertaines associated with pharmaceucal product development and commercializaon, we are unable to accurately predict the ming or amount of increased expenses or the associated revenue. The net losses we incur may ﬂuctuate signiﬁcantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operaons may not be a good indicaon of our future performance. In any parcular quarter, our product revenue, the progress of our clinical development and our operang results could be below the expectaons of securies analysts or investors, which could cause our stock price to decline. In addion, our ability to generate revenue would be negavely aﬀected if the size of our addressable paent populaon is not as signiﬁcant as we esmate, the indicaon approved by regulatory authories is narrower than we sought or the paent populaon for treatment is narrowed by compeon, physician choice, coverage or reimbursement, or payor or treatment guidelines. Even though we generate product revenue from Auryxia and royales from Riona and Vafseo in Japan, may generate royales from Vafseo in Europe and other territories where it is approved, and may generate revenue and royales from the sale of any products that may be approved in the future, including those that may be in-licensed or acquired, we may never generate revenue and royales that are signiﬁcant enough for us to become and remain proﬁtable, and we may need to obtain addional ﬁnancing to connue to fund our operang plan. Akebia Therapeucs, Inc. | Form 10-K | Page 52 Table of Contents We may require substanal addional ﬁnancing to fund our business. A failure to obtain this necessary capital when needed, or on acceptable terms, could force us to delay, limit, reduce or terminate our product development or commercializaon eﬀorts. As of December 31, 2023, our cash and cash equivalents were $42.9 million. We expect to connue to expend substanal amounts of cash for the foreseeable future as we connue to commercialize Auryxia; pursue approval for vadadustat in the U.S. with the FDA and develop and commercialize vadadustat in the U.S., if approved; and develop and commercialize any other product or product candidate, including those that may be in-licensed or acquired. These expenditures will include costs associated with R&D, manufacturing, potenally obtaining markeng approvals and markeng products approved for sale. In addion, other unancipated costs may arise. Because the outcomes of our current and ancipated clinical trials are highly uncertain, we cannot reasonably esmate the actual amount of funding necessary to successfully complete clinical development for any current or future product candidates, including the outcome of our NDA resubmission, or to complete post-markeng studies for Auryxia and vadadustat, if approved. Our future capital requirements depend on many factors, including: • • • • • • • • • • • • • • • the scope, progress, results and costs of conducng clinical trials or any post-markeng requirements or any other clinical trials for Auryxia, vadadustat and any other product or product candidate, including those that may be in-licensed or acquired; the cost and ming of commercializaon acvies, including product manufacturing, markeng, sales and distribuon costs, for Auryxia, vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired; the results of our meengs with the FDA, the EMA and other regulatory authories and any consequenal eﬀects, including on ming of and ability to obtain and maintain markeng approval, study design, study size and resulng operang costs; any diﬃcules or delays in conducng our clinical trials, or enrolling paents in our clinical trials, for Auryxia, vadadustat or any other product candidates; the outcome of our eﬀorts to obtain markeng approval for vadadustat in the U.S. and in other jurisdicons and any other product candidates, including those that may be in-licensed or acquired, including any addional clinical trials or post-approval commitments imposed by regulatory authories; the ming of, and the costs involved in obtaining, markeng approvals for vadadustat, including in the U.S. and certain other markets, and any other product candidate, including those that may be in-licensed or acquired, including to fund the preparaon, ﬁling and prosecuon of regulatory submissions; the costs of maintaining markeng approvals for Auryxia or any other product, including those that may be in-licensed or acquired; the number of generic versions of Auryxia that enter the market following loss of exclusivity, or LoE, for Auryxia in March 2025, and the ming of, and the magnitude of, the impact on the product revenue from Auryxia, including the impact on the price of Auryxia; the cost of securing and validang commercial manufacturing for any of our product candidates, including those that may be in-licensed or acquired, and maintaining our manufacturing arrangements for Auryxia and vadadustat or any other product, including those that may be in-licensed or acquired, or securing and validang addional arrangements; the costs involved in preparing, ﬁling and prosecung patent applicaons and maintaining, defending and enforcing our intellectual property rights, including ligaon costs and the outcome of such ligaon; the costs involved in any legal proceedings to which we are a party; our status as a publicly traded company on the Nasdaq Capital Market; our decisions with respect to personnel; our decisions with respect to infrastructure; and the extent to which we engage in transacons, including strategic, merger, collaboraon, acquision and licensing transacons, pursuant to which we could develop and market commercial products, or develop other product candidates and technologies. We may need to obtain substanal addional ﬁnancing to fund our business. If we are unable to raise capital when needed or on aracve terms, we could be forced to delay, reduce or eliminate our R&D programs or any future commercializaon eﬀorts. We failed to mely ﬁle our Quarterly Report on Form 10-Q for the three months ended June 30, 2023, or the Second Quarter 10-Q. Because of that failure to ﬁle, we are not currently eligible to ﬁle or use a Registraon Statement on Form S-3. This may make it more diﬃcult for us to conduct a public oﬀering of our securies. Akebia Therapeucs, Inc. | Form 10-K | Page 53 Table of Contents We believe our exisng cash resources and the cash we expect to generate from product, royalty, supply and license revenues as well as the borrowings and potenal future borrowings that are available under the BlackRock Credit Agreement and the working capital liability are suﬃcient to fund our current operang plan for at least twenty-four months if vadadustat is approved in the U.S and for at least twelve months from ﬁling the Form 10-K, if vadadustat is not approved in the U.S. However, if our operang performance deteriorates signiﬁcantly from the levels expected in our operang plan, or if vadadustat is not approved in the U.S., it would have an adverse eﬀect on our liquidity and capital resources and could aﬀect our ability to connue as a going concern in the future. Our forecast of the period of me through which our ﬁnancial resources will be adequate to support our operaons is a forward-looking statement and involves numerous risks and uncertaines, and actual results could vary as a result of a number of factors, many of which are outside our control. We have based this esmate on assumpons that may be substanally diﬀerent than actual results, and we could ulize our available capital resources sooner than we currently expect. In addion, if we fail to sasfy any of the covenants under the BlackRock Credit Agreement, and the loan is accelerated, or if certain pre-speciﬁed events occur and we are required to make principal payments to BlackRock sooner than we currently ancipate, such event could have a material adverse eﬀect on our business. There can be no assurance that the current operang plan will be achieved in the me frame ancipated by us, or that our cash resources and cash we expect to generate will fund our operang plan for the period ancipated by us, or that addional funding will be available on terms acceptable to us, or at all. Any addional fundraising eﬀorts may divert our management’s aenon away from their day-to-day acvies, which may adversely aﬀect our ability to develop and commercialize Auryxia and any other products or product candidates, including vadadustat and those that may be in-licensed or acquired, or to connue to seek regulatory approval for vadadustat. Also, addional funds may not be available to us in suﬃcient amounts or on acceptable terms or at all. In addion, raising funds in the current economic environment may present addional challenges. For example, any sustained disrupon in the capital markets from adverse macroeconomic condions and an uncertain geopolical environment, such as rising inﬂaon, increasing interest rates, slower economic growth or recession, global supply chain disrupons, the ongoing Russia-Ukraine war, the war in the Middle East and tensions between China and Taiwan, could negavely impact our ability to raise capital, and we cannot predict the extent or duraon of such macroeconomic disrupons. If we are unable to raise addional capital in suﬃcient amounts when needed or on terms acceptable to us, we may have to signiﬁcantly delay, scale back or disconnue the development and/or commercializaon of Auryxia and any other products or product candidates, including vadadustat and those that may be in-licensed or acquired, or to take any acons with respect to vadadustat depending on future decisions with respect to vadadustat in the U.S. Any of these events could signiﬁcantly harm our business, ﬁnancial condion and prospects. Raising addional capital may cause diluon to our exisng stockholders, restrict our operaons or require us to relinquish rights to our product and product candidates on unfavorable terms to us. We expect to ﬁnance future cash needs through product revenue and royalty and license revenue, and we may seek to sell public or private equity, enter into new debt transacons, explore potenal strategic transacons or a combinaon of these approaches or other strategic alternaves. To the extent that we raise addional capital through the sale of equity or converble debt securies, the ownership interests of our common stockholders will be diluted, our ﬁxed payment obligaons may increase, any such securies may have rights senior to those of our common stock, and the terms may include liquidaon or other preferences and an-diluon protecons that adversely aﬀect the rights of our common stockholders. Addional debt ﬁnancing, if available, may involve agreements that would restrict our operaons and potenally impair our compeveness, such as limitaons on our ability to incur addional debt, make capital expenditures, declare dividends, acquire, sell or license intellectual property rights, and other operang restricons that could adversely impact our ability to conduct our business. If we raise addional funds through strategic transacons, we may have to relinquish valuable rights to our porolio and future revenue streams, and enter into agreements that would restrict our operaons and strategic ﬂexibility. If we raise addional funds through strategic transacons with third pares, we may have to do so at an earlier stage than otherwise would be desirable. In connecon with any such strategic transacons, we may be required to relinquish valuable rights to our product and product candidates, future revenue streams or research programs or grant licenses on terms that are not favorable to us. If we are unable to raise addional funds when needed, we may not be able to pursue planned development and commercializaon acvies and we may need to grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. If we fail to comply with the connued lisng requirements of Nasdaq, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negavely impacted. We must sasfy Nasdaq’s connued lisng requirements, including, among other things, a minimum closing bid price of $1.00 per share and mely ﬁling of all periodic ﬁnancial reports, or risk delisng, which would have a material adverse eﬀect on our business. If we fail to maintain compliance with Nasdaq's connued lisng requirements, it could aﬀect our ability to raise capital on acceptable terms, or at all. In the event we are delisted from Nasdaq, the only established trading market for our common stock would be eliminated, and we would be forced to list our shares on the OTC Markets or another quotaon Akebia Therapeucs, Inc. | Form 10-K | Page 54 Table of Contents medium, depending on our ability to meet the speciﬁc lisng requirements of those quotaon systems. As a result, an investor would likely ﬁnd it more diﬃcult to trade or obtain accurate price quotaons for our shares. Delisng would likely also reduce the visibility, liquidity, and value of our common stock, reduce instuonal investor interest in our Company, and may increase the volality of our common stock. Delisng could also cause a loss of conﬁdence of potenal industry partners, lenders, and employees, which could further harm our business and our future prospects. On May 9, 2023, we received a leer from Nasdaq stang that we had not regained compliance with the minimum bid price rule during the compliance period and was subject to delisng. On May 22, 2023, we received a leer from the Oﬃce of General Counsel of Nasdaq informing us that Nasdaq conﬁrmed that we had regained compliance with the $1.00 per share minimum bid price requirement. On August 11, 2023, we received a noﬁcaon leer from Nasdaq informing us that since we had not yet ﬁled our Second Quarter 10-Q, we are not in compliance with Nasdaq's lisng rule requiring mely ﬁling of all required periodic ﬁnancial reports with the U.S. Securies and Exchange Commission, or the SEC. On August 30, 2023, we received a leer from the Oﬃce of General Counsel of Nasdaq informing us that Nasdaq conﬁrmed that we had regained compliance with Nasdaq's lisng rule requiring mely ﬁling of all required periodic ﬁnancial reports with the SEC. Although the minimum bid price deﬁciency and Nasdaq periodic reporng requirement maers are now closed, there can be no assurance that we will be able to connue to comply with the Nasdaq connued lisng requirements. We may not be successful in our eﬀorts to idenfy, acquire, in-license, discover, develop and commercialize addional products or product candidates or our decisions to priorize the development of certain product candidates over others may not be successful, which could impair our ability to grow. Although we connue to focus a substanal amount of our eﬀorts on the commercializaon of Auryxia and the pursuit of approval for vadadustat in the U.S. with the FDA, a key element of our long-term growth strategy is to develop addional product candidates and acquire, in-license, develop and/or market addional products and product candidates. Research programs to idenfy product candidates require substanal technical, ﬁnancial and human resources, regardless of whether product candidates are ulmately idenﬁed. Our R&D programs may inially show promise, yet fail to yield product candidates for clinical development or commercializaon for many reasons, including the following: • the research methodology used may not be successful in idenfying potenal indicaons and/or product candidates; • we may not be able or willing to assemble suﬃcient resources to acquire or discover addional product candidates; • • • • • • a product candidate may be shown to have harmful side eﬀects, a lack of eﬃcacy or other characteriscs that indicate that they are unlikely to be drugs that will receive markeng approval and/or achieve market acceptance; a product candidate we develop and seek regulatory approval for, including vadadustat, may not be approved by the FDA on a mely basis, or at all; product candidates we develop may nevertheless be covered by third party patents or other exclusive rights; the market for a product candidate may change during our program so that the connued development of that product candidate is no longer commercially reasonable; a product candidate may not be capable of being produced in commercial quanes at an acceptable cost, or at all; or a product candidate may not be accepted as safe and eﬀecve by paents, the medical community, or third party payors, if applicable. If any of these events occur, we may be forced to abandon our R&D eﬀorts for one or more of our programs, or we may not be able to idenfy, discover, develop or commercialize addional product candidates, including those that may be in-licensed or acquired, which may have a material adverse eﬀect on our business. Because we have limited ﬁnancial and managerial resources, especially as a result of the CRL for vadadustat that we received in March 2022 and the reducons in workforce that we implemented in 2022, we have focused on products, research programs and product candidates for speciﬁc indicaons. As a result, we have had to, and in the future may need to, forgo or delay pursuit of opportunies with other product candidates or for other indicaons, or may out license rights to product candidates, that later prove to have greater commercial potenal. For example, as a result of receipt of the CRL and implementaon of the reducons in workforce, we delayed certain research acvies. Our resource allocaon decisions may cause us to fail to capitalize on viable commercial products or proﬁtable market opportunies on a mely basis, or at all. Our spending on current and future R&D programs and product candidates for speciﬁc indicaons may not yield any commercially viable products. Because our internal research capabilies are limited, we may be dependent upon other pharmaceucal and biotechnology companies, academic sciensts and instuons, and other researchers to sell or license product candidates, products or Akebia Therapeucs, Inc. | Form 10-K | Page 55 Table of Contents technology to us. As a result, our rights to these product candidates may be limited or we may be required to make future payments to such third pares if we are successful in developing such product candidates. The success of this strategy depends partly upon our ability to idenfy, select, and acquire promising product candidates and products. The process of idenfying, selecng, negoang and implemenng a license or acquision of a product candidate or an approved product is lengthy and complex. Other companies, including some with substanally greater ﬁnancial, markeng and sales resources, may compete with us for the license or acquision of a product candidate or an approved product. We have limited resources to idenfy and execute the acquision or in- licensing of third party products, businesses, and technologies and integrate them into our current infrastructure. Moreover, we may devote resources to potenal acquisions or in-licensing opportunies that are never completed, or we may fail to realize the ancipated beneﬁts of such eﬀorts. Any product candidate that we acquire may require addional development eﬀorts prior to commercial sale, including extensive clinical tesng and approval by the FDA, the EMA, the Japanese Pharmaceucals and Medical Devices Agency, or PMDA, or other regulatory authories, or post-approval tesng or other requirements if approved. All product candidates are prone to risks of failure typical of pharmaceucal product development, including the possibility that a product candidate will not be shown to be suﬃciently safe and eﬀecve for approval by regulatory authories. In addion, we cannot provide assurance that any of our products will be manufactured in a cost eﬀecve manner, achieve market acceptance or not require substanal post-markeng clinical trials. Accordingly, there can be no assurance that we will ever be able to idenfy, acquire, in-license or develop suitable addional products or product candidates, which could materially adversely aﬀect our future growth and prospects. We may focus our eﬀorts and resources on potenal products, product candidates or other programs that ulmately prove to be unsuccessful. We may engage in strategic transacons to acquire assets, businesses, or rights to products, product candidates or technologies or form collaboraons or make investments in other companies or technologies that could harm our operang results, dilute our stockholders’ ownership, increase our debt, or cause us to incur signiﬁcant expense. As part of our business strategy, we may engage in addional strategic transacons to expand and diversify our porolio, including through the merger, acquision or in-license of assets, businesses, or rights to products, product candidates or technologies or through strategic alliances or collaboraons, similar to the Merger and our exisng and prior collaboraon and license arrangements. We may not idenfy suitable strategic transacons, or complete such transacons in a mely manner, on favorable terms, on a cost-eﬀecve basis, or at all. Moreover, we may devote resources to potenal opportunies that are never completed or we may incorrectly judge the value or worth of such opportunies. Even if we successfully execute a strategic transacon, we may not be able to realize the ancipated beneﬁts of such transacon and may experience losses related to our investments in such transacons. Integraon of an acquired company or assets into our exisng business may not be successful and may disrupt ongoing operaons, require the hiring of addional personnel and the implementaon and integraon of addional internal systems and infrastructure, and require management resources that would otherwise focus on developing our exisng business. Even if we are able to achieve the long-term beneﬁts of a strategic transacon, our expenses and short-term costs may increase materially and adversely aﬀect our liquidity. Any of the foregoing could have a detrimental eﬀect on our business, results of operaons and ﬁnancial condion. For example, on June 4, 2021, we entered into a license agreement, the Cyclerion Agreement, with Cyclerion Therapeucs Inc., or Cyclerion, pursuant to which Cyclerion granted us an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an invesgaonal oral soluble guanylate cyclase, or sGC, smulator. Although we have progressed preclinical studies for praliciguat, we need to do addional work to manufacture product for clinical trials than originally ancipated before we can iniate the trials, and when the clinical trials are started, we may be unsuccessful in developing praliciguat. If any of the assumpons that we made in valuing the transacon, including the costs or ming of development of praliciguat as a result of the addional manufacturing work or otherwise, or the potenal beneﬁts of praliciguat, were incorrect, we may not recognize the ancipated beneﬁts of the transacon and our business could be harmed. In addion, future transacons may entail numerous operaonal, ﬁnancial and legal risks, including: • • • • • incurring substanal debt, diluve issuances of securies or depleon of cash to pay for acquisions; exposure to known and unknown liabilies, including conngent liabilies, possible intellectual property infringement claims, violaons of laws, tax liabilies and commercial disputes; higher than expected acquision and integraon costs; diﬃculty in integrang operaons, processes, systems and personnel of any acquired business; increased amorzaon expenses or, in the case of a write-down of the value of acquired assets, impairment losses, such as the Auryxia intangible asset impairment in the second quarter of 2020 and corresponding adjustments to the esmated useful life of the developed product rights for Auryxia; • impairment of relaonships with key suppliers or customers of any acquired business due to changes in management and ownership; Akebia Therapeucs, Inc. | Form 10-K | Page 56 Table of Contents • • • • inability to retain personnel, customers, distributors, vendors and other business partners integral to an in-licensed or acquired product, product candidate or technology; potenal failure of the due diligence processes to idenfy signiﬁcant problems, liabilies or other shortcomings or challenges; entry into indicaons or markets in which we have no or limited development or commercial experience and where competors in such markets have stronger market posions; and other challenges associated with managing an increasingly diversiﬁed business. If we are unable to successfully manage any transacon in which we may engage, our ability to develop new products and connue to expand and diversify our porolio may be limited. Risks Related to our Financial Arrangements Our obligaons in connecon with the BlackRock Credit Agreement and requirements and restricons in the BlackRock Credit Agreement could adversely aﬀect our ﬁnancial condion and restrict our operaons. We entered into the BlackRock Credit Agreement, which provides for a senior secured term loan facility, in the aggregate principal amount of up to $55.0 million, or the Term Loan Facility. The inial tranche of $37.0 million, or the Tranche A Loan, closed on January 29, 2024, or the Closing Date. In addion to the Tranche A Loan, the Term Loan Facility includes addional tranches available as follows: $8.0 million available in a single draw through December 31, 2024, or the Tranche B Loan, and $10.0 million available in a single draw through December 31, 2024, or the Tranche C Loan and, together with the Tranche A Loan and the Tranche B Loan, the Term Loans. See Note 7, Indebtedness, to our audited consolidated ﬁnancial statements in Part II, Item 8. Financial Statements of this Form 10-K for addional informaon regarding our obligaons under the BlackRock Credit Agreement. Each Term Loan draw is subject to various condions precedent, including (x) the absence of any defaults or events of default and our connued compliance with the terms and provisions of the BlackRock Credit Agreement, (y) in the case of the Tranche B Loan and Tranche C Loan, receipt of markeng approval for vadadustat from the FDA, and (z) in the case of Tranche C, receipt of a certain amount of cumulave gross cash proceeds aer the Closing Date in the form of equity or equity linked securies in one or more series of transacons. The Term Loan Facility has an inial maturity date of March 31, 2025, which will be automacally extended to January 29, 2028 if we receive FDA approval on or prior to June 30, 2024, or the Maturity Date. If vadadustat is not approved by the FDA by June 30, 2024, we will be required to repay the Term Loan Facility sooner than ancipated. The BlackRock Credit Agreement contains certain representaons and warranes, aﬃrmave covenants, negave covenants, ﬁnancial covenants, events of default and other provisions and condions that are customarily required for similar ﬁnancings. The ﬁnancial covenants under the BlackRock Credit Agreement require us to either (i) maintain cash and cash equivalents, measured as of the last day of each ﬁscal month, greater than or equal to $15.0 million or (ii) earn consolidated revenue, measured as of the last day of each ﬁscal month for the trailing twelve-month period, of $150.0 million. Failure to maintain compliance with these or other covenants would result in an event of default under the BlackRock Credit Agreement, which could result in enforcement acon, including acceleraon of amounts due under the BlackRock Credit Agreement. The Term Loan Facility will accrue interest at a ﬂoang annual rate equal to the sum of (x) term Secured Overnight Financing Rate for a tenor of one month (subject to a ﬂoor of 4.25% per annum) plus (y) a margin of 6.75% per annum (subject to an overall cap of 15.00% per annum on the all-in interest rate). During the connuance of any payment event of default under the BlackRock Credit Agreement, the interest rate on such overdue sum will automacally increase by an addional 3.0% per annum, and may be subject to an addional late fee of 2.0% of such overdue sum. The Term Loan Facility does not amorze during the period commencing on the Closing Date and ending on December 31, 2025 (which was extended to December 31, 2026 at our opon), or the Interest Only Period. We are required to pay interest and, aer the Interest Only Period, principal on the ﬁrst calendar day of each month. In the event of certain prespeciﬁed events, the repayment schedule will be accelerated. For example, if FDA approval is not obtained on or prior to June 30, 2024, the Interest Only Period will automacally terminate on October 1, 2024, and we will be required to repay the Term Loans in seven equal monthly payments (comprised of principal and interest), commencing on October 1, 2024 and ending on the Maturity Date. If any of these events occur, and we are required to repay principal sooner than ancipate, it would have an adverse eﬀect on our business. In the event there is an acceleraon of our and certain of our subsidiaries’ liabilies under the BlackRock Credit Agreement as a result of an event of default or otherwise, we may not have suﬃcient funds or may be unable to arrange for addional ﬁnancing to repay the liabilies or to make any accelerated payments, and BlackRock could seek to enforce security interests in the collateral securing the BlackRock Credit Agreement, which would have a material adverse eﬀect on our business, ﬁnancial condion and results of operaons. Akebia Therapeucs, Inc. | Form 10-K | Page 57 Table of Contents In addion, our obligaons in connecon with the BlackRock Credit Agreement could have addional signiﬁcant adverse consequences, including, among other things: • • • • restricng our acvies, including limitaons on transferring certain of our assets, engaging in certain transacons, terminang certain agreements, incurring certain addional indebtedness, creang certain liens, paying cash dividends or making certain other distribuons and investments; liming our ﬂexibility in planning for, or reacng to, changes in our business and our industry; placing us at a possible compeve disadvantage compared to our competors who have a smaller amount of debt or competors with comparable debt at more favorable interest rates; and liming our ability to borrow addional amounts for working capital, capital expenditures, R&D eﬀorts, acquisions, debt service requirements, execuon of our business strategy and other purposes. Any of these factors could materially and adversely aﬀect our business, ﬁnancial condion and results of operaons. Our Royalty Interest Acquision Agreement with HealthCare Royalty Partners IV, L.P. contains various covenants and other provisions, which, if violated, could materially adversely aﬀect our ﬁnancial condion. In February 2021, we entered into a royalty interest acquision agreement, or the Royalty Agreement, with HealthCare Royalty Partners IV, L.P., or HCR, pursuant to which we sold to HCR our right to receive royales and sales milestones for vadadustat, collecvely the Royalty Interest Payments, in each case, payable to us under our Collaboraon Agreement dated December 11, 2015, or the MTPC Agreement, with Mitsubishi Tanabe Pharma Corporaon, or MTPC, subject to an annual maximum “cap” of $13.0 million, or the Annual Cap, and an aggregate maximum “cap” of $150.0 million, or the Aggregate Cap. Under the Royalty Agreement, we are required to comply with various covenants, including obligaons to take certain acons, such as acons with respect to the Royalty Interest Payments, the MTPC Agreement, our agreement with MTPC for the commercial supply of vadadustat drug product, and our intellectual property. In addion, the Royalty Agreement includes customary events of default upon the occurrence of enumerated events, including failure to perform certain covenants and the occurrence of insolvency events. Upon the occurrence of an event of default, HCR would have the ability to exercise all available remedies in law and equity, which could have a material adverse eﬀect on our ﬁnancial condion. Risks Related to Commercializaon Our business is substanally dependent on the commercial success of Auryxia and vadadustat, if approved. If we are unable to connue to successfully commercialize Auryxia or vadadustat, if approved and commercialized, our results of operaons and ﬁnancial condion will be materially harmed. Our business and our ability to generate product revenue largely depend on our, and our collaborators’, ability to successfully commercialize Auryxia and vadadustat. Our ability to generate revenue depends on our ability to execute on our commercializaon plans, and the size of the market for, and the level of market acceptance of, Auryxia, and vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired. If the size of any market for which a product or product candidate is approved decreases or is smaller than we ancipate, our revenue and results of operaons could be materially adversely aﬀected. Given the concentraon of dialysis clinics in large networks, with DaVita, Inc., or DaVita, and Fresenius Kidney Care Group LLC, accounng for a vast majority of the dialysis populaon in the U.S., treatment is usually driven by medical protocols that are implemented across the enre network of clinics. Dialysis organizaons require large data sets to adopt medical protocols. If dialysis organizaons do not add vadadustat, if approved, to their medical protocols in a mely manner, or at all, our operaons could be materially adversely aﬀected. If oral phosphate binders, including Auryxia, are included in the end-stage renal disease, or ESRD, Prospecve Payment System, or PPS, bundle payment, it will take me for dialysis organizaons to implement internal mechanisms to dispense phosphate binders which could divert their aenon from focusing on other therapeuc areas such as anemia management, which in turn could negavely impact the market for phosphate binders, including Auryxia. In addion, dialysis organizaons may choose lower cost binders over Auryxia, or binders that may have features or beneﬁts more aligned with the dialysis organizaon's operaonal acvies, which could negavely impact Auryxia revenue. In addion, we currently have exclusive rights under a series of patents and patent applicaons to commercialize Auryxia in the U.S. that protect us from generic drug compeon unl March 2025. Following LoE in March 2025, the number of generic versions of Auryxia that enter the market will aﬀect our revenue from Auryxia. We believe CMS's decision to include phosphate binders in the dialysis bundle could potenally lead to higher sales of Auryxia aer the LoE date than in other LoE scenarios, and plan to work with payors and providers to connue the use of Auryxia beyond LoE. However, our ability to connue to generate revenue from sales of Auryxia following LoE will depend on many factors, including our ability to Akebia Therapeucs, Inc. | Form 10-K | Page 58 Table of Contents successfully contract with dialysis organizaons, the ming and number of generics that enter the market and other products on the market that we compete with. If we are unable to maintain sales of Auryxia following LoE, our results of operaons and ﬁnancial condion will be materially harmed. We believe our revenue growth was negavely impacted by the recent COVID-19 pandemic in 2021, 2022 and 2023 primarily as the CKD paent populaons that we serve experienced both high hospitalizaon and mortality rates due to COVID-19, and the pandemic had an adverse impact on the phosphate binder market in which Auryxia competes. Labor shortages and costs have also adversely impacted dialysis providers. These impacts have refocused clinical eﬀorts in addressing bone and mineral disorders like hyperphosphatemia to more acute operaonal issues to ensure paents receive dialysis treatments and sll some paents have been rescheduled or missed treatments due to labor shortages. We believe, this and potenally other factors, led to the reducon in the phosphate binder market, which has not experienced growth since early 2020. While we are unable to quanfy the impact of the recent COVID-19 pandemic on future revenues and revenue growth, the recent COVID-19 pandemic and the ongoing impacts from the recent COVID-19 pandemic connue to adversely and disproporonately impact CKD paents and the phosphate binder market. Therefore, we expect the impacts from the pandemic to connue to have a negave impact on our revenue growth for the foreseeable future. Market acceptance is also crical to our ability to generate signiﬁcant product revenue. Any product may achieve only limited market acceptance or none at all. If Auryxia, or any of our future products, including vadadustat, if approved, is not accepted by the market to the extent that we expect or market acceptance decreases, we may not be able to generate signiﬁcant product revenue and our business would be materially harmed. Market acceptance of Auryxia, vadadustat, if approved, or any other approved product depends on a number of factors, including: • • • • • • • • • • • • • • • • the availability of adequate coverage and reimbursement by, and the availability of discounts, rebates and price concessions to third party payors, pharmacy beneﬁt managers, or PBMs, and governmental authories; the safety and eﬃcacy of the product, as demonstrated in clinical trials and in the post-markeng seng; the prevalence and complicaons of the disease treated by the product; the clinical indicaons for which the product is approved and the product label approved by regulatory authories, including any warnings or limitaons that may be required on the label as a consequence of potenal safety risks associated with the product; the countries in which markeng approvals are obtained; the claims we and our partners are able to make regarding the safety and eﬃcacy of the product; the success of our physician and paent communicaons and educaon programs; acceptance by physicians and paents of the product as a safe and eﬀecve treatment and the willingness of the target paent populaon to try new therapies and of physicians to prescribe new therapies; for vadadustat, if approved, use at dialysis organizaons and their willingness to include vadadustat in their protocols; the cost, safety and eﬃcacy of the product in relaon to alternave treatments; the ming of receipt of markeng approvals and product launch relave to compeng products and potenal generic entrants; relave convenience and ease of administraon; the frequency and severity of adverse side eﬀects; favorable or adverse publicity about our products or favorable or adverse publicity about compeng products; the eﬀecveness of our and our partners’ sales, markeng, manufacturing and distribuon strategies and operaons; and the restricons on the use of the product together with other medicaons, if any. In addion, our ability to generate net product revenue depends on our ability to control the expenses associated with commercializing a product, including internal expenses, manufacturing costs, rebates, product returns and other adjustments. We do not have control over many of the expenses required to commercialize our products, and if we experience increased costs or expenses, we may not be able to aﬀord the commercial acvies required to successfully commercialize our products, which could have an adverse eﬀect on our business. In addion, our net product revenue requires judgement and includes esmates for rebates and product returns, which can ﬂuctuate from quarter-to-quarter and year-over-year. If our net product revenue is lower than ancipated, including as a result of higher expenses, our business could be harmed. Several healthcare facilies, including DaVita, have previously restricted access for non-paents as a result of the recent COVID-19 pandemic, resulng in restricted access for certain members of our sales force. As a result, we connue to engage with some healthcare providers and other customers virtually where possible. The restricons on our customer-facing Akebia Therapeucs, Inc. | Form 10-K | Page 59 Table of Contents employees’ in-person interacons with healthcare providers have, and could connue to, negavely impact our access to healthcare providers and ulmately our sales, including with respect to vadadustat, if approved. Such precauonary measures have since been relaxed at certain healthcare facilies and, as a result, members of our sales force have resumed in person interacons with those customers. Nevertheless, some restricons remain, and more restricons may be put in place again due to a resurgence in COVID-19 cases, including those involving new variants of COVID-19, which may be more contagious and more severe than prior strains of the virus. Given this uncertain environment and the disproporonate impact of the recent COVID-19 pandemic on CKD paents, we are acvely monitoring the demand in the U.S. for Auryxia and will be for vadadustat, if approved, including the potenal for further declines or changes in prescripon trends and customer orders, which could have a material adverse eﬀect on our business, results of operaons, and ﬁnancial condion. If we are unable to maintain or expand, or, if vadadustat is approved, iniate, sales and markeng capabilies or enter into addional agreements with third pares, we may not be successful in commercializing Auryxia, vadadustat, if approved, or any other product candidates that may be approved. In order to market Auryxia and any other approved product, we intend to connue to invest in sales and markeng, which will require substanal eﬀort and signiﬁcant management and ﬁnancial resources. We have built a commercial infrastructure and sales force in the U.S. for Auryxia, our only commercial product. However, following receipt of the CRL, we implemented a reducon of our workforce in April and May 2022 by approximately 42% across all areas of the Company (47% inclusive of the closing of the majority of open posions), including several members of our sales and markeng team and management. In November 2022, we also implemented a reducon of our workforce, by approximately 14% consisng of individuals within our commercial organizaon, and we shied to a strategic account management focused model for our commercial eﬀorts. If the remaining sales and markeng team cannot successfully commercialize Auryxia, or if addional sales and markeng employees decide to leave, it could have a material adverse eﬀect on Auryxia revenue and our ﬁnancial condion. If we obtain regulatory approval to market vadadustat in the U.S., we believe that we can leverage the current commercial foundaon for vadadustat in the U.S., with incremental addional hires in our sales force and medical aﬀairs department, but if we are unable to do so successfully it would materially harm our business. Addionally, training a sales force to successfully sell and market a new commercial product is expensive and me-consuming and could delay any commercial launch of such product candidate or distract the sales force from promong Auryxia. We may underesmate the size of the sales force required for a successful product launch and we may need to expand our sales force to a greater extent or earlier than we currently plan and at a higher cost than we ancipated. In 2021 and early 2022, we incurred commercializaon expenses for vadadustat that were premature or unnecessary as a result of the receipt of the CRL for vadadustat, and may in the future incur addional commercializaon expenses prematurely or unnecessarily if we do not receive markeng approval for vadadustat in the meframe we expect, or at all. We devote signiﬁcant eﬀort to recruing individuals with experience in the sales and markeng of pharmaceucal products. Compeon for personnel with these skills is signiﬁcant and retaining qualiﬁed personnel with experience in our industry is diﬃcult. Further, our reducons in workforce may further exacerbate these condions and interfere with our ability to ﬁnd and retain qualiﬁed personnel. As a result, we may not be able to retain our exisng employees or hire new employees quickly enough to meet our needs. At the same me, we may face high turnover, requiring us to expend me and resources to source, train and integrate new employees. There are risks involved with maintaining our own sales and markeng capabilies, including the following: • • • potenal inability to recruit, train and retain adequate numbers of eﬀecve sales and markeng personnel; potenal lack of complementary products to be oﬀered by sales personnel, which may put us at a compeve disadvantage relave to companies with more extensive product lines, especially as a result of the receipt of the CRL for vadadustat; and costs and expenses associated with maintaining our own sales and markeng organizaon. If we are unable to maintain our own sales and markeng capabilies, we will not be successful in commercializing Auryxia, vadadustat, if approved, and any other product candidate that may be approved. Furthermore, if we are unable to maintain our arrangements with third pares with respect to sales and markeng, if we are unsuccessful in entering into addional arrangements with third pares to sell and market our products or we are unable to do so on terms that are favorable to us, or if such third pares are unable to carry out their obligaons under such arrangements, it will be diﬃcult to successfully commercialize our product and product candidates, including vadadustat, if approved. For example, if, in connecon with the Vifor Agreement, we experience diﬃcules with CSL Vifor, or if CSL Vifor is not successful in commercializing vadadustat, if approved, in the dialysis organizaons for which they are responsible in a mely manner, or at all, our revenue related to vadadustat will be adversely impacted. Akebia Therapeucs, Inc. | Form 10-K | Page 60 Table of Contents Our, or our partners', failure to obtain or maintain adequate coverage, pricing and reimbursement for Auryxia, vadadustat, if approved, or any other future approved products, could have a material adverse eﬀect on our or our collaboraon partners’ ability to sell such approved products proﬁtably and otherwise have a material adverse impact on our business. Market acceptance and sales of any approved products, including Auryxia and, if approved, vadadustat, depends signiﬁcantly on the availability of adequate coverage and reimbursement from third party payors and may be aﬀected by exisng and future healthcare reform measures. Governmental authories, third party payors, and PBMs decide which drugs they will cover, as well as establish formularies or implement other mechanisms to manage ulizaon of products and determine reimbursement levels. We cannot be sure that coverage or adequate reimbursement will be available for Auryxia, vadadustat, if approved, or any of our potenal future products. Even if we obtain coverage for an approved product, third party payors may not establish adequate reimbursement amounts, which may reduce the demand for our product and prompt us to have to reduce pricing for the product. If reimbursement is not available or is limited, we may not be able to successfully commercialize certain of our products. Coverage and reimbursement by a governmental authority, third-party payor or PBMs may depend upon a number of factors, including the determinaon that use of a product is: • • • • a covered beneﬁt under the health plan; safe, eﬀecve and medically necessary; appropriate for the speciﬁc paent; and cost eﬀecve. Obtaining coverage and reimbursement approval for a product from a governmental authority, PBM or a third-party payor is a me consuming and costly process that could require us to provide supporng scienﬁc, clinical and cost-eﬀecveness data for the use of our products to the payor. In the U.S., there are mulple governmental authories, PBMs and third-party payors with varying coverage and reimbursement levels for pharmaceucal products, and the ming of commencement of reimbursement by a governmental payor can be dependent on the assignment of codes via the Healthcare Common Procedural Coding System, which codes are assigned on a quarterly basis. Within Medicare, for oral drugs dispensed by pharmacies and also administered in facilies, coverage and reimbursement may vary depending on the seng. CMS, local Medicare administrave contractors, Medicare Part D plans and/or PBMs operang on behalf of Medicare Part D plans, may have some responsibility for determining the medical necessity of such drugs, and therefore coverage, for diﬀerent paents. Diﬀerent reimbursement methodologies may apply, and CMS may have some discreon in interpreng their applicaon in certain sengs. As an oral drug, Auryxia is covered by Medicare under Part D for the treatment of paents with hyperphosphatemia. In January 2011, CMS implemented the ESRD PPS, a prospecve payment system for dialysis treatment. Under the ESRD PPS, CMS generally makes a single bundled payment to the dialysis facility for each dialysis treatment that covers all items and services rounely required for dialysis treatments furnished to Medicare beneﬁciaries in Medicare-cerﬁed ESRD facilies or at their home. The inclusion of oral medicaons without injectable or intravenous equivalents such as Auryxia in the bundled payment was inially delayed by CMS unl January 1, 2014, and through several subsequent legislave acons has been delayed unl January 1, 2025. Absent further legislaon or regulaon on this maer, beginning in January 2025, oral ESRD-related drugs without injectable or intravenous equivalents, including Auryxia and all other phosphate lowering medicaons, will be included in the ESRD bundle and separate Medicare payment for these drugs will no longer be available, as is the case today under Medicare Part D. ESRD facilies may nonetheless receive a TDAPA for new renal dialysis drugs and biological products that meet certain criteria for a period of two years. The TDAPA will provide separate payment based on the drug’s Average Sales Price, or ASP, that will be in addion to the base rate in order to facilitate the adopon of innovave therapies. There can be no assurances that CMS will not again delay the inclusion of these oral ESRD-related drugs in the bundled payment. Even if Auryxia is deemed eligible by CMS, revenue for sales of Auryxia could be signiﬁcantly less in the TDAPA period than it would be if Auryxia is not bundled into the ESRD PPS. Moreover, in the post-TDAPA period, CMS currently expects to increase the single bundled payment base rate paid to the dialysis facility for each dialysis treatment to reﬂect that oral only phosphate lowering drugs will be reimbursed as part of the single bundled payment for Medicare paents. There can be no assurances that any increase in the single bundled payment base rate will be suﬃcient to adequately reimburse the dialysis facilies for Auryxia at a price that is proﬁtable for us. In addion, in September 2018, CMS decided that Auryxia would no longer be covered by Medicare for the treatment of iron deﬁciency anemia, or IDA, in adult paents with NDD-CKD, or the CMS Decision. While this decision does not impact CMS coverage for the control of serum phosphorus levels in adult paents with DD-CKD, or the Hyperphosphatemia Indicaon, it requires Part D Plan sponsors to impose prior authorizaon or other steps to ensure that Auryxia is reimbursed only for the Hyperphosphatemia Indicaon. We decided beginning in 2022 to terminate certain Part D contracts, as paents no longer had the access beneﬁt given the prior authorizaon, or PA, requirement. Now paents must go through a medical exempon process, which is very similar to a prior authorizaon review. While we believe this had, and may connue to have, a negave Akebia Therapeucs, Inc. | Form 10-K | Page 61 Table of Contents impact on our overall sales volume, we believe it had a signiﬁcant posive impact on our net selling price. However, if we experience addional negave impacts on our sales volume as a result of this change, it could have a negave impact on our product revenue. Medicaid reimbursement of drugs varies by state. Private third-party payor reimbursement policies also vary and may or may not be consistent with Medicare reimbursement methodologies. Manufacturers of outpaent prescripon drugs may be required to provide discounts or rebates under government healthcare programs or to certain third-party payors in order to obtain coverage of such products. Addionally, we may be required to enter into contracts with third party payors and/or PBMs oﬀering rebates or discounts on our products in order to obtain favorable formulary status and we may not be able to agree upon commercially reasonable terms with such third party payors or PBMs, or provide data suﬃcient to obtain favorable coverage and reimbursement for many reasons, including that we may be at a compeve disadvantage relave to companies with more extensive product lines. In addion, third party payors, PBMs and other enes that purchase our products may impose restricons on our ability to raise prices for our products over me without incurring addional costs. Four distributors, Fresenius Medical Care Rx, McKesson Corporaon, Cardinal Health, Inc. and Cencora, Inc., formerly known as AmerisourceBergen Drug Corporaon, in the aggregate, accounted for a signiﬁcant percentage of our gross revenue during the year ended December 31, 2023. If we are not able to maintain our arrangements with these key distributors on favorable terms, on a mely basis or at all, or if there is any adverse change in one or more of these distributors’ business pracces or ﬁnancial condion, it would adversely impact the market opportunity for Auryxia, our product revenues and operang results. In addion, vadadustat was approved in Japan for the treatment of adult paents with anemia due to CKD and is being marketed by MTPC in Japan under the trade name Vafseo. Pricing and reimbursement strategy is a key component of MTPC’s commercializaon plans for Vafseo in Japan. If coverage and reimbursement terms change, MTPC may not be able to, or may decide not to, connue commercializaon of Vafseo in Japan. Furthermore, vadadustat was approved in Europe and Australia for the treatment of anemia due to CKD in DD-CKD paents. In Europe, reimbursement is obtained on a country-by-country basis and it is a me consuming process. Medice is working on securing pricing and reimbursement in key markets in Europe, but there is no guarantee of the ming or extent of reimbursement that they will receive, if at all. We currently believe it is likely that vadadustat, if approved, will be reimbursed using the Transional Drug Add-on Payment Adjustment, or TDAPA, followed by inclusion in the bundled reimbursement model for Medicare beneﬁciaries, but reimbursement under TDAPA it is subject to review and approval by CMS. For those that obtain dialysis through commercial insurance during the 30-month coordinaon period or through Medicaid prior to Medicare becoming primary payor aer 90 days, paents may access vadadustat through contracts we negoate with third party payors for reimbursement of vadadustat, which would be subject to the risks and uncertaines described above. Addionally, applying for and obtaining reimbursement under the TDAPA is expected to take six months following ﬁling acceptance, which will aﬀect adopon, uptake and product revenue for vadadustat during that me, and if there are updates to the TDAPA rule that decrease the basis for reimbursement or eligibility criteria during the transion period or if the TDAPA is eliminated, then our proﬁtability may be adversely aﬀected. For example, the Medicare Payment Advisory Commission, or MedPAC, an independent legislave branch advisory body to Congress on issues related to the Medicare program, has recommended that TDAPA not be provided to newly approved drug products considered to fall within “funconal categories” for which costs are already accounted for in the bundled reimbursement model, such as for anemia management drugs. Further, if vadadustat is approved in the U.S., we expect it to be included in the ﬁxed reimbursement model for a bundle of dialysis services, or the bundle, which will require us to enter into contracts to supply vadadustat to speciﬁc dialysis providers, instead of through distributors, which we believe could be challenging. The dialysis market is unique and is dominated by two providers: DaVita and Fresenius Medical Care, which account for a vast majority of the dialysis populaon in the U.S. Under the Vifor Agreement, we granted CSL Vifor an exclusive license to sell vadadustat to Fresenius Medical Care North America and its aﬃliates, including Fresenius Kidney Care Group LLC, to certain third-party dialysis organizaons approved by us, to independent dialysis organizaons that are members of group purchase organizaons, and to certain non-retail specialty pharmacies in the U.S. We refer to Fresenius Medical Care North America and its aﬃliates, these organizaons and specialty pharmacies collecvely as the “Supply Group." See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, to our consolidated ﬁnancial statements in Part II, Item 8. Financial Statements of this Form 10-K for addional informaon regarding the Vifor Agreement. If vadadustat is approved, and we are not able to maintain the Vifor Agreement or enter into a supply agreement with DaVita or other dialysis clinics, or if Vifor is not able to successfully contract with the Supply Group, our business may be materially harmed. Similar to how payor coverage may aﬀect the sales of a product, formulary status within dialysis organizaons may aﬀect what products are prescribed within that speciﬁc organizaon. Therefore, if a product is not on a formulary, the prescribers within that organizaon may be less likely to prescribe that product or may have a diﬃcult me prescribing that product, resulng in less sales. Further, one dialysis organizaon’s determinaon to add a product to their formulary does not assure that other dialysis organizaons will also add the product to theirs. There is always a risk a dialysis organizaon will not Akebia Therapeucs, Inc. | Form 10-K | Page 62 Table of Contents contract with a drug manufacturer for a speciﬁc product, resulng in that product not being on that organizaon’s formulary. If any dialysis organizaon does not add vadadustat, if approved, to the formulary, our business may be materially harmed. In addion, we may be unable to sell Auryxia or vadadustat, if approved, to dialysis providers on a proﬁtable basis if CMS signiﬁcantly reduces the level of reimbursement for dialysis services and providers choose to use alternave therapies or look to re-negoate their contracts with us. Our proﬁtability may also be aﬀected if our costs of producon increase faster than increases in reimbursement levels. Adequate coverage and reimbursement of our products by government and private insurance plans are central to paent and provider acceptance of any products for which we receive markeng approval. Exisng compeve products may enter into sole source agreements with dialysis providers that impact the ability for new product innovaons and new competors may face price pressure based on exisng contracts with dialysis providers. Further, in many countries outside the U.S., a drug must be approved for reimbursement before it can be marketed or sold in that country. In some cases, the prices that we intend to charge for our products are also subject to approval. Approval by the EMA or another regulatory authority does not ensure approval by reimbursement authories in that jurisdicon, and approval by one reimbursement authority outside the U.S. does not ensure approval by any other reimbursement authories. However, the failure to obtain reimbursement in one jurisdicon may negavely impact our ability to obtain reimbursement in another jurisdicon. In addion, we plan to rely on a partner to obtain approval by reimbursement authories outside the U.S. Our partners may not be able to obtain such reimbursement approvals on a mely basis, if at all, and favorable pricing in certain countries depends on a number of factors, some of which are outside of our partners' control. In May 2023, we entered into the license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with chronic kidney disease in the Medice Territory. If Medice is not able to obtain favorable pricing in the Medice Territory, or if such approvals are delayed, it will aﬀect Medice’s sales of vadadustat in the Medice Territory, which could have an adverse eﬀect on our results of operaons. We face substanal compeon, which may result in others discovering, developing or commercializing products before, or more successfully than, we do. The development and commercializaon of new drugs is highly compeve and subject to rapid and signiﬁcant technological change. Our future success depends on our ability to demonstrate and maintain a compeve advantage with respect to the development and commercializaon of Auryxia, vadadustat, if approved, and any other product or product candidate, including those that may be in-licensed or acquired. Our objecve is to connue to commercialize Auryxia and develop and commercialize new products with clinically proven eﬃcacy, convenience, tolerability and/or safety. In many cases, any approved products that we commercialize will compete with exisng, market-leading products. If exisng or new competors of Auryxia take market share from us, it could have an adverse impact on Auryxia revenue and our business. Auryxia is compeng in the hyperphosphatemia market in the U.S. with other FDA-approved phosphate binders such as Renagel® (sevelamer hydrochloride) and Renvela® (sevelamer carbonate), both marketed by Sanoﬁ, PhosLo® and Phoslyra® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol® (lanthanum carbonate), marketed by Shire Pharmaceucals Group plc, and Velphoro® (sucroferric oxyhydroxide), marketed by Fresenius Medical Care North America, as well as over-the-counter calcium carbonate products such as TUMS® and metal-based opons such as aluminum, lanthanum and magnesium. Most of the phosphate binders listed above are now also available in generic forms. In addion, other agents are in development, including OPKO Health Inc.’s Alpharen™ Tablets (fermagate tablets) and Unicycive’s RENAZORB™ (lanthanum dioxycarbonate), or could otherwise enter the market that may impact the market for Auryxia. In October 2023, the FDA approved XPHOZAH® (tenapanor), a phosphate absorpon inhibitor that is marketed by Ardelyx, Inc. and indicated to reduce serum phosphorus in adults with CKD on dialysis as add-on therapy in paents who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy, which may impact the market for Auryxia. Auryxia is compeng in the IDA market in the U.S. with over-the-counter oral iron, ferrous sulfate, other prescripon oral iron formulaons, including ferrous gluconate, ferrous fumerate, and polysaccharide iron complex, and intravenous iron formulaons, including Feraheme® (ferumoxytol injecon), Venofer® (iron sucrose injecon), Ferrlicit® (sodium ferric gluconate complex in sucrose injecon), Injectafer® (ferric carboxymaltose injecon), and Triferic® (ferric pyrophosphate citrate). In addion, other new therapies for the treatment of IDA may impact the market for Auryxia, such as Shield Therapeucs plc's Feraccru® (ferric maltol), which is available in Europe for the treatment of IDA and Accrufer® (ferric maltol), which was launched in the U.S. for the treatment of IDA in July 2021. Furthermore, Auryxia’s commercial opportunies may be reduced or eliminated if our competors develop and market products that are less expensive, more eﬀecve, safer or oﬀer greater paent convenience than Auryxia. Other companies have product candidates in various stages of preclinical or clinical development to treat diseases and complicaons of the diseases for which we are markeng Auryxia. In addion, we and our licensors, Panion & BF Biotech, Inc., or Panion, and, as applicable, Dr. Hsu, entered into selement agreements with all but one of the third pares who submied Paragraph IV cerﬁcaon noce leers regarding Abbreviated New Drug Applicaons, or ANDAs, submied to the FDA, pursuant to which we granted licenses to market a generic version of Auryxia in the U.S. beginning in March 2025 (subject to FDA approval), or earlier under certain circumstances customary for selement agreements of this nature. While we expect that the availability Akebia Therapeucs, Inc. | Form 10-K | Page 63 Table of Contents of generic versions of Auryxia will negavely impact our net product revenue for Auryxia and our results of operaons, it is diﬃcult to esmate the impact of generics on Auryxia net product revenue, and if the impact is greater than we currently ancipate, it may materially adversely impact our business and results of operaons. Drugs that may compete with vadadustat, if approved, include Epogen® (epoen alfa) and Aranesp® (darbepoen alfa), both commercialized by Amgen, Procrit® (epoen alfa) and Eprex® (epoen alfa), commercialized by Johnson & Johnson in the U.S. and Europe, respecvely, and Mircera® (methoxy PEG- epoen beta), commercialized by CSL Vifor in the U.S. and Roche Holding Ltd. outside of the U.S. and Evrenzo® (roxadustat) in Europe commercialized by Astellas Pharma Inc. Further, in February 2023 the FDA approved daprodustat, an oral hypoxia-inducible factor prolyl hydroxylase, or HIF-PH, inhibitor marketed as Jesduvroq by GlaxoSmithKline plc, or GSK, in the U.S., as a once-a-day treatment of anemia due to CKD in adult paents who have been receiving dialysis for at least four months. We and our partners may also face compeon from potenal new anemia therapies. There are several other HIF-PH inhibitor product candidates in various stages of development for anemia indicaons that may be in direct compeon with vadadustat if and when they are approved and launched commercially. These candidates are being developed by companies such as Japan Tobacco Internaonal, or JT, and Bayer HealthCare AG, or Bayer. For example, FibroGen ﬁled an NDA for its product candidate, roxadustat, with the FDA, to which the FDA issued a complete response leer indicang the FDA will not approve the NDA in its present form and requested that an addional clinical trial for roxadustat be conducted prior to resubmission of the NDA or addional response to the FDA's complete response leer. In Europe however, roxadustat is approved for the treatment of anemia in paents with CKD. If we obtain approval for vadadustat in the U.S., and roxadustat is also approved by the FDA, then roxadustat will compete with vadadustat. Furthermore, certain companies are developing potenal new therapies for renal-related diseases that could potenally reduce injectable erythropoiesis smulang agent, or ESA, ulizaon and thus limit the market potenal for vadadustat if they are approved and launched commercially. Other new therapies are in development for the treatment of condions inclusive of renal anemia that may impact the market for anemia-targeted treatment. In Japan, vadadustat is sold under the name Vafseo, which is approved for paents with CKD, including both DD-CKD and NDD-CKD, and competes with roxadustat, daprodustat and enarodustat. Roxadustat is approved for the treatment of anemia due to CKD in paents on dialysis, or DD-CKD, and paents not on dialysis, or NDD-CKD. In addion, daprodustat, GSK’s product candidate, and enarodustat, JT’s product candidate, are approved in Japan for the treatment of anemia due to CKD, and molidustat, Bayer HealthCare AG's product, is approved in Japan for the treatment of renal anemia. In China, roxadustat is commercialized for the treatment of anemia due to CKD in DD-CKD paents and for the treatment of anemia due to CKD in NDD-CKD paents. A biosimilar is a biologic product that is approved based on demonstrang that it is highly similar to an exisng, FDA-approved branded biologic product. The patents for the exisng, branded biologic product must expire in a given market before biosimilars may enter that market without the risk of being sued for patent infringement. In addion, an applicaon for a biosimilar product can only be approved by the FDA 12 years aer the exisng, branded product was approved under a Biologics License Applicaon, or BLA. The patents for epoen alfa, an injectable ESA, expired in 2004 in the EU, and the remaining patents expired between 2012 and 2016 in the U.S. The introducon of biosimilars into the injectable ESA market in the U.S. will constute addional compeon for vadadustat if we are able to obtain approval for and commercially launch vadadustat. In the U.S., Pﬁzer’s biosimilar version of injectable ESAs, Retacrit® (epoen alfa-epbx), was approved by the FDA in May 2018 and launched in November 2018 and several biosimilar versions of injectable ESAs are available for sale in the EU. Many of our potenal competors have signiﬁcantly greater ﬁnancial, manufacturing, markeng, drug development, technical and human resources than we do. Large pharmaceucal companies, in parcular, have extensive experience in clinical tesng, obtaining markeng approvals, recruing paents and manufacturing pharmaceucal products. Large and established companies such as Amgen, Roche and GSK, among others, compete in the market for drug products to treat kidney disease. In parcular, these companies have greater experience and experse in conducng preclinical tesng and clinical trials, obtaining markeng approvals, manufacturing such products on a broad scale and markeng approved products. These companies also have signiﬁcantly greater research and markeng capabilies than we do and may also have products that have been approved or are in late stages of development and have collaborave arrangements in our target markets with leading companies and research instuons. Established pharmaceucal companies may also invest heavily to accelerate discovery and development of novel compounds or to in-license novel compounds that could make the product candidates that we are developing obsolete. Smaller and other early-stage companies may also prove to be signiﬁcant competors. As a result of all of these factors, our competors may succeed in obtaining patent protecon and/or markeng approval, or discovering, developing and commercializing compeve products, before, or more eﬀecvely than, we do. If we are not able to compete eﬀecvely against potenal competors, our business will not grow and our ﬁnancial condion and operaons will suﬀer. Akebia Therapeucs, Inc. | Form 10-K | Page 64 Table of Contents The commercializaon of Riona and Vafseo in Japan, Vafseo in Europe and other territories where it is approved, and our current and potenal future eﬀorts with respect to the development and commercializaon of our products and product candidates outside of the U.S. subject us to a variety of risks associated with internaonal operaons, which could materially adversely aﬀect our business. Our Japanese sublicensee, JT, and its subsidiary, Torii Pharmaceucal Co., Ltd., or Torii, commercialize Riona, the trade name for ferric citrate hydrate in Japan, as an oral treatment for the improvement of hyperphosphatemia in paents with CKD, including DD-CKD and NDD-CKD, and for the treatment of adult paents with IDA in Japan. In Japan and certain other countries in Asia, we granted MTPC exclusive rights to commercialize vadadustat, which has been approved and is being marketed by MTPC in Japan under the trade name Vafseo. We also granted Averoa SAS, or Averoa, an exclusive license to develop and commercialize ferric citrate in the EEA, Turkey, Switzerland and the UK. In 2023, the markeng authorizaon for vadadustat was granted by the EMA, the United Kingdom Medicines and Healthcare Products Regulatory Agency, or the MHRA, the Swiss Agency for Therapeuc Products, or Swissmedic, and the Australian Therapeuc Goods Administraon, or TGA. In May 2023, we entered into the license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with chronic kidney disease in the Medice Territory, and we transferred the markeng authorizaon issued by the EMA and Swissmedic to Medice. We will transfer the other markeng authorizaons for the Medice Territory to Medice, if approved. In addion, we have conducted and in the future plan to conduct clinical trials outside of the U.S. for Auryxia, vadadustat and any other product or product candidate that may be in-licensed or acquired. As a result of these and other acvies, we are or may become subject to addional risks in developing and commercializing Auryxia and vadadustat outside the U.S., including, among others: • • • • • • • • • • • • polical, regulatory, compliance and economic developments, weakness or instability that could restrict our ability to manufacture, market and sell our products; changes in internaonal medical reimbursement policies and programs; changes in healthcare policies of foreign jurisdicons; trade protecon measures, including import or export licensing requirements and tariﬀs and our compliance therewith; our ability to develop or manage relaonships with qualiﬁed local distributors and trading companies; diminished protecon of intellectual property in some countries outside of the U.S.; diﬀering labor regulaons and business pracces; compliance with laws, including the U.S. Foreign Corrupt Pracces Act, or FCPA, the UK Bribery Act or similar local regulaon, the EU General Data Protecon Regulaon, or GDPR, and similar data protecon laws, and tax, employment, immigraon and labor laws; economic weakness, including inﬂaon, increasing interest rates, or polical instability in parcular foreign economies and markets; foreign currency ﬂuctuaons, which could result in increased operang expenses and reduced revenues, and other obligaons incident to doing business in another country; producon shortages resulng from any events aﬀecng raw material supply or manufacturing capabilies abroad; and business interrupons resulng from geopolical acons, including war and terrorism, global pandemics, or natural disasters including earthquakes, typhoons, ﬂoods and ﬁres. In addion, we receive revenues from royalty payments converted to U.S. dollars based on net sales of Riona and Vafseo in Japanese yen. The exchange rates between the Japanese yen on the one hand, and the U.S. dollar, on the other hand, have changed substanally in recent years and may ﬂuctuate substanally in the future. Our results of operaons could be adversely aﬀected over me by certain movements in exchange rates, parcularly if the Japanese yen depreciates against the U.S. dollar. Any of these factors may, individually or as a group, have a material adverse eﬀect on our business and results of operaons. As and if we connue to expand our commercializaon eﬀorts, we may encounter new risks. Akebia Therapeucs, Inc. | Form 10-K | Page 65 Table of Contents Risks Related to Product Development Clinical drug development involves a lengthy and expensive process with an uncertain outcome, and we will incur addional costs in connecon with, and may experience delays in compleng, or ulmately be unable to complete, the development of vadadustat and any other product candidates. The risk of failure in drug development is high. Before obtaining markeng approval from regulatory authories for the sale of any product candidate, we must complete preclinical development and conduct extensive clinical trials to demonstrate the safety and eﬃcacy of our product candidates in humans. Preclinical studies and clinical trials are expensive, diﬃcult to design and implement, can take several years to complete, and their outcomes are inherently uncertain. Failure can occur at any me during the process. We may be unable to successfully complete clinical trials of Auryxia, vadadustat and other product candidates or to successfully obtain approval of vadadustat or other product candidates, if the results of those trials and studies are not posive or are only modestly posive, or if there are concerns with the proﬁle due to eﬃcacy or safety. Further, the results of preclinical studies and early clinical trials of our product candidates may not be predicve of the results of later-stage clinical trials, interim results of a clinical trial do not necessarily predict ﬁnal results, and results of Phase 3 clinical trials for one indicaon may not be predicve of results of Phase 3 clinical trials for another indicaon. For example, we announced posive top-line results from INNO VATE and vadadustat achieved the primary and key secondary eﬃcacy endpoint in each of the two PRO TECT studies, but the PRO TECT program did not meet the primary major adverse cardiovascular event, or MACE, safety endpoint. Many companies in the biopharmaceucal industry have suﬀered signiﬁcant setbacks in late-stage clinical trials aer achieving posive results in early-stage development, and we may face similar setbacks. Moreover, preclinical and clinical data are oen suscepble to varying interpretaons and analyses, and many companies that have believed their product candidates performed sasfactorily in preclinical studies and clinical trials have nonetheless failed to obtain markeng approval of their product candidates. In addion, in March 2022, we received the CRL for vadadustat indicang that the FDA had determined that it could not approve the NDA in its present form, thus delaying any potenal approval of vadadustat. In October 2022, we submied the FDRR to the FDA. In May 2023, the OND denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. In September 2023, we ﬁled our resubmission to our NDA, and in October 2023, the FDA acknowledged that the resubmission was complete and set a PDUFA date of March 27, 2024. However, it is impossible to predict when or if vadadustat or any of our other product candidates will prove eﬀecve or safe in humans or will receive markeng approval or on what terms. If we are unsuccessful in obtaining approval for vadadustat in the U.S., it would have an adverse eﬀect on our results of operaons. 2 2 2 Beyond seeking U.S. approval, we have several lifecycle management and indicaon expansion opportunies currently under evaluaon for vadadustat, including the potenal for alternave dosing and label expansion for the treatment of anemia due to CKD in adult paents not on dialysis. However, we may be required to complete addional clinical trials before seeking approval for these indicaons, which are me consuming and expensive, and even if vadadustat is approved as a treatment for anemia due to CKD for dialysis dependent paents, we may not be successfully in any of these areas in the meframe ancipated by us, or at all. We may experience numerous unforeseen events during, or as a result of, preclinical development or clinical trials that could delay, prevent or make more challenging our ability to receive or maintain markeng approval or commercialize our product candidates. We may be required to complete addional clinical trials for Auryxia, vadadustat and any other product or product candidate, including those that may be in-licensed or acquired, in order to obtain or maintain required regulatory approvals. Our preclinical studies and clinical trials may take longer to complete than currently ancipated, or may be delayed, suspended, required to be repeated, prematurely terminated or may not successfully demonstrate safety and/or eﬃcacy needed to obtain or maintain regulatory approval for a variety of other reasons, such as: • • • • • • the costs may be greater than we ancipate; the number of paents required for clinical trials may be larger than we ancipate; enrollment in our clinical trials may be slower than we ancipate, or parcipants may drop out of these clinical trials at a higher rate than we ancipate; our third party contractors, such as our CROs, may fail to comply with regulatory requirements, perform eﬀecvely, or meet their contractual obligaons to us in a mely manner, or at all, or we may fail to communicate eﬀecvely or provide the appropriate level of oversight of such third party contractors; the supply or quality of our starng materials, drug substance and drug product necessary to conduct clinical trials of our product candidates may be insuﬃcient or inadequate; regulators, independent data monitoring commiees, or IDMCs, instuonal review boards, or IRBs, safety commiees, or ethics commiees, may require that we suspend or terminate our clinical trials for various reasons, including noncompliance with regulatory requirements, unforeseen safety issues or adverse side eﬀects, failure to Akebia Therapeucs, Inc. | Form 10-K | Page 66 Table of Contents demonstrate a beneﬁt from using our product candidate, or a ﬁnding that the parcipants are being exposed to unacceptable health risks; • • clinical trials of our product candidates may produce negave or inconclusive results or results that may be interpreted in a manner diﬀerent than we interpret them, and we may decide, or regulators may require us, to conduct addional clinical trials, repeat a clinical trial or abandon product development programs; lack of adequate funding to connue a clinical trial, including unforeseen costs due to enrollment delays, requirements to conduct addional clinical trials or repeat a clinical trial and increased expenses associated with the services of our CROs and other third pares; • we may fail to iniate, delay of or failure to complete a clinical trial as a result of an Invesgaonal New Drug applicaon, or IND, being placed on clinical hold by the FDA, the EMA, the PMDA, or other regulatory authories, or for other reasons, such as failure to recruit or enroll suitable paents or paents' failure to return for post-treatment follow up; • we may determine to change or expand a clinical trial, including aer it has begun; • • • • • • • • • clinical trial sites and invesgators deviang from the clinical protocol, failing to conduct the trial in accordance with regulatory requirements, or dropping out of a trial, or failure by us or our CROs to communicate eﬀecvely or provide the appropriate level of oversight of such clinical sites and invesgators; there may be an inability, delay, or failure in idenfying and maintaining a suﬃcient number of clinical trial sites, many of which may already be engaged in other clinical programs; there may be a delay or failure in reaching agreement with the FDA, the EMA, the PMDA or other regulatory authories on a clinical trial design upon which we are able to execute; there may be a delay or failure in obtaining authorizaon to commence a clinical trial or inability to comply with condions imposed by a regulatory authority regarding the scope or design of a clinical trial; there may be delays in reaching, or failure to reach, agreement on acceptable terms with prospecve clinical trial sites and prospecve CROs, the terms of which can be subject to extensive negoaon and may vary signiﬁcantly among diﬀerent CROs and clinical trial sites; the FDA, the EMA, the PMDA or other regulatory authories may require us to submit addional data or impose further requirements before perming us to iniate a clinical trial or during an ongoing clinical trial; the FDA, the EMA, the PMDA or other regulatory authories may disagree with our clinical trial design and our interpretaon of data from clinical trials, or may change the requirements for approval even aer it has reviewed and commented on the design for our clinical trials; third pares with which we work may fail to comply with good pracce quality guidelines and regulaons, or GxP, including good laboratory pracce, good clinical pracce, or GCP, and current good manufacturing pracce, or cGMP; or there may be changes in governmental regulaons or administrave acons. If any of the foregoing occurs, the following may occur: • regulators may require that we conduct addional clinical trials, repeat clinical trials or conduct other studies beyond those that we currently contemplate; • we may be delayed in obtaining markeng approval for vadadustat or other product candidates; • we may not obtain markeng approval for vadadustat or other product candidates at all; • we may obtain approval for indicaons or paent populaons that are not as broad as intended or desired; • we may obtain approval with labeling that includes signiﬁcant use or distribuon restricons or safety warnings that would reduce the potenal market for any approved product or inhibit our ability to successfully commercialize any approved product; • a REMS or FDA-imposed risk management plan that use risk minimizaon strategies to ensure that the beneﬁts of certain prescripon drugs outweigh their risks, may be required; • we may be subject to addional post-markeng restricons and/or requirements; or • the product may be removed from the market aer obtaining markeng approval. Our product development costs may also increase if we experience development delays or delays in receiving the requisite markeng approvals. Our preclinical studies or clinical trials may need to be restructured or may not be completed on schedule, or at all. Signiﬁcant preclinical or clinical trial delays also could shorten any periods during which we may have the exclusive right to commercialize vadadustat, if approved, or any other product candidate, including those that may be in- Akebia Therapeucs, Inc. | Form 10-K | Page 67 Table of Contents licensed or acquired, or allow our competors to bring products to market before we do. This could impair our ability to successfully commercialize our product candidates and may harm our business and results of operaons. We may ﬁnd it diﬃcult to enroll paents in our clinical trials, which could delay or prevent clinical trials of Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired. Idenfying and qualifying paents to parcipate in clinical trials is crical to our success. The ming of our clinical trials depends, in part, on the speed at which we can recruit paents to parcipate in our clinical trials. Paents may be unwilling to parcipate in our clinical trials because of concerns about invesgaonal research studies, the me and commitment needed to parcipate in a study, adverse events observed with the product candidate under study, the current standard of care, competor products and/or other invesgaonal agents, in each case for the same indicaons and/or similar paent populaons. In addion, in the case of clinical trials of any product candidate, paents currently receiving treatment with the current standard of care or a competor product may be reluctant to parcipate in a clinical trial with an invesgaonal drug. Addionally, it is oen more diﬃcult to enroll special or parcular subpopulaons of paents, such as pediatric or elderly paents, due to a number of factors including parental or other caregiver consideraons, concerns and burdens. For example, we enrolled sites in a post-approval pediatric study for the Hypophosphatemia Indicaon of Auryxia in the second quarter of 2022, which began paent recruitment in the third quarter of 2022, but enrollment of eligible pediatric paents in study sites connues to be very slow despite eﬀorts to do so. Finally, compeon for clinical trial sites may limit our access to paents appropriate for our clinical trials. As a result, the meline for recruing paents and conducng studies may be delayed. These delays could result in increased costs, delays in advancing our development of any product or product candidate, or terminaon of the clinical trial altogether. We may not be able to idenfy, recruit and enroll a suﬃcient number of paents, or those with required or desired characteriscs, to complete our clinical trials in a mely manner. Paent enrollment is aﬀected by many factors, including: • • • • • • • • • • • • severity of the disease under invesgaon; design of the study protocol; size and nature of the paent populaon; eligibility criteria for, and design of, the study in queson, including study complexity; perceived risks and beneﬁts of the product or product candidate under study, including as a result of adverse eﬀects observed in similar or compeng therapies; proximity and availability of clinical trial sites for prospecve paents; availability of compeng therapies and clinical trials and clinicians’ and paents’ percepons as to the potenal advantages of the product or product candidate being studied in relaon to available therapies or other product candidates in development; eﬀorts to facilitate mely enrollment in clinical trials; parcipaon length and demands on paents and caregivers; site staﬃng shortages and turnover; clinical trial sites and invesgators failing to perform eﬀecvely; and paent referral pracces of physicians. We may not be able to iniate or complete clinical trials in a mely manner, or at all, if we cannot enroll a suﬃcient number of eligible paents to parcipate in the clinical trials required by regulatory agencies. If we have diﬃculty enrolling a suﬃcient number of paents to conduct our clinical trials as planned, we may need to delay, limit or terminate ongoing or planned clinical trials, any of which may delay approval, or result in failure to maintain or obtain approval, of our products or product candidates, which would have a material adverse eﬀect on our business. Further, if we are slow or unable to adapt to changes in exisng requirements or the adopon of new requirements or policies governing clinical trials, our development plans may be impacted. For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, Congress required sponsors to develop and submit a diversity acon plan for each phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. These plans are meant to encourage the enrollment of more diverse paent populaons in late-stage clinical trials of FDA-regulated products. Conducng clinical trials outside of the U.S., as we have done historically and as we may decide to do in the future, presents addional risks and complexies and, if we decide to conduct a clinical trial outside of the U.S. in the future, we may not complete such trials successfully, in a mely manner, or at all, which could aﬀect our ability to obtain regulatory approvals. Our ability to successfully iniate, enroll and complete a clinical trial in any country outside of the U.S. is subject to numerous addional risks unique to conducng business in jurisdicons outside the U.S., including: Akebia Therapeucs, Inc. | Form 10-K | Page 68 Table of Contents • • • • diﬃculty in establishing or managing relaonships with qualiﬁed CROs, physicians and clinical trial sites; diﬃculty in complying with diﬀerent local standards for the conduct of clinical trials; diﬃculty in complying with various and complex import laws and regulaons when shipping drug to certain countries; and the potenal burden of complying with a variety of laws, medical standards and regulatory requirements, including the regulaon of pharmaceucal and biotechnology products and treatments. Data obtained from studies conducted in the U.S. may not be accepted by the EMA, the PMDA and other regulatory authories outside of the U.S. Also, certain jurisdicons require data from studies conducted in their country in order to obtain approval in that country. Further, when a foreign clinical trial is not conducted under an IND, the sponsor must ensure that the study complies with certain regulatory requirements of the FDA in order to use the study as support for an IND or applicaon for markeng approval. Speciﬁcally, the studies must be conducted in accordance with GCP, including undergoing review and receiving approval by an independent ethics commiee, and seeking and receiving informed consent from subjects. Thus, to the extent that we rely on data from foreign clinical trials that are not the subject of an IND but are used to support of an NDA, there is a risk that FDA may not review such data in connecon with its review of the NDA. If we or our collaboraon partners have diﬃculty conducng future clinical trials in jurisdicons outside the U.S. as planned, we may need to delay, limit or terminate such clinical trials, any of which could have an adverse eﬀect on our business. Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired, may cause undesirable side eﬀects or have other properes that may delay or prevent markeng approval or limit their commercial potenal. Undesirable eﬀects caused by, or other undesirable properes of, Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired, or compeng commercial products or product candidates in development that ulize a common mechanism of acon could cause us or regulatory authories to interrupt, delay or halt clinical trials, could result in a more restricve label or the delay, denial or withdrawal of markeng approval by the FDA or other regulatory authories, and could lead to potenal product liability claims. In addion, results of our clinical trials could reveal a high frequency of undesirable eﬀects or unexpected characteriscs. For example, in March 2022, we received the CRL from the FDA for our NDA for vadadustat in which the FDA concluded that the data in the NDA did not support a favorable beneﬁt-risk assessment of vadadustat for dialysis and non- dialysis paents. The FDA expressed safety concerns nong failure to meet non-inferiority in MACE in the non-dialysis paent populaon, the increased risk of thromboembolic events, driven by vascular access thrombosis in dialysis paents, and the risk of drug-induced liver injury. In October 2022, we submied the FDRR to the FDA and focused on the favorable balance between the beneﬁts and risks of vadadustat for the treatment of anemia due to CKD in adult paents on dialysis in light of safety concerns expressed by the FDA in the CRL for dialysis paents related to the rate of adjudicated thromboembolic events driven by vascular access thrombosis for vadadustat compared to the acve comparator and the risk of drug-induced liver injury. In May 2023, the OND denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. In September 2023, we ﬁled our resubmission to our NDA, and in October 2023, the FDA acknowledged that the resubmission was complete and set a PDUFA date of March 27, 2024. There can be no assurances that we will be successful in our NDA resubmission. If we are unable to overcome these concerns, vadadustat may not be approved by the FDA on favorable terms, or at all, and our ﬁnancial condion could be materially harmed. If we or others idenfy undesirable eﬀects caused by, or other undesirable properes of, Auryxia, vadadustat, or any other product or product candidate, including those that may be in-licensed or acquired, or if known undesirable eﬀects are more frequent or severe than in the past, or if any of the foregoing are perceived to have occurred, either before or aer receipt of markeng approval, a number of potenally signiﬁcant negave consequences could result, including: • • • • • our product candidates may not be approved by regulatory authories; our clinical trials may be put on hold; paent recruitment could be slowed, and enrolled paents may not want to complete the clinical trial; regulatory authories may require warnings on the label, such as the warning on Auryxia’s label regarding iron overload; REMS or FDA-imposed risk management plans that use restricve risk minimizaon strategies may be required; • we may decide to, or be required to, send drug warnings or safety alerts to physicians, pharmacists and hospitals (or the FDA or other regulatory authories may choose to issue such alerts), or we may decide to conduct a product recall or be requested to do so by the FDA or other regulatory authority; Akebia Therapeucs, Inc. | Form 10-K | Page 69 Table of Contents • reformulaon of the product, addional non-clinical or clinical trials, restricve changes in labeling or changes to or re-approvals of manufacturing facilies may be required; • we may be precluded from pursuing addional development opportunies to enhance the clinical proﬁle of a product within its indicated populaons, or studying the product or product candidate in addional indicaons and populaons or in new formulaons; and • we could be invesgated by the government or sued and held liable for harm caused to paents, including in class acon lawsuits; and • our reputaon may suﬀer. Any of these events could prevent us from achieving or maintaining, whether on a restricted basis or at all, markeng approval and, ulmately, market acceptance or penetraon of Auryxia, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired. In addion, any of these events could substanally increase our costs, and could signiﬁcantly impact our ability to successfully commercialize Auryxia, vadadustat or any other product and product candidate, including those that may be in-licensed or acquired, and generate product revenue. The paent populaons treated with Auryxia and potenal paent populaons for vadadustat, if approved, have CKD, a serious disease that increases the risk of cardiovascular disease including heart aacks and stroke and, in its most severe form, results in, kidney failure and the need for dialysis or kidney transplant. Many paents with CKD are elderly with comorbidies making them suscepble to signiﬁcant health risks. Therefore, the likelihood of these paents having adverse events, including serious adverse events is high. 2 With respect to the global INNO VATE Phase 3 program, the incidence of treatment emergent adverse events, or TEAEs, during the Correcon and Conversion study in vadadustat treated paents was 83.8% and 85.5% in darbepoen alfa treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa treated paents were hypertension (16.2%/ 12.9%) and diarrhea (10.1%/ 9.7%). Serious TEAEs were lower in vadadustat treated paents at 49.7% compared to 56.5% for darbepoen alfa treated paents. The incidence of TEAEs during the prevalent dialysis paent study (Conversion) in the vadadustat treated paents was 88.3%, and 89.3% in darbepoen alfa treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa treated paents were diarrhea (13.0%/ 10.1%), pneumonia (11.0%/ 9.7%), hypertension (10.6%/ 13.8%), and hyperkalemia (9.0%/ 10.8%). Serious TEAEs were slightly lower for vadadustat treated paents at 55.0% and 58.3% for darbepoen alfa-treated paents. Paents with DD- CKD experienced an increased risk of thromboembolic events compared to darbepoen alfa with a me to ﬁrst event HR of 1.20 (95% CI 0.96 - 1.50) driven by thrombosis of vascular access. 2 With respect to the global PRO TECT Phase 3 program, the incidence of TEAEs during the erythropoiesis smulang agent, or ESA, untreated paents study (Correcon) in the vadadustat-treated paents was 90.9%, and 91.6% in darbepoen alfa-treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa-treated paents were end-stage renal disease (34.7%/ 35.2%), hypertension (17.7%/ 22.1.%), hyperkalemia (12.3.%/ 15.6%), urinary tract infecon (12.9%/ 12.0%), diarrhea (13.9%/ 10.0%), peripheral oedema (12.5%/ 10.5%), fall (9.6%/ 10%) and nausea (10%/ 8.2%). Serious TEAEs were 65.3% for vadadustat-treated paents and 64.5% for darbepoen alfa-treated paents. The incidence of TEAEs during the ESA-treated paents study (Conversion) in vadadustat treated paents was 89.1% and 87.7% in darbepoen alfa-treated paents. During the study, the most common TEAEs reported in vadadustat/darbepoen alfa-treated paents were end-stage renal disease (27.5%/ 28.4%), hypertension (14.4%/ 14.8%), urinary tract infecon (12.2%/ 14.5%), diarrhea (13.8.%/ 8.8.%), peripheral oedema (9.9%/ 10.1%) and pneumonia (10.0%/ 9.7%). Serious TEAEs were 58.5% for vadadustat-treated paents and 56.6% for darbepoen alfa-treated paents. For example, during the conduct of our Phase 3 program our team and hepac experts analyzed hepac cases (unblinded to treatment) and, following the compleon of our global Phase 3 clinical program for vadadustat, there was a review of hepac safety across the vadadustat clinical program, which included eight completed Phase 2 and 3 studies in NDD-CKD paents, 10 completed Phase 1, 2, and 3 studies, and two then-ongoing Phase 3b studies in DD-CKD paents, and 18 completed studies in healthy subjects (17 Phase 1 and one Phase 3). This review consisted of a blinded re-assessment of hepac events conducted by a separate panel of hepac experts. While hepatocellular injury aributed to vadadustat was reported in less than 1% of paents, there was one case of severe hepatocellular injury with jaundice, and we cannot guarantee that similar events will not happen in the future. Addionally, the FDA expressed safety concerns related to the risk of drug-induced liver injury in the CRL that it issued in March 2022. Serious adverse events considered related to vadadustat, including those noted in the CRL, and any other product candidates could have material adverse consequences on the development and potenal approval of vadadustat or our other product candidates and our business as a whole. Our understanding of adverse events in prior clinical trials of our product candidates may change as we gather more informaon, the FDA may not agree with our assessment of adverse events and addional unexpected adverse events may be observed in future clinical trials or in the market. Akebia Therapeucs, Inc. | Form 10-K | Page 70 Table of Contents Any of the above safety data or other occurrences could delay or prevent us from achieving or maintaining markeng approval, harm or prevent sales of Auryxia or, if approved, vadadustat or any other product or product candidate, including those that may be in-licensed or acquired, increase our expenses and impair or prevent our ability to successfully commercialize Auryxia, vadadustat or any other products or product candidates. In addion, any post-markeng clinical trials conducted, if successful, may expand the paent populaons treated with Auryxia, vadadustat or any other product we acquire or for which we receive markeng approval, within or outside of their current indicaons or paent populaons, which could result in the idenﬁcaon of previously unknown undesirable eﬀects, increased frequency or severity of known undesirable eﬀects, or result in the idenﬁcaon of unexpected safety signals. In addion, as vadadustat, if approved, and any other products are commercialized, they will be used in signiﬁcantly larger paent populaons, in less rigorously controlled environments and, in some cases, by less experienced and less expert treang praconers, than in clinical trials, which could result in increased or more serious adverse eﬀects being reported. As a result, regulatory authories, healthcare praconers, third party payors or paents may perceive or conclude that the use of Auryxia, vadadustat, if approved, or any other products are associated with serious adverse eﬀects, undermining our commercializaon eﬀorts. Risks Related to Regulatory Approval We may not be able to obtain markeng approval for vadadustat or any other product candidate, or we may experience signiﬁcant delays in doing so, any of which would materially harm our business. Clinical trials, manufacturing and markeng of any product or product candidate are subject to extensive and rigorous review and regulaon by numerous governmental authories in the U.S. and other jurisdicons. Before obtaining markeng approval for the commercial sale of any product candidate, we must demonstrate through extensive preclinical tesng and clinical trials that the product candidate is safe and eﬀecve for use in each target indicaon. This process can take many years and markeng approval may never be achieved. Of the large number of drugs in development in the U.S. and in other jurisdicons, only a small percentage successfully complete the FDA’s and other jurisdicons’ markeng approval processes and are commercialized. Accordingly, even if we are able to obtain the requisite capital to connue to fund our development eﬀorts, we may be unable to successfully obtain regulatory approval for vadadustat or any other product or product candidate, including those that may be in-licensed or acquired. We are not permied to market vadadustat in the U.S. unless and unl we receive approval from the FDA or in any other jurisdicon unl the requisite approval from regulatory authories in such jurisdicon is received. As a condion to receiving markeng approval for vadadustat, we may be required by the FDA or other regulatory authories to conduct addional preclinical studies or clinical trials. In March 2022, we received the CRL from the FDA regarding our NDA for vadadustat for the treatment of anemia due to CKD. The FDA concluded that the data in the NDA did not support a favorable beneﬁt-risk assessment of vadadustat for dialysis and non-dialysis paents. In October 2022, we submied the FDRR to the FDA and focused on the favorable balance between the beneﬁts and risks of vadadustat for the treatment of anemia due to CKD in adult paents on dialysis in light of safety concerns expressed by the FDA in the CRL for dialysis paents related to the rate of adjudicated thromboembolic events driven by vascular access thrombosis for vadadustat compared to the acve comparator and the risk of drug-induced liver injury. In May 2023, the OND denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. In September 2023, we ﬁled our resubmission to our NDA, and in October 2023, the FDA acknowledged that the resubmission was complete and set a PDUFA date of March 27, 2024. There can be no assurances that we will obtain approval for vadadustat in a mely manner, on favorable terms, or at all. As a result, the regulatory approval process for vadadustat in the U.S. is highly uncertain. Even if we are able to obtain approval, it will only be for paents with DD-CKD and, in any event, the expense and me to do so could adversely impact our ability to successfully commercialize vadadustat, and our ﬁnancial condion could be materially harmed. Further, vadadustat and any other product candidate may not receive markeng approval in the U.S. even if it is approved in other countries. For example, although vadadustat is approved in Japan for the treatment of anemia due to CKD in DD-CKD and NDD-CKD adult paents and in Europe for the treatment of anemia due to CKD in DD-CKD paents, such approval does not guarantee approval in the U.S. by the FDA for these indicaons or at all. In addion, while each regulatory authority makes their own assessment as to the safety and eﬃcacy of a drug, FDA’s concern about the safety or eﬃcacy of vadadustat or any other product candidate could impact the regulatory authority’s decision in another country. Obtaining markeng approval in the U.S. and other jurisdicons for any product candidate depends upon numerous factors, many of which are subject to the substanal discreon of the regulatory authories, including that regulatory agencies may not complete their review processes in a mely manner and, following compleon of the review process, may not grant markeng approval or such markeng approval may be limited. Furthermore, approval of a drug does not ensure successful commercializaon. For example, on September 23, 2015, the European Commission, or EC, approved Fexeric for the control Akebia Therapeucs, Inc. | Form 10-K | Page 71 Table of Contents of hyperphosphatemia in adult paents with CKD. Pursuant to the sunset clause under EU law, the EC’s approval of Fexeric in the EU was conngent on, among other things, our commencing markeng of Fexeric within three years; although we successfully negoated an extension to December 23, 2019, we did not commence markeng Fexeric by such date and therefore the Fexeric approval in the EU has ceased to be valid. In addion, the safety concerns associated with the current standard of care for the indicaons for which we are seeking markeng approval for vadadustat may aﬀect the FDA’s or other regulatory authories’ review of the safety results of vadadustat. Addionally, these regulatory authories may not agree with our assessment of adverse events. Further, the policies or regulaons, or the type and amount of clinical data necessary to gain approval, may change during the course of a product candidate’s clinical development and may vary among jurisdicons. It is possible that vadadustat will never obtain markeng approval in the U.S. or certain other jurisdicons or for some or all of the indicaons for which we seek approval. For example, changes in or the enactment of addional statutes, promulgaon of regulaons or issuance of guidance during preclinical or clinical development, or comparable changes in the regulatory review process for each submied product applicaon, may cause delays in the approval or rejecon of an applicaon. For example, in December 2022, with the passage of Food and Drug Omnibus Reform Act, Congress required sponsors to develop and submit a diversity acon plan for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product. Further, on January 31, 2022, the new Clinical Trials Regulaon (EU) No 536/2014 became applicable in the EU and replaced the prior Clinical Trials Direcve 2001/20/EC. The new regulaon aims at simplifying and streamlining the authorizaon, conduct and transparency of clinical trials in the EU. Under the new coordinated procedure for the approval of clinical trials, the sponsor of a clinical trial to be conducted in more than one EU Member State will only be required to submit a single applicaon for approval. The submission will be made through the Clinical Trials Informaon System, a new clinical trials portal overseen by the EMA and available to clinical trial sponsors, competent authories of the EU Member States and the public. We have not previously secured authorizaon to conduct clinical studies in the EU pursuant to this new regulaon and, accordingly, there is a risk that we may be delayed in commencing such studies. The FDA or other regulatory authories may delay, limit or deny approval of vadadustat for many reasons including, among others: • we may not be able to demonstrate that vadadustat is safe and eﬀecve in treang adult paents with anemia due to CKD to the sasfacon of the relevant regulatory authority; • • • • • • • • • • the results of our clinical trials may only be modestly posive, or there may be concerns with the proﬁle due to eﬃcacy or safety; the results of our clinical trials may not meet the level of stascal or clinical signiﬁcance required by the relevant regulatory authority for review and/or markeng approval; the relevant regulatory authority may disagree with our interpretaon of data from our preclinical studies and clinical trials; the relevant regulatory authority may disagree with the number, design, size, conduct or implementaon of our clinical trials; the relevant regulatory authority may not approve the formulaon, labeling or speciﬁcaons we request for vadadustat; the relevant regulatory authority may approve vadadustat or any other product candidate for use only in a small paent populaon or for fewer or more limited indicaons than we request; the relevant regulatory authority may require that we conduct addional clinical trials or repeat one or more clinical trials; the FDA or other relevant regulatory authority may require development of a REMS as a condion of approval or post-approval; the relevant regulatory authority may grant approval conngent on the performance of costly post-markeng clinical trials; the relevant regulatory authority's onsite inspecons may be delayed due to the recent COVID-19 pandemic or otherwise; • we, or our CROs or other vendors, may fail to comply with GxP or fail to pass any regulatory inspecons or audits; • we or our third party manufacturers may fail to perform in accordance with the FDA’s or other relevant regulatory authority's cGMP requirements and guidance; • the FDA may disagree with inclusion of data obtained from certain regions outside the U.S. to support the NDA for potenal reasons such as diﬀerences in clinical pracce from U.S. standards; Akebia Therapeucs, Inc. | Form 10-K | Page 72 Table of Contents • • • • • the relevant regulatory authority could deem that our ﬁnancial relaonships with certain principal invesgators constute a conﬂict of interest, such that the data from those principal invesgators may not be used to support our applicaons; as part of any future regulatory process, the FDA may ask an Advisory Commiee to review porons of the NDA, the FDA may have diﬃculty scheduling an Advisory Commiee meeng in a mely manner or, if convened, an FDA Advisory Commiee could recommend non-approval, condions of approval or restricons on approval, and the FDA may ulmately agree with the recommendaons; the relevant regulatory authority’s review process and decision-making regarding vadadustat and any other product candidate may be impacted by the results of our and our competors’ clinical trials and safety concerns of marketed products used to treat the same indicaons as the indicaons for which vadadustat and any other product candidate are being developed; the relevant regulatory authority may not approve the manufacturing processes or facilies of third party manufacturers with whom we contract; or the policies or regulaons of the relevant regulatory authority may signiﬁcantly change in a manner that renders our clinical data insuﬃcient for approval or requires us to amend or submit new clinical protocols. If we experience further delays in obtaining approval of, or if we fail to obtain approval of vadadustat for some or all of the indicaons for which we have sought approval, the commercial prospects for vadadustat may be harmed and our ability to generate revenues will be materially impaired, which could have a material adverse eﬀect on our business. For example, our resubmission to our NDA for vadadustat in September 2023 focused on the favorable balance between the beneﬁts and risks of vadadustat for the treatment of anemia due to CKD in adult paents on dialysis. Finally, our ability to develop and market new drug products may be impacted by ongoing ligaon challenging the FDA’s approval of mifepristone. Speciﬁcally, on April 7, 2023, the U.S. District Court for the Northern District of Texas stayed the approval by the FDA of mifepristone, a drug product which was originally approved in 2000 and whose distribuon is governed by various condions adopted under a REMS. In reaching that decision, the district court made a number of ﬁndings that may negavely impact the development, approval and distribuon of drug products in the U.S. Among other determinaons, the district court held that plainﬀs were likely to prevail in their claim that FDA had acted arbitrarily and capriciously in approving mifepristone without suﬃciently considering evidence bearing on whether the drug was safe to use under the condions idenﬁed in its labeling. Further, the district court read the standing requirements governing ligaon in federal court as perming a plainﬀ to bring a lawsuit against the FDA in connecon with its decision to approve an NDA or establish requirements under a REMS based on a showing that the plainﬀ or its members would be harmed to the extent that FDA’s drug approval decision eﬀecvely compelled the plainﬀs to provide care for paents suﬀering adverse events caused by a given drug. On April 12, 2023, the district court decision was stayed, in part, by the U.S. Court of Appeals for the Fih Circuit. Thereaer, on April 21, 2023, the U.S. Supreme Court entered a stay of the district court’s decision, in its enrety, pending disposion of the appeal of the district court decision in the Court of Appeals for the Fih Circuit and the disposion of any peon for a writ of cerorari to the Supreme Court. The Court of Appeals for the Fih Circuit held oral argument in the case on May 17, 2023 and, on August 16, 2023, issued its decision. The court declined to order the removal of mifepristone from the market, ﬁnding that a challenge to the FDA’s inial approval in 2000 is barred by the statute of limitaons. But the court did hold that plainﬀs were likely to prevail in their claim that changes allowing for expanded access of mifepristone that FDA authorized in 2016 and 2021 were arbitrary and capricious. On September 8, 2023, the Jusce Department and a manufacturer of mifepristone ﬁled peons for a writ of cerorari, requesng that the U.S. Supreme Court review the court’s decision. On December 13, 2023, the U.S. Supreme Court granted these peons for writ of cerorari for the appeals court. Products approved for markeng are subject to extensive post-markeng regulatory requirements and could be subject to post-markeng restricons or withdrawal from the market, and we may be subject to penales, including withdrawal of markeng approval, if we fail to comply with regulatory requirements or if we experience unancipated problems with our products, or product candidates, when and if any of them is approved. Markeng approvals may be subject to limitaons on the approved indicated uses for which the product may be marketed or other condions of approval, or contain requirements or commitments for potenally costly post-markeng studies and surveillance to monitor the safety and eﬃcacy of the product, including REMS, or registries or observaonal studies. For example, in connecon with the FDA approvals of Auryxia, we inially commied to the FDA to conduct certain post-approval pediatric studies of Auryxia under the Pediatric Research Equity Act of 2003, or PREA. Under PREA, an NDA or supplement to an NDA for certain drug products must contain data to assess the safety and eﬀecveness of the drug product in all relevant pediatric subpopulaons and to support dosing and administraon for each pediatric subpopulaon for which the product is safe and eﬀecve, unless the sponsor receives a deferral or waiver from the FDA. A deferral may be granted for several reasons, including a ﬁnding that the product or therapeuc candidate is ready for approval for use in adults before pediatric Akebia Therapeucs, Inc. | Form 10-K | Page 73 Table of Contents trials are complete or that addional safety or eﬀecveness data needs to be collected before the pediatric trials begin. With regard to the Hyperphosphatemia Indicaon for Auryxia, we inially commied to compleng the original post-approval pediatric study and subming a ﬁnal report to the FDA by December 31, 2019. However, we did not complete the study according to the original schedule and therefore did not submit the required ﬁnal report by December 31, 2019. Consequently, we received a noﬁcaon of noncompliance with PREA. We have since been released from the original post markeng requirement, or PMR, and a new PMR was issued that provided that the ﬁnal report is due in April 2024. Therefore, this PMR trial is no longer considered delayed and is open and acvely enrolling paents. In June 2023 we requested an extension of me for the submission of the ﬁnal report and such request was denied by the FDA in August 2023. Therefore, the ﬁnal report for this PMR trial is sll due in April 2024, and we are unlikely to complete the trial by that me. With regard to our IDA Indicaon, we inially commied to compleng the post-approval pediatric study and subming a ﬁnal report to the FDA by January 2023. We did not meet a milestone relang to this post-approval pediatric study of Auryxia in a mely manner and received a noﬁcaon from the FDA. Subsequently, the FDA agreed to extend the pediatric clinical trial melines for the IDA Indicaon. We subsequently communicated to the FDA that we would be delaying the start of the clinical trial in the IDA Indicaon while we work to produce smaller size tablets. In response, the FDA issued a paral clinical hold unl we manufacture the smaller tablets and provide the FDA with relevant informaon regarding the smaller sized tablets for review. The FDA lied the paral clinical hold in June 2022, however, we have not commenced start-up of this study pending resoluon of the manufacturing of the smaller size tablets. If we are unable to complete these studies successfully by the applicable deadline, or have further delays in compleng these studies, we will need to inform the FDA, have further discussions and, if the FDA ﬁnds that we failed to comply with pediatric study requirements, in violaon of applicable law, it could instute enforcement proceedings to seize or enjoin the sale of Auryxia or seek civil penales, which would have a material adverse impact on our ability to commercialize Auryxia and our ability to generate revenues from Auryxia. In addion, the manufacturing processes, labeling, packaging, distribuon, adverse event reporng, storage, adversing, promoon and recordkeeping for Auryxia, vadadustat, if approved, and any other product for which we receive regulatory approval will be subject to extensive and ongoing regulatory requirements and guidance. These requirements and guidance include manufacturing processes and procedures (including record keeping), the implementaon and operaon of quality systems to control and assure the quality of the product, submissions of safety and other post-markeng informaon and reports, as well as connued compliance with cGMPs and GCPs for any clinical trials that we conduct post-approval. If we, our contract manufacturing organizaons, or CMOs, or other third pares we engage fail to adhere to such regulatory requirements and guidance, we could suﬀer signiﬁcant consequences, including product seizures or recalls, loss of product approval, ﬁnes and sancons, reputaonal damage, loss of customer conﬁdence, shipment delays, inventory shortages, inventory write-oﬀs and other product-related charges and increased manufacturing costs, and our development or commercializaon eﬀorts may be materially harmed. Post-approval discovery of previously unknown problems with an approved product, including adverse events of unancipated severity or frequency or relang to manufacturing operaons or processes, or failure to comply with regulatory requirements, may result in, among other things: • restricons on the markeng, distribuon, use or manufacturing of the product; • withdrawal of the product from the market, or product recalls; • • restricons on the labeling or markeng of a product; ﬁnes, restuon or disgorgement of proﬁts or revenues; • warning or untled leers or clinical holds; • • • • refusal by the FDA or other regulatory authories to approve pending applicaons or supplements to approved applicaons ﬁled by us, or suspension or revocaon of product approvals; product seizure or detenon, or refusal to permit the import or export of products; REMS; and injuncons or the imposion of civil or criminal penales. For example, we previously had three limited, voluntary recalls of Auryxia. These and any other recalls or any supply, quality or manufacturing issues in the future could result in signiﬁcant negave consequences, including reputaonal harm, loss of customer conﬁdence, and a negave impact on our ﬁnancials, any of which could have a material adverse eﬀect on our business and results of operaons, and may impact our ability to supply Auryxia in Japan, Vafseo in Japan and Europe or vadadustat, if approved in other countries, for commercial and clinical use. Non-compliance with the FDA, the EMA, the PMDA and other regulatory authories’ requirements regarding safety monitoring or pharmacovigilance can also result in signiﬁcant ﬁnancial penales. The FDA’s policies and those of other regulatory authories may change, and addional government regulaons may be enacted. We cannot predict the likelihood, nature or extent of government regulaons that may arise from future legislaon Akebia Therapeucs, Inc. | Form 10-K | Page 74 Table of Contents or administrave acon, either in the U.S. or in other jurisdicons. If we are slow or unable to adapt to changes in exisng requirements or the adopon of new requirements or policies, or are not able to maintain regulatory compliance, we may lose any markeng approval that we may have obtained and we may not achieve or sustain proﬁtability, which would materially adversely aﬀect our business. Risks Related to Governmental Regulaon and Compliance We are subject to complex regulatory schemes that require signiﬁcant resources to ensure compliance and our failure to comply with applicable laws could subject us to government scruny or enforcement, potenally resulng in costly invesgaons, ﬁnes, penales or sancons, contractual damages, reputaonal harm, administrave burdens and diminished proﬁts and future earnings. In general, a variety of laws apply to us or may otherwise restrict our acvies, including the following: • • • • • • • laws and regulaons governing the conduct of preclinical studies and clinical trials in the U.S. and other countries in which we are conducng such studies; an-corrupon and an-bribery laws, including the FCPA, the UK Bribery Act and various other an-corrupon laws in countries outside of the U.S.; data privacy laws exisng in the U.S., the EU, the UK and other countries in which we operate, including the U.S. Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Informaon Technology for Economic and Clinical Health Act, or HITECH, state privacy and data protecon laws, such as the California Consumer Privacy Act, or CCPA, as amended by the California Privacy Rights Act of 2020, or CPRA, as well as other state consumer protecon laws, GDPR, any addional applicable EU member state, or EU Member State, data protecon laws in force from me to me, the retained EU law version of the General Data Protecon Regulaon as saved into United Kingdom law by virtue of secon 3 of the United Kingdom's European Union (Withdrawal) Act 2018, or the EU GDPR; federal and state laws requiring the submission of accurate product prices and noﬁcaons of price increases; federal and state securies laws; environmental, health and safety laws and regulaons; and internaonal trade laws, which are laws that regulate the sale, purchase, import, export, re-export, transfer and shipment of goods, products, materials, services and technology. In addion, our relaonships with healthcare providers, physicians and third party payors expose us to broadly applicable fraud and abuse laws that may constrain the business or ﬁnancial arrangements and relaonships through which we market, sell and distribute Auryxia and vadadustat, if approved, and any other products for which we may obtain markeng approval. As such, these arrangements are subject to applicable an-kickback, fraud and abuse, false claims, transparency, health informaon privacy and security, and other healthcare laws and regulaons at federal, state and internaonal levels. These restricons include, but are not limited to, the following: • • • • • the Food, Drug and Cosmec Act of 1938, as amended, or FDCA, which among other things, strictly regulates drug product markeng and promoon and prohibits manufacturers from markeng such products for oﬀ-label use; federal laws that require pharmaceucal manufacturers to report certain calculated product prices to the government or provide certain discounts or rebates to government authories or private enes, oen as a condion of reimbursement under government healthcare programs, and laws requiring noﬁcaon of price increases; the federal An-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully solicing, oﬀering, receiving or providing remuneraon, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendaon or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid; the federal False Claims Act, which imposes criminal and civil penales, including through civil whistleblower or qui tam acons, against individuals or enes for, among other things, knowingly presenng, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligaon to pay money to the federal government, with potenal liability including mandatory treble damages and signiﬁcant per-claim penales, and violaons of the FDCA, the federal government pricing laws, and the federal An-Kickback Statute trigger liability under the federal False Claims Act; HIPAA, which imposes criminal and civil liability for execung a scheme to defraud any healthcare beneﬁt program or making false statements relang to healthcare maers; Akebia Therapeucs, Inc. | Form 10-K | Page 75 Table of Contents • • • HIPAA, as amended by the HITECH, and their respecve implemenng regulaons, also imposes obligaons, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually idenﬁable health informaon; the federal Open Payments Act (the former Physician Payments Sunshine Act) requires applicable manufacturers of covered drugs to report payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; analogous state and foreign laws and regulaons, such as state an-kickback and false claims laws and gi ban and transparency statutes, which may apply to sales or markeng arrangements and claims involving healthcare items or services reimbursed by state Medicaid or other programs, or non- governmental third party payors, including private insurers, and which are not preempted by federal laws and oen diﬀer from state to state, thus complicang compliance eﬀorts; and • U.S. state laws restricng interacons with healthcare providers and other members of the healthcare community or requiring pharmaceucal manufacturers to implement certain compliance standards, which vary from state to state. Because of the breadth of these U.S. laws, and their non-U.S. equivalents, and the narrowness of the statutory excepons and safe harbors available, it is possible that some of our business acvies could be subject to challenge under one or more of such laws. In addion, recent healthcare reforms have strengthened these laws. For example, the Health Care Reform Act, among other things, amended the intent requirement of the federal An-Kickback Statute. A person or enty no longer needs to have actual knowledge of the statute or speciﬁc intent to violate the law. The Health Care Reform Act also amended the False Claims Act, such that violaons of the An-Kickback Statute are now deemed violaons of the False Claims Act. Some state laws require pharmaceucal companies to comply with the pharmaceucal industry’s voluntary compliance guidelines, such as the Pharmaceucal Research and Manufacturers of America Code on Interacons with Health Care Professionals, known as the PhRMA Code. Addionally, some state and local laws require the registraon and speciﬁc training of pharmaceucal sales representaves in the jurisdicon. State and foreign laws also govern the privacy and security of health informaon in some circumstances, many of which diﬀer from each other in signiﬁcant ways and oen are not preempted by HIPAA. Eﬀorts to ensure that our business complies with applicable healthcare laws and regulaons involves substanal costs and requires us to expend signiﬁcant resources. One of the potenal areas for governmental scruny involves federal and state requirements for pharmaceucal manufacturers to submit accurate price reports to the government. Because our processes for calculang applicable government prices and the judgments involved in making these calculaons involve subjecve decisions and complex methodologies, these calculaons are subject to risk of errors and diﬀering interpretaons. In addion, they are subject to review and challenge by the applicable governmental agencies, or potenal qui tam complaints, and it is possible that such reviews could result in changes, recalculaons, or defense costs that may have adverse legal or ﬁnancial consequences. It is possible that governmental authories will conclude that our business pracces may not comply with current or future statutes, regulaons or case law involving applicable fraud and abuse or other healthcare laws and regulaons. If our operaons are found to be in violaon of any of these laws or any other governmental regulaons that may apply to us, we may be subject to signiﬁcant civil, criminal and administrave penales, damages, ﬁnes, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operaons, any of which could materially adversely aﬀect our business and would result in increased costs and diversion of management aenon and could negavely impact the development, regulatory approval and commercializaon of Auryxia or vadadustat, any of which could have a material adverse eﬀect on our business. Further, if any of the physicians or other healthcare providers or enes with whom we expect to do business is found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrave sancons, including exclusions from parcipaon in government funded healthcare programs. We will incur signiﬁcant liability if it is determined that we are promong any “oﬀ-label” use of Auryxia or any other product we may develop, in-license or acquire or if it is determined that any of our acvies violates the federal An-Kickback Statute. Physicians are permied to prescribe drug products for uses that diﬀer from those approved by the FDA or other applicable regulatory agencies. Although the FDA and other regulatory agencies do not regulate a physician’s choice of treatments, the FDA and other regulatory agencies do restrict manufacturer communicaons regarding unapproved uses of an approved drug. Companies are not permied to promote drugs for unapproved uses or in a manner that is inconsistent with the FDA-approved labeling. There are also restricons about making comparave or superiority claims based on safety or eﬃcacy that are not supported by substanal evidence. Accordingly, we may not promote Auryxia in the U.S. for use in any indicaons other than the Hyperphosphatemia Indicaon and the IDA Indicaon, and all promoonal claims must be consistent with the FDA-approved labeling for Auryxia. Akebia Therapeucs, Inc. | Form 10-K | Page 76 Table of Contents Promong a drug oﬀ-label is a violaon of the FDCA and can give rise to liability under the federal False Claims Act, as well as under addional federal and state laws and insurance statutes. The FDA, the Department of Jusce and other regulatory and enforcement authories enforce laws and regulaons prohibing promoon of oﬀ-label uses and the promoon of products for which markeng approval has not been obtained, as well as the false adversing or misleading promoon of drugs. In September 2021, the FDA published ﬁnal regulaons which describe the types of evidence that the agency will consider in determining the intended use of a drug product. In addion, laws and regulaons govern the distribuon and tracing of prescripon drugs and prescripon drug samples, including the Prescripon Drug Markeng Act of 1976 and the Drug Supply Chain Security Act, which regulate the distribuon and tracing of prescripon drugs and prescripon drug samples at the federal level and set minimum standards for the regulaon of drug distributors by the states. A company that is found to have improperly promoted oﬀ-label uses or to have otherwise engaged in false or misleading promoon or improper distribuon of drugs will be subject to signiﬁcant liability, potenally including civil and administrave remedies as well as criminal sancons. It may also be subject to exclusion and debarment from federal healthcare reimbursement programs. Notwithstanding the regulatory restricons on oﬀ-label promoon, the FDA and other regulatory authories allow companies to engage in truthful, non- misleading, and non-promoonal scienﬁc communicaons concerning their products in certain circumstances. For example, in October 2023, the FDA published dra guidance outlining the agency’s non-binding policies governing the distribuon of scienﬁc informaon on unapproved uses to healthcare providers. This dra guidance calls for such communicaons to be truthful, non-misleading, factual, and unbiased and include all informaon necessary for healthcare providers to interpret the strengths and weaknesses and validity and ulity of the informaon about the unapproved use. In addion, under some relavely recent guidance from the FDA and the Pre-Approval Informaon Exchange Act, or PIE Act, signed into law as part of the Consolidated Appropriaons Act of 2023, or the Consolidated Appropriaons Act, companies may also promote informaon that is consistent with the prescribing informaon and proacvely speak to formulary commiee members of payors regarding data for an unapproved drug or unapproved uses of an approved drug. We intend to engage in these discussions and communicate with healthcare providers, payors and other constuencies in compliance with all applicable laws, regulatory guidance and industry best pracces. Although we believe we have put in place a robust compliance program and processes designed to ensure that all such acvies are performed in a legal and compliant manner, such program and processes may not be suﬃcient to deter or detect all violaons, and we will need to carefully navigate the FDA’s various regulaons, guidance and policies, along with recently enacted legislaon, to ensure compliance with restricons governing promoon of our products. In addion, if a company’s acvies are determined to have violated the federal An-Kickback Statute, this can also give rise to liability under the federal False Claims Act and such violaons can result in signiﬁcant ﬁnes, criminal and civil remedies, and exclusion from Medicare and Medicaid. There is increased government focus on relaonships between the pharmaceucal industry and physicians, pharmacies (especially specialty pharmacies), and other sources of referrals. Common industry acvies, such as speaker programs, insurance assistance and support, relaonships with foundaons providing copayment assistance, and relaonships with paent organizaons and paents are receiving increased governmental aenon. If any of our relaonships or acvies is determined to violate applicable federal and state an-kickback laws, false claims laws, or other laws or regulaons, the company and/or company execuves, employees, and other representaves could be subject to signiﬁcant ﬁnes and criminal sancons, imprisonment, and potenal exclusion from Medicare and Medicaid, and could harm our reputaon or result in signiﬁcant legal expenses and distracon of management. Disrupons in the FDA, regulatory authories outside the U.S. and other government agencies caused by global health concerns or funding shortages could prevent new products and services from being developed or commercialized in a mely manner, which could negavely impact our business. The ability of the FDA and regulatory authories outside the U.S. to review and approve new products can be aﬀected by a variety of factors, including global health concerns, government budget and funding levels, staﬃng shortages, statutory, regulatory, and policy changes and other events that may otherwise aﬀect the FDA’s or other regulatory authories' ability to perform roune funcons. Average review mes at the FDA have ﬂuctuated in recent years as a result of certain of these factors. In addion, government funding of other government agencies that fund R&D acvies is subject to the polical process, which is inherently ﬂuid and unpredictable. Disrupons at the FDA and other agencies may increase the me necessary for new drugs to be reviewed or approved by necessary government agencies, which would adversely aﬀect our business. If a prolonged government shutdown occurs, it could signiﬁcantly impact the ability of the FDA or other regulatory authories to mely review and process our, or our collaboraon partners', regulatory submissions, which could have a material adverse eﬀect on our business. If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authories from conducng their regular inspecons, reviews, or other regulatory acvies, it could signiﬁcantly impact the ability of the FDA or other regulatory authories to mely review and process our regulatory submissions, which could have a material adverse eﬀect on our business. Akebia Therapeucs, Inc. | Form 10-K | Page 77 Table of Contents Compliance with privacy and data security requirements could result in addional costs and liabilies to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us to signiﬁcant ﬁnes and penales, which may have a material adverse eﬀect on our business, ﬁnancial condion or results of operaons. The regulatory framework for the collecon, use, safeguarding, sharing, transfer and other processing of informaon worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every jurisdicon in which we operate has established its own data security and privacy frameworks with which we must comply. For example, the collecon, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the GDPR, which took eﬀect across all member states of the EEA, in May 2018. Following the withdrawal of the UK from the EU, the UK Data Protecon Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligaons to those set forth by GDPR. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data when required, including requirements relang to processing health and other sensive data, obtaining consent of the individuals to whom the personal data relates, when required, providing informaon to individuals regarding data processing acvies, implemenng safeguards to protect the security and conﬁdenality of personal data, providing noﬁcaon of data breaches, and taking certain measures when engaging third party processors. The GDPR increases our obligaons as a sponsor in clinical trials in the EEA by expanding the deﬁnion of personal data to include coded data and requiring changes to informed consent pracces and more detailed noces for clinical trial paents and invesgators. The GDPR also permits data protecon authories to require destrucon of improperly gathered or used personal informaon and/or impose substanal ﬁnes for violaons of the GDPR, which can be up to four percent of the total worldwide annual turnover of a group of companies from the preceding ﬁnancial year or 20 million Euros, whichever is greater, and it also confers a private right of acon on data subjects and consumer associaons to lodge complaints with supervisory authories, seek judicial remedies, and obtain compensaon for damages resulng from violaons of the GDPR. In addion, the GDPR provides that EU Member States may make their own further laws and regulaons liming the processing of personal data, including genec, biometric or health data and permits EU Member States to adopt further penales for violaons that are not subject to the administrave ﬁnes outlined in the GDPR. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the U.S. and, as a result, increases the scruny that we should apply to transfers of personal data from such sites to countries that are considered to lack an adequate level of data protecon, such as the U.S. There is ongoing uncertainty about the transfer mechanisms that companies rely upon to enable the legal transfer of personal data from the EU to other countries. For example, in July 2020, the Court of Jusce of the European Union, or the CJEU, invalidated the EU-U.S. Privacy Shield, one of the mechanisms used to legimize the transfer of personal data from the EEA to the U.S. Although a new Data Privacy Framework has been adopted, as court decisions and regulatory guidance evolves, challenges remain with respect to GDPR compliance. Companies must connue to monitor the regulatory landscape and implement necessary changes, all of which may be costly and may put the company out of compliance while any changes are being implemented. Following the withdrawal of the UK from the EU, the UK Data Protecon Act 2018 applies to the processing of personal data that takes place in the UK and includes parallel obligaons to those set forth by GDPR. In relaon to data transfers, both the UK and the EU have determined, through separate “adequacy” decisions, that data transfers between the two jurisdicons are in compliance with the UK Data Protecon Act and the GDPR, respecvely. The UK and the U.S. have also agreed to a U.S.-UK “Data Bridge”, which funcons similarly to the EU-U.S. Data Privacy Framework and provides an addional legal mechanism for companies to transfer data from the UK to the U.S. In addion to the UK, Switzerland has approved an adequacy decision in relaon to the Swiss-U.S. Data Privacy Framework (which would funcon similarly to the EU-U.S. Data Privacy Framework and the U.S.-UK Data Bridge in relaon to data transfers from Switzerland to the U.S.). Any changes or updates to these developments have the potenal to impact our business. Addionally, in October 2022, President Biden signed an execuve order to implement the EU-U.S. Data Privacy Framework, which serves as a replacement to the EU-U.S. Privacy Shield. The EU iniated the process to adopt an adequacy decision for the EU-U.S. Data Privacy Framework in December 2022, and the EC adopted the adequacy decision on July 10, 2023. The adequacy decision permits U.S. companies who self-cerfy to the EU-U.S. Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S. However, some privacy advocacy groups have already challenged or suggested that they will be challenging the EU-U.S. Data Privacy Framework. If these challenges are successful, they may not only impact the EU-U.S. Data Privacy Framework, but also further limit the viability of the standard contractual clauses and other data transfer mechanisms. The uncertainty around this issue has the potenal to impact our business internaonally. Given the breadth and depth of changes in data protecon obligaons, complying with the GDPR’s requirements is rigorous and me intensive and requires signiﬁcant resources and a review of our technologies, systems and pracces, as well as those of any third party collaborators, service providers, contractors or consultants that process or transfer personal data collected in the EU. The GDPR and other changes in laws or regulaons associated with the enhanced protecon of certain types of sensive data, such as healthcare data or other personal informaon from our clinical trials, could require us to change our Akebia Therapeucs, Inc. | Form 10-K | Page 78 Table of Contents business pracces and put in place addional compliance mechanisms, may interrupt or delay our development, regulatory and commercializaon acvies and increase our cost of doing business, and could lead to government enforcement acons, private ligaon and signiﬁcant ﬁnes and penales against us and could have a material adverse eﬀect on our business, ﬁnancial condion or results of operaons. Similar privacy and data security requirements are either in place or underway in the U.S. There are a broad variety of data protecon laws that may be applicable to our acvies, and a range of enforcement agencies at both the state and federal levels that can review companies for privacy and data security concerns. The Federal Trade Commission, or the FTC, and state Aorneys General all are aggressive in reviewing privacy and data security protecons for consumers. For example, the FTC has been parcularly focused on the unpermied processing of health and genec data through its recent enforcement acons and is expanding the types of privacy violaons that it interprets to be “unfair” under Secon 5 of the Federal Trade Commission Act, as well as the types of acvies it views to trigger the Health Breach Noﬁcaon Rule (which the FTC also has the authority to enforce). The agency is also in the process of developing rules related to commercial surveillance and data security that may impact our business. We will need to account for the FTC’s evolving rules and guidance for proper privacy and data security pracces in order to migate our risk for a potenal enforcement acon, which may be costly. If we are subject to a potenal FTC enforcement acon, we may be subject to a selement order that requires us to adhere to very speciﬁc privacy and data security pracces, which may impact our business. We may also be required to pay ﬁnes as part of a selement (depending on the nature of the alleged violaons). If we violate any consent order that we reach with the FTC, we may be subject to addional ﬁnes and compliance requirements. New laws also are being considered at both the state and federal levels. For example, the CCPA, which went into eﬀect on January 1, 2020, and the CPRA, which amends CCPA by expanding the scope and applicability, while also introducing new privacy protecons, is creang similar risks and obligaons as those created by GDPR. In November 2020, California voters passed a ballot iniave for the CPRA, which went into eﬀect on January 1, 2023 and signiﬁcantly expanded the CCPA to incorporate addional GDPR-like provisions including requiring that the use, retenon and sharing of personal informaon of California residents be reasonably necessary and proporonate to the purposes of collecon or processing, granng addional protecons for sensive personal informaon, and requiring greater disclosures related to noce to residents regarding retenon of informaon. The CPRA also creates a new agency that is speciﬁcally responsible for enforcing the new law and other California privacy laws. Because of this, we may need to engage in addional acvies (e.g., data mapping) to idenfy the personal informaon we are collecng and the purposes for which such informaon is collected. In addion, we will need to ensure that our policies recognize the rights granted to consumers (as that phrase is broadly deﬁned in the CCPA and can include business contact informaon). In addion to California, at least eleven other states have passed comprehensive privacy laws similar to the CCPA and CPRA. These laws are either in eﬀect or will go into eﬀect someme before the end of 2026. Like the CCPA and CPRA, these laws create obligaons related to the processing of personal informaon, as well as special obligaons for the processing of “sensive” data (which includes health data in some cases). Some of the provisions of these laws may apply to our business acvies. There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2023 legislave sessions that will go into eﬀect in 2025 and beyond, including New Hampshire and New Jersey. Other states will be considering these laws in the future, and Congress has also been debang passing a federal privacy law. There are also states that are speciﬁcally regulang health informaon that may aﬀect our business. For example, Washington state passed a health privacy law in 2023 that will regulate the collecon and sharing of health informaon, and the law also has a private right of acon, which further increases the relevant compliance risk. Conneccut and Nevada have also passed similar laws regulang consumer health data and addional states (including Vermont) are considering such legislaon for 2024. These laws may impact our business acvies, including our idenﬁcaon of research subjects, relaonships with business partners and ulmately the markeng and distribuon of our products. A broad range of legislave measures also have been introduced at the federal level. Accordingly, failure to comply with current and any future federal and state laws regarding privacy and security of personal informaon could expose us to ﬁnes and penales. We also face a threat of potenal consumer class acons related to these laws and the overall protecon of personal data. Even if we are not determined to have violated these laws, invesgaons into these issues typically require the expenditure of signiﬁcant resources and generate negave publicity, which could harm our reputaon and our business. Legislave and regulatory healthcare reform may increase the diﬃculty and cost for us to obtain markeng approval of and commercialize our product candidates and aﬀect the prices we may obtain for any products that are approved in the U.S. or foreign jurisdicons. In the U.S. and some foreign jurisdicons, there have been a number of legislave and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay markeng approval of vadadustat, or any other product candidate, restrict or regulate post-approval acvies and aﬀect our ability to proﬁtably sell Auryxia and vadadustat, if approved. The pharmaceucal industry has been a parcular focus of these eﬀorts and has been signiﬁcantly aﬀected by legislave iniaves. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result Akebia Therapeucs, Inc. | Form 10-K | Page 79 Table of Contents in more rigorous coverage criteria and addional downward pressure on the price that we receive for any FDA approved product, such as Auryxia or vadadustat, if approved, or any reimbursement that physicians receive for administering any approved product. In the U.S. the Medicare Prescripon Drug, Improvement, and Modernizaon Act of 2003, or the MMA, changed the way Medicare covers and pays for pharmaceucal products. The legislaon expanded Medicare coverage for drug purchases by the elderly and introduced a new reimbursement methodology based on average sales prices for physician-administered drugs. In addion, this legislaon provided authority for liming the number of drugs that will be covered in any therapeuc class. Cost reducon iniaves and other provisions of this legislaon could decrease the coverage and price that we receive for Auryxia and any other approved products. While the MMA applies only to drug beneﬁts for Medicare beneﬁciaries, private payors oen follow Medicare coverage policy and payment limitaons in seng their own reimbursement rates. Therefore, any reducon in reimbursement that results from the MMA may result in a similar reducon in payments from private payors. In March 2010, President Obama signed into law the Paent Protecon and Aﬀordable Care Act, as amended by the Health Care and Educaon Reconciliaon Act of 2010, or, collecvely, the ACA. In addion, other legislave and regulatory changes have been proposed and adopted since the ACA was enacted. These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reducons to Medicare payments to providers of up to 2% per ﬁscal year, which will remain in eﬀect through 2031. Under current legislaon, the actual reducons in Medicare payments may vary up to 4%. The Consolidated Appropriaons Act, which was signed into law by President Biden in December 2022, made several changes to sequestraon of the Medicare program. Secon 1001 of the Consolidated Appropriaons Act delays the 4% Statutory Pay-As-You-Go Act of 2010 (PAYGO) sequester for two years, through the end of calendar year 2024. Triggered by enactment of the American Rescue Plan Act of 2021, the 4% cut to the Medicare program would have taken eﬀect in January 2023. The Consolidated Appropriaons Act’s health care oﬀset tle includes Secon 4163, which extends the 2% Budget Control Act of 2011 Medicare sequester for six months into ﬁscal year 2032 and lowers the payment reducon percentages in ﬁscal years 2030 and 2031. The American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the statute of limitaons period for the government to recover overpayments to providers from three to ﬁve years. In addion, other legislave and regulatory changes have been proposed, but not yet adopted. For example, in July 2019, the U.S. Department of Health and Human Services, or HHS, proposed regulatory changes in kidney health policy and reimbursement. Any new legislave or regulatory changes may result in addional reducons in Medicare and other healthcare funding and otherwise aﬀect the prices we may obtain for Auryxia or vadadustat, if approved, or the frequency with which Auryxia and vadadustat, if approved, is prescribed or used. The costs and prices of prescripon pharmaceucals have also been the subject of considerable discussion in the U.S. To date, there have been several recent U.S. congressional inquiries and proposed and enacted state and federal legislaon designed to, among other things, bring more transparency to drug pricing, review the relaonship between pricing and manufacturer paent programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products. At the federal level, Congress and the current administraon have each indicated that it will connue to seek new legislave and/or administrave measures to control drug costs. For example, the former administraon issued several execuve orders intended to lower the costs of prescripon products and certain provisions in these orders have been incorporated into regulaons. These regulaons include an interim ﬁnal rule implemenng a most favored naon model for prices that would e Medicare Part B payments for certain physician-administered pharmaceucals to the lowest price paid in other economically advanced countries, eﬀecve January 1, 2021. That rule, however, has been subject to a naonwide preliminary injuncon and, on December 29, 2021, CMS issued a ﬁnal rule to rescind it. With issuance of this rule, CMS stated that it will explore all opons to incorporate value into payments for Medicare Part B pharmaceucals and improve beneﬁciaries' access to evidence-based care. In addion, in October 2020, the HHS and the FDA published a ﬁnal rule allowing states and other enes to develop a Secon 804 Importaon Program to import certain prescripon drugs from Canada into the U.S. That regulaon was challenged in a lawsuit by the Pharmaceucal Research and Manufacturers of America, or PhRMA, but the case was dismissed by a federal district court in February 2023 aer the court found that PhRMA did not have standing to sue HHS. Nine states (Colorado, Florida, Maine, New Hampshire, New Mexico, North Dakota, Texas, Vermont and Wisconsin) have passed laws allowing for the importaon of drugs from Canada. Certain of these states have submied Secon 804 Importaon Program proposals and are awaing FDA approval. On January 5, 2023, the FDA approved Florida’s plan for Canadian drug importaon. Further, on July 9, 2021, President Biden signed Execuve Order 14063, which focuses on, among other things, the price of pharmaceucals. The Order directs HHS to create a plan within 45 days to combat “excessive pricing of prescripon pharmaceucals and enhance domesc pharmaceucal supply chains, to reduce the prices paid by the federal government for such pharmaceucals, and to address the recurrent problem of price gouging.” On September 9, 2021, HHS released its Akebia Therapeucs, Inc. | Form 10-K | Page 80 Table of Contents plan to reduce pharmaceucal prices. The key features of that plan are to: (a) make pharmaceucal prices more aﬀordable and equitable for all consumers and throughout the health care system by supporng pharmaceucal price negoaons with manufacturers; (b) improve and promote compeon throughout the prescripon pharmaceucal industry by supporng market changes that strengthen supply chains, promote biosimilars and generic drugs, and increase transparency; and (c) foster scienﬁc innovaon to promote beer healthcare and improve health by supporng public and private research and making sure that market incenves promote discovery of valuable and accessible new treatments. On August 16, 2022, the Inﬂaon Reducon Act of 2022, or IRA, was signed into law by President Biden. The new legislaon has implicaons for Medicare Part D, which is a program available to individuals who are entled to Medicare Part A or enrolled in Medicare Part B to give them the opon of paying a monthly premium for outpaent prescripon drug coverage. Among other things, the IRA imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inﬂaon (ﬁrst due in 2023); and replaces the Part D coverage gap discount program with a new discounng program (beginning in 2025). The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulaon, for the inial years. We consider many factors when we implement a price increase for a product, including historical and potenal future inﬂaon rates. However, there are many variables that are outside of our control and if we increase the price of Auryxia or vadadustat, if approved, faster than the pace of inﬂaon, we would be subject to addional rebates under Medicare, which could have a material adverse eﬀect on our product revenues. As an oral drug, Auryxia is covered by Medicare under Part D. In January 2011, CMS implemented the ESRD PPS, a prospecve payment system for dialysis treatment. Under the ESRD PPS, CMS generally makes a single bundled payment to the dialysis facility for each dialysis treatment that covers all items and services rounely required for dialysis treatments furnished to Medicare beneﬁciaries in Medicare-cerﬁed ESRD facilies or at their home. The inclusion of oral medicaons without injectable or intravenous equivalents such as Auryxia in the bundled payment was inially delayed by CMS unl January 1, 2014, and through several subsequent legislave acons has been delayed unl January 1, 2025. Absent further legislaon or regulaon on this maer, beginning in January 2025, oral ESRD-related drugs without injectable or intravenous equivalents, including Auryxia and all other phosphate lowering medicaons, will be included in the ESRD bundle and separate Medicare payment for these drugs will no longer be available, as is the case today under Medicare Part D. ESRD facilies may nonetheless receive a TDAPA for new renal dialysis drugs and biological products that meet certain criteria for a period of two years. The TDAPA will provide separate payment based on the drug's ASP that will be in addion to the base rate in order to facilitate the adopon of innovave therapies. There can be no assurances that CMS will determine that Auryxia will qualify for TDAPA status or that CMS will not again delay the inclusion of these oral ESRD-related drugs in the bundled payment. Even if Auryxia is deemed eligible by CMS, revenue for sales of Auryxia could be signiﬁcantly less in the TDAPA period than it would be if Auryxia is not bundled into the ESRD PPS. Moreover, in the post- TDAPA period, CMS currently expects to increase the single bundled payment base rate paid to the dialysis facility for each dialysis treatment to reﬂect that oral only phosphate lowering drugs will be reimbursed as part of the single bundled payment for Medicare paents. There can be no assurances that any increase in the single bundled payment base rate will be suﬃcient to adequately reimburse the dialysis facilies for Auryxia at a price that is proﬁtable for us. Speciﬁcally, with respect to price negoaons, Congress authorized Medicare to negoate lower prices for certain costly single-source drug and biologic products that do not have compeng generics or biosimilars and are reimbursed under Medicare Part B and Part D. CMS may negoate prices for ten high- cost drugs paid for by Medicare Part D starng in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond. This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condion. Further, the legislaon subjects drug manufacturers to civil monetary penales and a potenal excise tax for failing to comply with the legislaon by oﬀering a price that is not equal to or less than the negoated “maximum fair price” under the law or for taking price increases that exceed inﬂaon. The legislaon also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inﬂaon. The new law also caps Medicare out-of-pocket drug costs at an esmated $4,000 a year in 2024 and, thereaer beginning in 2025, at $2,000 a year. On June 6, 2023, Merck & Co. Inc., or Merck, ﬁled a lawsuit against HHS and CMS asserng that, among other things, the IRA’s Drug Price Negoaon Program for Medicare constutes an uncompensated taking in violaon of the Fih Amendment of the Constuon. Subsequently, a number of other pares, including the U.S. Chamber of Commerce, the Chamber, Bristol Myers Squibb Company, the PhRMA, Astellas, Novo Nordisk, Janssen Pharmaceucals, Novars, AstraZeneca and Boehringer Ingelheim, also ﬁled lawsuits in various courts with similar constuonal claims against HHS and CMS. We expect that ligaon involving these and other provisions of the IRA will connue, with unpredictable and uncertain results. Accordingly, while it is currently unclear how the IRA will be eﬀectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our acvies or result in reduced reimbursement for our products, any of which could adversely aﬀect our business, results of operaons and ﬁnancial condion. Akebia Therapeucs, Inc. | Form 10-K | Page 81 Table of Contents At the state level, individual states are increasingly aggressive in passing legislaon and implemenng regulaons designed to control pharmaceucal and biological product pricing, including price or paent reimbursement constraints, discounts, restricons on certain product access, markeng cost disclosure and transparency measures, and, in some cases, designed to encourage importaon from other countries and bulk purchasing. A number of states, for example, require drug manufacturers and other enes in the drug supply chain, including health carriers, pharmacy beneﬁt managers, wholesale distributors, to disclose informaon about pricing of pharmaceucals. In addion, regional healthcare authories and individual hospitals are increasingly using bidding procedures to determine what pharmaceucal products and which suppliers will be included in their prescripon drug and other healthcare programs. These measures could reduce the ulmate demand for our products or put pressure on our product pricing. It is likely that federal and state legislatures within the U.S. and foreign governments will connue to consider changes to exisng healthcare legislaon. We expect that addional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand for Auryxia and any product candidates for which we receive markeng approval or addional pricing pressures. We cannot predict the reform iniaves that may be adopted in the future or whether iniaves that have been adopted will be repealed or modiﬁed. The connuing eﬀorts of the government, insurance companies, managed care organizaons and other payors of healthcare services to contain or reduce costs of healthcare may adversely aﬀect: • • • • • the demand for Auryxia and any products candidates for which we receive markeng approval; our ability to set a price that we believe is fair for our products; our ability to obtain and maintain coverage and reimbursement approval for Auryxia or any other approved product; our ability to generate revenues and achieve or maintain proﬁtability; and the level of taxes that we are required to pay. In addion, in some countries, including EU Member States, the pricing of prescripon pharmaceucals is subject to governmental control. In these countries, pricing negoaons with governmental authories can take a signiﬁcant amount of me aer receipt of markeng approval for a product. In addion, there can be considerable pressure by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Polical, economic and regulatory developments may further complicate pricing negoaons, and pricing negoaons may connue aer reimbursement has been obtained. Reference pricing used by various EU Member States and parallel distribuon, or arbitrage between low-priced and high-priced EU Member States, can further reduce prices, and in certain instances render commercializaon in certain markets infeasible or disadvantageous from a ﬁnancial perspecve. In some countries, we or our collaborators may be required to conduct a clinical trial or other studies that compare the cost-eﬀecveness of our product and/or our product candidates to other available products in order to obtain or maintain reimbursement or pricing approval. Publicaon of discounts by third party payors or government authories may lead to further pressure on the prices or reimbursement levels. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsasfactory levels, the commercial launch of our product and/or product candidates could be delayed, possibly for lengthy periods of me, we or our collaborators may not launch at all in a parcular country, we may not be able to recoup our investment in one or more product candidates, and there could be a material adverse eﬀect on our business. Our reporng and payment obligaons under the Medicaid Drug Rebate Program and other governmental drug pricing programs are complex and may involve subjecve decisions. Any failure to properly comply with those obligaons could subject us to penales and sancons. As a condion of reimbursement by various federal and state health insurance programs, we are required to calculate and report certain pricing informaon to federal and state agencies. The regulaons governing the calculaons, price reporng and payment obligaons are complex and subject to interpretaon by various government and regulatory agencies, as well as the courts. Reasonable assumpons have been made where there is lack of regulaons or clear guidance and such assumpons involve subjecve decisions and esmates. We are required to report any revisions to our calculaon, price reporng and payment obligaons previously reported or paid. Such revisions could aﬀect our liability to federal and state payors and also adversely impact our reported ﬁnancial results of operaons in the period of such restatement. Further, a number of states have either implemented or are considering implementaon of drug price transparency legislaon that may prevent or limit our ability to take price increases at certain rates or frequencies. Requirements under such laws include advance noce of planned price increases, reporng price increase amounts and factors considered in taking such increases, wholesale acquision cost informaon disclosure to prescribers, purchasers, and state agencies, and new product noce and reporng. Such legislaon could limit the price or payment for certain drugs, and a number of states are authorized to impose civil monetary penales or pursue other enforcement mechanisms against manufacturers for the unmely, inaccurate, or incomplete reporng of drug pricing informaon or for otherwise failing to comply with drug price transparency Akebia Therapeucs, Inc. | Form 10-K | Page 82 Table of Contents requirements. If we are found to have violated state law requirements, we may become subject to signiﬁcant penales or other enforcement mechanisms, which could have a material adverse eﬀect on our business. Uncertainty exists as new laws, regulaons, judicial decisions, or new interpretaons of exisng laws, or regulaons related to our calculaons, price reporng or payments obligaons increases the chances of a legal challenge, restatement or invesgaon. If we become subject to invesgaons, restatements, or other inquiries concerning our compliance with price reporng laws and regulaons, we could be required to pay or be subject to addional reimbursements, penales, sancons or ﬁnes, which could have a material adverse eﬀect on our business, ﬁnancial condion and results of operaons. In addion, it is possible that future healthcare reform measures could be adopted, which could result in changes to how we calculate or report certain pricing informaon to federal and state agencies, or increased pressure on pricing and reimbursement of our products and thus have an adverse impact on our ﬁnancial posion or business operaons. Further, state Medicaid programs may be slow to invoice pharmaceucal companies for calculated rebates resulng in a lag between the me a sale is recorded and the me the rebate is paid. This results in us having to carry a liability on our consolidated balance sheets for the esmate of rebate claims expected for Medicaid paents. If actual claims are higher than current esmates, our ﬁnancial posion and results of operaons could be adversely aﬀected. In addion to retroacve rebates and the potenal for 340B Program refunds, if we are found to have knowingly submied any false price informaon related to the Medicaid Drug Rebate Program to CMS, we may be liable for civil monetary penales. Such failure could also be grounds for CMS to terminate our Medicaid drug rebate agreement, pursuant to which we parcipate in the Medicaid program. In the event that CMS terminates our rebate agreement, federal payments may not be available under government programs, including Medicaid or Medicare Part B, for our covered outpaent drugs. Addionally, if we overcharge the government in connecon with the Federal Supply Schedule pricing program or Tricare Retail Pharmacy Program, whether due to a misstated Federal Ceiling Price or otherwise, we are required to refund the diﬀerence to the government. Failure to make necessary disclosures and/or to idenfy contract overcharges can result in allegaons against us under the FDCA and other laws and regulaons. Unexpected refunds to the government, and responding to a government invesgaon or enforcement acon, would be expensive and me-consuming, and could have a material adverse eﬀect on our business, ﬁnancial condion, results of operaons and growth prospects. Our collaborators are also subject to similar requirements outside of the U.S. and thus the aendant risks and uncertaines. If our collaborators suﬀer material and adverse eﬀects from such risks and uncertaines, our rights and beneﬁts for our licensed products could be negavely impacted, which could have a material and adverse impact on our revenues. With the passage of the CREATES Act, we are exposed to possible ligaon and damages by competors who may claim that we are not providing suﬃcient quanes of our approved products on commercially reasonable, market-based terms for tesng in support of their abbreviated new drug applicaons, or ANDAs, 505(b)(2) NDAs and biosimilar product applicaons. In December 2019, former President Trump signed legislaon intended to facilitate the development of generic and biosimilar products. The bill, previously known as the CREATES Act, authorizes sponsors of ANDAs, 505(b)(2) NDAs or biosimilar product applicaons to ﬁle lawsuits against companies holding NDAs or BLAs that decline to provide suﬃcient quanes of an approved reference drug or biological product on commercially reasonable, market-based terms. Drug or biological products on FDA’s drug shortage list are exempt from these new provisions unless the product has been on the list for more than six connuous months or the FDA determines that the supply of the product will help alleviate or prevent a shortage. To bring an acon under the statute, the developer of a product candidate that seeks to develop the product and seek approval under an ANDA, 505(b)(2) NDA, or biosimilar product applicaon must take certain steps to request the reference product from the reference product manufacturer, which, in the case of products covered by a REMS with elements to assure safe use, include obtaining authorizaon from the FDA for the acquision of the reference product. If the reference product manufacturer does not provide the reference product and the ANDA, 505(b)(2) NDA, or biosimilar product sponsor does bring an acon for failure to provide a reference product, there are certain aﬃrmave defenses available to the reference product manufacturer, which must be shown by a preponderance of evidence, including that the NDA or BLA holder sells the reference product through agents, distributors, or wholesalers and has placed no restricons, explicit or implicit, on selling the reference product to ANDA, 505(b)(2) or biosimilar sponsors. If the sponsor prevails in ligaon, it is entled to a court order direcng the reference product manufacturer to provide, without delay, suﬃcient quanes of the applicable product on commercially reasonable, market-based terms, plus reasonable aorney fees and costs. Addionally, the new statutory provisions authorize a federal court to award the product developer an amount “suﬃcient to deter” the reference product manufacturer from refusing to provide suﬃcient product quanes on commercially reasonable, market-based terms, up to a certain maximum amount based on revenue earned while in noncompliance, if the court ﬁnds, by a preponderance of the evidence, that the reference product manufacturer did not have a legimate business jusﬁcaon to delay providing the product or failed to comply with the court’s order. For the purposes of the statute, the Akebia Therapeucs, Inc. | Form 10-K | Page 83 Table of Contents term “commercially reasonable, market-based terms” is deﬁned as (1) the nondiscriminatory price at or below the most recent wholesale acquision cost for the product, (2) a delivery schedule that meets the statutorily deﬁned metable, and (3) no addional condions on the sale. Although we intend to comply fully with the terms of these statutory provisions, we are sll exposed to potenal ligaon and damages by competors who may claim that we are not providing suﬃcient quanes of our approved products on commercially reasonable, market-based terms for tesng in support of ANDAs, 505(b)(2) NDA applicaons or biosimilar product applicaons. Such ligaon would subject us to addional ligaon costs, damages and reputaonal harm, which could lead to lower revenues. The CREATES Act may facilitate future compeon with Auryxia and any of our product candidates, if approved, which could impact our ability to maximize product revenue. If we fail to comply with environmental, health and safety laws and regulaons, we could become subject to ﬁnes or penales or incur costs that could harm our business. We are subject to numerous environmental, health and safety laws and regulaons, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operaons involve the use of hazardous and ﬂammable materials, including chemicals and biological materials. Our operaons also produce hazardous waste products. We generally contract with third pares for the use and disposal of these materials and wastes. We cannot eliminate the risk of contaminaon or injury from these materials. In the event of contaminaon or injury resulng from the use of hazardous materials by our employees, contractors or consultants, we could be held liable for any resulng damages, and any liability could exceed our resources. We also could incur signiﬁcant costs associated with civil or criminal ﬁnes and penales for failure to comply with such laws and regulaons. Although we maintain workers’ compensaon insurance to cover us for costs and expenses we may incur due to injuries to our employees resulng from the use of hazardous materials, this insurance may not provide adequate coverage against potenal liabilies. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connecon with our storage or disposal of biological, hazardous or radioacve materials. In addion, we may incur substanal costs in order to comply with current or future environmental, health and safety laws and regulaons. These current or future laws and regulaons may impair our research, development or producon eﬀorts. Our failure to comply with these laws and regulaons also may result in substanal ﬁnes, penales or other sancons. Risks Related to our Reliance on Third Pares We depend on collaboraons with third pares for the development and commercializaon of Auryxia, Riona, Vafseo and vadadustat and if these collaboraons are not successful or if our collaborators terminate their agreements with us, we may not be able to capitalize on the market potenal of Auryxia, Riona, Vafseo and vadadustat, and our business could be materially harmed. We sublicensed the rights to commercialize Riona to JT and Torii in Japan. We also entered into a collaboraon agreement with MTPC to develop and commercialize vadadustat in Japan and certain other Asian countries. In addion, we entered into the Vifor Agreement pursuant to which we granted CSL Vifor an exclusive license to sell vadadustat to the Supply Group in the U.S. We also granted to Averoa an exclusive license to develop and commercialize ferric citrate in the EEA, Turkey, Switzerland and the United Kingdom. Furthermore, in May 2023, we entered into a license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with chronic kidney disease in the Medice Territory. We may form or seek other strategic alliances, joint ventures, or collaboraons, or enter into addional licensing arrangements with third pares that we believe will complement or augment our and our partners' commercializaon eﬀorts with respect to Auryxia, Riona, Vafseo and our partners' development and, if approved, commercializaon eﬀorts with respect to vadadustat and any other product candidates. We may not be able to maintain our collaboraons for development and commercializaon. For example, on May 13, 2022, Otsuka Pharmaceucal Co. Ltd., or Otsuka, elected to terminate our collaboraon agreements with them, and we subsequently negoated a Terminaon and Selement Agreement with Otsuka. This terminaon by Otsuka may have delayed the launch of vadadustat in Europe or other territories previously licensed to Otsuka or adversely aﬀect how we are perceived in scienﬁc and ﬁnancial communies. For example, in August 2023, Medice informed us that their launch of Vafseo in certain countries in the Medice Territory was going to be later than previously ancipated due to the acvies required to enable the launch. If we are unable to maintain our collaboraons, we may not be able to capitalize on the market potenal of our products or product candidates, and our business could be materially harmed. In addion, our current and any future collaboraons may not be successful due to a number of important factors, including the following: • collaborators may have signiﬁcant discreon in determining the eﬀorts and resources that they will apply to these collaboraons; Akebia Therapeucs, Inc. | Form 10-K | Page 84 Table of Contents • • • • • • • • • collaboraons may be terminated in accordance with the terms of the collaboraon agreements and, if terminated, may make it diﬃcult for us to aract new collaborators or adversely aﬀect how we are perceived in scienﬁc and ﬁnancial communies, and may result in a need for addional capital and expansion of our internal capabilies to pursue further development or commercializaon of the applicable products and product candidates; if permied by the terms of the collaboraon agreements, collaborators may elect not to connue or renew development or commercializaon programs based on clinical trial results, changes in their strategic focus, availability of funding or other external factors such as a business combinaon that diverts resources or creates compeng priories; if permied by the terms of the collaboraon agreements, collaborators may delay clinical trials, provide insuﬃcient funding for a clinical trial program, stop a clinical trial, abandon a product candidate, repeat or conduct new clinical trials or require a new formulaon of a product candidate for clinical tesng; a collaborator with markeng and distribuon rights to our products may not commit suﬃcient resources to their markeng and distribuon; if permied by the terms of the collaboraon agreements, we and our collaborator may have a diﬀerence of opinion regarding the development or commercializaon strategy for a parcular product or product candidate, and our collaborator may have ulmate decision making authority; disputes may arise between a collaborator and us that cause the delay or terminaon of acvies related to research, development, supply or commercializaon of Auryxia, Riona, Vafseo or vadadustat and any other product candidate, or that result in costly ligaon or arbitraon that diverts management aenon and resources; collaboraons may not lead to development or commercializaon of products and product candidates, if approved, in the most eﬃcient manner or at all; ineﬃciencies or structural changes in internal operaons or processes of our collaborators may lead to increased expenses associated with commercializing a product, including manufacturing costs, rebates, returns and other adjustments which would negavely impact net product revenue; a signiﬁcant change in the senior management team, a change in the ﬁnancial condion or a change in the business operaons, including a change in control or internal corporate restructuring, of any of our collaborators, could result in delayed melines, re-priorizaon of our programs, decreasing resources or funding allocated to support our programs, or terminaon of the collaboraons; and • collaborators may not comply with all applicable regulatory and legal requirements. If any of these events occur, the market potenal of Auryxia, Riona, Vafseo or vadadustat, if and where approved, and any other products or product candidates, could be reduced, and our business could be materially harmed. Collaboraons may also divert resources, including the aenon of management and other employees, from other parts of our business, which could have an adverse eﬀect on other parts of our business, and we cannot be certain that the beneﬁts of the collaboraon will outweigh the potenal risks. We may seek to establish addional collaboraons and, if we are not able to establish them on commercially reasonable terms, or at all, we may have to alter our development and commercializaon plans. We may decide to enter into addional collaboraons for the development and commercializaon of Auryxia or our product candidates, including vadadustat, both within and outside of the U.S. For example, in May 2023, we entered into the license agreement with Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with chronic kidney disease in the Medice Territory. Any of these relaonships may require us to incur non-recurring and other charges, increase our near and long-term expenditures, issue securies that dilute our exisng stockholders, divert management’s aenon, or disrupt our business. We may not be successful in entering into addional collaboraons as a result of many factors, including the following: • • • • • • • compeon in seeking appropriate collaborators; a reduced number of potenal collaborators due to recent business combinaons in the pharmaceucal industry; an inability to negoate collaboraons on acceptable terms, on a mely basis or at all; any internaonal rules, regulaons, guidance, laws, risks or uncertaines with respect to potenal partners outside of the U.S.; a potenal collaborator’s evaluaon of Auryxia, vadadustat or any other product or product candidate may diﬀer substanally from ours; a potenal collaborator’s evaluaon of our ﬁnancial stability and resources; a potenal collaborator’s resources and experse; and Akebia Therapeucs, Inc. | Form 10-K | Page 85 Table of Contents • restricons due to an exisng collaboraon agreement. If we are unable to enter into addional collaboraons in a mely manner, or at all, we may have to delay or curtail the commercializaon of Auryxia or the development and potenal commercializaon of any of our product candidates, including vadadustat, if approved, reduce or delay our development programs, or increase our expenditures and undertake addional development or commercializaon acvies at our own expense. For example, following the terminaon of our collaboraon agreements with Otsuka in 2022, we incurred addional expenses in connecon with the development of vadadustat in Europe and other countries. If we elect to increase our expenditures to fund development or commercializaon acvies on our own, we may need to obtain addional capital, which may not be available to us on acceptable terms or at all. If we do not have suﬃcient funds, we may not be able to further develop or commercialize Auryxia or our other product candidates, including vadadustat, if approved. Even if we enter into addional collaboraon agreements and strategic partnerships or license our intellectual property, we may not be able to maintain them or they may be unsuccessful, which could delay our melines or otherwise adversely aﬀect our business. Royales from commercial sales of vadadustat under our MTPC Agreement will likely ﬂuctuate and will impact our rights to receive future payments under our Royalty Agreement with HCR. Pursuant to the Royalty Agreement with HCR, we sold to HCR our right to receive the Royalty Interest Payments payable to us under the MTPC Agreement, subject to the Annual Cap and the Aggregate Cap. Aer HCR receives Royalty Interest Payments equal to the Annual Cap in a given calendar year, we will receive 85% of the Royalty Interest Payments for the remainder of that year. Aer HCR receives Royalty Interest Payments equal to the Aggregate Cap, or we pay the Aggregate Cap to HCR (net of the Royalty Interest Payments already received by HCR), the Royalty Interest Payments will revert back to us, and HCR would have no further right to any Royalty Interest Payments. We received $44.8 million from HCR (net of certain transacon expenses) under the Royalty Agreement, and we were eligible to receive up to an addional $5.0 million in each year from 2021 through 2023 under the Royalty Agreement if speciﬁed sales milestones were achieved for vadadustat in the territory covered by the MTPC Agreement, subject to the sasfacon of certain customary condions, and we did not achieve such milestones. The royalty revenues under the MTPC Agreement may ﬂuctuate considerably because they depend upon, among other things, the rate of growth of sales of vadadustat in the territory covered by the MTPC Agreement. Negave ﬂuctuaons in these royalty revenues could delay, diminish or eliminate our ability to receive 85% of the Royalty Interest Payments aer the Annual Cap is achieved in a given calendar year, or our ability to receive 100% of the Royalty Interest Payments aer the Aggregate Cap is achieved. We rely upon third pares to conduct all aspects of our product manufacturing and commercial distribuon, and in many instances only have a single supplier or distributor, and the loss of these manufacturers or distributors, their failure to supply us on a mely basis, or at all, or their failure to successfully carry out their contractual dues or comply with regulatory requirements, cGMP requirements or guidance could cause delays in or disrupons to our supply chain and substanally harm our business. We do not have any manufacturing facilies and do not expect to independently manufacture any products or product candidates. We currently rely, and expect to connue to rely, on third party manufacturers to produce all of our commercial, clinical and preclinical supply. We also ulize third pares for the commercial distribuon of Auryxia, including wholesale distributors and certain specialty pharmacy providers. Our reliance on third party manufacturers, who have control over the manufacturing process, increases the risk that we will not have or be able to maintain or distribute suﬃcient quanes of Auryxia and vadadustat or the ability to obtain such quanes at an acceptable cost or quality, which could delay, prevent or impair our and our partners' development or commercializaon eﬀorts. We currently rely on a single source supplier for each of Auryxia drug substance and drug product and vadadustat drug substance and drug product, and alternate sources of supply may not be readily available. We have also engaged Cardinal Health, Inc. as the exclusive third-party logiscs distribuon agent for commercial sales of Auryxia. If any of the following occurs, we may not have suﬃcient quanes of Auryxia and/or vadadustat to support our clinical trials, development, commercializaon, or obtaining and maintaining markeng approvals, which could materially and adversely impact our business and results of operaons: • we are unsuccessful in maintaining our current supply arrangements for commercial quanes of Auryxia and vadadustat; • we are unsuccessful in validang new sites; • our commercial supply arrangements for Auryxia or vadadustat are terminated; Akebia Therapeucs, Inc. | Form 10-K | Page 86 Table of Contents • • • any of our third party manufacturers are unable to fulﬁll the terms of their agreements with us due to technical issues, natural disasters or other reasons, including with respect to quality and quanty, or are unable or unwilling to connue to manufacture on the manufacturing lines included in our regulatory ﬁlings; any of our third party manufacturers breach our supply agreements, do not comply with quality or regulatory requirements and guidance, including cGMP or are subject to regulatory review or ceases their operaons for any reason; or any of our third party distributors fail to perform or encounter any damage or other disrupon at their facilies. If we, or any of our third party manufacturers or distributors cannot or do not perform as agreed or expected, or any of our customers were to experience further shutdowns, delays or other business disrupons, including as a result of catastrophic events, including pandemics, terrorist aacks, wars or other armed conﬂicts, geopolical tensions or natural disasters, if they misappropriate our proprietary informaon, if they terminate their engagements with us, if we terminate our engagements with them, or if there is a signiﬁcant disagreement, we may be forced to manufacture or distribute the materials ourselves, for which we currently do not have the capabilies or resources, or enter into agreements with other third party manufacturers or distributors, which we may not be able to do in a mely manner or on favorable or reasonable terms, if at all. If any of these events occur, especially with respect to one of our sole source suppliers, we may not have suﬃcient quanes of product for the commercializaon of Auryxia and/or vadadustat, if approved, or may experience delays in the development of our products or product candidates, which could materially and adversely impact our business and results of operaon. For example, one of our manufacturers has noﬁed us that it will be disconnuing operaons at one site at a future date and then we will only be able to manufacture at their other site. In some cases, there may be a limited number of qualiﬁed replacement manufacturers, or the technical skills or equipment required to manufacture a product or product candidate may be unique or proprietary to the original manufacturer and we may have diﬃculty transferring such skills or technology to another third party, or a feasible alternave may not exist. These factors would increase our reliance on our current manufacturers or require us to obtain necessary regulatory approvals and licenses in order to have another third party manufacture Auryxia or vadadustat. If we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilies and procedures that comply with quality standards and with all applicable regulaons and guidelines. The delays and costs associated with the qualiﬁcaon of a new manufacturer and validaon of manufacturing processes would negavely aﬀect our ability to supply clinical trials, obtain and maintain markeng approval, or commercialize or sasfy paent demand for Auryxia and vadadustat, where approved, in a mely manner, within budget, or at all. In addion, the cost of obtaining Auryxia and vadadustat is subject to adjustment based on our third party manufacturers’ costs of obtaining raw materials and producing the product. We have limited control over the producon costs of Auryxia and vadadustat, including the costs of raw materials, and have seen increases in the producon costs of Auryxia and vadadustat, and any signiﬁcant increase in the cost of obtaining our products could materially adversely aﬀect our revenue for Auryxia and vadadustat, if approved. Moreover, issues that may arise in any scale-up and technology transfer and connued commercial scale manufacture of our products may lead to signiﬁcant delays in our development, markeng approval and commercial melines for new products or aﬀect commercial supply of Auryxia and negavely impact our ﬁnancial performance. For example, a producon-related issue resulted in an interrupon in the supply of Auryxia in the third and fourth quarters of 2016. This supply interrupon negavely impacted our revenues in 2016. This supply interrupon was resolved, and we have taken and connue to take acons designed to prevent future interrupons in the supply of Auryxia. However, we recently experienced issues in manufacturing Auryxia, and if we connue to experience manufacturing issues, or incur addional costs, or our acons to prevent future interrupons are not successful, we may experience addional supply issues. In addion, before we can manufacture product at a new site, we must validate the process at that site. If the process validaon is unsuccessful, or takes longer than we ancipate, we may have to expend addional resources and could experience a supply interrupon. Any future supply interrupons, whether quality or quanty based, for Auryxia or vadadustat, if and where approved, would negavely and materially impact our reputaon and ﬁnancial condion. There are a limited number of manufacturers that are capable of manufacturing Auryxia and vadadustat for us and complying with cGMP regulaons and guidance and other stringent regulatory requirements and guidance enforced by the FDA, EMA, PMDA and other regulatory authories. These requirements include, among other things, quality control, quality assurance and the maintenance of records and documentaon, which occur in addion to our own quality assurance releases. The facilies and processes used by our third party manufacturers to manufacture Auryxia may be inspected by the FDA and other regulatory authories at any me, and the facilies and processes used by our third party manufacturers to manufacture vadadustat will be inspected by the FDA, the EMA and other regulatory authories prior to or aer we submit our markeng applicaons. Although we have general visibility into the manufacturing processes of our third party manufacturers, we do not ulmately control such manufacturing processes of, and have lile control over, our third party manufacturers, including, without limitaon, their compliance with cGMP requirements and guidance for the manufacture of certain starng materials, Akebia Therapeucs, Inc. | Form 10-K | Page 87 Table of Contents drug substance and ﬁnished drug product. Similarly, although we review ﬁnal producon, we have lile control over the ability of our third party manufacturers to maintain adequate quality control, quality assurance and qualiﬁed personnel. Our third party manufacturers may experience problems with their manufacturing and distribuon operaons and processes, including, for example, quality issues, such as product speciﬁcaon and stability failures, procedural deviaons, improper equipment installaon or operaon, ulity failures, contaminaon, natural disasters and public health epidemics. We may also encounter diﬃcules relang to our own quality processes and procedures, including regulatory compliance, lot release, quality control and quality assurance, as well as shortages of qualiﬁed personnel. If our third party manufacturers cannot successfully manufacture material that conforms to our speciﬁcaons and regulatory requirements and guidance, or if we or our third party manufacturers experience manufacturing, operaons and/or quality issues, including an inability or unwillingness to connue manufacturing our products at all, in accordance with agreed-upon processes or on currently validated manufacturing lines, we may not be able to supply paent demand or maintain markeng approval for Auryxia, secure and maintain markeng approval for vadadustat, and we might be required to expend addional resources to obtain material from other manufacturers. If any of these events occur, our reputaon and ﬁnancial condion would be negavely and materially impacted. In addion, during the year ended December 31, 2022, we had higher write-downs to inventory reserves related to Auryxia drug substance that will not be forward processed into drug product. If we have addional write-downs to inventory reserves in the future, it could negavely impact our ability to supply Auryxia, and our ﬁnancial condion could be harmed. If the FDA or other regulatory authories do not approve the facilies being used to manufacture vadadustat, or if the EMA or other regulatory authories withdraws any approval of the facilies being used to manufacture Auryxia and/or Vafseo, we may need to ﬁnd alternave manufacturing facilies, which would signiﬁcantly impact our ability to connue commercializing Auryxia or Vafseo in Japan, or to commercialize Vafseo in Europe and other countries, or to develop, obtain markeng approval for or market vadadustat or our other product candidates, if approved. Moreover, our failure or the failure of our third party manufacturers or distributors to comply with applicable regulaons or guidance, or our failure to oversee or facilitate such compliance, could result in sancons being imposed on us or our third party manufacturers or distributors, including, where applicable, clinical holds, ﬁnes, injuncons, civil penales, delays in, suspension of or withdrawal of approvals, license revocaon, seizures or recalls of Auryxia or Vafseo in Japan, operang restricons, receipt of a Form 483 or warning leer, or criminal prosecuons, any of which could signiﬁcantly and adversely aﬀect the supply of Auryxia or vadadustat. For example, we previously conducted three limited, voluntary recalls of Auryxia. These and any other recalls or any supply, quality or manufacturing issues in the future and any related write-downs of inventory or other consequences could result in signiﬁcant negave consequences, including reputaonal harm, loss of customer conﬁdence, and a negave impact on our ﬁnancials, any of which could have a material adverse eﬀect on our business and results of operaons, and may impact our ability to supply Auryxia, Vafseo in Japan, Europe or other countries or vadadustat, if approved in other countries, for clinical and commercial use. Also, if our starng materials, drug substance or drug product are damaged or lost while in our or our third party manufacturers’ or distributors' control, it may adversely impact our ability to supply Auryxia or vadadustat, and we may incur signiﬁcant ﬁnancial harm. In addion, Auryxia, Vafseo and vadadustat may compete with other products and product candidates for access to third party manufacturing facilies. A third party manufacturer or distributor may also encounter delays or operaonal issues brought on by sudden internal resource constraints, labor disputes, shiing priories or shiing regulatory protocols. Certain of these third party manufacturing facilies may be contractually prohibited from manufacturing Auryxia, Vafseo or vadadustat due to exclusivity provisions in agreements with our competors. Any of the foregoing could negavely impact our third party manufacturers' or distributors' ability to meet our demand, which could adversely impact our ability to supply Auryxia, Vafseo or vadadustat, and we may incur signiﬁcant ﬁnancial harm. Our current and ancipated future dependence on third pares for the manufacture and distribuon of Auryxia, Vafseo and vadadustat may adversely aﬀect our and our partners' ability to commercialize Auryxia, Vafseo and vadadustat, where approved, on a mely and compeve basis and may reduce any future proﬁt margins. We rely upon third pares to conduct our clinical trials and certain of our preclinical studies. If they do not successfully carry out their contractual dues, comply with regulatory requirements or meet expected deadlines, we may not be able to obtain or maintain markeng approval for Auryxia, vadadustat or any of our product candidates, and our business could be substanally harmed. We do not have the ability to independently conduct certain preclinical studies and clinical trials. We are currently relying, and expect to connue to rely, upon third pares, such as CROs, clinical data management organizaons, medical instuons and clinical invesgators, to conduct our current and future preclinical studies and clinical trials. The third pares upon whom we rely may fail to perform eﬀecvely, or terminate their engagement with us, for a number of reasons, including the following: • • if they experience staﬃng diﬃcules; if we fail to communicate eﬀecvely or provide the appropriate level of oversight; Akebia Therapeucs, Inc. | Form 10-K | Page 88 Table of Contents • • if they undergo changes in priories or corporate structure including as a result of a merger or acquision or other transacon, or become ﬁnancially distressed; or if they form relaonships with other enes, some of which may be our competors. If the third pares upon whom we rely to conduct our trials fail to adhere to clinical trial protocols or to regulatory requirements, the quanty, quality or accuracy of the data obtained by the third pares may be compromised. We are exposed to risk of fraud or other misconduct by such third pares. Any of these events could cause our preclinical studies and clinical trials, including post-approval clinical trials, to be extended, delayed, suspended, required to be repeated or terminated, or we may receive untled warning leers or be the subject of an enforcement acon, which could result in our failing to obtain and maintain markeng approval of vadadustat or any other product candidates on a mely basis, or at all, or fail to maintain markeng approval of Auryxia, or any other products, any of which would adversely aﬀect our business operaons. In addion, if the third pares upon whom we rely fail to perform eﬀecvely or terminate their engagement with us, we may need to enter into alternave arrangements, which could delay, perhaps signiﬁcantly, the development and commercializaon of vadadustat, if approved, or any other product candidates. Even though we do not directly control the third pares upon whom we rely to conduct our preclinical studies and clinical trials and therefore cannot guarantee the sasfactory and mely performance of their obligaons to us, we are nevertheless responsible for ensuring that each of our clinical trials and preclinical studies is conducted in accordance with the applicable protocol, legal and regulatory requirements, including GxP requirements, and scienﬁc standards, and our reliance on these third pares, including CROs, will not relieve us of our regulatory responsibilies. If we or any of our CROs, their subcontractors, or clinical or preclinical trial sites fail to comply with applicable GxP requirements, the clinical data generated in our trials may be deemed unreliable or insuﬃcient, our clinical trials could be put on hold, and/or the FDA, the EMA or other regulatory authories may require us to perform addional clinical trials before approving our markeng applicaons. In addion, our clinical and preclinical trials must be conducted with drug product that meets certain speciﬁcaons and is manufactured under applicable cGMP regulaons. These requirements include, among other things, quality control, quality assurance, and the sasfactory maintenance of records and documentaon. We also rely upon third pares to store and distribute drug product for our clinical trials. For example, we use third pares to store product at various sites in the U.S. to distribute to our clinical trial sites. Any performance failure on the part of our storage or distributor partners could delay clinical development, markeng approval or commercializaon, resulng in addional costs and depriving us of potenal product revenue. If the licensor of certain intellectual property relang to Auryxia terminates, modiﬁes or threatens to terminate exisng contracts or relaonships with us, our business may be materially harmed. We do not own all of the rights to our product, Auryxia. We have licensed and sublicensed certain rights, patent and otherwise, to Auryxia from a third party, Panion, who in turn licenses certain rights to Auryxia from one of the inventors of Auryxia. The license agreement with Panion, or the Panion License Agreement, requires us to meet development milestones and imposes development and commercializaon due diligence requirements on us. In addion, under the Panion License Agreement, we must pay royales based on a mid-single digit percentage of net sales of product resulng from the licensed technologies, including Auryxia, and pay the patent ﬁling, prosecuon and maintenance costs related to the license. If we do not meet our obligaons in a mely manner, or if we otherwise breach the terms of the Panion License Agreement, Panion could terminate the agreement, and we would lose the rights to Auryxia. For example, following announcement of the Merger, Panion noﬁed us in wring that Panion would terminate the Panion License Agreement on November 21, 2018 if we did not cure the breach alleged by Panion, speciﬁcally, that we failed to use commercially reasonable best eﬀorts to commercialize Auryxia outside the U.S. We disagreed with Panion’s claims, and the pares entered discussions to resolve this dispute. On October 24, 2018, prior to the consummaon of the Merger, we and Panion entered into a leer agreement, or the Panion Leer Agreement, pursuant to which Panion agreed to rescind any and all prior terminaon threats or noces relang to the Panion License Agreement and waived its rights to terminate the license agreement based on any breach by us of our obligaon to use commercially reasonable eﬀorts to commercialize Auryxia outside the U.S. unl the pares executed an amendment to the Panion License Agreement in accordance with the terms of the Panion Leer Agreement, following consummaon of the Merger. On April 17, 2019, we and Panion entered into an amendment and restatement of the Panion License Agreement, or the Panion Amended License Agreement, which reﬂects certain revisions consistent with the terms of the Panion Leer Agreement. See Note 10, Commitments and Conngencies, to our consolidated ﬁnancial statements in Part II, Item 8. Financial Statements of this Form 10-K for addional informaon regarding the Panion Amended License Agreement. Even though we entered into the Panion Amended License Agreement, there are no assurances that Panion will not allege other breaches of the Panion Amended License Agreement or otherwise aempt to terminate the Panion Amended License Agreement in the future. In addion, if Panion breaches its agreement with the inventor from whom it licenses rights to Auryxia, Panion could lose its license, which could impair or delay our ability to develop and commercialize Auryxia. Akebia Therapeucs, Inc. | Form 10-K | Page 89 Table of Contents From me to me, we may have disagreements with Panion, or Panion may have disagreements with the inventor from whom it licenses rights to Auryxia, regarding the terms of the agreements or ownership of proprietary rights, which could impact the commercializaon of Auryxia, could require or result in ligaon or arbitraon, which would be me-consuming and expensive, could lead to the terminaon of the Panion Amended License Agreement, or force us to negoate a revised or new license agreement on terms less favorable than the original. In addion, in the event that the owners and/or licensors of the rights we license were to enter into bankruptcy or similar proceedings, we could potenally lose our rights to Auryxia or our rights could otherwise be adversely aﬀected, which could prevent us from connuing to commercialize Auryxia. Risks Related to our Intellectual Property If we are unable to adequately protect our intellectual property, third pares may be able to use our intellectual property, which could adversely aﬀect our ability to compete in the market. Our commercial success will depend in part on our ability, and the ability of our licensors, to obtain and maintain patent protecon on our drug product and technologies, and to successfully defend these patents against third party challenges. We seek to protect our proprietary products and technology by ﬁling patent applicaons in the U.S. and certain foreign jurisdicons. The process for obtaining patent protecon is expensive and me consuming, and we may not be able to ﬁle and prosecute all necessary or desirable patent applicaons in a cost eﬀecve or mely manner. In addion, we may fail to idenfy patentable subject maer early enough to obtain patent protecon. Further, license agreements with third pares may not allow us to control the preparaon, ﬁling and prosecuon of patent applicaons, or the maintenance or enforcement of patents. Such third pares may decide not to enforce such patents or enforce such patents without our involvement. Thus, these patent applicaons and patents may not, under these circumstances, be prosecuted or enforced in a manner consistent with the best interests of the company. Our pending patent applicaons may not issue as patents and may not issue in all countries in which we develop, manufacture or potenally sell our product or in countries where others develop, manufacture and potenally sell products using our technologies. Moreover, our pending patent applicaons, if issued as patents, may not provide addional protecon for our product. The patent posions of pharmaceucal and biotechnology companies can be highly uncertain and involve complex legal and factual quesons. No consistent policy regarding the breadth of claims allowed in pharmaceucal and biotechnology patents has emerged to date. Changes in the patent laws or the interpretaon of the patent laws in the U.S. and other jurisdicons may diminish the value of our patents or narrow the scope of our patent protecon. Accordingly, the patents we own or license may not be suﬃciently broad to prevent others from praccing our technologies or from developing compeng products. Furthermore, others may independently develop similar or alternave drug products or technologies or design around our patented drug product and technologies which may have an adverse eﬀect on our business. If our competors prepare and ﬁle patent applicaons in the U.S. that claim technology also claimed by us, we may have to parcipate in interference or derivaon proceedings in front of the U.S. Patent and Trademark Oﬃce, or USPTO, to determine priority of invenon, which could result in substanal cost, even if the eventual outcome is favorable to us. Because of the extensive me required for development, tesng and regulatory review of a potenal product, it is possible that any related patent may expire prior to, or remain in existence for only a short period following, commercializaon, which may signiﬁcantly diminish our ability to exclude others from commercializing products that are similar or idencal to ours. The patents we own or license may be challenged or invalidated or may fail to provide us with any compeve advantage. Since we have licensed or sublicensed many patents from third pares, we may not be able to enforce such licensed patents against third party infringers without the cooperaon of the patent owner and the licensor, which may not be forthcoming. In addion, we may not be successful or mely in obtaining any patents for which we submit applicaons. Generally, the ﬁrst to ﬁle a patent applicaon is entled to the patent if all other requirements of patentability are met. However, prior to March 16, 2013, in the U.S., the ﬁrst to invent was entled to the patent. Since publicaons of discoveries in the scienﬁc literature oen lag behind the actual discoveries, and patent applicaons in the U.S. and other jurisdicons are typically not published unl 18 months aer ﬁling, or in some cases not at all, we cannot know with certainty whether we were the ﬁrst to make the invenons claimed in our patents or pending patent applicaons, or that we were the ﬁrst to ﬁle for patent protecon of such invenons. Moreover, the laws enacted by the Leahy-Smith America Invents Act of 2011, which reformed certain patent laws in the U.S., introduce procedures that permit competors to challenge our patents in the USPTO aer grant, including inter partes review and post grant review. Similar laws exist outside of the U.S. The laws of the European Patent Convenon, for example, provide for post-grant opposion procedures that permit competors to challenge, or oppose, our European patents administravely at the European Patent Oﬃce, or EPO. We may become involved in addressing patentability objecons based on third party submission of references, or we may become involved in defending our patent rights in opposions, derivaon proceedings, reexaminaon, inter partes review, post grant review, interference proceedings or other patent oﬃce proceedings or ligaon, in the U.S. or elsewhere, challenging our patent rights or the patent rights of others. An adverse result in any such proceeding or ligaon could reduce Akebia Therapeucs, Inc. | Form 10-K | Page 90 Table of Contents the scope of, or invalidate, our patent rights, allow third pares to commercialize our technology or products and compete directly with us, without payment to us. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged on such a basis in the courts or patent oﬃces in the U.S. and abroad. As a result of such challenges, we may lose exclusivity or freedom-to-operate or patent claims may be narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to prevent third pares from using or commercializing similar or idencal products, or limit the duraon of the patent protecon for our products. Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the lifeme of the patent. The USPTO and governmental patent agencies in other jurisdicons also require compliance with a number of procedural, documentary, fee payment (such as annuies) and other similar provisions during the patent applicaon process. While an inadvertent lapse in many cases can be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situaons in which non-compliance can result in abandonment or lapse of the patent or patent applicaon, resulng in paral or complete loss of patent rights in the relevant jurisdicon. Non-compliance events that could result in abandonment or lapse of a patent or patent applicaon include, but are not limited to, failure to respond to oﬃcial acons within prescribed me limits, non-payment of fees, and failure to properly legalize and submit formal documents. In such an event, our competors might be able to enter the market sooner than we expect, which would have a material adverse eﬀect on our business. In addion, patents protecng our product candidate might expire before or shortly aer such candidate is commercialized. Thus, our patent porolio may not provide suﬃcient rights to exclude others from commercializing products similar or idencal to ours. We also rely on trade secrets and know-how to protect our intellectual property where we believe patent protecon is not appropriate or obtainable. Trade secrets are diﬃcult to protect. While we require our employees, licensees, collaborators and consultants to enter into conﬁdenality agreements, this may not be suﬃcient to adequately protect our trade secrets or other proprietary informaon. In addion, in some cases, we share certain ownership and publicaon rights to data relang to some of our products and product candidates with research collaborators, licensees and other third pares. If we cannot maintain the conﬁdenality of this informaon, our ability to receive patent protecon or protect our trade secrets or other proprietary informaon will be at risk. We may not be able to protect our intellectual property rights throughout the world. Filing, prosecung and defending patents on our products and product candidates in all countries throughout the world would be prohibively expensive. Consequently, the breadth of our intellectual property rights in some countries outside the U.S. may be less extensive than those in the U.S. In addion, the laws of some countries do not protect intellectual property rights to the same extent as laws in the U.S. As a result, we may not be able to prevent third pares from praccing our invenons in all countries outside the U.S., or from selling or imporng products made using our invenons in and into the U.S. or other countries. Competors may use our technologies in countries where we have not obtained patent protecon to develop their own products and, further, may infringe our patents in territories where we have patent protecon, but where enforcement is not as strong as in the U.S. These products may compete with our products and our patents or other intellectual property rights may not be eﬀecve or suﬃcient to prevent them from compeng. Many companies have encountered signiﬁcant problems in protecng and defending intellectual property rights in certain countries. The legal systems of certain countries, parcularly certain developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property, parcularly those relang to pharmaceucal and biotechnology products, which could make it diﬃcult for us to stop the infringement of our patents or the markeng of compeng products in violaon of our proprietary rights generally. Proceedings to enforce our patent rights in countries outside of the U.S. could result in substanal costs and divert our eﬀorts and aenon from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applicaons at risk of not issuing, and could provoke third pares to assert claims against us. We may not prevail in any lawsuits that we iniate, and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our eﬀorts to enforce our intellectual property rights around the world may be inadequate to obtain a signiﬁcant commercial advantage for our products and product candidates from the intellectual property that we develop or license. The intellectual property that we own or have licensed and related non-patent exclusivity relang to our current and future products is, and may be, limited, which could adversely aﬀect our ability to compete in the market and adversely aﬀect the value of Auryxia, vadadustat, if approved, or other future products. The patent rights and related non-patent exclusivity that we own or have licensed relang to Auryxia, vadadustat, or other future products, are, or may be limited in ways that may aﬀect our ability to exclude third pares from compeng against us. Akebia Therapeucs, Inc. | Form 10-K | Page 91 Table of Contents For example, a third party may design around our owned or licensed composion of maer patent claims or market a product for the methods of use not covered by our owned or licensed patents. Obtaining proof of direct infringement by a competor for a method of use patent requires us to demonstrate that the competors make and market a product for the patented use(s). Alternavely, we can prove that our competors induce or contribute to others in engaging in direct infringement. Proving that a competor contributes to or induces infringement of a patented method by another has addional proof requirements. For example, proving inducement of infringement requires proof of intent by the competor. If we are required to defend ourselves against claims or to protect our own proprietary rights against others, it could result in substanal costs to us and the distracon of our management. An adverse ruling in any ligaon or administrave proceeding could prevent us or our partners from markeng and selling Auryxia, Vafseo or vadadustat, if approved, or other future products, increase the risk that a generic or other similar version of Auryxia, Vafseo or vadadustat, if approved, or other future products could enter the market to compete with Auryxia, Vafseo or vadadustat, if approved, or other future products, limit our or our partners' development and commercializaon of Auryxia, Vafseo or vadadustat, if approved, or other future products, or otherwise harm our compeve posion and result in addional signiﬁcant costs. Moreover, physicians may prescribe a compeve idencal product for indicaons other than the one for which the product has been approved, or “oﬀ-label” indicaons, that are covered by the applicable patents. Although such oﬀ-label prescripons may directly infringe or contribute to or induce infringement of method of use patents, such infringement is diﬃcult to prevent. In addion, any limitaons of our patent protecon described above may adversely aﬀect the value of our drug product and may inhibit our ability to obtain a collaboraon partner at terms acceptable to us, if at all. In addion to patent rights in the U.S., we may seek non-patent exclusivity for vadadustat and other future products under other provisions of the FDCA such as new chemical enty, or NCE, exclusivity, or exclusivity for a new use or new formulaon, but there is no guarantee that vadadustat or any other future products will receive such exclusivity. The FDCA provides a ﬁve-year period of non-patent exclusivity within the U.S. to the ﬁrst sponsor to gain approval of an NDA for an NCE. A drug is an NCE if the FDA has not previously approved any other new drug containing the same acve moiety, which consists of the molecule(s) or ion(s) responsible for the acon of the drug substance (but not including those porons of the molecule that cause it to be a salt or ester or which are not bound to the molecule by covalent or similar bonds). During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submied by another company for another version of such drug where the sponsor does not own or have a legal right of reference to all the data required for approval. An ANDA that references an NDA product with NCE exclusivity may be submied aer four years if it contains a cerﬁcaon of patent invalidity or non- infringement. The FDCA also provides three years of exclusivity for an NDA, parcularly a 505(b)(2) NDA or supplement to an exisng NDA, if new clinical invesgaons, other than bioavailability studies, that were conducted or sponsored by the sponsor are deemed by the FDA to be essenal to the approval of the applicaon (for example, for new indicaons, dosages, or strengths of an exisng drug). This three-year exclusivity covers only the condions associated with the new clinical invesgaons and does not prohibit the FDA from approving ANDAs for drugs containing the original acve agent. The three-year exclusivity period, unlike ﬁve-year exclusivity, does not prevent the submission of a compeng ANDA or 505(b)(2) NDA. Instead, it only prevents the FDA from granng ﬁnal approval to such a product unl expiraon of the exclusivity period. Five-year and three-year exclusivity will not delay the submission (in the case of ﬁve-year exclusivity) or the approval (in the case of three-year exclusivity) of a full NDA submied under secon 505(b)(1) of the FDCA; however, a sponsor subming a full NDA would be required to conduct all of its own studies needed to independently support a ﬁnding of safety and eﬀecveness for the proposed product, or have a full right of reference to all studies not conducted by the sponsor. In cases where NCE exclusivity has been granted to a new drug product, the 30-month stay triggered by such ligaon is extended by the amount of me such that seven years and six months will elapse from the date of approval of the NDA for that product. Without NCE exclusivity, the 30-month stay on FDA ﬁnal approval of an ANDA runs from the date on which the sponsor of the reference listed drug receives noce of a Paragraph IV cerﬁcaon from the ANDA sponsor. In addion to NCE, in the U.S., the FDA has the authority to grant addional regulatory exclusivity protecon for approved drugs where the sponsor conducts speciﬁed tesng in pediatric or adolescent populaons. If granted, this pediatric exclusivity may provide an addional six months which are added to the term of any non-patent exclusivity that has been awarded as well as to the regulatory protecon related to the term of a relevant patent, to the extent these protecons have not already expired. We cannot assure you that Auryxia, vadadustat, if approved, or any of our potenal future products will obtain such pediatric exclusivity, NCE exclusivity or any other market exclusivity in the U.S., EU or any other territory, or that we will be the ﬁrst to receive the respecve regulatory approval for such drugs so as to be eligible for any non-patent exclusivity protecon. We Akebia Therapeucs, Inc. | Form 10-K | Page 92 Table of Contents also cannot assure you that Auryxia, vadadustat, if approved, or any of our potenal future products will obtain patent term extension. The market entry of one or more generic competors or any third party’s aempt to challenge our intellectual property rights will likely limit Auryxia sales and have an adverse impact on our business and results of operaon. Although the composion and use of Auryxia is currently claimed by 14 issued patents that are listed in the FDA’s Orange Book, we cannot assure you that we will be successful in defending against third pares aempng to invalidate or design around our patents or asserng that our patents are invalid or otherwise unenforceable or not infringed, or in compeng against third pares introducing generic equivalents of Auryxia or any of our potenal future products. If our Orange Book-listed patents are successfully challenged by a third party and a generic version of Auryxia is approved and launched sooner than we ancipate, revenue from Auryxia could decline signiﬁcantly, which would have a material adverse eﬀect on our sales, results of operaons and ﬁnancial condion. We previously received Paragraph IV cerﬁcaon noce leers regarding ANDAs submied to the FDA requesng approval for generic versions of Auryxia tablets (210 mg ferric iron per tablet). We ﬁled complaints for patent infringement relang to such ANDAs, and subsequently entered into selement and license agreements with all such ANDA ﬁlers that allow such ANDA ﬁlers to market a generic version of Auryxia in the U.S. beginning on March 20, 2025. It is possible that we may receive Paragraph IV cerﬁcaon noce leers from addional ANDA ﬁlers and may not ulmately be successful in an ANDA ligaon. Generic compeon for Auryxia or any of our potenal future products could have a material adverse eﬀect on our sales, results of operaons and ﬁnancial condion. Ligaon and administrave proceedings, including third party claims of intellectual property infringement and opposion/invalidaon proceedings against third party patents, may be costly and me consuming and may delay or harm our drug discovery, development and commercializaon eﬀorts. We may be forced to iniate ligaon to enforce our contractual and intellectual property rights, or we may be sued by third pares asserng claims based on contract, tort or intellectual property infringement. Competors may infringe our patents or misappropriate our trade secrets or conﬁdenal informaon. We may not be able to prevent infringement of our patents or misappropriaon of our trade secrets or conﬁdenal informaon, parcularly in countries where the laws may not protect those rights as fully as in the U.S. In addion, third pares may have or may obtain patents in the future and claim that our products or other technologies infringe their patents. If we are required to defend against suits brought by third pares, or if we sue third pares to protect our rights, we may be required to pay substanal ligaon costs, and our management’s aenon may be diverted from operang our business. In addion, any legal acon against our licensor, licensees or us that seeks damages or an injuncon of commercial acvies relang to Auryxia, vadadustat or any other product candidates or other technologies, including those that may be in-licensed or acquired, could subject us to monetary liability, a temporary or permanent injuncon prevenng the development, markeng and sale of such products or such technologies, and/or require our licensor, licensees or us to obtain a license to connue to develop, market or sell such products or other technologies. In addion, in an infringement proceeding, a court may decide that a patent of ours is not valid or is unenforceable, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in queson. We cannot predict whether our licensor, licensees or we would prevail in any of these types of acons or that any required license would be made available on commercially acceptable terms, if at all. Our commercial success depends in part on our avoiding infringement of the patents and proprietary rights of third pares. However, there may be patents of third pares of which we are currently unaware with claims to compounds, materials, formulaons, methods of manufacture or methods for treatment related to the use or manufacture of our product candidates. Also, because patent applicaons can take many years to issue, there may be currently pending patent applicaons which may later result in issued patents that our product candidates may infringe. The pharmaceucal and biotechnology industries are characterized by extensive ligaon over patent and other intellectual property rights. We have in the past and may in the future become a party to, or be threatened with, future adversarial ligaon or other proceedings regarding intellectual property rights with respect to our product and product candidates. As the pharmaceucal and biotechnology industries expand and more patents are issued, the risk increases that our product candidates may give rise to claims of infringement of the patent rights of others. While our product candidates are in preclinical studies and clinical trials, we believe that the use of our product candidates in these preclinical studies and clinical trials in the U.S. falls within the scope of the exempons provided by 35 U.S.C. Secon 271(e), which provides that it shall not be an act of infringement to make, use, oﬀer to sell, or sell within the U.S. or import into the U.S. a patented invenon solely for uses reasonably related to the development and submission of informaon to the FDA. There is an increased possibility of a patent infringement claim against us with respect to commercial products. Our porolio includes one commercial product, Auryxia. We received the CRL from the FDA regarding our NDA for vadadustat in March 2022, and we resubmied our NDA in September 2023. If in the future vadadustat is approved, vadadustat could be commercialized. We aempt to ensure that our products and product candidates and the methods we employ to Akebia Therapeucs, Inc. | Form 10-K | Page 93 Table of Contents manufacture them, as well as the methods for their use which we intend to promote, do not infringe other pares’ patents and other proprietary rights. There can be no assurance they do not, however, and competors or other pares may assert that we infringe their proprietary rights in any event. FibroGen has ﬁled patent applicaons in the U.S. and other countries directed to purportedly new methods of using previously known heterocyclic carboxamide compounds for purposes of treang or aﬀecng speciﬁed condions, and some of these applicaons have since issued as patents. In November 2023, we and our collaboraon partner, MTPC, entered into a Selement and Cross License Agreement, or the Selement Agreement, with FibroGen and its collaboraon partner, Astellas. The Selement Agreement resolves all patent disputes between us, MTPC, FibroGen and Astellas in the EU, the contracng states to the European Patent Convenon, the UK and Japan, or the Selement Territory. We discuss the status of the opposion and proceedings against certain FibroGen patents in Part I, Item 3. Legal Proceedings of this Form 10-K. We may in the future iniate invalidity acons or other legal proceedings with respect to FibroGen patents outside of the Selement Territory. If we are not successful in such proceedings, FibroGen could try to claim that our products infringe their patent rights. Third pares, including FibroGen, may in the future claim that our product and product candidates and other technologies infringe upon their patents and may challenge our ability to commercialize Auryxia and vadadustat, if approved. Pares making claims against us or our licensees may seek and obtain injuncve or other equitable relief, which could eﬀecvely block our or their ability to connue to commercialize Auryxia or further develop and commercialize vadadustat or any other product candidates, including those that may be in-licensed or acquired. If any third party patents were held by a court of competent jurisdicon to cover the manufacturing process of any of our products or product candidates, any molecules formed during the manufacturing process or any ﬁnal product itself, the holders of any such patents may be able to block our ability to commercialize such product or product candidate unless we obtained a license under the applicable patents, or unl such patents expire or they are ﬁnally determined to be held invalid or unenforceable. Similarly, if any third party patent were held by a court of competent jurisdicon to cover aspects of our formulaons, processes for manufacture or our intended methods of use, the holders of any such patent may be able to block or impair our ability to develop and commercialize the applicable product candidate unless we obtained a license or unl such patent expires or is ﬁnally determined to be held invalid or unenforceable. We may also elect to enter into a license in order to sele ligaon or in order to resolve disputes prior to ligaon. Furthermore, even in the absence of ligaon, we may need to obtain licenses from third pares to advance our research or allow commercializaon of our products or product candidates. Should a license to a third party patent become necessary, we cannot predict whether we would be able to obtain a license or, if a license were available, whether it would be available on commercially reasonable terms. If such a license is necessary and a license under the applicable patent is unavailable on commercially reasonable terms, or at all, our ability to commercialize our product or product candidate may be impaired or delayed, which could in turn signiﬁcantly harm our business. Further, defense of infringement claims, regardless of their merit, would involve substanal ligaon expense and would be a substanal diversion of employee resources from our business. In the event of a successful claim of infringement against us, we may have to pay substanal damages, including treble damages and aorneys’ fees for willful infringement, pay royales or redesign our products, which may be impossible or require substanal me and monetary expenditure. In addion, there may be a challenge or dispute regarding inventorship or ownership of patents or applicaons currently idenﬁed as being owned by or licensed to us. Defense of these claims, regardless of their merit, would involve substanal ligaon expense and would be a substanal diversion of employee resources from our business. Interference proceedings provoked by third pares or brought by the USPTO may be necessary to determine the priority of invenons with respect to our patents or patent applicaons. Various administrave proceedings are also available for challenging patents, including interference, reexaminaon, inter partes review, and post-grant review proceedings before the USPTO or opposions and other comparable proceedings in foreign jurisdicons. Competors may iniate an administrave proceeding challenging our issued patents or pending patent applicaons, which can be expensive and me-consuming to defend. An adverse result in any current or future defense proceedings could put one or more of our patents at risk of being invalidated, held unenforceable, or interpreted narrowly and held not infringed and could put our patent applicaons at risk of not issuing. In addion, an unfavorable outcome in any current or future proceeding in which we are challenging third party patents could require us to cease using the patented technology or to aempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not oﬀer us a license on commercially reasonable terms or at all. Even if we are successful, parcipaon in interference or other administrave proceedings before the USPTO or a foreign patent oﬃce may result in substanal costs and distract our management and other employees. We are currently involved in opposion proceedings in the European Patent Oﬃce and Indian Patent Oﬃce. These proceedings may be ongoing for a number of years and may involve substanal expense and diversion of employee resources from our business. In addion, we may become involved in addional opposion proceedings or other legal or administrave proceedings in the future. For more informaon, see the other risk factors under “Risks Related to our Intellectual Property”. Akebia Therapeucs, Inc. | Form 10-K | Page 94 Table of Contents Furthermore, because of the substanal amount of discovery required in connecon with intellectual property ligaon and some administrave proceedings, there is a risk that some of our conﬁdenal informaon could be compromised by disclosure during discovery. In addion, there could be public announcements of the results of hearings, moons or other interim proceedings or developments. If securies analysts or investors perceive these results to be negave, it could have a substanal adverse eﬀect on the price of our common stock. We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed conﬁdenal informaon of third pares. We have received conﬁdenal and proprietary informaon from potenal collaborators, prospecve licensees and other third pares. In addion, we employ individuals who were previously employed at other biotechnology or pharmaceucal companies. We may be subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed conﬁdenal informaon of these third pares or our employees’ former employers. We may also be subject to claims that former employees, collaborators or other third pares have an ownership interest in our patents or other intellectual property. We may be subject to ownership disputes in the future arising, for example, from conﬂicng obligaons of consultants or others who are involved in developing our product candidates. Ligaon may be necessary to defend against these claims. If we fail in defending any such claims, in addion to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse eﬀect on our business. Even if we are successful in defending against these claims, ligaon could result in substanal cost and be a distracon to our management and employees. Risks Related to our Business and Managing Growth If we fail to aract, retain and movate senior management and qualiﬁed personnel, we may be unable to successfully develop, obtain and/or maintain markeng approval of and commercialize vadadustat or commercialize Auryxia. Recruing and retaining qualiﬁed personnel is crical to our success. We are also highly dependent on our execuves, certain members of our senior management and certain members of our commercial organizaon. The loss of the services of our execuves, senior managers or other employees could impede the achievement of our research, development, regulatory and commercializaon objecves and seriously harm our ability to successfully implement our business strategy. Speciﬁcally, following receipt of the CRL, we implemented a reducon of our workforce in April and May 2022 by approximately 42% across all areas of our Company (47% inclusive of the closing of the majority of open posions), including several members of management. In November 2022, we also implemented a reducon of our workforce, by approximately 14% consisng of individuals within our commercial organizaon as a result of our decision to shi to a strategic account management focused model for our commercial eﬀorts. In addion, uncertainty related to the outcome of regulatory decisions, could increase arion. Losing members of management and other key personnel subjects us to a number of risks, including the failure to coordinate responsibilies and tasks, the necessity to create new management systems and processes, the impact on corporate culture, and the retenon of historical knowledge. Furthermore, replacing execuves, senior managers and other key employees may be diﬃcult and may take an extended period of me because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, obtain and/or maintain markeng approval of and commercialize Auryxia, vadadustat and other product candidates. Our future ﬁnancial performance and our ability to develop, obtain and/or maintain markeng approval of and commercialize Auryxia and vadadustat and to compete eﬀecvely will depend, in part, on our ability to manage any future growth eﬀecvely. To that end, we must be able to hire, train, integrate, and retain addional qualiﬁed personnel with suﬃcient experience. We may be unable to hire, train, retain or movate these personnel on acceptable terms given the intense compeon for our personnel from our competors and other companies throughout our industry, parcularly in our geographic region. Over the last several years, the challenges in recruing and retaining employees across the pharmaceucal and biotechnology industries have increased substanally due to current industry job market dynamics. In addion, we rely on contractors, consultants and advisors, including scienﬁc and clinical advisors, to assist us in formulang and execung our R&D and commercializaon strategy. Our contractors, consultants and advisors may become employed by companies other than ours and may have commitments with other enes that may limit their availability to us. If addional members of management or other personnel leave, or we are unable to connue to aract and retain high quality personnel, our ability to grow and pursue our business strategy will be limited. Our cost savings plan and the associated workforce reducons implemented in April, May and November 2022 may not result in ancipated savings, could result in total costs and expenses that are greater than expected and could disrupt our business. Following receipt of the CRL we implemented a reducon in workforce in April and May 2022 by approximately 42% across all areas of our Company, including several members of management. In November 2022, we also implemented a reducon of Akebia Therapeucs, Inc. | Form 10-K | Page 95 Table of Contents our workforce, by approximately 14% consisng of individuals within our commercial organizaon as a result of our decision to shi to a strategic account management focused model for our commercial eﬀorts. The reducons in workforce reﬂected our determinaon to refocus our strategic priories around our commercial product, Auryxia, and our development porolio, and were steps in a broader cost savings plan to signiﬁcantly reduce our operang expense proﬁle. We may not realize, in full or in part, the ancipated beneﬁts, savings and improvements in our cost structure from our restructuring eﬀorts due to unforeseen diﬃcules, delays or unexpected costs. We recorded a restructuring charge of approximately $0.2 million and $15.9 million in the years ended December 31, 2023 and 2022, respecvely, primarily related to contractual terminaon beneﬁts including severance, non-cash stock-based compensaon expense, healthcare and related beneﬁts. If we are unable to realize the expected operaonal eﬃciencies and cost savings from the restructuring, our operang results and ﬁnancial condion would be adversely aﬀected. We also cannot guarantee that we will not have to undertake addional workforce reducons or restructuring acvies in the future, including as a result of the FDA's decision related to our NDA resubmission for vadadustat. Furthermore, our cost savings plan may be disrupve to our operaons, including our commercializaon of Auryxia, which could aﬀect our ability to generate product revenue. In addion, our workforce reducons could yield unancipated consequences, such as arion beyond planned staﬀ reducons, or disrupons in our day-to-day operaons. Our workforce reducons could also harm our ability to aract and retain qualiﬁed management, scienﬁc, clinical, manufacturing and sales and markeng personnel who are crical to our business. Any failure to aract or retain qualiﬁed personnel could prevent us from successfully commercializing Auryxia and from successfully developing and commercializing our product candidates in the future, including vadadustat, if approved. If we are ulmately successful in obtaining approval of vadadustat in the U.S., we will need to hire addional employees to support the commercializaon of vadadustat in the U.S., and if we are unsuccessful or delayed in doing so, the potenal launch of vadadustat could be delayed. We may encounter diﬃcules in managing our growth, including with respect to our employee base, and managing our partnerships and operaons successfully. In our day-to-day operaons, we may encounter diﬃcules in managing the size of our operaons as well as challenges associated with managing our business. We have strategic collaboraons for the commercializaon of Riona and the development and commercializaon of vadadustat, which is now being or will be marketed under the trade name Vafseo by our collaboraon partner, MTPC, in Japan and our collaboraon partner, Medice, in the Medice Territory. Addionally, in the U.S., we have a strategic relaonship with CSL Vifor related to the commercializaon of vadadustat, if approved. As our operaons connue, we expect that we will need to manage our current relaonships and enter into new relaonships with various strategic collaborators, consultants, vendors, suppliers and other third pares. These relaonships are complex and create numerous risks as we deal with issues that arise. For example, we supply or have agreed to supply, as applicable, Auryxia in Europe, Vafseo in Japan, Europe and other territories where it is approved, and vadadustat in the U.S., if approved, for commercial and clinical use to MTPC, Medice, Averoa and CSL Vifor, which will require us to successfully manage our limited ﬁnancial and managerial resources. In addion, we may not be able to obtain the raw materials or product that we need, or the cost of the raw materials or product may be higher than expected. If we are unable to successfully manage our supply obligaons, our ability to commercialize our products or supply such products to our partners could have a material adverse eﬀect on our relaonships with our partners and our results of operaons. Our future ﬁnancial performance and our ability to commercialize Auryxia and vadadustat, if and where approved, and to compete eﬀecvely will depend, in part, on our ability to manage any future growth eﬀecvely. This future growth will impose signiﬁcant added responsibilies on the business and members of management. To manage any future growth, we must connue to implement and improve our managerial, operaonal and ﬁnancial systems, procedures and processes. We may not be able to implement these improvements in an eﬃcient or mely manner and may discover deﬁciencies in exisng systems, procedures and processes. Moreover, the systems, procedures and processes currently in place or to be implemented may not be adequate for any such growth. Any expansion of our operaons may lead to signiﬁcant costs and may divert our management and business development resources. Any inability to manage growth could delay the execuon of our business plans or disrupt our operaons. We may not be able to accomplish these tasks, and our failure to accomplish any of them could prevent us from successfully managing and, as applicable, growing our Company. In addion, we may need to further adjust the size of our workforce as a result of changes to our expectaons for our business, which can result in management being required to divert a disproporonate amount of its aenon away from our day-to-day acvies and devote a substanal amount of me to managing these growth-related acvies and related expenses. Further, we rely on independent third pares to provide certain services to us. We structure our relaonships with these outside service providers in a manner that we believe results in an independent contractor relaonship, not an employee relaonship. If any of our service providers are later legally deemed to be employees, we could be subject to employment and tax withholding liabilies and other addional costs as well as other mulple damages and aorneys’ fees. We have idenﬁed a material weakness in our internal control over ﬁnancial reporng as of December 31, 2023 relang to our accounng for inventory and inventory related transacons. If we are not able to remediate this material weakness, or Akebia Therapeucs, Inc. | Form 10-K | Page 96 Table of Contents if we experience addional material weaknesses or other deﬁciencies in our internal control over ﬁnancial reporng in the future or otherwise fail to maintain an eﬀecve system of internal control over ﬁnancial reporng, we may not be able to accurately or mely report our ﬁnancial results or prevent fraud, and we may conclude that our internal control over ﬁnancial reporng is not eﬀecve, which may adversely aﬀect our business. Eﬀecve internal control over ﬁnancial reporng is necessary for us to provide reliable ﬁnancial reports and, together with adequate disclosure controls and procedures, is designed to prevent fraud. Any failure to maintain or implement required new or improved controls, or diﬃcules encountered in implementaon could cause us to fail to meet our reporng obligaons. In addion, any tesng by us, as and when required, conducted in connecon with Secon 404 of the Sarbanes-Oxley Act, or Secon 404, or any tesng by our independent registered public accounng ﬁrm may reveal deﬁciencies in our internal control over ﬁnancial reporng that are deemed to be material weaknesses or that may require prospecve or retroacve changes to our consolidated ﬁnancial statements or idenfy other areas for further aenon or improvement. We idenﬁed a material weakness in our internal control over ﬁnancial reporng as of December 31, 2023. A material weakness is a deﬁciency, or combinaon of deﬁciencies, in internal control over ﬁnancial reporng, such that there is a reasonable possibility that a material misstatement of our annual or interim consolidated ﬁnancial statements will not be prevented or detected on a mely basis. Speciﬁcally, our management concluded that we did not design and maintain eﬀecve controls over the completeness and accuracy of accounng for inventory and inventory related transacons, including inventory reconciliaons, calculaon of overheads, presentaon of inventory in our balance sheet between short-term and long-term and our liabilies related to the calculaon of ﬁrm purchase commitments. For further discussion of the material weakness, see Part II, Item 9A, “Controls and Procedures.” We have taken certain steps and plan to take addional steps to remediate this material weakness, including (i) implemenng and documenng new processes and controls to help ensure the completeness and accuracy of our inventory reconciliaons, (ii) engaging addional third party subject maer experts and accounng personnel with U.S. GAAP experience speciﬁc to inventory accounng, (iii) enhancing the accuracy of key reports used to calculate the ﬁrm purchase commitment and (iv) establishing eﬀecve monitoring and oversight controls to help to ensure the completeness and accuracy of inventory included in our ﬁnancial statements and related disclosures. However, we cannot provide assurance that we will be able to correct this material weakness in a mely manner or that our remediaon eﬀorts will be adequate to allow us to conclude that our internal control over ﬁnancial reporng will be eﬀecve in the future. Even if this material weakness is remediated in the future, we could idenfy addional material weaknesses or deﬁciencies in our internal control over ﬁnancial reporng that could require correcon or remediaon. For example, we previously idenﬁed a material weakness in our internal control over ﬁnancial reporng as of December 31, 2022 relang to our product return reserves that resulted in a revision of our ﬁnancial statements for the years ended December 31, 2022, 2021 and 2020. In addion, our conclusion that we have a material weakness could give rise to increased scruny, review, audit and invesgaon over our accounng controls and procedures, which could then lead to addional areas of deﬁciency or errors in our ﬁnancial statements. We will need to connue to dedicate internal resources, engage outside consultants and maintain a detailed work plan to assess and document the adequacy of internal control over ﬁnancial reporng, connue steps to remediate the material weakness relang to our accounng for inventory and inventory related transacons described above and any future control deﬁciencies or material weaknesses, and improve control processes as appropriate, validate through tesng that controls are funconing as documented and maintain a connuous reporng and improvement process for internal control over ﬁnancial reporng. If we are not able to correct material weaknesses or deﬁciencies in internal controls in a mely manner or otherwise comply with the requirements of Secon 404 in a mely manner, our ability to record, process, summarize and report ﬁnancial informaon accurately and within applicable me periods may be adversely aﬀected, and we could be subject to sancons or invesgaons by the SEC, the Nasdaq Stock Market or other regulatory authories as well as stockholder ligaon which, even if resolved in our favor, would require addional ﬁnancial and management resources and could adversely aﬀect the market price of our common stock. Any failure to maintain or implement required eﬀecve internal control over ﬁnancial reporng, or any diﬃcules we encounter in their implementaon, could result in addional material weaknesses, cause us to fail to meet our reporng obligaons or result in material misstatements in our ﬁnancial statements. Furthermore, if we cannot provide reliable ﬁnancial reports or prevent fraud, our business and results of operaons could be harmed. Inferior internal controls could also cause investors to lose conﬁdence in our reported ﬁnancial informaon, which could have a negave eﬀect on the trading price of our common stock and could also aﬀect our ability to raise capital to fund future business iniaves. Security breaches and unauthorized use of our informaon technology systems and informaon, or the informaon technology systems or informaon in the possession of our collaborators and other third pares, could damage the integrity of our clinical trials, impact our regulatory ﬁlings, compromise our ability to protect our intellectual property, and subject us to regulatory acons that could result in signiﬁcant ﬁnes or other penales. Akebia Therapeucs, Inc. | Form 10-K | Page 97 Table of Contents We, our collaborators, contractors and other third pares rely signiﬁcantly upon informaon technology, and any failure, inadequacy, interrupon or security lapse of that technology, including any cybersecurity incidents, could harm our ability to operate our business eﬀecvely. In addion, we and our collaborators, contractors and other third pares rely on informaon technology networks and systems, including the Internet and arﬁcial intelligence based soware, to process, transmit and store clinical trial data, paent informaon, and other electronic informaon, and manage or support a variety of business processes, including operaonal and ﬁnancial transacons and records, personal idenfying informaon, payroll data and workforce scheduling informaon. We purchase most of our informaon technology from vendors, on whom our systems depend. We rely on commercially available systems, soware, tools and monitoring to provide security for the processing, transmission and storage of company and customer informaon. In the ordinary course of our business, we and our third party contractors maintain personal and other sensive data on our and their respecve networks, including our intellectual property and proprietary or conﬁdenal business informaon relang to our business and that of our clinical trial paents and business partners. In parcular, we rely on CROs and other third pares to store and manage informaon from our clinical trials. We also rely on third pares to manage paent informaon for Auryxia. Addionally, the use of arﬁcial intelligence based soware is increasingly being used in the biopharmaceucal industry. Use of arﬁcial intelligence based soware may lead to the release of conﬁdenal proprietary informaon, which may impact our ability to realize the beneﬁt of our intellectual property. The secure maintenance of this sensive informaon is crical to our business and reputaon. Companies and other enes and individuals have been increasingly subject to a wide variety of security incidents, cyber-aacks and other aempts to gain unauthorized access to systems and informaon. These threats can come from a variety of sources, ranging in sophiscaon from individual hackers to state- sponsored aacks. Aackers have used arﬁcial intelligence and machine learning to launch more automated, targeted and coordinated aacks against targets. Cyber threats may be broadly targeted, or they may be custom-craed against our informaon systems or those of our vendors or third party service providers. A security breach, cyberaack or unauthorized access of our clinical data or other data could damage the integrity of our clinical trials, impact our regulatory ﬁlings, cause signiﬁcant risk to our business, compromise our ability to protect our intellectual property, and subject us to regulatory acons, including under the GDPR and CCPA discussed elsewhere in these risk factors and the privacy or security rules under federal, state, or other local laws outside of the U.S. protecng conﬁdenal or personal informaon, that could be expensive to defend and could result in signiﬁcant ﬁnes or other penales. Cyberaacks can include malware, computer viruses, hacking, social engineering, zero day vulnerabilies or other unauthorized access or other signiﬁcant compromise of our computer, communicaons and related systems. Although we take steps to manage and avoid these risks and to be prepared to respond to aacks, our prevenve and any remedial acons may not be successful and no such measures can eliminate the possibility of the systems’ improper funconing or the improper access or disclosure of conﬁdenal or personally idenﬁable informaon such as in the event of cyberaacks. Security breaches, whether through physical or electronic break-ins, computer viruses, ransomware, impersonaon of authorized users, aacks by hackers or other means, can create system disrupons or shutdowns or the unauthorized disclosure of conﬁdenal informaon. Although we believe our collaborators, vendors and service providers, such as our CROs, take steps to manage and avoid informaon security risks and respond to aacks, we may be adversely aﬀected by aacks against our collaborators, vendors or service providers, and we may not have adequate contractual remedies against such collaborators, vendors and service providers to remedy any harm to our business caused by such event. Addionally, outside pares may aempt to fraudulently induce employees, collaborators, or other contractors to disclose sensive informaon or take other acons, including making fraudulent payments or downloading malware, by using “spooﬁng” and “phishing” emails or other types of aacks. Our employees may be targeted by such fraudulent acvies. Outside pares may also subject us to distributed denial of services aacks or introduce viruses or other malware through “trojan horse” programs to our users’ computers in order to gain access to our systems and the data stored therein. Cyber-aacks have become more prevalent and much harder to detect and defend against. Because the techniques used to obtain unauthorized access, disable or degrade service, or sabotage systems change frequently and connuously become more sophiscated, including the use of arﬁcial intelligence to generate sophiscated spoofed emails and deep fake voice and video, oen are not recognized unl launched against a target and may be diﬃcult to detect for a long me, we may be unable to ancipate these techniques or to implement adequate prevenve or detecve measures, and we might not immediately detect such incidents and the damage caused by such incidents. Such aacks, whether successful or unsuccessful, or other compromises with respect to our informaon security and the measures we implement to prevent, detect and respond to them, could: • • result in our incurring signiﬁcant costs related to, for example, rebuilding internal systems, defending against ligaon, responding to regulatory inquiries or acons, paying damages or ﬁnes, or taking other remedial steps with respect to third pares; lead to public exposure of personal informaon of parcipants in our clinical trials, Auryxia paents and others; Akebia Therapeucs, Inc. | Form 10-K | Page 98 Table of Contents • • • • damage the integrity of our studies or delay their compleon, disrupt our development programs, our business operaons and commercializaon eﬀorts; compromise our ability to protect our trade secrets and proprietary informaon; damage our reputaon and deter business partners from working with us; or divert the aenon of our management and key informaon technology resources. Any failure to maintain proper funconality and security of our internal computer and informaon systems could result in a loss of, or damage to, our data or markeng applicaons or inappropriate disclosure of conﬁdenal or proprietary informaon, interrupt our operaons, damage our reputaon, subject us to liability claims or regulatory penales, under a variety of federal, state or other applicable privacy laws, such as HIPAA, the GDPR, or state data protecon laws including the CCPA, harm our compeve posion and delay the further development and commercializaon of our products and product candidates, or impact our relaonships with customers and paents. Our employees, independent contractors, principal invesgators, CROs, CMOs, consultants and vendors may engage in misconduct or other improper acvies, including non-compliance with regulatory standards and requirements and insider trading. In addion, laws and regulaons governing any internaonal operaons we have or may have in the future may require us to develop and implement costly compliance programs. We are exposed to the risk that our employees, independent contractors, principal invesgators, CROs, CMOs, consultants and vendors may engage in fraudulent conduct or other illegal acvity. Misconduct by these pares could include intenonal, reckless and/or negligent conduct or unauthorized acvies that violate applicable laws, including the following: • • • • • FDA and other healthcare authories’ regulaons, including those laws that require the reporng of true, complete and accurate informaon to regulatory authories, and those prohibing the promoon of unapproved drugs or approved drugs for an unapproved use; quality standards, including GxP; federal and state healthcare fraud and abuse laws and regulaons and their non-U.S. equivalents; an-bribery and an-corrupon laws, such as the FCPA and the UK Bribery Act or country-speciﬁc an-bribery or an-corrupon laws, as well as various import and export laws and regulaons; laws that require the reporng of true and accurate ﬁnancial informaon and data; and • U.S. state and federal securies laws and regulaons and their non-U.S. equivalents, including those related to insider trading. We hold a markeng authorizaon for vadadustat from the MHRA and TGA, and we conducted our global clinical trials for vadadustat, and may in the future conduct addional trials, in countries where corrupon is prevalent, and violaons of any of these laws by our personnel or by any of our vendors or agents, such as our CROs or CMOs, could have a material adverse impact on our clinical trials and our business and could result in criminal or civil ﬁnes and sancons. We are subject to complex laws that govern our internaonal business pracces. These laws include the FCPA, which prohibits U.S. companies and their intermediaries, such as CROs or CMOs, from making improper payments to foreign government oﬃcials for the purpose of obtaining or keeping business or obtaining any kind of advantage for the company. The FCPA also requires companies to keep accurate books and records and maintain adequate accounng controls. A number of past and recent FCPA invesgaons by the Department of Jusce and the SEC have focused on the life sciences sector. Compliance with the FCPA is expensive and diﬃcult, parcularly in countries in which corrupon is a recognized problem. Some of the countries in which we have conducted clinical trials and in which we have CMOs have a history of corrupon, which increases our risks of FCPA violaons. In addion, the FCPA presents unique challenges in the pharmaceucal industry because in many countries’ hospitals are operated by the government, and doctors and other hospital employees are considered foreign government oﬃcials. Certain payments made by pharmaceucal companies, or on their behalf by CROs, to hospitals in connecon with clinical trials and other work have been deemed to be improper payments to government oﬃcials and have led to FCPA enforcement acons. Addionally, the UK Bribery Act applies to our global acvies and prohibits bribery of private individuals as well as public oﬃcials. The UK Bribery Act prohibits both the oﬀering and accepng of a bribe and imposes strict liability on companies for failing to prevent bribery, unless the company can show that it had “adequate procedures” in place to prevent bribery. There are also local an-bribery and an-corrupon laws in countries where we have conducted clinical trials, and many of these also carry the risk of signiﬁcant ﬁnancial or criminal penales. We are also subject to trade control regulaons and trade sancon laws that restrict the movement of certain goods, currency, products, materials, services and technology to, and certain operaons in, various countries or with certain persons. Our ability to transfer commercial and clinical product and other clinical trial supplies, and for our employees, independent Akebia Therapeucs, Inc. | Form 10-K | Page 99 Table of Contents contractors, principal invesgators, CROs, CMOs, consultants and vendors ability to travel, between certain countries is subject to maintaining required licenses and complying with these laws and regulaons. Employee misconduct could also involve the improper use of informaon obtained in the course of clinical trials, which could result in regulatory sancons and serious harm to our reputaon. This could include violaons of HIPAA, other U.S. federal and state laws, and requirements of non-U.S. jurisdicons, including the GDPR. We are also exposed to risks in connecon with any insider trading violaons by employees or others aﬃliated with us. The internal controls, policies and procedures, and training and compliance programs we have implemented to deter prohibited pracces may not be eﬀecve in prevenng our employees, contractors, consultants, agents or other representaves from violang or circumvenng such internal policies or violang applicable laws and regulaons. The failure to comply with laws governing internaonal business pracces may impact any future clinical trials, result in substanal civil or criminal penales for us and any such individuals, including imprisonment, suspension or debarment from government contracng, withdrawal of our products, if approved, from the market, or being delisted from The Nasdaq Capital Market. In addion, we may incur signiﬁcant costs in implemenng suﬃcient systems, controls and processes to ensure compliance with the aforemenoned laws. The laws and regulaons referenced above may restrict or prohibit a wide range of pricing, discounng, markeng and promoon, sales commission, customer incenve programs and other business arrangements that could adversely aﬀect our business. Addionally, it is not always possible to idenfy and deter misconduct by employees and third pares, and the precauons we take to detect and prevent this acvity may not be eﬀecve in controlling known or unknown risks or prevenng losses or in protecng us from governmental invesgaons or other acons or lawsuits stemming from a failure to be in compliance with such laws or regulaons. If any such acons are instuted against us, and we are not successful in defending ourselves or asserng our rights, or if any such acon is instuted against our employees, consultants, independent contractors, CROs, CMOs, vendors or principal invesgators, those acons could have a signiﬁcant impact on our business, including the imposion of civil, criminal and administrave penales, damages, monetary ﬁnes, possible exclusion from parcipaon in Medicare, Medicaid and other federal healthcare programs, contractual damages, reputaonal harm, diminished proﬁts and future earnings, curtailment of our operaons, disclosure of our conﬁdenal informaon and imprisonment, any of which could adversely aﬀect our ability to operate our business and our results of operaons. Our ﬁnancial statements include long-lived assets, including goodwill and an intangible asset as a result of the Merger. The intangible asset has become impaired and could become further impaired in the future under certain condions. In addion, other long lived assets, including property and equipment, right-of-use assets or goodwill could become impaired in the future under certain condions. Any potenal future impairment of property and equipment, our right-of-use assets, goodwill or intangible asset may signiﬁcantly impact our results of operaons and ﬁnancial condion. As of December 31, 2023, we had approximately $95.1 million in the aggregate of goodwill and a deﬁnite lived intangible asset from the Merger, $3.6 million of property and equipment and $12.4 million right-of-use assets. In accordance with ASC 350, Goodwill and Other, we are required annually for goodwill, or more frequently upon certain indicators of impairment, to review our esmates and assumpons underlying the fair value of our goodwill and intangible asset. In addion, under ASC 360, Property, Plant and Equipment, we are required to review our property and equipment and right-of-use assets whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable. Events giving rise to impairment of long-lived assets are an inherent risk in the pharmaceucal industry and oen cannot be predicted. Condions that could indicate impairment and necessitate such a review include, but are not limited to, Auryxia’s commercial performance, our inability to execute on our strategic iniaves, the deterioraon of our market capitalizaon such that it is signiﬁcantly below our net book value, a signiﬁcant adverse change in legal factors, unexpected adverse business condions, and an adverse acon or assessment by a regulator. To the extent we conclude our long-lived assets have become impaired, we may be required to incur material write-oﬀs relang to such impairment and any such write-oﬀs could have a material impact on our future operang results and ﬁnancial posion. The esmates, judgments and assumpons used in our impairment analyses, and the results of our analyses, are discussed in Note 2, Summary of Signiﬁcant Accounng Policies, to our consolidated ﬁnancial statements in Part II, Item 8. Financial Statements and Supplementary Data of this Form 10-K. If these esmates, judgments and assumpons change in the future, including if the Auryxia asset group does not meet its current forecasted projecons, addional impairment charges related to plant and equipment, right-of-use assets, goodwill or our intangible asset could be recorded in the future and addional corresponding adjustments may need to be made to the esmated useful life of the developed product rights for Auryxia, which could materially impact our ﬁnancial posion, certain of our material agreements, and our future operang results. If product liability lawsuits are brought against us, we may incur substanal liabilies and may be required to limit commercializaon of Auryxia or vadadustat, if approved. We face an inherent risk of product liability as a result of the clinical and commercial use of Auryxia and vadadustat. For example, we may be sued if Auryxia or vadadustat allegedly causes injury or is found to be otherwise unsuitable during clinical Akebia Therapeucs, Inc. | Form 10-K | Page 100 Table of Contents trials, manufacturing, markeng or sale. Any such product liability claims may include allegaons of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product or product candidate, negligence, strict liability and breach of warranes. Claims could also be asserted under state consumer protecon acts. If we cannot successfully defend ourselves against product liability claims, we may incur substanal liabilies or be required to limit commercializaon of Auryxia or vadadustat, if approved. Even a successful defense would require signiﬁcant ﬁnancial and management resources. Regardless of the merits or eventual outcome, product liability claims may result in: • • decreased demand for Auryxia or vadadustat, if approved; injury to our reputaon and signiﬁcant negave media aenon; • withdrawal of clinical trial parcipants; • • • • • • • • • • delay or terminaon of clinical trials; our inability to connue to develop Auryxia or vadadustat; signiﬁcant costs to defend the related ligaon; a diversion of management’s me and our resources; substanal monetary awards to study subjects or paents; product recalls or withdrawals, or labeling, markeng or promoonal restricons; decreased demand for Auryxia or vadadustat, if approved; loss of revenue; the inability to commercialize Auryxia or vadadustat, if approved; and a decline in our stock price. Failure to obtain and retain suﬃcient product liability insurance at an acceptable cost to protect against potenal product liability claims could prevent or inhibit the commercializaon of products we develop. We currently carry product liability insurance that we believe is appropriate for our Company. Although we maintain product liability insurance, any claim that may be brought against us could result in a court judgment or selement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance policies also have various exclusions, and we may be subject to a product liability claim for which we have insuﬃcient or no coverage. If we have to pay any amounts awarded by a court or negoated in a selement that exceed our coverage limitaons or that are not covered by our insurance, we may not have, or be able to obtain, suﬃcient capital to pay such amounts. In addion, insurance coverage is becoming increasingly expensive, and we may not be able to maintain insurance coverage at a reasonable cost. We also may not be able to obtain addional insurance coverage that will be adequate to cover addional product liability risks that may arise. Consequently, a product liability claim may result in losses that could be material to our business. We will connue to incur increased costs as a result of operang as a public company, and our management will be required to devote substanal me to compliance iniaves and corporate governance pracces. As a public company, we operate in a demanding regulatory environment, and we have and will connue to incur signiﬁcant legal, accounng, auding and other expenses. The Sarbanes-Oxley Act of 2002, or the Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protecon Act, the lisng requirements of The Nasdaq Capital Market and other applicable securies rules and regulaons impose various requirements on public companies, including establishment and maintenance of eﬀecve disclosure and ﬁnancial controls and certain corporate governance pracces. In parcular, our compliance with Secon 404 of the Sarbanes-Oxley Act has required and will connue to require that we incur substanal accounng-related expenses and expend signiﬁcant management eﬀorts. Our tesng, or the tesng by our independent registered public accounng ﬁrm, may reveal deﬁciencies in our internal controls that we would be required to remediate in a mely manner. If we are not able to comply with the requirements of the Sarbanes-Oxley Act, we could be subject to sancons or invesgaons by the SEC, the Nasdaq Capital Market or other regulatory authories, which would require addional ﬁnancial and management resources and could adversely aﬀect the market price of our securies. Furthermore, if we cannot provide reliable ﬁnancial reports or prevent fraud, including as a result of remote working by our employees, our business and results of operaons would likely be materially and adversely aﬀected. We cannot predict or esmate the amount of addional costs we may incur to connue to operate as a public company, nor can we predict the ming of such costs. These rules and regulaons are oen subject to varying interpretaons, in many cases due to their lack of speciﬁcity and, as a result, their applicaon in pracce may evolve over me as new guidance is provided by regulatory and governing bodies, which could result in connuing uncertainty regarding compliance maers and higher costs necessitated by ongoing revisions to disclosure and governance pracces. Akebia Therapeucs, Inc. | Form 10-K | Page 101 Table of Contents Claims for indemniﬁcaon by our directors and oﬃcers may reduce our available funds to sasfy successful third-party claims against us and may reduce the amount of money available to us. Our Ninth Amended and Restated Cerﬁcate of Incorporaon, as amended, or Charter, and our Second Amended and Restated Bylaws, or Bylaws, as amended to date, contain provisions that eliminate, to the maximum extent permied by the General Corporaon Law of the State of Delaware, or DGCL, the personal liability of our directors and execuve oﬃcers for monetary damages for breach of their ﬁduciary dues as a director or oﬃcer. Our Charter and our Bylaws also provide that we will indemnify our directors and execuve oﬃcers and may indemnify our employees and other agents to the fullest extent permied by the DGCL. In addion, as permied by Secon 145 of the DGCL our Bylaws and our indemniﬁcaon agreements that we have entered into with our directors and execuve oﬃcers provide that: • We will indemnify our directors and oﬃcers, as deﬁned in our Bylaws, for serving us in those capacies or for serving other related business enterprises at our request, to the fullest extent permied by Delaware law. Delaware law provides that a corporaon may indemnify such person if such person acted in good faith and in a manner such person reasonably believed to be in or not opposed to the best interests of Akebia and, with respect to any criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful. • We may, in our discreon, indemnify employees and agents in those circumstances where indemniﬁcaon is permied by applicable law. • We are required to advance expenses, as incurred, to our directors and oﬃcers in connecon with defending a proceeding, except that such directors or oﬃcers shall undertake to repay such advances if it is ulmately determined that such person is not entled to indemniﬁcaon. • The rights conferred in our Bylaws are not exclusive, and we are authorized to enter into indemniﬁcaon agreements with our directors, oﬃcers, employees and agents and to obtain insurance to indemnify such persons. Any claims for indemniﬁcaon made by our directors or oﬃcers could impact our cash resources and our ability to fund the business. Our ability to use net operang losses to oﬀset future taxable income may be subject to certain limitaons. Under Secon 382 of the Internal Revenue Code, or Secon 382, a corporaon that undergoes an “ownership change” is subject to limitaons on its ability to ulize its pre-change net operang losses, or NOLs, to oﬀset future taxable income. On December 12, 2018, we completed the Merger, which we believe has resulted in an ownership change under Secon 382. In addion, the Tax Cuts and Jobs Act, including amendments made by the CARES Act, includes changes to U.S. federal tax rates and the rules governing net operang loss carryforwards that may signiﬁcantly impact our ability to ulize our net operang losses to fully oﬀset taxable income in the future. Future changes in our stock ownership, many of which are outside of our control, could result in an addional ownership change under Secon 382. As a result, if we generate taxable income, our ability to use our pre-change NOL carryforwards to oﬀset federal taxable income may be subject to limitaons, which could potenally result in increased future tax liability to us. At the state level, state net operang losses generated in one state cannot be used to oﬀset income generated in another state and there may be periods during which the use of NOL carryforwards is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed. Furthermore, our ability to ulize our NOLs is condioned upon our aaining proﬁtability and generang U.S. taxable income. As described above under “— Risks Related to our Financial Posion, Need for Addional Capital and Growth Strategy,” we have incurred signiﬁcant net losses since our incepon and ancipate that we will connue to incur losses for the foreseeable future; thus, we do not know whether or when we will generate the U.S. taxable income necessary to ulize our NOLs. Our Charter designates the Court of Chancery of the State of Delaware as the sole and exclusive forum for certain types of acons and proceedings that may be iniated by our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, oﬃcers or employees. Our Charter provides that, subject to limited excepons, the Court of Chancery of the State of Delaware will be the sole and exclusive forum for (i) any derivave acon or proceeding brought on our behalf, (ii) any acon asserng a claim of breach of a ﬁduciary duty owed by any of our directors, oﬃcers or other employees to us or our stockholders, (iii) any acon asserng a claim against us arising pursuant to any provision of the DGCL our Charter or our Bylaws, or (iv) any other acon asserng a claim against us, our directors, oﬃcers or other employees that is governed by the internal aﬀairs doctrine. Under our Charter, this exclusive forum provision will not apply to claims that are vested in the exclusive jurisdicon of a court or forum other than the Court of Chancery of the State of Delaware, or for which the Court of Chancery of the State of Delaware does not have subject maer jurisdicon. For instance, the provision would not apply to acons arising under federal securies laws, including suits brought to enforce any liability or duty created by the Securies Exchange Act of 1934, as amended, or the Exchange Act, or the rules and regulaons thereunder. Any person or enty purchasing or otherwise acquiring any Akebia Therapeucs, Inc. | Form 10-K | Page 102 Table of Contents interest in shares of our capital stock shall be deemed to have noce of and to have consented to the provisions of our Charter described above. This choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it ﬁnds favorable for disputes with us or our directors, oﬃcers or other employees, which may discourage such lawsuits against us and our directors, oﬃcers and employees. Alternavely, if a court were to ﬁnd these provisions of our Charter inapplicable to, or unenforceable with respect to, one or more of the speciﬁed types of acons or proceedings, we may incur addional costs associated with resolving such maers in other jurisdicons, which could adversely aﬀect our business and ﬁnancial condion. We are currently subject to legal proceedings that could result in substanal costs and divert management's aenon, and we could be subject to addional legal proceedings. We are currently subject to legal proceedings, including those described in Part I, Item 3. Legal Proceedings in this Form 10-K, and addional claims may arise in the future. In addion, securies class acon and derivave lawsuits and other legal proceedings are oen brought against companies for any of the risks described in this Form 10-K following a decline in the market price of their securies. For example, we were party to a putave class acon lawsuit in state court ﬁled by purported Keryx stockholders challenging the disclosures made in connecon with the Merger, including those that relate to vadadustat’s safety, approvability and commercial viability. Oral argument was held on October 7, 2022, and the Court dismissed the complaint without prejudice on October 17, 2022, giving plainﬀs thirty days to amend their complaint. On November 16, 2022, plainﬀs ﬁled an amended consolidated complaint, asserng the same claims and seeking the same relief as the consolidated complaint. On January 18, 2023, defendants moved to dismiss the amended consolidated complaint in its enrety. Brieﬁng on defendants’ moon to dismiss the amended consolidated complaint was completed on April 5, 2023 and oral argument was held on March 13, 2024. At the conclusion of the hearing, the Court granted our moon to dismiss. In connecon with any ligaon or other legal proceedings, we could incur substanal costs, and such costs and any related selements or judgments may not be covered by insurance. Monetary damages or any other adverse judgment would have a material adverse eﬀect on our business and ﬁnancial posion. In addion, if other resoluon or acons taken as a result of legal proceedings were to restrain our ability to operate or market our products and services, our consolidated ﬁnancial posion, results of operaons or cash ﬂows could be materially adversely aﬀected. We could also suﬀer an adverse impact on our reputaon, negave publicity and a diversion of management’s aenon and resources, which could have a material adverse eﬀect on our business. Risks Related to our Common Stock Our stock price has been and may connue to be volale, which could result in substanal losses for holders or future purchasers of our common stock and lawsuits against us and our oﬃcers and directors. Our stock price has been and will likely connue to be volale. The stock market in general and the market for similarly situated biopharmaceucal companies speciﬁcally have experienced extreme volality that has oen been unrelated to the operang performance of parcular companies, such as rising inﬂaon and increasing interest rates. Since our inial public oﬀering in March 2014, the price of our common stock as reported on The Nasdaq Stock Market has ranged from a low of $0.24 on October 24, 2022 to a high of $31.00 on June 20, 2014. The daily closing market price for our common stock varied between a high price of $1.84 on August 1, 2023 and a low price of $0.51 on April 5, 2023 in the twelve-month period ending on December 31, 2023. During that me, the price of our common stock ranged from an intra-day low of $0.49 per share to an intra-day high of $1.84 per share. The market price of shares of our common stock could be subject to wide ﬂuctuaons in response to many risk factors listed in this secon, including, among others, developments related to and results of our research or clinical trials, developments related to our regulatory submissions and meengs with regulatory authories, in parcular as it relates to vadadustat, commercializaon of Auryxia, vadadustat in Europe and, if and as approved in the U.S. and other foreign markets, and any other product candidates, announcements by us or our competors of signiﬁcant transacons or strategic collaboraons, negave publicity around Auryxia or vadadustat, regulatory or legal developments in the U.S. and other countries, developments or disputes concerning our intellectual property, the recruitment or departure of key personnel including as a result of our reducons in workforce, actual or ancipated changes in esmates as to ﬁnancial results, changes in the structure of healthcare payment systems, market condions in the biopharmaceucal sector, potenal delisng from The Nasdaq Stock Market and other factors beyond our control. As a result of this volality, our stockholders may not be able to sell their common stock at or above the price at which they purchased it. In addion, companies that have experienced volality in the market price of their stock have frequently been the subject of securies class acon and shareholder derivave ligaon. See Part I, Item 3. Legal Proceedings of this Form 10-K for informaon concerning securies class acon iniated against Keryx and certain current and former directors and oﬃcers of ours and Keryx’s. In addion, we could be the target of other such ligaon in the future. Class acon and shareholder derivave lawsuits, whether successful or not, could result in substanal costs, damage or selement awards and a diversion of our management’s resources and aenon from running our business, which could materially harm our reputaon, ﬁnancial condion and results of operaons. Akebia Therapeucs, Inc. | Form 10-K | Page 103 Table of Contents The issuance of addional shares of our common stock or the sale of shares of our common stock by any of our directors, oﬃcers or signiﬁcant stockholders will dilute our stockholders’ ownership interest in Akebia and may cause the market price of our common stock to decline. Most of our outstanding common stock can be traded without restricon at any me. As such, sales of a substanal number of shares of our common stock in the public market could occur at any me. These sales, or the percepon in the market that the holders of a large number of shares intend to sell such shares, could reduce the market price of our common stock. As of December 31, 2023 and based on the amounts reported in the most recent ﬁlings made under Secon 13(d) and 13(g) of the Exchange Act, Muneer A. Saer, or Saer, beneﬁcially owned approximately 8.3% of our outstanding shares of common stock, the Vanguard Group, or Vanguard, beneﬁcially owned approximately 4.0% of our outstanding shares of common stock, and CSL Vifor beneﬁcially owned approximately 4% of our outstanding shares of common stock. By selling a large number of shares of common stock, Saer or Vanguard could cause the price of our common stock to decline. The shares beneﬁcially owned by CSL Vifor have not been registered pursuant to the Securies Act and were issued and sold in reliance upon the exempon from registraon contained in Secon 4(a)(2) of the Securies Act and Rule 506 promulgated thereunder, but if they are registered in the future, those shares would become freely tradable and, if a large poron of such shares are sold, could cause the price of our common stock to decline. In addion, we entered into a warrant agreement with Kreos Capital VII Aggregator SCSp, an aﬃliate of Kreos, or the Warrant Holder, pursuant to which (i) we issued a warrant to the Warrant Holder to purchase 3,076,923 shares of our common stock, at an exercise price per share of $1.30 (subject to standard adjustments for stock splits, stock dividends, rights oﬀerings and pro rata distribuons), or the Exercise Price, and (ii) if we drawdown the Tranche C Loan, at that me we will issue a warrant to the Warrant Holder to purchase 1,153,846 shares of our common stock, at an exercise price per share equal to the Exercise Price. Each warrant is exercisable for eight years from date of issuance. If any or all of the warrants are exercised, our stockholders could realize diluon, and the value of their shares could decrease. We have a signiﬁcant number of shares that are subject to outstanding opons and restricted stock units, and in the future we may issue addional opons, restricted stock units, or other derivave securies converble into our common stock. The exercise or vesng of any such opons, restricted stock units, or other derivave securies, and the subsequent sale of the underlying common stock, could cause a further decline in our stock price. These sales also might make it diﬃcult for us to sell equity securies in the future at a me and at a price that we deem appropriate. Such sales of our common stock could result in higher than average trading volume and may cause the market price for our common stock to decline. Sales of substanal amounts of shares of our common stock or other securies by our employees or our other stockholders or by us under any shelf registraon statement, pursuant to at-the-market oﬀerings or otherwise, could dilute our stockholders, lower the market price of our common stock and impair our ability to raise capital through the sale of equity securies. Our execuve oﬃcers, directors and principal stockholders maintain the ability to signiﬁcantly inﬂuence all maers submied to stockholders for approval. As of December 31, 2023, our execuve oﬃcers, directors and principal stockholders, in the aggregate, beneﬁcially owned shares represenng a signiﬁcant percentage of our capital stock. As a result, if these stockholders were to choose to act together, they would be able to signiﬁcantly inﬂuence all maers submied to our stockholders for approval, as well as our management and aﬀairs. For example, these persons could signiﬁcantly inﬂuence the elecon of directors and approval of any merger, consolidaon or sale of all or substanally all of our assets. This concentraon of vong power could delay or prevent an acquision of our Company on terms that other stockholders may desire. Provisions in our organizaonal documents and Delaware law may have an-takeover eﬀects that could discourage an acquision of us by others, even if an acquision would be beneﬁcial to our stockholders, and may prevent aempts by our stockholders to replace or remove our current management. Provisions in our Charter and our Bylaws contain provisions that may have the eﬀect of discouraging, delaying or prevenng a change in control of us or changes in our management. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addion, because our Board of Directors is responsible for appoinng certain members of our management team, these provisions may frustrate or prevent any aempts by our stockholders to replace or remove our current management by making it more diﬃcult for stockholders to replace members of our Board of Directors. Among other things, these provisions: • • • authorize “blank check” preferred stock, which could be issued by our Board of Directors without stockholder approval and may contain vong, liquidaon, dividend and other rights superior to our common stock; create a classiﬁed Board of Directors whose members serve staggered three-year terms; specify that special meengs of our stockholders can be called only by our Board of Directors pursuant to a resoluon adopted by a majority of the total number of directors; Akebia Therapeucs, Inc. | Form 10-K | Page 104 Table of Contents • • • • • • prohibit stockholder acon by wrien consent; establish an advance noce procedure for stockholder approvals to be brought before an annual meeng of our stockholders, including proposed nominaons of persons for elecon to our Board of Directors; provide that our directors may be removed only for cause; provide that vacancies on our Board of Directors may be ﬁlled only by a majority of directors then in oﬃce, even though less than a quorum; require a supermajority vote of 75% of the holders of our capital stock entled to vote or the majority vote of our Board of Directors to amend our Bylaws; and require a supermajority vote of 85% of the holders of our capital stock entled to vote to amend the classiﬁcaon of our Board of Directors and to amend certain other provisions of our Charter. These provisions, alone or together, could delay or prevent hosle takeovers, changes in control or changes in our management. In addion, Secon 203 of the DGCL prohibits a publicly-held Delaware corporaon from engaging in a business combinaon with an interested stockholder, generally a person which together with its aﬃliates owns, or within the last three years has owned, 15% of our vong stock, for a period of three years aer the date of the transacon in which the person became an interested stockholder, unless the business combinaon is approved in a prescribed manner. Because we do not ancipate paying any cash dividends on our capital in the foreseeable future, capital appreciaon, if any, will be our stockholders’ sole source of gain. We have never declared or paid cash dividends on our capital stock and we currently intend to retain all of our future earnings, if any, to ﬁnance the development and growth of our business. Any payment of cash dividends in the future would be at the discreon of our Board of Directors and would depend on, among other things, our earnings, ﬁnancial condion, capital requirements, level of indebtedness, statutory and contractual restricons applying to the payment of dividends and other consideraons that the Board of Directors deems relevant. In addion, the terms of the BlackRock Credit Agreement preclude us from paying cash dividends without prior wrien consent of the lender and future debt agreements may preclude us from paying cash dividends. As a result, capital appreciaon, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future. Item 1B. Unresolved Staﬀ Comments None. Item 1C. Cybersecurity. Cybersecurity Risk Management and Strategy We have certain processes for assessing, idenfying, and managing material risks from cybersecurity threats, which are integrated into our enterprise risk management processes. Speciﬁcally, we have processes for: • • • Idenfying and Managing Cybersecurity Risks — We have implemented a cross-funconal approach to assessing, idenfying and managing material cybersecurity threats and incidents. We periodically review, assess, update and test our policies, standards, processes and pracces in a manner intended to address cybersecurity threats and events. The results of such reviews, assessments and tests are evaluated by management and reported to our Audit Commiee of the Board of Directors, or the Audit Commiee, and our Board of Directors. Technical Safeguards — We have integrated cybersecurity into our overall informaon technology operaons and designed our processes and systems to help protect our informaon assets and operaons from internal and external cyber threats, protect employee and paent informaon from unauthorized access or aack as well as secure our networks and systems. Incident Response and Recovery Planning — To beer facilitate our cybersecurity program, our cybersecurity team works collaboravely across our Company to implement programs designed to protect our informaon systems from cybersecurity threats and to promptly respond to any material cybersecurity incidents. We conduct regular tabletop exercises, including incident simulaons to test these plans and ensure personnel are familiar with their roles and responsibilies in a response scenario. Akebia Therapeucs, Inc. | Form 10-K | Page 105 Table of Contents • • Third-Party Risk Management — We maintain a risk-based approach to idenfying and overseeing material cybersecurity threats presented by third pares and the systems of third pares that could adversely impact our business in the event of a material cybersecurity incident aﬀecng those third-party systems. Educaon and Awareness — We provide training regarding cybersecurity threats as a means to equip our employees and consultants with tools to make employees and consultants aware of and to address cybersecurity threats, and to communicate our evolving informaon security policies, standards, processes and pracces. We also use technology-based tools to migate cybersecurity risks and to bolster our employee-based cybersecurity programs. We adjust our cybersecurity policies, standards, processes, and pracces as necessary based on the informaon provided by our assessments, audits and reviews. Such processes include (i) procedural and technical safeguards, (ii) response plans, (iii) annual tests on our systems, (iv) incident simulaons and (v) roune review of our cybersecurity policies and procedures to idenfy risks and improve our pracces. We engage certain external cybersecurity ﬁrms to enhance our cybersecurity oversight. We include conﬁdenality provisions in all contracts with third-party service providers, and data protecon provisions in certain contracts with third-party service providers where applicable, to help protect us and our employees and paents from any related vulnerabilies. Governance Our Board of Directors is responsible for exercising oversight of management’s idenﬁcaon and management of, and planning for, risks from cybersecurity threats. While the full Board of Directors has overall responsibility for risk oversight, the Board of Directors has delegated oversight responsibility related to risks from cybersecurity threats to the Audit Commiee. The Audit Commiee reports to the Board of Directors at least annually, and noﬁes the Board of Directors as necessary regarding signiﬁcant new cybersecurity threats or incidents. The Audit Commiee of our Board of Directors meets annually to discuss our approach to overseeing cybersecurity threats with management, including with members of our internal cybersecurity team. We use an internal management commiee to run our informaon and technology team and our informaon and technology team includes our cybersecurity team lead who has served in various roles in informaon technology and informaon security for over 25 years, including at other public companies. Through ongoing communicaons with this management commiee, senior management is informed about and monitors the prevenon, detecon, migaon and remediaon of cybersecurity threats and incidents in real-me and reports such threats and incidents to the Audit Commiee, when appropriate. Management updates the Audit Commiee quarterly with an overview of our cybersecurity threat risk management and strategy processes. Members of the Audit Commiee are also encouraged to regularly engage in ad hoc conversaons with management on cybersecurity-related topics and discuss any updates to our cybersecurity risk management and strategy programs. The Audit Commiee is noﬁed between such updates regarding signiﬁcant new cybersecurity threats or incidents that meet pre-established reporng thresholds and any ongoing updates regarding any risk, as needed. We have not idenﬁed any risks from cybersecurity threats, including as a result of any previous cybersecurity incidents, that have materially aﬀected or are reasonably likely to materially aﬀect our company, including our business strategy, results of operaons or ﬁnancial condion. However, as discussed under “Risk Factor — Risks Related to our Business and Managing Growth” in Part I, Item 1A of this Form 10-K, cybersecurity threats could pose mulple risks to us. As cybersecurity threats become more frequent, sophiscated, and coordinated, it is reasonably likely that we will be required to expend greater resources to connue to modify and enhance our protecve measures. Item 2. Properes We currently lease approximately 65,167 square feet of oﬃce, storage and laboratory space in Cambridge, Massachuses, which is our corporate headquarters. Excluding renewal opons, the lease for our Cambridge, Massachuses oﬃce and storage space expires on September 11, 2026 and the lease for our laboratory space expires on January 31, 2025. In the third quarter of 2022, as a result of the reducons in our workforce and our transion to primarily hybrid and remote work schedules, we ceased using two-thirds of the oﬃce space, and began to market up to 59,216 square feet of furnished oﬃce space for sublease. We believe our exisng facilies are adequate to meet our operaonal needs. Item 3. Legal Proceedings Opposion Proceedings Against Akebia In September 2018, Dr. Reddy’s Laboratories Limited ﬁled an opposion to our issued Indian Patent No. 287720 in the Indian Patent Oﬃce. Akebia Therapeucs, Inc. | Form 10-K | Page 106 Table of Contents On July 26, 2022, Sandoz AG ﬁled an opposion against our issued European Patent No. 3277270 in the European Patent Oﬃce, or the EPO. During an oral proceeding held on February 6, 2024, the EPO's Opposion Division rejected the opposion and upheld the patent as granted. Seled Opposion Proceedings Against Akebia On February 13, 2023, FibroGen, Inc., or FibroGen, ﬁled an opposion against our issued European Patent No. 3357911, or the ’911 EP Patent, in the EPO. On November 21, 2023, we and our collaboraon partner in Japan, Mitsubishi Tanabe Pharma Corporaon, or MTPC, entered into a Selement and Cross License Agreement, or the Selement Agreement, with FibroGen and its collaboraon partner in Europe and Japan, Astellas Pharma Inc., or Astellas. This Selement Agreement resolves all patent disputes between Akebia, MTPC, FibroGen and Astellas in the EU, the contracng states to the European Patent Convenon, the UK, and Japan with no cash payment. On November 22, 2023, FibroGen withdrew the opposion against the ’911 EP Patent pursuant to the terms of the Selement Agreement. Seled Proceedings Filed by Akebia Against FibroGen Europe We ﬁled an opposion in the EPO against FibroGen’s European Patent No. 1463823, or the ’823 EP Patent on December 5, 2013, and an oral proceeding took place March 8 and 9, 2016. Following the oral proceeding, the Opposion Division of EPO ruled that the patent as granted did not meet the requirements for patentability under the European Patent Convenon and, therefore, revoked the patent in its enrety. FibroGen appealed that decision. On February 27, 2023, FibroGen withdrew its appeal, and the patent remains revoked. On April 3, 2019, we ﬁled opposions to FibroGen’s European Patent Nos. 2289531, or the ’531 EP Patent, and 2298301, or the ’301 EP Patent in the EPO, respecvely, requesng the patents be revoked in their enrety. Oral proceedings for opposions to the two patents were held on September 7, 8 and 10, 2021. Following oral proceedings, the Opposion Division of the EPO maintained certain claims in amended form in the two patents. On January 26, 2022, we ﬁled noce to appeal the Opposion Division’s decision for ’531 EP Patent. On July 8, 2022, FibroGen ﬁled noce to appeal the Opposion Division’s decision for the ’301 EP Patent, which it withdrew on August 17, 2022. On November 21, 2023, we withdrew our appeal to the Opposion Division’s decision for ’531 EP Patent pursuant to the terms of the Selement Agreement. Japan In 2018, we and MTPC jointly ﬁled a Request for Trial before the Japan Patent Oﬃce, or JPO to challenge the validity of certain of FibroGen’s HIF-related patents in Japan: JP4845728, JP5474872 and JP5474741. On September 26, 2019, the JPO conducted an invalidaon trial for JP5474872 and JP4845728. On November 11, 2019, the JPO conducted an invalidaon trial for JP5474741. On April 1, 2022, the JPO issued a ﬁnal decision for JP4845728, which invalidated all claims except claims directed to the medical use to treat anemia that does not respond to erythropoiesis. On May 18, 2022, the JPO issued a ﬁnal decision for JP5474741 and JP5474872, which maintained the claims in amended form. In May 2022, MTPC ﬁled revocaon lawsuits for the three patents in the Intellectual Property High Court requesng cancellaon of the JPO’s decisions. In July 2022, we ﬁled a revocaon lawsuit for JP4845728 in the Intellectual Property High Court requesng cancellaon of the JPO’s decision. In August 2022, we ﬁled revocaon lawsuits for JP5474741 and JP5474872 in the Intellectual Property High Court requesng cancellaon of the JPO’s decisions. In September 2022, FibroGen ﬁled a revocaon lawsuit for JP4845728 in the Intellectual Property High Court requesng cancellaon of the JPO’s decision on the claims that were invalidated. In November 2023, Akebia, MTPC, and FibroGen ﬁled with the Japan Intellectual High Court wrien consent to withdraw the revocaon lawsuits related to JP4845728, JP5474872 and JP5474741 pursuant to the terms of the Selement Agreement. United Kingdom On December 13, 2018, we ﬁled Parculars of Claim in the Patents Court of the United Kingdom to challenge the validity of FibroGen’s six HIF-related patents in the UK: the ’823 EP Patent (UK), European Patent (UK) No. 1633333, or the ’333 EP Patent (UK), European Patent (UK) No. 2322153, or the ’153 EP Patent (UK), European Patent (UK) No. 2322155, or the ’155 EP Patent (UK), European Patent (UK) No. 2,289,531, or the ’531 EP Patent (UK), and European Patent (UK) No. 2,298,301, or the ’301 EP Patent (UK). In May 2019, Astellas, the exclusive licensee of FibroGen’s HIF-related patents, sued Akebia for patent infringement in the Patents Court of the UK. In September 2019, we ﬁled an Amended Parculars of Claim to include FibroGen’s European Patent No. 1487472, or the ’472 EP Patent (UK). On February 28, 2020, the pares agreed to dismiss the ’472 EP Patent (UK) from the trial. A trial was conducted in March 2020. On April 20, 2020, the Patents Court of the UK issued a judgment in favor of Akebia, which invalidated all the claims at issue in each of the ’823 EP Patent (UK), the ’333 EP Patent (UK), the ’153 EP Patent (UK), the ’155 EP Patent (UK) and the ’301 EP Patent (UK). The ’531 EP Patent (UK) was amended to a single claim to recite one speciﬁc compound; this claim was held to be valid but not infringed by vadadustat. On June 11, 2020, FibroGen and Astellas appealed the Patents Court’s judgment on the invalidity of the ’823 EP Patent (UK), the ’301 EP Patent (UK), the ’333 EP Akebia Therapeucs, Inc. | Form 10-K | Page 107 Table of Contents Patent (UK), the ’153 EP Patent (UK), and the ’155 EP Patent (UK) in the Court of Appeal (Civil Division). On June 8, 2021 - June 10, 2021, the United Kingdom Court of Appeal held a three-day hearing for the appeal. On August 24, 2021, the Court of Appeal issued a judgment, which reversed the Patents Court’s judgment on the invalidity of the ’823 EP Patent (UK) and maintained certain claims of the ’823 EP Patent (UK) and the ’301 EP Patent (UK) in amended form, and which aﬃrmed the Patents Court’s judgment on the invalidity of the ’333 EP Patent (UK), the ’155 EP Patent (UK), and the ’153 EP Patent (UK). Akebia sought permission to appeal to the UK Supreme Court, which was granted on October 3, 2022. On November 28, 2023, we ﬁled an applicaon for withdrawal of the Appeal at the UK Supreme Court pursuant to the terms of the Selement Agreement. On December 15, 2023, the UK Supreme Court ordered that the Appeal be withdrawn. Legal Proceedings Relang to Auryxia Stockholder Ligaon Relang to the Merger On June 28, 2018, we entered into an Agreement and Plan of Merger with Keryx and Alpha Therapeucs Merger Sub, Inc., or the Merger Sub, pursuant to which the Merger Sub merged with and into Keryx, with Keryx becoming a wholly owned subsidiary of ours, or the Merger. On December 12, 2018, we completed the Merger. On July 15, 2021, a purported former Keryx stockholder ﬁled a putave class acon in the Supreme Court of the State of New York against Akebia, a current oﬃcer of Akebia (John P. Butler), a former oﬃcer of Akebia (Jason A. Amello), former directors of Akebia (Muneer A. Saer, Sco A. Canute, Michael D. Clayman, Maxine Gowen, Duane Nash, Ronald C. Renaud, Jr., and Michael S. Wyzga), a current director of Akebia (Cynthia Smith), a former director and oﬃcer of Keryx (Jodie P. Morrison), a former oﬃcer of Keryx (Sco A. Holmes) and former directors of Keryx (Michael Rogers, Kevin J. Cameron, Steven C. Gilman, Daniel P. Regan, Mark J. Enyedy, and Michael T. Heﬀernan, some of whom are current members of our Board of Directors). The acon is caponed Loper v. Akebia Therapeucs, Inc., et al., or the Loper Acon. The complaint in the Loper Acon alleges that the registraon statement ﬁled in connecon with the Merger contained allegedly false and misleading statements or failed to disclose certain allegedly material informaon in violaon of Secon 11, 12(a)(2), and 15 of the Securies Act of 1933, as amended. It alleges, among other things, that Akebia failed to disclose heightened safety risks that allegedly threatened the prospects of the Phase 3 PRO2TECT clinical trial and the commercial viability of vadadustat. The complaint in the Loper Acon seeks damages including interest thereon, an award of plainﬀs’ and the class’s costs and expenses, including counsel fees and expert fees, and rescission, disgorgement, or such other equitable or injuncve relief that the Court deems appropriate. On August 16, 2021, another purported former Keryx stockholder ﬁled a putave class acon making substanally similar allegaons and asserng the same claims as the Loper Acon, also in the Supreme Court of the State of New York against Akebia and many of the same individual defendants named in the Loper Acon. The acon is caponed Panicho v. Akebia Therapeucs, Inc., et al., or the Panicho Acon. On September 13, 2021, the pares in the Loper Acon and Panicho Acon entered into a joint spulaon and proposed order, which provided for the consolidaon of the two acons under the capon In re Akebia Therapeucs, Inc. Securies Ligaon, or the Consolidated State Acon. On October 27, 2021, plainﬀs ﬁled a consolidated complaint in the Consolidated State Acon. On January 10, 2022, defendants moved to dismiss the consolidated complaint in its enrety. Brieﬁng on defendants’ moon to dismiss was completed on April 22, 2022. Oral argument was held on October 7, 2022, and the Court dismissed the complaint without prejudice on October 17, 2022, giving plainﬀs thirty days to amend their complaint. On November 16, 2022, plainﬀs ﬁled an amended consolidated complaint, asserng the same claims and seeking the same relief as the consolidated complaint. On January 18, 2023, defendants moved to dismiss the amended consolidated complaint in its enrety, and the plainﬀs ﬁled their opposion on March 6, 2023. Brieﬁng on defendants’ moon to dismiss the amended consolidated complaint was completed on April 5, 2023. Oral argument was held on March 13, 2024. At the conclusion of the hearing, the Court granted our moon to dismiss. We deny any allegaons of wrongdoing and intend to connue vigorously defending against the one acve stockholder lawsuit described in this Legal Proceedings secon, the Consolidated State Acon. There is no assurance, however, that we will be successful in the defense of this acon, or any associated appeals, or that insurance will be available or adequate to fund any selement or judgment or the ligaon costs of this acon. Moreover, we are unable to predict the outcome or reasonably esmate a range of possible losses at this me. A resoluon of the Consolidated State Acon in a manner adverse to us, however, could have a material eﬀect on our ﬁnancial posion and results of operaons in the period in which the acon is resolved. Seled ANDA Ligaon In February 2023, we received a Paragraph IV cerﬁcaon noce leer regarding an Abbreviated New Drug Applicaon, or ANDA, submied to the U.S. Food and Drug Administraon, or FDA, by Zydus Worldwide DMCC requesng approval for a generic version of Auryxia tablets (210 mg ferric iron per tablet). On March 24, 2023, we and Panion & BF Biotech, Inc., or Panion, ﬁled a complaint for patent infringement against Zydus Worldwide DMCC, Zydus Pharmaceucals (USA) Inc., and Zydus Lifesciences Limited, or collecvely Zydus, in the United States District Court for the District of Delaware arising from Akebia Therapeucs, Inc. | Form 10-K | Page 108 Table of Contents Zydus’ ANDA ﬁling with the FDA. On May 30, 2023, we and Panion entered into a selement and license agreement with Zydus, which resolved the patent ligaon brought by we and Panion. Such selement and license agreement, consistent with our prior ANDA selements, granted Zydus a license to market a generic version of Auryxia in the U.S. beginning on March 20, 2025 (subject to FDA approval), or earlier under certain circumstances customary for selement agreements of this nature. Addionally, in accordance with the selement and license agreement, the pares terminated all ongoing ligaon among us, Panion and Zydus regarding Auryxia patents pending in the Delaware District Court. The selement and license agreement is conﬁdenal and subject to review by the U.S. Federal Trade Commission and the U.S. Department of Jusce. On June 5, 2023, the Delaware District Court entered a spulaon and order of dismissal ﬁled by the pares to terminate the acon against Zydus. Item 4. Mine Safety Disclosures Not applicable. Akebia Therapeucs, Inc. | Form 10-K | Page 109 Table of Contents PART II Item 5. Market for Registrant’s Common Equity, Related Stockholder Maers and Issuer Purchases of Equity Securies Market Informaon Our common stock is traded on The Nasdaq Capital Market under the symbol “AKBA”. Holders At March 12, 2024, there were approximately 30 holders of record of our common stock. The number of record holders is based upon the actual number of holders registered on our books at such date and does not include shares held in street name by brokers or other nominees, and shares held by persons, partnerships, associaons, corporaons or other enes whose shares are held by depository trust companies. Dividends We have never declared or paid any cash dividends on our common stock and we do not ancipate paying cash dividends in the foreseeable future. In addion, the terms of our BlackRock Credit Agreement preclude us from paying cash dividends without prior wrien consent and future debt agreements may preclude us from paying cash dividends. Issuer Purchases of Equity Securies None. Recent Sales of Unregistered Securies None. Purchases of Equity Securies by the Issuer and Aﬃliated Purchasers None. Comparave Stock Performance Graph We are a smaller reporng company, as deﬁned by Rule 12b-2 of the Exchange Act, and are not required to provide a stock performance graph. Securies Authorized for Issuance under Equity Compensaon Plans Informaon about our equity compensaon plans is incorporated herein by reference to Item 12, Security Ownership of Certain Beneﬁcial Owners and Management and Related Stockholder Maers, of this Form 10-K. Item 6. [Reserved] Item 7. Management’s Discussion and Analysis of Financial Condion and Results of Operaons This Annual Report on Form 10-K, or Form 10-K, including this management's discussion and analysis of ﬁnancial condion and results of operaons, contains forward-looking statements based upon current expectaons that involve risks and uncertaines. Our actual results may diﬀer materially from those described in or implied in these forward-looking statements as a result of various factors, including those factors set forth in the “Risk Factors” secon included in Part I, Item 1A of this Form 10-K. All references to years, unless otherwise noted, refer to our ﬁscal years, which end on December 31. For purposes of this secon, all references to “we,” “us,” “our,” “Akebia,” or the “Company” refer to Akebia Therapeucs, Inc. and its consolidated subsidiaries. The following discussion and analysis should also be read in conjuncon with the accompanying audited consolidated ﬁnancial statements and related notes included in Part II, Item 8 of this Form 10-K. This secon discusses 2023 and 2022 ﬁnancial condion, and results of operaons and year-to-year comparisons between 2023 and 2022. For discussion of 2022 items and year-over-year comparisons between 2022 and 2021 that are not included in this 2023 Form 10-K, refer to “Item 7. – Management’s Discussion and Analysis of Financial Condion and Results of Operaons” found in our Form 10-K/A for the year ended December 31, 2022, that was ﬁled with the Securies and Exchange Commission on August 28, 2023. Business Overview We are a fully integrated commercial-stage biopharmaceucal company commied to addressing paents’ unmet needs. We have built a business focused on developing and commercializing innovave therapeucs that we believe serves as a foundaon for future growth. Our purpose is to beer the life of each person impacted by kidney disease, and we have established ourselves as a leader in the kidney community. We believe our demonstrated ability to deliver value broadly to the kidney community has enabled us to build a sustainable company. Upon this solid foundaon and our connued Akebia Therapeucs, Inc. | Form 10-K | Page 110 Table of Contents commitment to paents, we believe focusing on all paents who can realize a meaningful beneﬁt from our medicines, will result in delivering value for our shareholders. Our current porolio includes: • • Auryxia® (ferric citrate) is an an orally administered medicine approved and marketed in the United States, or U.S., for two indicaons: (1) the control of serum phosphorus levels in adult paents with dialysis dependent chronic kidney disease, or DD-CKD, and (2) the treatment of iron deﬁciency anemia, or IDA, in adult paents with non-dialysis-dependent chronic kidney disease, or NDD-CKD. Today, we market Auryxia in the U.S. with our well-established, nephrology-focused commercial organizaon. Our Japanese sublicensee, Japan Tobacco, Inc., and its subsidiary, Torii Pharmaceucal Co., Ltd., collecvely, JT and Torii, commercialize ferric citrate hydrate as Riona in Japan. Averoa SAS, or Averoa, has an exclusive license to develop and commercialize ferric citrate in the European Economic Area, or EEA, Turkey, Switzerland and the United Kingdom, or UK. We expect Averoa will apply for markeng authorizaon for ferric citrate in Europe. Vafseo™ (vadadustat) is an oral hypoxia-inducible factor prolyl hydroxylase, or HIF-PH, inhibitor, approved in 36 countries as a treatment for anemia due to CKD. In the European Union, or EU, the UK, Switzerland and Australia, vadadustat is approved under the trade name Vafseo for the treatment of symptomac anemia associated with chronic kidney disease, or CKD, in adults on chronic maintenance dialysis. In May 2023, we entered into a License Agreement with MEDICE Arzneimiel Püer GmbH & Co. KG, or Medice, pursuant to which we granted Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in paents with CKD in the EEA, the UK, Switzerland and Australia, or the Medice Territory. In Japan, vadadustat is approved as a treatment for anemia due to CKD in both dialysis dependent and non-dialysis dependent paents under the trade name Vafseo, and is marketed and sold by our collaborator Mitsubishi Tanabe Pharma Corporaon, or MTPC. In Taiwan, vadadustat is approved for the treatment of symptomac anemia due to CKD in adult paents on chronic maintenance dialysis and in Korea as an anemia treatment for paents with CKD on hemodialysis. MTPC plans to commercialize vadadustat in Taiwan. We connue to pursue approval for vadadustat in the U.S., and in September 2023, we completed our resubmission to our New Drug Applicaon, or NDA, for the treatment of anemia due to CKD for dialysis dependent paents to the U.S. Food and Drug Administraon, or FDA. In October 2023, the FDA acknowledged that the resubmission was complete, classiﬁed it as a Class 2 response and set a user fee goal date, or PDUFA Date, of March 27, 2024. Beyond seeking U.S. approval, we have several lifecycle management and indicaon expansion opportunies currently under evaluaon for vadadustat, including the potenal for alternave dosing and label expansion for treatment of adult paents not on dialysis. • Our HIF-based pipeline assets are molecules being evaluated to target areas of unmet needs in acute care sengs. The discovery of hypoxia- inducible factor, or HIF, laid the foundaon to explore the central role of oxygen sensing in many diseases. As we have seen through the development of vadadustat as a treatment for anemia due to CKD, when stabilized, HIF triggers wide-ranging adapve, protecve responses during hypoxic or ischemic condions. We have selected two addional HIF molecules for preclinical development: AKB-9090, for use in an acute care seng, potenally for acute kidney disease, or AKI, or acute respiratory distress syndrome, or ARDS, and AKB-10108 for renopathy of prematurity, or ROP, in neonates. We connue to explore addional commercial and development opportunies to expand our pipeline and porolio of novel therapeucs through both internal research and external innovaon to leverage our fully integrated team. Factors Aﬀecng Our Performance and Results of Operaon Financial Highlights Net product revenue in 2023 decreased by approximately 4% to $170.3 million from $176.9 million in 2022, primarily due to a decrease in Auryxia product volume parally oﬀset by increases in pricing, improved payor mix and execuon of our contracng strategy with third-party payors. We have incurred net losses in each year since incepon. Our net losses were $51.9 million and $94.2 million for the years ended December 31, 2023 and 2022, respecvely. Substanally all of our net losses resulted from costs incurred in connecon with the connued commercializaon of Auryxia and development eﬀorts relang to vadadustat, including conducng clinical trials of, and seeking regulatory approval for, vadadustat, providing general and administrave support for these operaons and protecng our intellectual property. Financial Components Product Revenue We generate product revenue from commercial sales of Auryxia to a limited number of wholesale distributors as well as certain specialty pharmacy providers. Our net product revenue includes many variables, including judgments and esmates of discounts, rebates and product returns, which can ﬂuctuate from quarter-to-quarter and year-over-year. We evaluate, at least Akebia Therapeucs, Inc. | Form 10-K | Page 111 Table of Contents annually and more frequently, if needed, the price of Auryxia, which will lose exclusivity, or LoE, in March 2025. We expect our product revenue to connue to be generated primarily from our commercial sales of Auryxia. Due to the buying paerns of our customers we tend to have seasonality from quarter to quarter. In general, our ﬁrst quarter usually has lower revenues than the preceding fourth quarter, the second and third quarters have higher revenues than the ﬁrst quarter, and the fourth quarter revenues are the highest in the year. While seasonality may aﬀect quarterly comparisons within a ﬁscal year, it generally is not material to our annual consolidated results. However, we expect Auryxia to be included in the ESRD bundle starng in January 2025, which coupled with Auryxia's LoE in March 2025 may impact the buying paerns of our exisng customers during 2024, and therefore their buying paern in 2024 may be diﬀerent than their historical pracces. We believe the Centers for Medicare & Medicaid Services', or CMS, decision to include phosphate binders in the dialysis bundle could potenally lead to higher sales of Auryxia aer the LoE date than in other LoE scenarios, and plan to work with payors and providers to seek to connue the use of Auryxia beyond LoE. License, Collaboraon and Other Revenue License, collaboraon and other revenue includes revenue earned under collaboraon agreements, license fees, royalty payments and revenue from product we supply under our license and supply agreements with our collaboraon partners. We expect to connue to generate revenue from our collaboraon and, if applicable, supply agreements with Medice, MTPC, JT and Torii and any other collaboraons into which we have entered or may enter, including our collaboraon with Vifor (Internaonal) Ltd. (now a part of CSL Limited), or CSL Vifor, if vadadustat is approved in the U.S. In 2022, we recorded a nonrefundable, non-creditable terminaon fee pursuant to the terms of the Terminaon and Selement Agreement, or Terminaon Agreement, with Otsuka Pharmaceucal Co. Ltd, or Otsuka. Furthermore, in 2023 we recorded a payment received from Otsuka, in connecon with the Packaging Validaon Transfer Agreement, to license, collaboraon and other revenue. Also in 2022, we recorded revenue from cost sharing agreements under which we were reimbursed by our collaboraon partner for expenses incurred by us for research and development, or R&D, acvies and, may in the future generate revenue from potenal co-promoon acvies, under our collaboraon agreements. We do not expect to recognize any future revenue under any of our collaboraon agreements with Otsuka, which were terminated on June 30, 2022. Cost of Goods Sold Cost of goods sold, or COGS, - Cost of product and other revenue - COGS - Cost of product and other revenue includes costs closely correlated or directly related to the costs to manufacture commercial drug substance and drug product for Auryxia, including at our contract manufacturing organizaons, or CMOs, as well as indirect costs. Direct and indirect costs include fees for packaging, shipping, insurance and quality assurance, idle capacity charges, changes in reserves for excess inventory, write-oﬀs for inventory that fails to meet speciﬁcaons or is otherwise no longer suitable for commercial sale, including scrap, changes in our ﬁrm purchase commitment liability and royales due to the licensor of Auryxia related to U.S. and Japan product sales recognized during the period. COGS also includes costs to manufacture drug product provided to MTPC and Medice for commercial sale of Vafseo in Japan and the Medice Territory, respecvely, as well as personnel-related costs, including salaries and bonuses, employee beneﬁts and stock-based compensaon aributable to employees in parcular funcons and associated directly with the manufacturing of our commercial products. Cost of product and other revenue for a newly launched product does not include the full cost of manufacturing unl the inial pre-launch inventory is depleted and addional inventory is manufactured and sold. Unless and unl we receive regulatory approval for vadadustat, in the U.S. we record costs incurred to manufacture the U.S. pre-launch inventory, such as raw materials, drug substance and drug product conversion costs as R&D, expense. Likewise, the cost of product and other does not include the full cost of manufacturing unl the inial pre-launch inventory, for the supply of vadadustat product to Medice which was previously expensed as R&D is depleted. Cost of goods sold - Amorzaon of intangible asset - In addion, COGS includes the amorzaon of development product rights for Auryxia through the end of 2024. Research and Development Expenses R&D expenses consist primarily of costs incurred for the development of vadadustat and costs associated with our pipeline which includes: • personnel-related expenses, including salaries, bonuses, employee beneﬁts, stock-based compensaon and travel expenses for employees engaged in R&D funcons; Akebia Therapeucs, Inc. | Form 10-K | Page 112 Table of Contents • • • • • • • costs associated with feasibility and potenal new manufacturing processes and methods for our commercial products; regulatory registraon and related fees for non-commercial products; expenses incurred under agreements with contract research organizaons, or CROs, and invesgave sites that conduct our clinical trials; the cost of acquiring, developing and manufacturing clinical trial materials through contract manufacturing organizaons, or CMOs; facilies, depreciaon and other expenses, which include direct and allocated expenses for rent and maintenance of facilies, insurance and other supplies associated with our laboratory space as well as our R&D team; costs associated with discovery and development for preclinical, clinical and regulatory acvies; and costs associated with the pre-launch inventory build for vadadustat in the U.S., for which the FDA set a PDUFA date of March 27, 2024 for our NDA resubmission, and in Europe prior to the European Commission, or EC, approval in April 2023. R&D costs are expensed as incurred. Advance payments made for goods or services to be received in the future for use in R&D acvies are recorded as prepaid expenses and other current assets. The prepaid amounts are expensed as the beneﬁts are consumed. Costs for certain development acvies are recognized based on an evaluaon of the progress to compleon of speciﬁc tasks using informaon and data provided to us by our vendors and our clinical sites. We cannot determine with certainty the duraon and compleon costs of our R&D projects, the costs of related clinical development, or if, when, or to what extent we will generate revenue from the commercializaon or sale of any of our product candidates. In addion, we may never obtain markeng approval for vadadustat in the U.S. From incepon through December 31, 2023, we have incurred $1.6 billion in R&D expenses. We expect to incur signiﬁcant R&D expenditures for the foreseeable future as we connue the development of Auryxia, vadadustat and any other product or product candidate, including those that may be in- licensed or acquired. A signiﬁcant poron of our R&D costs have been external costs, which we track on a program-by-program basis as well as costs related to possible new manufacturing processes and methods associated with our commercial product. These external costs include fees paid to invesgators, consultants, central laboratories and CROs in connecon with our clinical trials and costs related to acquiring and manufacturing clinical trial materials, including costs paid to CMOs to manufacture clinical trial materials. We do not track our internal personnel and facilies costs on a program-by-program basis as our personnel are deployed across mulple R&D projects. Each of our products and product candidates has technical, clinical, regulatory, and commercial risk, including those discussed more fully under the heading “Risk Factors” in Part I, Item 1A of this Form 10-K. A change in the outcome of any of the variables with respect to the development of Auryxia, vadadustat or any other product or product candidate could result in a signiﬁcant change in the costs and ming associated with that development. Selling, General and Administrave Expenses Selling, general and administrave, or SG&A, expenses consist primarily of compensaon for personnel, including stock-based compensaon related to commercial, markeng, execuve, ﬁnance and accounng, informaon technology, corporate and business development and human resource funcons. Other SG&A expenses include costs for markeng iniaves for our commercial products, market research and analysis on our commercial product and potenal product candidates, conferences and trade shows, travel expenses, professional services fees (including legal, patent, accounng, audit, tax, and consulng fees), insurance costs, general corporate expenses and allocated facilies-related expenses, including rent and maintenance of facilies. License Expense License expense relates to royales due to Panion & BF Biotech, Inc., or Panion, for sales of Auryxia in the U.S. and Riona in Japan. Other Income (Expense), Net Other income (expense), net consists primarily of interest income on our interest-bearing accounts, interest expense related to our term loans, accreon of the debt discount on our term loans as well as changes in the fair value of our derivave liabilies, amorzaon of the discount on the liability related to the terminaon fees associated with the terminaon agreement with BioVectra Inc., or BioVectra, entered into in December 2022, or the BioVectra Terminaon Agreement, and the amorzaon of the discount and deferred gain related to our refund liability to CSL Vifor. See Note 10, Commitments and Akebia Therapeucs, Inc. | Form 10-K | Page 113 Table of Contents Conngencies, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon on the BioVectra Terminaon Agreement. Recent Events Borrowing Under BlackRock Term Loans and Repayment of Pharmakon Term Loans On January 29, 2024, we entered into a secured term loan facility with Kreos Capital VII (UK) Limited, or Kreos, which are funds and accounts managed by BlackRock Inc., collecvely BlackRock, or the BlackRock Credit Agreement, that provides for an aggregate principal amount of up to $55.0 million made available under the following three tranches: (i) Tranche A — $37.0 million, drawn down on the closing date of the BlackRock Credit Agreement, of which we received $34.5 million, net of debt issuance costs, fees and expenses and was used to repay our senior secured term loans, or the Pharmakon Term Loans, with Pharmakon Advisors LP, or Pharmakon, of $35.0 million, (ii) Tranche B — $8.0 million available in a single draw through December 31, 2024 and (iii) Tranche C — $10.0 million available in a single draw through December 31, 2024. Tranche B and C are only available subject to certain condions, including receipt of markeng approval for vadadustat from the FDA and, in the case of Tranche C, receipt of a certain amount of cumulave gross cash proceeds from the sale of common stock. On January 29, 2024, we also entered into a warrant agreement with Kreos Capital VII Aggregator SCSp, an aﬃliate of Kreos, pursuant to which we (i) issued a warrant to purchase 3,076,923 shares of our common stock, at an exercise price per share of $1.30 (subject to standard adjustments for stock splits, stock dividends, rights oﬀerings and pro rata distribuons), or the Exercise Price, and (ii) will issue at the me of drawdown of the Tranche C Loan, if applicable, a warrant to purchase 1,153,846 shares of our common stock, at the Exercise Price. Each warrant shall be exercisable for eight years from date of issuance. See Note 7, Indebtedness, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon. At-the-Market (ATM) Oﬀering On April 7, 2022, we entered into an Open Market Sale Agreement , or Sales Agreement, with Jeﬀeries LLC as agent, to sell up to $26.0 million of our common stock at current market prices from me to me. During the quarter and year ended December 31, 2023, we sold 6,189,974 shares of common stock under this program with net proceeds of $6.7 million, aer deducng commissions and other oﬀering expenses. Including the amount sold during the year ended December 31, 2023, through the date of the ﬁling of this Form 10-K, we sold 19,451,285 shares of our common stock under the Sales Agreement with net proceeds of $25.4 million, aer deducng commissions and other oﬀering expenses. SM PDUFA Date - March 27, 2024 On March 29, 2022, we received a complete response leer, or CRL, from the FDA, in response to our NDA for vadadustat for the treatment of anemia due to CKD in adult paents in its present form. In October 2022, we submied a Formal Dispute Resoluon Request with the FDA and in May 2023, the Oﬃce of New Drugs, or OND, denied our appeal but provided a path forward for us to resubmit the NDA for vadadustat for the treatment of anemia due to CKD for dialysis dependent paents without the need for us to generate addional clinical data. In September 2023, we completed our resubmission to our NDA for vadadustat for the treatment of anemia due to CKD in adult paents on dialysis. In October 2023, the FDA acknowledged our NDA resubmission was complete, classiﬁed it as a Class 2 response and set a PDUFA date of March 27, 2024. Impact of Inﬂaon We are experiencing rising costs for certain inﬂaon-sensive operang expenses, such as labor, and certain of our service providers are heavily dependent on labor. We do not believe these impacts were material to our net loss during the year ended December 31, 2023 or will be going forward. However, signiﬁcant sustained inﬂaon rates driven by the macroeconomic environment or other factors could negavely impact our margins, proﬁtability and results of operaons in future periods. Results of Operaons The tables and discussion below present the results for the periods indicated. The year ended December 31, 2022 has been updated to reﬂect the errors revised in prior periods and as described in more detail in Note 1, Revision of Previously Issued Financial Statements, in the notes to the consolidated ﬁnancial statements found in Part II, Item 8 of our 2022 Form 10-K/A ﬁled with the SEC on August 28, 2023: Akebia Therapeucs, Inc. | Form 10-K | Page 114 Table of Contents (dollars in thousands) Revenues Product revenue, net License, collaboraon and other revenue Total revenues Cost of goods sold Cost of product and other revenue Amorzaon of intangible asset Total cost of goods sold Operang expenses R&D SG&A License Restructuring Total operang expenses Operang loss Other expense, net Loss on exnguishment of debt Loss on terminaon of lease Net loss *Percentage change not meaningful. Years ended December 31, 2023 2022 Change 2023-2022 $ % $ $ 170,301 $ 24,322 194,623 38,107 36,042 74,149 63,079 100,233 3,237 181 166,730 (46,256) (5,145) — (524) (51,925) $ 176,949 $ 115,535 292,484 49,526 36,042 85,568 129,986 138,601 3,175 15,933 287,695 (80,779) (12,541) (906) — (94,226) $ (6,648) (91,213) (97,861) (11,419) — (11,419) (66,907) (38,368) 62 (15,752) (120,965) 34,523 7,396 906 (524) 42,301 (4)% (79)% (33)% (23)% — % (13)% (51)% (28)% 2 % (99)% (42)% (43)% (59)% (100)% * (45)% Product Revenue, Net—Net product revenue is derived from sales of our only commercial product in the U.S., Auryxia. We distribute Auryxia principally through a limited number of wholesale distributors as well as certain specialty pharmacy providers. Net product revenue was $170.3 million for the year ended December 31, 2023, compared to net product revenue of $176.9 million for the year ended December 31, 2022. The decrease was primarily due to a reducon in volume, parally oﬀset by price increases, favorable payor mix and execuon of our contracng strategy with third party payors. Auryxia will lose exclusivity in the U.S. in March 2025, which may have a negave impact on revenue. We believe CMS's decision to include phosphate binders in the dialysis bundle could potenally lead to higher sales of Auryxia aer the LoE date than in other LoE scenarios, and plan to work with third-party payors and providers to connue the use of Auryxia beyond LoE. License, Collaboraon and Other Revenue—License, collaboraon and other revenue was $24.3 million for the year ended December 31, 2023, compared to $115.5 million for the year ended December 31, 2022. The decrease was due primarily to the terminaon of the Otsuka agreements in June 2022 under which we recognized $92.3 million and a reducon of $12.5 million in revenue recognized from the supply of drug product to MTPC, parally oﬀset by a one- me $10.0 million upfront payment from Medice received in 2023 in connecon with entering into our license agreement with Medice for their development and commercializaon of vadadustat in the EU. We do not expect to recognize any future revenue under any of the Otsuka agreements, which were terminated on June 30, 2022. Addionally, we expect our revenue under our supply agreement with MTPC to connue to decline due to the assignment of our supply agreement with Esteve Química, S.A. to MTPC in December 2022. See Note 12, License, Collaboraon and Other Revenue, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon. Akebia Therapeucs, Inc. | Form 10-K | Page 115 Table of Contents A further breakdown of the license, collaboraon and other revenue is as follows: License, Collaboraon and Other Revenue (dollars in thousands) License Fees: Medice upfront license payment Drug Product Supply: MTPC vadadustat drug product supply Medice vadadustat drug product supply Drug Product Supply Subtotal Royales: JT and Torii royales MTPC royales Royales Subtotal Years Ended December 31, 2023 2022 $ 10,000 $ 3,738 968 4,706 5,394 1,997 7,391 2,225 24,322 $ — 16,191 — 16,191 5,291 1,777 7,068 92,276 115,535 Otsuka U.S. and Internaonal Agreements (Terminated) Total License, Collaboraon and Other Revenue $ Cost of Goods Sold: Cost of Product and Other Revenue—Cost of product and other revenue was $38.1 million for the year ended December 31, 2023, compared to $49.5 million for the year ended December 31, 2022. The decrease was driven by lower year-over-year sales volume and a reducon in the write-downs of inventories to net realizable value in 2023. In addion, for the year ended December 31, 2023, we realized a lower cost of product and other revenue of $4.3 million due to our ability to commercially sell inventory previously wrien-down as excess inventory. Primarily during the ﬁrst half of 2024, we ancipate realizing lower costs of up to $12.3 million related to our ability to commercially sell inventory previously wrien-down as excess inventory. For the year ended December 31, 2023, we recorded $1.5 million related to our ﬁrm purchase commitment liability. For the year ended December 31, 2022, we recorded a net beneﬁt of $37.2 million comprised of a one-me $28.7 million terminaon fee in connecon with the BioVectra Terminaon Agreement oﬀset by a one-me beneﬁt of $65.9 million due to the reducon of our ﬁrm purchase commitment liability in connecon with the BioVectra Terminaon Agreement. We expense pre-launch inventory for the U.S. and Medice Territory, including certain manufacturing related expenses as R&D expenses unl the product receives the required approval. Medice obtained markeng authorizaon from the EMA for Vafseo in April 2023. During 2023, under a side-leer, we sold certain lots of Vafseo to Medice. If the pre-launch inventory had been capitalized and the associated cost recognized when we sold the product, cost of product and other revenue for the year ended December 31, 2023 would have increased by approximately $0.8 million. The selling of the remaining zero cost inventories of Vafseo on hand of approximately $28.4 million as of December 31, 2023 will be dependent on the ming of sales of Vafseo related in the U.S., if approved, and Medice Territory. Cost of Goods Sold: Amorzaon of Intangible Asset—Amorzaon of intangible asset relates to the acquired developed product rights for Auryxia, which is being amorzed using a straight-line method over its esmated useful life of approximately six years. Amorzaon of the intangible asset during each of the years ended December 31, 2023 and 2022 was $36.0 million and will connue through the end of 2024. R&D Expenses— R&D expenses were $63.1 million for the year ended December 31, 2023, compared to $130.0 million for the year ended December 31, 2022. The decrease of $66.9 million was a result of the compleon of certain clinical trials coupled with cost reducon eﬀorts that began in 2022 following the complete response leer for vadadustat in the U.S. In 2022, we began streamlining and opmizing our operaons to align with our business goals which yielded savings of approximately $15.8 million in 2023, primarily due to the reduced headcount related costs as a result of the 2022 reducon in force and the overall lower headcount in 2023. In 2023, clinical trial costs decreased by approximately $23.7 million, which is largely aributed to the wind-down of certain clinical trials. We also slowed the producon of pre-launch inventory while we resubmied our NDA to the FDA. We submied the revised NDA in September 2023 and are awaing a response from the FDA on our PDUFA date of March 27, 2024. We believe we have suﬃcient levels of pre-launch inventory on hand to support both the U.S., if approved, and the European launch that were previously expensed in the current or prior years to R&D expenses. During 2022, we incurred higher regulatory compliance fees associated with vadadustat, higher costs associated with the exploraon of a new manufacturing method and process costs related to Auryxia and recorded a $8.8 million non-cash Akebia Therapeucs, Inc. | Form 10-K | Page 116 Table of Contents expense in connecon with the R&D services the Company received from Otsuka. In addion, in 2022, received $5.4 million from our then collaboraon partner which was used to oﬀset the cost of the pre-launch inventory of $13.0 million ($7.6 million net). The following table summarizes our R&D expenses for the years ended December 31, 2023 and 2022 Years ended December 31, (in thousands): 2023 2022 Vadadustat clinical trial and other external costs Vadadustat pre-launch inventory External costs for other programs, including feasibility and new processes and methods associated with commercial products Total external R&D expenses Internal personnel, consulng, facilies and other Total R&D expenses $ $ 14,792 $ 6,434 7,902 29,128 33,951 63,079 $ 51,196 7,589 21,422 80,207 49,779 129,986 We expect to incur signiﬁcant R&D expenses in future periods in support of ongoing or planned studies with respect to the development of potenal product candidates and our product candidate porolio as well as vadadustat. Selling, General and Administrave Expenses—SG&A expenses were $100.2 million for the year ended December 31, 2023, compared to $138.6 million for the year ended December 31, 2022. The decrease of $38.4 million was primarily due to decreased headcount related costs, including stock-based compensaon, as a result of the 2022 reducons in force, decreased professional service, consulng and outsourced contract expenses and lower markeng and promoonal expenses. In addion, we successfully reduced our facilies footprint in May 2023 when we assigned our lease for 27,924 square feet of oﬃce space that was located in the Boston, Massachuses, or the Boston Lease, allowing us to reduce our costs by approximately $2.4 million annually. See Note 9, Leases, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon on the Boston Lease. While we expect to connue to ﬁnd ways to operate more eﬃciently and reduce our general and administrave expenses, we will invest those savings in our sales and markeng and commercial eﬀorts as we prepare for the launch of vadadustat, if approved in the U.S. License Expenses—License expense related to royales due to Panion for sales of Riona in Japan were $3.2 million for each of the years ended December 31, 2023 and 2022. Restructuring Expenses—Restructuring expenses were $0.2 million for the year ended December 31, 2023, compared to $15.9 million for the year ended December 31, 2022. Following the receipt of the complete response leer, or CRL, for vadadustat in the second quarter of 2022, we implemented a reducon of our workforce which reduced our headcount by approximately 42% and impacted all departments, including several members of senior management. On November 7, 2022, we implemented a further reducon in our workforce by approximately 14% consisng solely of individuals within the commercial organizaon as a result of our decision to shi to a strategic account management focused model for our commercial eﬀorts. These acons reﬂected our determinaon to refocus our strategic priories around our commercial product, Auryxia, and our development porolio, and were steps in a broader cost savings plan to signiﬁcantly reduce our operang expense proﬁle. We connue to decrease our operang expenses by seeking to operate more eﬃciently and curtail non-headcount related expense growth. We expect to slightly increase our headcount primarily on our commercial and medical aﬀairs teams in 2024 in connecon with a vadadustat launch, if approved. Other Expense, Net—Other expense, net, was $5.1 million for the year ended December 31, 2023, compared to $12.5 million for the year ended December 31, 2022. The decrease was primarily due to a decrease in interest expense as a result of reducing our outstanding principal balance on the Pharmakon Term Loans by $32.0 million oﬀset by a nearly 228 basis point increase in the interest rate since the year ended December 31, 2022. In addion, we no longer record interest on our liability for the sale of future royales. Loss on Exnguishment of Debt—During the year ended December 31, 2022, we recorded a debt exnguishment loss of $0.9 million related to the principal prepayments made on the Pharmakon Term Loans pursuant to the Second Amendment and Waiver. Loss on Lease Terminaon—On May 26, 2023 we incurred a loss on lease terminaon of $0.5 million in connecon with the assignment of our Boston Lease. In accordance with ASC 842, Leases, we wrote oﬀ the right-of-use asset and lease liability associated with the Boston Lease, and recognized the diﬀerence between the right-of-use asset and the lease liability oﬀset by the payment we made to LG Chem Life Sciences Innovaon Center, Inc. in connecon with the assignment of $1.3 million. See Note 9, Leases, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10- K for further informaon. Akebia Therapeucs, Inc. | Form 10-K | Page 117 Table of Contents Liquidity and Capital Resources As of December 31, 2023, we had cash and cash equivalents of approximately $42.9 million and restricted cash of $1.7 million. To date, we have funded our operaons principally through sales of our common stock, including through our employee stock purchase plan, product sales, payments received from our collaboraon and licensing partners, borrowings under term loans, a working capital payment from CSL Vifor also referred to as a refund liability and a royalty transacon. From incepon through December 31, 2023, we raised approximately $820.2 million of net proceeds from the sale of equity, including $519.8 million from various underwrien public oﬀerings, $230.4 million from at-the-market oﬀerings, or ATM Oﬀerings, pursuant to our sales agreement with Jeﬀeries LLC and prior sales agreements with Cantor Fitzgerald & Co., and $70.0 million from the sale of 7,571,429 shares of common stock to CSL Vifor. From January 1, 2024 through February 23, 2024, we sold 13,261,311 shares of our common stock under our Sales Agreement, resulng in proceeds to us of $18.7 million, net of oﬀering expenses, which are not included in the above amounts reported under the ATM sales agreement. We have incurred recurring losses and negave cash ﬂow from operaons in each year since incepon and ancipate net losses and negave cash ﬂows for the near future. For the years ended December 31, 2023 and 2022, we incurred net operang losses of $51.9 million and $94.2 million, respecvely. As of December 31, 2023 and 2022, we had an accumulated deﬁcit of $1.6 billion. We currently have exclusive rights under a series of patents and patent applicaons to commercialize Auryxia in the U.S. that protect us from generic drug compeon unl March 2025. Following LoE, in the U.S., we may not be able to realize enough product revenue from sales of Auryxia to realize net proﬁts from product sales. While we believe CMS's decision to include phosphate binders in the dialysis bundle could potenally lead to higher sales of Auryxia aer the LoE date than in other LoE scenarios, and plan to work with payors and providers to connue the use of Auryxia beyond LoE, Auryxia product sales have not generated, and may not generate, now or following LoE in the U.S., suﬃcient product revenue to realize net proﬁts from product sales to cover our current or long-term operang costs. We believe our exisng cash resources and the cash we expect to generate from product, royalty, supply and license revenues as well as the borrowings and potenal future borrowing that are available under the BlackRock Credit Agreement and the working capital liability are suﬃcient to fund our current operang plan for at least twenty-four months if vadadustat is approved in the U.S. and for at least twelve months from ﬁling the Form 10-K, if vadadustat is not approved in the U.S. However, if our operang performance deteriorates signiﬁcantly from the levels expected in our operang plan, or if vadadustat is not approved in the U.S., it would have an adverse eﬀect on our liquidity and capital resources and could aﬀect our ability to connue as a going concern in the future. In addion, we may also seek to sell addional private or public equity, enter into new debt transacons, explore potenal strategic transacons or a combinaon of these approaches or other strategic alternaves. If we raise addional funds by issuing equity securies, our shareholders would experience diluon. Debt ﬁnancing, if available, may involve covenants restricng our operaons or our ability to incur addional debt. Any debt ﬁnancing or addional equity that we raise may contain terms that are not favorable to us or our stockholders. Addional ﬁnancing may not be available to us in amounts or on terms acceptable to us, if at all. If we are unable to raise addional capital in suﬃcient amounts when needed or on aracve terms, we may not be able to pursue development and commercial acvies related to Auryxia and vadadustat, if approved, or any addional products and product candidates, including those that may be in-licensed or acquired. Any of these events could signiﬁcantly harm our business, ﬁnancial condion and prospects. There can be no assurance that the current operang plan will be achieved in the me frame ancipated by us, or that our cash resources will fund our operang plan for the period of me ancipated by us, or that addional funding will be available on terms acceptable to us, or at all. Our forecast of the period of me through which our ﬁnancial resources will be adequate to support our operaons is a forward-looking statement and involves numerous risks and uncertaines, and actual results could vary as a result of a number of factors, many of which are outside our control. We have based this esmate on assumpons that may be substanally diﬀerent than actual results, and we could ulize our available capital resources sooner than we currently expect. Our future funding requirements, both near- and long-term, will depend on many factors including, but not limited to, those described under Part I, Item 1A. Risk Factors under the heading "Risks Related to our Financial Posion, Need for Addional Capital and Growth Strategy." Contractual Obligaons and Commitments Debt Agreements and Other Funding Arrangements BlackRock Term Loans On January 29, 2024, or the Closing Date, we entered into the BlackRock Credit Agreement, which provides for a senior secured term loan facility, in the aggregate principal amount of up to $55.0 million, or the Term Loan Facility. The inial tranche of $37.0 million, or the Tranche A Loan, was funded on the Closing Date and used to pay oﬀ the Pharmakon Term Loans. The Term Loan Facility provides for addional tranches available as follows: (i) $8.0 million available in a single draw Akebia Therapeucs, Inc. | Form 10-K | Page 118 Table of Contents through December 31, 2024, or the Tranche B Loan, and (ii) $10.0 million available in a single draw through December 31, 2024, or the Tranche C Loan and, together with the Tranche A Loan and the Tranche B Loan, the Term Loans. The Term Loan Facility matures on March 31, 2025, which will be automacally extended to January 29, 2028 if we receive FDA approval for vadadustat on or prior to June 30, 2024, or the BlackRock Maturity Date. We are required to make interest-only payments unl December 31, 2026 aer which, we will begin making equal monthly principal payments. The Term Loan Facility will accrue interest at a ﬂoang annual rate equal to the sum of (i) term Secured Overnight Financing Rate, or SOFR, for a tenor of one month (subject to a ﬂoor of 4.25% per annum) plus (ii) a margin of 6.75% per annum (subject to an overall cap of 15.00% per annum on the all-in interest rate). During the connuance of any payment event of default the interest rate on such overdue sum will automacally increase by an addional 3.0% per annum, and may be subject to an addional late fee of 2.0% of such overdue sum. In the event of certain prespeciﬁed events, the repayment schedule will be accelerated. For example, if FDA approval of vadadustat is not obtained on or prior to June 30, 2024, the interest only period will automacally terminate on October 1, 2024, and we will be required to repay the Term Loans in seven equal monthly payments (comprised of principal and interest), commencing on October 1, 2024 and ending on the BlackRock Maturity Date. All obligaons under the Term Loan Facility are secured by substanally all of our exisng and aer-acquired assets. The BlackRock Credit Agreement requires us to either (i) maintain cash and cash equivalents, measured as of the last day of each ﬁscal month, greater than or equal to $15.0 million or (ii) earn consolidated revenue, measured as of the last day of each ﬁscal month for the trailing twelve-month period, of $150.0 million. The BlackRock Credit Agreement contains certain representaons and warranes, aﬃrmave and negave covenants that limit our ability to engage in speciﬁed types of transacons and other provisions typical within a credit agreement. If an event of default occurs and is connuing under the BlackRock Credit Agreement, BlackRock is entled to take enforcement acon, including acceleraon of amounts due. If we prepay the Term Loans prior to the BlackRock Maturity Date, we will be required to pay a prepayment fee ranging from 1.0% to 4.0% of the amount prepaid. On the Closing Date, Kreos Capital VII Aggregator SCSp, an aﬃliate of Kreos, or the Warrant Holder, received a warrant to purchase 3,076,923 shares of our common stock, at an exercise price per share of $1.30, and upon borrowing of Tranche C, we will become obligated to issue addional warrants to purchase 1,153,846 shares of our common stock at an exercise price per share of $1.30. Each warrant shall be exercisable for eight years from date of issuance. As of December 31, 2023, we had outstanding debt of $35.0 million, net of debt issuance costs of $0.3 million with Pharmakon. In connecon with the entry into the BlackRock Credit Agreement, on the Closing Date, we terminated the Pharmakon Loan Agreement, all obligaons thereunder were paid in full and discharged and Pharmakon's security interests in our assets and property were released. See Note 7, Indebtedness, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon. Working Capital Fund/Refund Liability In February 2022, we amended our agreement with CSL Vifor and they contributed $40.0 million to a working capital fund, or the Working Capital Fund, established to parally fund our costs of purchasing vadadustat from our contract manufacturers. The Working Capital Fund amount may ﬂuctuate, and will be repaid to CSL Vifor over me. We have recorded the Working Capital Fund as a refund liability under ASC 606, Revenue from Contracts with Customers. The refund liability is considered a debt arrangement with zero coupon interest and we impute interest on the refund liability at a rate of 15.0% per annum. As of December 31, 2023, the $40.1 million refund liability is classiﬁed as a long-term liability based on management's esmated ming of the repayment of the refund liability to CSL Vifor exceeding one-year. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, in the accompanying notes to the consolidated ﬁnancial statements in Part II, Item 8 of this Form 10-K for further informaon. Liability Related to Sale of Future Royales In February 2021, we sold to HealthCare Royalty Partners IV L.P., or HCR, our right to receive royales and sales milestones for vadadustat in Japan and certain other Asian countries, such countries collecvely, the MTPC Territory, such payments collecvely the Royalty Interest Payments, in each case, payable to us under the MTPC Agreement. The Royalty Interest Payments are subject to an annual maximum “cap” of $13.0 million, aer which we will receive 85% of the Royalty Interest Payments for the remainder of that year. The Royalty Interest Payments are also subject to an aggregate maximum “cap” of $150.0 million, aer which the Royalty Interest Payments will revert back to us. Akebia Therapeucs, Inc. | Form 10-K | Page 119 Table of Contents We received $44.8 million from HCR, net of certain transacon expenses, which we recorded as a liability at the transacon date. We amorze the liability related to the sale of future royales using the eﬀecve interest method over the life of the arrangement. The annual eﬀecve interest rate as of December 31, 2023 was 0%. We retain the right to receive all potenal future regulatory milestones for vadadustat under the MTPC Agreement. During the year ended December 31, 2023 and 2022, we recorded $2.0 million and $1.8 million of non-cash royalty revenue, respecvely. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, in the accompanying notes to the consolidated ﬁnancial statements in Part II, Item 8 of this Form 10-K for further informaon. Oﬀ-Balance Sheet Arrangements Leer of Credit As of December 31, 2023, in connecon with the Cambridge Lease (as deﬁned below), we had $1.7 million in a leer of credit outstanding. Director and Oﬃcer Indemniﬁcaon We have entered into indemniﬁcaon agreements with our directors and certain oﬃcers that will require us, among other things, to indemnify them against certain liabilies that may arise by reason of their status or service as directors or oﬃcers. No demands have been made upon us to provide indemniﬁcaon under such agreements and there are no claims that we are aware of that could have a material eﬀect on our consolidated ﬁnancial statements. Contractual Obligaons and Commitments Other Than Debt Agreements We are party to contractual obligaons involving commitments to make payments to third pares in the future. Certain contractual obligaons are reﬂected on our consolidated balance sheet as of December 31, 2023, while others are considered future obligaons. Our material cash requirements as of December 31, 2023, include contractual obligaons and commitments arising in the normal course of business, including leases, license agreements, manufacturing agreements and uncondional purchases commitments which are described in more detail below. Cambridge Leases We lease approximately 65,167 square feet of oﬃce, storage and laboratory space in Cambridge, Massachuses under non-cancelable operang leases, collecvely the Cambridge Lease. The oﬃce and storage lease expires on September 11, 2026 and the lease for the laboratory space expires on January 31, 2025. We ceased using approximately two-thirds of our oﬃce space in 2022 and we are currently markeng the furnished oﬃce space for sublease. See Note 9, Leases, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon. License Agreements We have a license agreement with Panion, under which we are required to pay royales related to the sale of Auryxia. The royalty payment obligaons are conngent upon generang product revenue, and the amount and ming of such payments are not known. See Note 10, Commitments and Conngencies, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K for further informaon. In June 2021, we entered into a license agreement, or Cyclerion Agreement, with Cyclerion Therapeucs Inc. under which we obtained an exclusive global license under certain intellectual property rights to research, develop and commercialize praliciguat, an invesgaonal oral soluble guanylate cyclase smulator. We may be obligated to pay up to an aggregate of $222.0 million in speciﬁed development and regulatory milestone payments, certain speciﬁed commercial milestones and ered royales ranging from a low-single-digit to mid-double-digit percentage of net sales, on a product-by-product basis, and subject to reducon upon expiraon of patent rights or the launch of a generic product in the territory. Unless earlier terminated, the Cyclerion Agreement will expire on a product-by-product and country-by-country basis upon the expiraon of the last royalty term, which ends upon the longest of (i) the expiraon of the patents licensed under the Cyclerion Agreement, (ii) the expiraon of regulatory exclusivity for such product and (iii) ten years from ﬁrst commercial sale of such product. We may terminate the Cyclerion Agreement in its enrety or only with respect to a parcular licensed compound or product upon 180 days' prior wrien noce to Cyclerion. The pares also have customary terminaon rights, subject to a cure period, in the event of the other party’s material breach of the Cyclerion Agreement or in the event of certain addional circumstances. Manufacturing Agreements We have various supply arrangements to which we are a party, and we are obligated to pay for drug substance and drug product for commercial use. Under one of our agreements, we are required to purchase a minimum quanty of Auryxia drug substance at a predetermined price. We are also obligated to purchase a certain percentage of the global demand for Akebia Therapeucs, Inc. | Form 10-K | Page 120 Table of Contents vadadustat drug substance and drug product based on certain quarterly and annual forecasts we provide to certain suppliers. Our supply agreements for vadadustat drug substance and drug product provide for a volume-based pricing structure. We may also be required to reimburse certain suppliers for reasonable expenses. See Note 10, Commitments and Conngencies, in the accompanying notes to the consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10- K for further informaon. Amounts Due Under Former Manufacturing and Uncondional Purchase Commitments On December 22, 2022, we and BioVectra terminated any and all exisng agreements for BioVectra to supply us Auryxia drug substance. Under the BioVectra Terminaon Agreement, we agreed to pay BioVectra a total of $32.5 million consisng of (i) an upfront payment of $17.5 million that was paid in December 2022 and (ii) six quarterly payments of $2.5 million commencing in April 2024. In addion, we and BioVectra have released one another from all exisng and future claims and liabilies and agreed to return certain materials and documents. Other Third Party Contracts Uncondional Purchase Commitments We enter into agreements in the normal course of business with various vendors, which are generally cancellable upon noce. Payments due upon cancellaon consist only of payments for services provided or expenses incurred, including non-cancellable obligaons of service providers, up to the date of cancellaon. In addion, we contract with various organizaons to conduct R&D acvies with remaining contract costs to us of approximately $44.7 million as of December 31, 2023. The scope of the services under these R&D contracts can be modiﬁed and the contracts cancelled by us upon wrien noce. In some instances, the contracts may be cancelled by the third party upon wrien noce. Cash Flows The following table provides a summary of cash ﬂow data for each applicable period: NET CASH PROVIDED BY/(USED IN) (in thousands): Operang acvies Invesng acvies Financing acvies Net decrease in cash, cash equivalents and restricted cash Cash, cash equivalents and restricted cash — beginning of period Cash, cash equivalents and restricted cash — end of period Operang Acvies Years ended December 31, 2022 2023 (23,384) $ — (25,206) (48,590) $ 93,169 44,579 $ (73,154) (114) 14,598 (58,670) 151,839 93,169 $ $ $ Net cash used in operang acvies during the year ended December 31, 2023 was $23.4 million. Net cash used in operang acvies during the year ended December 31, 2023 consisted of a net loss of $51.9 million and net non-cash adjustments of $49.3 million, including amorzaon of our intangible asset of $36.0 million, and a reducon of $20.7 million in working capital. Net cash used in operang acvies during the year ended December 31, 2022 was $73.2 million. Net cash used in operang acvies consisted of a net loss of $94.2 million and non-cash adjustments of $22.5 million, including amorzaon of our intangible asset of $36.0 million and decrease in our inventory ﬁrm purchase commitments that reduced our net loss by $65.9 million, primarily due to the terminaon of our supply agreement with BioVectra, and a reducon of $1.4 million in working capital. Invesng Acvies No net cash was used in invesng acvies during the year ended December 31, 2023. Net cash used in invesng acvies during the year ended December 31, 2022 of $0.1 million was used to purchase equipment. Financing Acvies Net cash used in ﬁnancing acvies for the year ended December 31, 2023 was $25.2 million and consisted of principal payments of $32.0 million parally oﬀset by $6.7 million of net proceeds from the sale of common stock under our ATM Facility and from the sale of stock under our employee stock purchase plan. Akebia Therapeucs, Inc. | Form 10-K | Page 121 Table of Contents Net cash provided by ﬁnancing acvies for the year ended December 31, 2022 was $14.6 million and consisted of net proceeds from a refund liability to a customer of $40.0 million, net proceeds from the issuance of common stock of $7.1 million under our then current at-the-market oﬀering facility and proceeds from the exercise of common stock opons and from the sale of stock under our employee stock purchase plan, parally oﬀset by principal payments of debt of $33.0 million. Recent Accounng Pronouncements For a discussion of recent accounng pronouncements not yet adopted, see Note 2, Summary of Signiﬁcant Accounng Policies, to our consolidated ﬁnancial statements included in Part II, Item 8 of this Form 10-K. Crical Accounng Policies and Signiﬁcant Judgments and Esmates Our management's discussion and analysis of our ﬁnancial condion and results of operaons are based upon our consolidated ﬁnancial statements included elsewhere in this Form 10-K, which consolidated ﬁnancial statements have been prepared in accordance with U.S. generally accepted accounng principles, or U.S. GAAP. The preparaon of these consolidated ﬁnancial statements requires us to make esmates and judgments that aﬀect the reported amounts of assets, liabilies, revenues and expenses, including the current or long-term classiﬁcaon of such assets, liabilies and expenses, classiﬁcaon of the expenses and the related disclosure of conngent assets and liabilies. We monitor our esmates on an ongoing basis for changes in facts and circumstances, and material changes in these esmates could occur in the future. Changes in esmates are recorded in the period in which they become known. We base our esmates on historical experience and other assumpons that we believe to be reasonable under the circumstances. Actual results may diﬀer from our esmates if past experience or other assumpons do not turn out to be substanally accurate. While our signiﬁcant accounng policies are described in more detail in Note 2, Summary of Signiﬁcant Accounng Policies, to our consolidated ﬁnancial statements in Part II, Item 8 of this Form 10-K, we believe the following accounng policies are those most crical to the judgments and esmates used in the preparaon of our consolidated ﬁnancial statements and to understanding of our results of operaons. Inventories, including Pre-Launch Inventory We assess the value of our inventories quarterly at the lower-of-cost or net realizable value, with approximate cost determined using the ﬁrst-in, ﬁrst-out method. Work-in-process and ﬁnished goods inventories include materials, labor, and overhead. Other long-term assets include inventory expected to remain on hand beyond one year. We write down inventories based on quality control tesng data, or when product is obsolete or condions exist that suggest that inventory may be in excess of the ancipated demand based on assumpons about future demand for our products and market condions. Our esmates of forecasted demand are based upon our analysis and assumpons including, but not limited to, expected product lifecycles, market condions, product development plans and historical usage by product. If actual market condions are less favorable than our forecasts, or actual demand from our customers is lower than our esmates, we may be required to record addional inventory write-downs. If actual market condions are more favorable than ancipated, inventory previously wrien down may be sold, resulng in lower cost of sales and higher income from operaons than expected in that period. Impairment charges are recorded as a component of cost of product sales in the consolidated statements of operaons and comprehensive loss in the period in which the impairment or excess quanty is idenﬁed. The costs incurred to manufacture pre-launch inventory in advance of markeng authorizaon in the EU and FDA approval in the U.S. is expensed to R&D. Impairment of Long-Lived Assets and Intangible Assets Subject to Amorzaon Long-lived assets primarily include property and equipment, right-of-use assets, intangible assets and goodwill. Right-of-use assets pertain to leases of our oﬃce and laboratory spaces and the property and equipment primarily related to the leasehold improvements made to the right-of-use assets as well as furniture and laboratory equipment. In 2018, we recorded a deﬁnite-lived intangible asset related to developed product rights for Auryxia in connecon with our merger with Keryx Biopharmaceucals, Inc., or Keryx. We amorze our intangible asset that has a ﬁnite life using the straight-line method, which we esmated to be six years. As of December 31, 2023, we had $36.0 million on our consolidated balance sheet that is being amorzed through December 2024. Goodwill is the amount by which the purchase price of acquired net assets in a business combinaon exceeded the fair values of net idenﬁable assets on the date of acquision. Goodwill is not amorzed but is subject to impairment test annually or more frequently if events or changes in circumstances suggest that the carrying value of goodwill may not be recoverable, Akebia Therapeucs, Inc. | Form 10-K | Page 122 Table of Contents ulizing either the qualitave or quantave method. The goodwill recorded in our ﬁnancial statements pertains to the merger with Keryx in 2018. Annually, or more frequently upon certain indicators of impairment, we review our esmates and assumpons underlying the fair value of our long-lived assets when indicators of impairment are present. If an impairment indicator exists, we perform a recoverability test by a comparison of the carrying amount of an asset or reporng unit to the future undiscounted net cash ﬂows expected to be generated by the asset or reporng unit. If such assets are considered to be impaired, the impairment to be recognized is measured by the amount by which the carrying amount of the asset exceeds the fair value of the asset or reporng unit. We calculate the fair value of the long-lived asset group as the present value of esmated future cash ﬂows expected to be generated from the long-lived asset group using a risk-adjusted discount rate. In determining esmated future cash ﬂows associated with the long-lived asset group, we use market parcipant assumpons pursuant to ASC Topic 820, Fair Value Measurements and Disclosures. Working Capital Fund/Refund Liability to Customer We treat the refund liability related to the Vifor Working Capital Fund as a debt arrangement with zero coupon interest, which is recorded at net present value. On March 18, 2022, when the funds were received from CSL Vifor, we recorded an inial discount on the refund liability and a corresponding deferred gain to the refund liability on the consolidated balance sheets. The discount on the refund liability is being amorzed to interest expense using the eﬀecve interest method over the expected term of the Vifor Agreement. The deferred gain is being amorzed to interest income on a straight-line basis over the expected term of the Vifor Agreement. Product Revenue, Net We recognize revenue on product sales when the customer obtains control of our product, which occurs at a point in me, typically upon delivery to the customer. We expense incremental costs of obtaining a contract as and when incurred if the expected amorzaon period of the asset that we would have recognized is one year or less. The most signiﬁcant esmate we are required to make is related to government and private payor rebates, chargebacks, discounts and fees, collecvely rebates (collecvely considered variable consideraon). The values of the rebates provided to third-party payors vary signiﬁcantly and are based on government-mandated discounts and our arrangements with other third-party payors. To esmate our total rebates, we esmate the percentage of prescripons that will be covered by each third-party payor, which is referred to as the payor mix. Thus, revenue from product sales is recorded at the net sales price (transacon price), which includes esmates of variable consideraon, which are described below. We track available informaon regarding changes, if any, to the payor mix for our products, to our contractual terms with third-party payors and to applicable governmental programs and regulaons and levels of our products in the distribuon channel. We adjust our esmated rebates based upon new informaon as it becomes available, including informaon regarding actual rebates for our products and forecasted customer buying and payment demands. Claims by third-party payors for rebates are submied to us signiﬁcantly aer the related sales, potenally resulng in adjustments in the period in which the new informaon becomes known. Our adjustments to revenue related to prior period sales have not been signiﬁcant. Further details on the variable consideraon components or reserves include: • • • Trade Discounts and Allowances—Discounts that include incenve fees that are explicitly stated in our contracts. In addion, we compensate (through trade discounts and allowances) our customers for sales order management, data and distribuon services. Product Returns—Consistent with industry pracce, subject to certain caps for certain customers, we generally oﬀer customers a limited right of return which allows for the product to be returned when the product expiry is within an allowable window, when the quanty delivered is diﬀerent than quanty ordered, the product is damaged in transit prior to receipt by the customer, or is subject to a recall. This right of return generally lapses once the product is provided to a paent. We esmate the amount of our product sales that may be returned for credit by our customers. Product return reserves are esmated primarily based on our gross sales mulplied by an esmated return rate calculated using our historical actual rate of return for product sales as well as recent trends on lots sll subject to the return window. In addion, certain customers are subject to an annual cap on returns of 2% of gross sales in any given year. Provider Chargebacks and Discounts—Chargebacks for fees and discounts to providers represent the esmated obligaons resulng from contractual commitments to sell products to qualiﬁed healthcare providers at prices lower than the list prices charged to customers who directly purchase the product from us. Customers charge us for the diﬀerence between what they pay for the product and the ulmate selling price to the qualiﬁed healthcare providers. Reserves for chargebacks consist of credits that we expect to issue for units that remain in the distribuon Akebia Therapeucs, Inc. | Form 10-K | Page 123 Table of Contents channel at each reporng period end that we expect will be sold to qualiﬁed healthcare providers and chargebacks that customers have claimed but for which we have not yet issued a credit. • Commercial and Medicare Part D Rebates—We contract with various commercial payor organizaons, primarily health insurance companies and pharmacy beneﬁt managers, for the payment of rebates with respect to ulizaon of our products. We esmate the rebates for commercial and Medicare Part D payors based upon (i) our contracts with the payors and (ii) informaon obtained from our customers and other third pares regarding the payor mix for Auryxia. • Other Government Rebates—We are subject to discount obligaons under state Medicaid programs and other government programs. We esmate Medicaid and other government programs rebates based upon a range of possible outcomes that are probability-weighted for the esmated payor mix. For Medicare, we also esmate the number of paents in the prescripon drug coverage gap for whom we will owe an addional liability under the Medicare Part D program. Our liability for these rebates consists of invoices received for claims from prior quarters that have not been paid or for which an invoice has not yet been received, esmates of claims for the current quarter, and esmated future claims that will be made for product that has been recognized as revenue, but which remains in the distribuon channel at the end of each reporng period. • Other Incenves—Other incenves that we oﬀer include voluntary paent assistance programs such as our co-pay assistance program, which are intended to provide ﬁnancial assistance to qualiﬁed commercially insured paents with prescripon drug co-payments required by payors. The calculaon of the accrual for co-pay assistance is based on actual claims processed during a given period, as well as historical ulizaon data to esmate the amount we expect to receive associated with product that has been recognized as revenue, but remains in in the distribuon channel at the end of each reporng period. Overall, these reserves reﬂect our best esmates of the amount of consideraon to which we are entled based on the terms of the respecve underlying contracts. Our calculaon of the reserves, include esmates and judgments that materially aﬀect our recognion of net product revenues. Changes in our esmates of net product revenues could have a material eﬀect on net product revenues recorded in the period in which we determine that change occurs. Research and Development Expense R&D costs are expensed as incurred. Internal R&D expenses are comprised of costs incurred in providing R&D acvies, including salaries and bonuses, employee beneﬁts and stock-based compensaon for personnel engaged in R&D acvies. In addion, they include facility costs, including the laboratory and an allocaon of oﬃce space for ulizaon by R&D staﬀ, depreciaon expense on the laboratory equipment as well as other direct costs such as lab supplies. External R&D costs include development of potenal new manufacturing processes and methods for both commercial and non-commercial products, conceptual formulaon and design of possible product and process alternaves for commercial and non-commercial products, research compounds and clinical manufacturing costs, costs incurred for consultants and other outside services, such as data management and stascal analysis support and materials and supplies used in support of the clinical and preclinical programs and costs paid to CROs including invesgave sites that conduct our clinical trials. We also expense pre-launch inventory to R&D unl approval from the respecve regulatory body is obtained. We esmate certain costs and expenses and accrue for these liabilies as part of our process of preparing ﬁnancial statements. Examples of areas in which subjecve judgments may be required include, among other things, costs associated with services provided by contract organizaons for preclinical development and manufacturing of our product candidates and clinical trials. We accrue for costs incurred as the services are being provided by monitoring the status of the trial or services provided, and the invoices received from our external service providers which can at mes be signiﬁcantly delayed. As actual costs become known to us, we adjust our accruals. To date, our esmates have not diﬀered materially from the actual costs incurred. However, subsequent changes in esmates may result in a material change in our accruals, which could also materially aﬀect our balance sheet and results of operaons. Item 7A. Quantave and Qualitave Disclosures about Market Risk We are a smaller reporng company as deﬁned by Rule 12b-2 of the Exchange Act, and are not required to provide informaon under this item. Akebia Therapeucs, Inc. | Form 10-K | Page 124 Table of Contents Item 8. Financial Statements and Supplementary Data Index to Consolidated Financial Statements Report of Independent Registered Public Accounng Firm (PCAOB ID: 42) Consolidated Balance Sheets Consolidated Statements of Operaons and Comprehensive Loss Consolidated Statements of Stockholders’ (Deﬁcit) Equity Consolidated Statements of Cash Flows Notes to Consolidated Financial Statements Page 126 128 129 130 131 132 All ﬁnancial statement schedules have been omied, since the required informaon is not applicable or is not present in amounts suﬃcient to require submission of the schedule, or because the informaon required is included in the consolidated ﬁnancial statements and accompanying notes. Akebia Therapeucs, Inc. | Form 10-K | Page 125 Table of Contents To the Stockholders and the Board of Directors of Akebia Therapeucs, Inc. Opinion on the Financial Statements Report of Independent Registered Public Accounng Firm We have audited the accompanying consolidated balance sheets of Akebia Therapeucs, Inc. (the Company) as of December 31, 2023 and 2022, the related consolidated statements of operaons and comprehensive loss, stockholders' (deﬁcit) equity and cash ﬂows for each of the two years in the period ended December 31, 2023, and the related notes (collecvely referred to as the “consolidated ﬁnancial statements”). In our opinion, the consolidated ﬁnancial statements present fairly, in all material respects, the ﬁnancial posion of the Company at December 31, 2023 and 2022, and the results of its operaons and its cash ﬂows for each of the two years in the period ended December 31, 2023, in conformity with U.S. generally accepted accounng principles. We also have audited, in accordance with the standards of the Public Company Accounng Oversight Board (United States) (PCAOB), the Company's internal control over ﬁnancial reporng as of December 31, 2023, based on criteria established in Internal Control-Integrated Framework issued by the Commiee of Sponsoring Organizaons of the Treadway Commission (2013 framework) and our report dated March 14, 2024 expressed a qualiﬁed opinion thereon. Basis for Opinion These ﬁnancial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s ﬁnancial statements based on our audits. We are a public accounng ﬁrm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securies laws and the applicable rules and regulaons of the Securies and Exchange Commission and the PCAOB. We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether the ﬁnancial statements are free of material misstatement, whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the ﬁnancial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the ﬁnancial statements. Our audits also included evaluang the accounng principles used and signiﬁcant esmates made by management, as well as evaluang the overall presentaon of the ﬁnancial statements. We believe that our audits provide a reasonable basis for our opinion. Crical Audit Maer The crical audit maer communicated below is a maer arising from the current period audit of the ﬁnancial statements that was communicated or required to be communicated to the audit commiee and that: (1) relates to accounts or disclosures that are material to the ﬁnancial statements and (2) involved our especially challenging, subjecve or complex judgments. The communicaon of the crical audit maer does not alter in any way our opinion on the consolidated ﬁnancial statements, taken as a whole, and we are not, by communicang the crical audit maer below, providing a separate opinion on the crical audit maer or on the accounts or disclosures to which it relates. Akebia Therapeucs, Inc. | Form 10-K | Page 126 Table of Contents Descripon of the Maer Revenue Recognion - Payor Mix Impact on Measuring Variable Consideraon, Speciﬁcally Payor Rebates As of December 31, 2023, the Company recorded accrued product revenue allowances of $29.9 million, which includes payor rebates. As discussed in Note 2 to the Company’s consolidated ﬁnancial statements, the Company recognizes revenue from product sales at the net sales price (transacon price), which includes esmates of variable consideraon for which reserves are established. The Company contracts with various commercial payor organizaons, primarily health insurance companies and pharmacy beneﬁt managers, for the payment of rebates with respect to ulizaon of its products. The Company esmates the rebates for payors based upon (i) its contracts with the payors and (ii) informaon obtained from its customers and other third pares regarding the payor mix. The Company esmates these payor rebates and records such esmates in the same period the related revenue is recognized, resulng in a reducon of product revenue and the establishment of an accrued liability. Auding the measurement of the Company’s net product revenues was complex and judgmental due to the signiﬁcant esmaon required in determining the amount of consideraon that will be collected net of esmates for payor rebates. In parcular, the payor rebate is aﬀected by assumpons in payor behavior such as changes in payor mix, payor collecons and current customer contractual requirements. How We Addressed the Maer in Our Audit We obtained an understanding, evaluated the design and tested the operang eﬀecveness of controls over the Company’s revenue recognion process, including controls over the underlying assumpons and inputs used by management to esmate the payor rebates. Speciﬁcally, this included controls to assess the completeness and accuracy of the current and historical data used in calculang the esmate. Our audit procedures to test the Company’s recognion of net product revenues and speciﬁcally the variable consideraon component of payor rebates included, among others, assessing the methodology used to determine the esmate and tesng the signiﬁcant assumpons and the underlying data used by the Company in its analysis. This included tesng the reasonableness of management’s esmates to other inputs into their calculaons such as contract terms, product in the distribuon channel, and actual invoices received. We assessed the historical accuracy of management’s esmates by comparing actual acvity to previous esmates and performed analycal procedures to evaluate the completeness of the payor rebate reserves. /s/ Ernst & Young LLP We have served as the Company’s auditor since 2013. Boston, Massachuses March 14, 2024 Akebia Therapeucs, Inc. | Form 10-K | Page 127 AKEBIA THERAPEUTICS, INC. CONSOLIDATED BALANCE SHEETS Table of Contents (dollars in thousands, except per share amounts) Assets Current assets: Cash and cash equivalents Inventories Accounts receivable, net Prepaid expenses and other current assets Total current assets Property and equipment, net Operang right-of-use assets Intangible asset, net Goodwill Other long-term assets Total assets Liabilies and stockholders' (deﬁcit) equity Current liabilies: Accounts payable Accrued expenses and other current liabilies Short-term deferred revenue Current poron of long-term debt Total current liabilies Deferred revenue, net of current poron Long-term operang lease liabilies Embedded debt derivave Long-term debt, net Liability related to sale of future royales Refund liability to customer Other long-term liabilies Total liabilies Commitments and conngencies (Note 10) Stockholders' (deﬁcit) equity: Preferred stock $0.00001 par value, 25,000,000 shares authorized; no shares issued and outstanding at December 31, 2023 and 2022 Common stock: $0.00001 par value; 350,000,000 shares authorized at December 31, 2023 and 2022; 194,582,539 and 184,135,714 shares issued and outstanding at December 31, 2023 and 2022, respecvely Addional paid-in capital Accumulated other comprehensive income Accumulated deﬁcit Total stockholders' (deﬁcit) equity Total liabilies and stockholders' (deﬁcit) equity December 31, 2023 2022 42,925 $ 15,691 39,290 20,243 118,149 3,629 12,416 36,042 59,044 12,423 241,703 $ 14,635 $ 67,735 — 17,500 99,870 43,296 8,947 — 17,183 54,013 40,093 8,885 272,287 90,466 21,568 40,284 32,864 185,182 5,214 29,158 72,084 59,044 5,372 356,054 18,021 75,777 3,738 32,000 129,536 43,296 28,961 760 34,078 57,484 40,992 15,717 350,824 — 2 1,578,358 6 (1,608,950) (30,584) 241,703 $ — 2 1,562,247 6 (1,557,025) 5,230 356,054 $ $ $ $ The accompanying notes are an integral part of these consolidated ﬁnancial statements. Akebia Therapeucs, Inc. | Form 10-K | Page 128 Table of Contents AKEBIA THERAPEUTICS, INC. CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (dollars in thousands, except per share amounts) Revenues: Product revenue, net License, collaboraon and other revenue Total revenues Cost of goods sold: Cost of product and other revenue Amorzaon of intangible asset Total cost of goods sold Operang expenses: Research and development Selling, general and administrave License Restructuring Total operang expenses Loss from operaons Other income (expense): Interest expense Other income Loss on exnguishment of debt Loss on terminaon of lease Net loss before income taxes Net loss Comprehensive loss Net loss per share: Basic and diluted Weighted average number of common shares outstanding: Basic and diluted Years Ended December 31, 2022 2023 $ $ $ 170,301 $ 24,322 194,623 38,107 36,042 74,149 63,079 100,233 3,237 181 166,730 (46,256) (6,032) 887 — (524) (51,925) (51,925) $ (51,925) $ 176,949 115,535 292,484 49,526 36,042 85,568 129,986 138,601 3,175 15,933 287,695 (80,779) (15,687) 3,146 (906) — (94,226) (94,226) (94,226) $(0.28) $(0.52) 187,465,448 182,782,680 The accompanying notes are an integral part of these consolidated ﬁnancial statements. Akebia Therapeucs, Inc. | Form 10-K | Page 129 Table of Contents (dollars in thousands) Balance at December 31, 2021 Akebia Therapeucs, Inc. CONSOLIDATED STATEMENTS OF STOCKHOLDERS' (DEFICIT) EQUITY Common Stock Shares Amount Addional Paid-In Capital Accumulated Other Comprehensive Income (Loss) 177,000,963 $ 1 $ 1,536,800 $ Accumulated Deﬁcit (1,462,799) $ 6 $ Total Stockholders' (Deﬁcit) Equity 74,008 Issuance of common stock, net of issuance costs Proceeds from sale of stock under employee stock purchase plan Stock-based compensaon expense Restricted stock unit vesng Exercise of opons Net loss Balance at December 31, 2022 Issuance of common stock, net of issuance costs Proceeds from sale of stock under employee stock purchase plan Stock-based compensaon expense Restricted stock unit vesng Exercise of opons Net loss Balance at December 31, 2023 4,404,600 335,146 — 2,252,565 142,440 — 184,135,714 $ 6,189,974 200,194 — 4,054,407 2,250 — 194,582,539 $ 1 — — — — — 2 $ — — — — — — 2 $ 7,121 410 17,849 — 67 — 1,562,247 $ 6,708 85 9,317 — 1 — 1,578,358 $ — — — — — — 6 $ — — — — — — 6 $ — — — — — (94,226) (1,557,025) $ — — — — — (51,925) (1,608,950) $ 7,122 410 17,849 — 67 (94,226) 5,230 6,708 85 9,317 — 1 (51,925) (30,584) The accompanying notes are an integral part of these consolidated ﬁnancial statements. Akebia Therapeucs, Inc. | Form 10-K | Page 130 Table of Contents Akebia Therapeucs, Inc. CONSOLIDATED STATEMENT OF CASH FLOWS (dollars in thousands) Operang Acvies: Net loss Adjustments to reconcile net loss to net cash used in operang acvies: Depreciaon expense Amorzaon of intangible asset Interest expense related to sale of future royales (non-cash) Accreon of interest expense and amorzaon of refund liability Royalty revenue from MTPC (non-cash) Collaboraon revenue in connecon with the terminaon of the Otsuka Agreement (non-cash) R&D expense in connecon with the terminaon of the Otsuka Agreement (non-cash) Amorzaon of right-of-use assets Write-oﬀ on terminaon of Boston Lease (non-cash) Loss on exnguishment of debt Provision of inventories Change in ﬁrm purchase commitments Stock-based compensaon expense Change in fair value of embedded debt derivave Changes in operang assets and liabilies: Accounts receivable Inventories Prepaid expenses and other current assets Other long-term assets Accounts payable Accrued expense and other current liabilies Lease liabilies Deferred revenue Other long-term liabilies Net cash used in operang acvies Invesng Acvies: Purchase of property and equipment Net cash provided by (used in) invesng acvies Financing Acvies: Proceeds from refund liability to customer Proceeds from the issuance of common stock, net of issuance costs Proceeds from the sale of stock under employee stock purchase plan Proceeds from the exercise of common stock opons Principal payments on debt Net cash (used in) provided by ﬁnancing acvies Decrease in cash, cash equivalents and restricted cash Cash, cash equivalents and restricted cash at beginning of the period Cash, cash equivalents and restricted cash at end of the period Supplemental disclosure of cash ﬂow informaon: Cash paid for interest Years Ended December 31, 2022 2023 $ (51,925) $ (94,226) 1,585 36,042 — (2,228) (1,977) — 782 4,219 (825) — 1,580 1,533 9,317 (760) 994 (2,542) 11,839 (1,361) (5,244) (10,021) (4,963) (3,738) (5,691) (23,384) — — — 6,708 85 1 (32,000) (25,206) (48,590) 93,169 44,579 $ 1,654 36,043 6,182 2,121 (1,777) (9,550) 8,768 (2,417) — 406 30,242 (65,946) 17,849 (1,060) 11,297 19,087 1,058 (5,623) 1,501 (38,005) 2,311 4,654 2,277 (73,154) (114) (114) 40,000 7,121 410 67 (33,000) 14,598 (58,670) 151,839 93,169 6,059 $ 6,755 $ $ The accompanying notes are an integral part of these consolidated ﬁnancial statements. Akebia Therapeucs, Inc. | Form 10-K | Page 131 Table of Contents 1. NATURE OF BUSINESS Organizaon Akebia Therapeucs, Inc. NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS Akebia Therapeucs, Inc., referred to as Akebia or the Company, was incorporated in the State of Delaware in 2007 and became a public company in 2014. Akebia is a fully integrated commercial-stage biopharmaceucal company commied to addressing paents’ unmet needs. Our purpose is to beer the life of each person impacted by kidney disease. ® The Company has one commercial product in the United States, or U.S, Auryxia (ferric citrate), which is approved by the U.S. Food and Drug Administraon, or FDA, and marketed for two indicaons: (i) the control of serum phosphorus levels in adult paents with dialysis dependent chronic kidney disease, or DD- CKD, and (ii) the treatment of iron deﬁciency anemia, or IDA, in adult paents with non-dialysis chronic kidney disease, or NDD-CKD. Auryxia will lose exclusivity in the U.S. in March 2025. Ferric citrate is also approved in Japan, and is marketed and sold by the Company's collaboraon partner, as an oral treatment for the improvement of hyperphosphatemia in paents with chronic kidney disease, or CKD, including DD-CKD and NDD-CKD and for the treatment of adult paents with IDA under the trade name Riona (ferric citrate hydrate). The Company has early to late-stage clinical programs, including vadadustat, the Company’s lead invesgaonal product candidate. Vadadustat is an invesgaonal oral hypoxia-inducible factor prolyl hydroxylase, or HIF-PH, inhibitor. In October 2023, the FDA acknowledged the Company's New Drug Applicaon, or NDA, resubmission for vadadustat was complete, classiﬁed it as a Class 2 response and set a user fee goal date, or PDUFA date, of March 27, 2024. Vadadustat is approved for the treatment of symptomac anemia associated with CKD under the trade name Vafseo in the European Economic Area, or EEA, the United Kingdom, or UK, Switzerland, Australia and Taiwan in adult paents on chronic maintenance dialysis, in Korea for adult paents with CKD on hemodialysis and in Japan for adult dialysis-dependent and non-dialysis paents. The Company will connue to support its partners in preparaon to launch vadadustat in Europe, Taiwan and potenally other countries to pursue our goal of enabling broad access to vadadustat for paents globally. Since its incepon, the Company has devoted most of its resources to research and development, or R&D, including its preclinical and clinical development acvies, commercializing Auryxia and providing general and administrave support for these operaons. The Company began recording revenue from the U.S. sales of Auryxia and revenue from sublicensing rights to Auryxia in Japan from the Company’s Japanese partners, Japan Tobacco, Inc. and its subsidiary Torii Pharmaceucal Co., Ltd., collecvely, JT and Torii, in 2018. In addion, the Company connues to explore addional development opportunies to expand its pipeline and porolio of novel therapeucs. If the Company does not successfully commercialize vadadustat in the U.S., if approved, or any other potenal product candidate, it may be unable to achieve proﬁtability. As of December 31, 2023, the Company had cash and cash equivalents of approximately $42.9 million. Based on its current operang plan, the Company believes that its cash resources and the cash the Company expects to generate from product, royalty, supply and license revenues will be suﬃcient to allow the Company to fund its current operang plan through at least twelve months from the ﬁling of this Annual Report on Form 10-K, or Form 10-K. However, if the Company’s operang performance deteriorates signiﬁcantly from the levels expected in the Company’s operang plan, or if vadadustat is not approved in the U.S., it would aﬀect the Company’s liquidity and its ability to connue as a going concern in the future. The Company expects to ﬁnance future cash needs through product and collaboraon, license and other revenue, including royales and revenue from supply agreements. If the Company believes its resources are insuﬃcient to sasfy its liquidity requirements, we may seek to sell public or private equity, enter into new debt transacons, explore potenal strategic transacons, consider other cash-generang or saving measures or a combinaon of these approaches or other strategic alternaves. There can be no assurance that the current operang plan will be achieved in the me frame ancipated by the Company or that its cash resources will fund its operang plan for the period of me ancipated by the Company, or that addional funding will be available on terms acceptable to the Company, or at all. 2. SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES Basis of Presentaon and Principles of Consolidaon The accompanying consolidated ﬁnancial statements have been prepared in conformity with accounng principles generally accepted in the U.S., or GAAP. Any reference in these notes to applicable guidance is meant to refer to the authoritave GAAP as found in the Accounng Standards Codiﬁcaon, or ASC, and Accounng Standards Update, or ASU, of the Financial Accounng Standards Board, or FASB. Akebia Therapeucs, Inc. | Form 10-K | Page 132 Table of Contents The accompanying consolidated ﬁnancial statements include the accounts of the Company and its wholly owned subsidiaries. All signiﬁcant intercompany balances and transacons have been eliminated in the consolidated ﬁnancial statements herein. Certain monetary amounts, percentages and other ﬁgures included elsewhere in these consolidated ﬁnancial statements have been subject to rounding adjustments. Accordingly, ﬁgures shown as totals in certain tables may not be the arithmec aggregaon of the ﬁgures that precede them, and ﬁgures expressed as percentages in the text may not total 100% or, as applicable, when aggregated, may not be the arithmec aggregaon of the percentages that precede them. Use of Esmates The preparaon of ﬁnancial statements in conformity with GAAP, requires management to make esmates and assumpons that aﬀect the reported amounts of assets and liabilies, revenue and expenses, classiﬁcaon of the expenses, assets and liabilies and the disclosure of conngent assets and liabilies as of and during the reported period. On an ongoing basis, management evaluates its esmates. Management bases its esmates and assumpons on historical experience when available and on various factors, including expected business and operaonal changes, sensivity and volality associated with the assumpon that it believes to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of the assets and liabilies that are not readily apparent from other sources. In certain circumstances, management must apply signiﬁcant judgment in these processes. The esmaon process oen may yield a range of potenally reasonable esmates of the ulmate future outcomes, and management selects an amount that falls within that range of reasonable esmates. Although, we regularly assesses these esmates, actual results may diﬀer materially from those esmates and changes in esmates are recorded in the period they become known. Signiﬁcant esmates and judgments reﬂected in these consolidated ﬁnancial statements include, but are not limited to: accrued expenses, other long-term liabilies, product revenues, including various rebates, returns and reserves related to product sales, inventories, classiﬁcaon of expenses between cost of goods sold, R&D and selling, general and administrave, long-term assets, including the Company's right-of-use assets, intangible asset and goodwill. Cash, Cash Equivalents and Restricted Cash In determining cash, cash equivalents and restricted cash, the Company considers only those highly liquid investments, readily converble to cash within 90 days from the date of purchase to be cash equivalents. As of December 31, 2023, cash and cash equivalents primarily included cash on hand and funds invested in money market funds. Restricted cash represents amounts required to secure the outstanding leer of credit in connecon with the Company’s oﬃce and laboratory space in Cambridge, Massachuses, or the Cambridge Lease. Restricted cash is included in “other long-term assets” in the consolidated balance sheets. The following table reconciles cash, cash equivalents and restricted cash reported within the Company's consolidated balance sheets to the total amounts reported consolidated statements ﬂows: cash the of in Reconciliaon of cash, cash equivalents and restricted cash (in thousands) Cash and cash equivalents Restricted cash included in other long-term assets Total cash, cash equivalents and restricted cash Fair Value of Financial Instruments December 31, 2023 2022 $ $ 42,925 $ 1,654 44,579 $ 90,466 2,703 93,169 Fair value is deﬁned as the price that would be received from selling an asset or paid to transfer a liability in an orderly transacon between market parcipants at the measurement date. When determining the fair value measurements for assets and liabilies required to be recorded at fair value, management considers the principal or most advantageous market in which it would transact and considers assumpons that market parcipants would use when pricing the asset or liability. ASC Topic 820, Fair Value Measurement, establishes a fair value hierarchy that requires an enty to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value. To the extent the valuaon is based on models or inputs that are less observable in the market, the determinaon of fair values requires more judgment. A ﬁnancial instrument categorizaon within the fair value hierarchy is based upon the lowest level of input that is signiﬁcant to the fair value measurement. The three levels of inputs that may be used to measure fair value are: • • Level 1 – unadjusted quoted prices in acve markets for idencal assets or liabilies to the reporng enty at the measurement date. Level 2 – quoted prices for similar assets or liabilies in markets that are not acve, or for which all signiﬁcant inputs are observable, either directly or indirectly, for substanally the full term of the asset or liability. Akebia Therapeucs, Inc. | Form 10-K | Page 133 Table of Contents • Level 3 – unobservable inputs for the asset or liability used to measure fair value to the extent that observable inputs are not available, thereby allowing for situaons in which there is lile, if any, market acvity for the asset or liability at the measurement date. Accounts Receivable The Company’s accounts receivable represent amounts due to the Company from product sales (see Note 11) and from its collaboraon, license and other agreements (see Note 12). Reimbursable costs that have not been invoiced as of the balance sheet date are recorded as unbilled accounts receivable. Accounts receivable arising from product sales primarily represent amounts due from the Company's customers, net of allowances for customer discounts and chargebacks. The Company deducts trade allowances for prompt payment, among other certain discounts or chargebacks, from its accounts receivable based on its experience that the Company’s customers will earn these discounts and fees. The Company makes judgments as to its ability to collect outstanding receivables and provides an allowance for receivables when collecon becomes doubul. Provisions are made based upon a speciﬁc review of all signiﬁcant outstanding receivables and the overall quality and age of those invoices not speciﬁcally reviewed as well as historical payment paerns and exisng economic factors. The Company believes that credit risks associated with its customers and collaboraon partners are not signiﬁcant. The Company's allowance for credit losses was $1.0 million and $1.1 million as of December 31, 2023 and 2022, respecvely. The write-oﬀs for the year ended December 31, 2023 and 2022 were $0.1 million and $0.4 million, respecvely. Concentraons of Risk and Oﬀ-Balance Sheet Risk Credit Risk Cash, cash equivalents and accounts receivable are the only ﬁnancial instruments that potenally subject the Company to concentraons of credit risk. The Company maintains cash accounts principally at three ﬁnancial instuons in the U.S., which at mes, may exceed the Federal Deposit Insurance Corporaon's limits. The Company has not experienced any losses from cash balances in excess of the insurance limit. The Company's management does not believe the Company is exposed to signiﬁcant credit risk at this me due to the ﬁnancial condion of the ﬁnancial instuons where its cash is held. Gross revenues and accounts receivable from each of the Company’s customers or collaboraon partners who individually accounted for 10% or more of total gross revenues and/or 10% or more of total gross accounts receivable consisted of the following: Customer Fresenius Medical Care Rx Cencora, Inc., formerly known as AmerisourceBergen Drug Corporaon McKesson Corporaon Cardinal Health, Inc. Otsuka Pharmaceucal Co. Ltd. Customer Fresenius Medical Care Rx Cencora, Inc., formerly known as AmerisourceBergen Drug Corporaon Cardinal Health, Inc. McKesson Corporaon Oﬀ-Balance Sheet Accounts % of Total Gross Revenues Years Ended December 31, 2022 2023 34% 40% 15% 21% —% 11% —% 10% 20% —% % of Gross Accounts Receivable December 31, 2023 31% 25% 16% 12% 2022 44% 16% 13% 10% The Company has no signiﬁcant oﬀ-balance sheet concentraons of credit risk, such as foreign currency exchange contracts, opon contracts or other hedging arrangement. See Note 9, Leases, for further details. Manufacturing and Distribuon Risk. The Company is dependent on third-party manufacturers, logiscs company and distributors to supply products for commercial acvies associated with its product and product candidates, as applicable. In parcular, the Company relies and Akebia Therapeucs, Inc. | Form 10-K | Page 134 Table of Contents expects to connue to rely on a small number of manufacturers to supply it with its requirements for the acve pharmaceucal ingredients and formulated drugs related to the Company's product and product candidate acvies. These acvies, including the commercializaon of Auryxia, could be adversely aﬀected by a signiﬁcant interrupon in the supply of acve pharmaceucal ingredients and formulated drugs or distribuon of ﬁnished product to the market. Inventories, including Pre-Launch Inventories The Company values its inventories at the lower-of-actual cost or net realizable value. The Company determines the cost of its inventories, which includes amounts related to materials and manufacturing overhead, on a ﬁrst-in, ﬁrst-out basis. When the Company expects to ulize the inventory beyond one year we record it in inventories, long-term on its consolidated balance sheets. Prior to obtaining inial regulatory approval for an invesgaonal product candidate the Company expenses costs relang to producon of pre-launch inventory as R&D expense in its consolidated statements of operaons and comprehensive loss in the period incurred. Aer regulatory approval has been received, the Company capitalizes such inventory costs. Products used in clinical trials are expensed as R&D expense in the statement of operaons and comprehensive loss. The Company performs an assessment of the recoverability of capitalized inventory during each reporng period, and writes down any excess or obsolete inventory to its net realizable value in the period in which the impairment is idenﬁed through cost of product and other revenue in the consolidated statements of operaons and comprehensive loss. Addionally, the Company’s product is subject to strict quality control and monitoring that is performed throughout the manufacturing process, including release of work-in-process to ﬁnished goods. In the event that certain batches or units of product do not meet quality speciﬁcaons, the Company will record a write-down of any potenal unmarketable inventory to its esmated net realizable value and record the expense as cost of product and other revenue in the consolidated statements of operaons and comprehensive loss. The Company prepays for certain manufacturing costs, including the raw materials to its CMOs which are included in prepaid manufacturing on the consolidated balance sheet. Property and Equipment Property and equipment are recorded at cost, less accumulated depreciaon. Expenditures for repairs and maintenance are expensed as incurred. Depreciaon expense is recognized using the straight-line method over the esmated useful lives, which are typically: Computer equipment and soware Furniture and ﬁxtures Laboratory and other equipment Leasehold improvements Asset Category Esmated Useful Life 3 years - 7 years Shorter of the useful life or remaining lease term 7 years 5 years Maintenance and repairs to an asset that do not improve or extend its life are charged to operaons. When assets are rered or otherwise disposed of, the assets and related accumulated depreciaon are eliminated from the accounts and any resulng gain or loss is reﬂected in the Company's consolidated statements of operaons and comprehensive loss. Intangible Asset The Company maintains a deﬁnite-lived intangible asset related to developed product rights for Auryxia. The intangible asset was inially recorded at fair value and is stated net of accumulated amorzaon. The Company amorzes its intangible asset that has a ﬁnite life using the straight-line method. Amorzaon for the Company’s intangible asset is recorded over its remaining esmated useful life, which as of December 31, 2023 is esmated to be six years. Goodwill Goodwill reﬂects the excess purchase price over the fair value of the net tangible and intangible assets acquired in a business combinaon. Goodwill is evaluated for impairment on an annual basis, and more frequently if indicators are present or changes in circumstances suggest that impairment may exist. The Company compares the fair value of its reporng unit to its carrying value. If the carrying value of the net assets assigned to the reporng unit exceeds the fair value of its reporng unit, the Company would record an impairment loss equal to the diﬀerence. As described above, the Company operates in one operang segment which the Company considers to be the only reporng unit. Akebia Therapeucs, Inc. | Form 10-K | Page 135 Table of Contents Impairment of Long-Lived Assets and Intangible Assets Subject to Amorzaon Long-lived assets primarily include property and equipment, intangible assets. The Company evaluates its long-lived assets for impairment whenever events or changes in circumstances indicate that the carrying amount of such assets may not be recoverable. The recoverability of assets to be held and used is measured by a comparison of the carrying amount of an asset to the future undiscounted net cash ﬂows expected to be generated by the asset. If such assets are considered to be impaired, the impairment to be recognized is measured by the amount by which the carrying amount of the asset exceeds the fair value of the asset. The Company did not recognize any impairment losses on long-lived assets for the years ended December 31, 2023 and 2022, respecvely. Leases The Company made an accounng policy elecon not to recognize leases with an inial term of twelve months or less within its consolidated balance sheets and to recognize those lease payments as an expense on a straight-line basis in its consolidated statements of operaons and comprehensive loss. The Company also made the accounng policy elecon not to separate the non-lease components from the lease components for its building leases and, rather, account for each non-lease component and lease component as a single component. The Company determines if an arrangement is a lease at incepon. An arrangement is determined to contain a lease if the contract conveys the right to control the use of an idenﬁed property, plant or equipment for a period of me in exchange for consideraon. If the Company can beneﬁt from the various underlying assets of a lease on their own or together with other resources that are readily available, or if the various underlying assets are neither highly dependent on nor highly interrelated with other underlying assets in the arrangement, they are considered to be a separate lease component. In the event mulple underlying assets are idenﬁed, the lease consideraon is allocated to the various components based on each of the component’s relave fair value. Operang lease assets represent the Company’s right to use an underlying asset for the lease term and operang lease liabilies represent its obligaon to make lease payments arising from the leasing arrangement. The right-of-use asset and operang lease liabilies are recognized at the commencement date based on the present value of lease payments over the lease term. The Company uses the implicit rate when readily determinable and uses an esmate of its incremental borrowing rate when the implicit rate is not readily determinable based upon the available informaon at the commencement date of lease incepon. The incremental borrowing rate is determined using a credit rang scoring model to esmate the Company’s credit rang, adjusted for collateralizaon. The calculaon of the right-of-use asset includes any lease payments made and excludes any lease incenves. If a lease includes an opon to extend or terminate the lease, the Company reﬂects the opon in the lease term if it is reasonably certain the Company will exercise the opon. The Company’s operang leases are reﬂected in operang right-of-use assets, accrued expenses and other current liabilies and long-term operang lease liabilies in its consolidated balance sheets. Derivave Financial Instruments The Company accounts for derivave ﬁnancial instruments as either equity or liabilies in accordance with ASC Topic 815, Derivaves and Hedging, or ASC 815, based on the characteriscs and provisions of each instrument. Embedded derivaves are required to be bifurcated from the host instruments and recorded at fair value if the derivaves are not clearly and closely related to the host instruments on the date of issuance. Derivave instrument liabilies are classiﬁed in the consolidated balance sheets as current or non-current based on whether or not net-cash selement of the derivave instrument could be required within 12 months of the balance sheet date. The embedded derivaves are revalued on each subsequent balance sheet date unl such instruments are exercised or expire, with any changes in the fair value between reporng periods recorded as other income or expense in the consolidated statements of operaons and comprehensive loss. The derivave liability recorded in connecon with the Company’s prior Loan Agreement with Pharmakon was classiﬁed as a liability in the Company’s consolidated balance sheets. See Note 3, Fair Value Measurements, and Note 7, Indebtedness, for more informaon. Liability Related to Sale of Future Royales The Company accounts for the liability related to sale of future royales as a debt ﬁnancing, amorzed under the eﬀecve interest rate method over the esmated life of the related expected royalty stream. The liability related to sale of future royales and the debt amorzaon are based on the Company’s current esmates of future royales expected to be paid over the life of the arrangement. The Company will periodically assess the expected royalty payments. To the extent the Company’s esmates of future royalty payments are greater or less than previous esmates or the esmated ming of such payments is materially diﬀerent than previous esmates, the Company will adjust the eﬀecve interest rate and recognize related non-cash interest expense on a prospecve basis. In the event the Company's esmates of future royales are less Akebia Therapeucs, Inc. | Form 10-K | Page 136 Table of Contents than the proceeds from the sale of future royales, the Company will not recognize related non-cash interest expense. Non-cash royalty revenue is reﬂected as royalty revenue within License, collaboraon and other revenue, and non-cash amorzaon of debt is reﬂected as interest expense in the consolidated statements of operaons and comprehensive loss. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for more informaon. Refund Liability to Customer The Company accounts for the refund liability as a debt arrangement, which is recorded at net present value. When the funds were received from the customer, the Company recorded an inial discount on the refund liability and a corresponding deferred gain to the refund liability. The discount on the refund liability is being amorzed to interest expense on the consolidated statement of operaons and comprehensive loss and the deferred gain is being amorzed to other income on the consolidated statement of operaons and comprehensive loss over the expected term of the arrangement. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for more informaon. Excess Firm Purchase Commitment Liabilies At each reporng period, the Company assesses whether there are excess ﬁrm non-cancelable purchase commitment liabilies, resulng from supply agreements with third-party CMOs. The determinaon of excess ﬁrm purchase commitment liabilies requires judgment, including consideraon of many factors, such as esmates of future product demand, current and future market condions, impact of our loss of exclusivity, expiraon and ulizaon of drug substance under ﬁrm purchase commitments, and contractual minimums. Inventory receipts, if any, that have been previously idenﬁed as excess are recorded as a reducon to the ﬁrm purchase commitment liability. Any changes in the ﬁrm purchase commitment liability are recorded in cost of product and other revenue in the consolidated statements of operaons and comprehensive loss. Revenue Recognion The Company recognizes revenue in accordance with ASC Topic 606, Revenue from Contracts with Customers, or ASC 606, which applies to all contracts with customers, except for contracts that are within the scope of other standards. Under ASC 606, the Company recognizes revenue when its customer obtains control of promised goods or services, in an amount that reﬂects the consideraon which the enty expects to receive in exchange for those goods or services. To determine revenue recognion for arrangements that the Company determines are within the scope of ASC 606, it performs the following ﬁve steps: (i) idenfy the contract(s) with a customer; (ii) idenfy the performance obligaons in the contract; (iii) determine the transacon price; (iv) allocate the transacon price to the performance obligaons in the contract; and (v) recognize revenue when (or as) the enty sasﬁes a performance obligaon. The Company only applies the ﬁve-step model to contracts when it is probable that the enty will collect the consideraon it is entled to in exchange for the goods or services it transfers to the customer. At contract incepon, once the contract is determined to be within the scope of ASC 606, the Company assesses the goods or services promised within each contract and determines those that are performance obligaons, and assesses whether each promised good or service is disnct. The Company then recognizes as revenue the amount of the transacon price that is allocated to the respecve performance obligaon when, or as, the performance obligaon is sasﬁed. The Company does not include a ﬁnancing component to its esmated transacon price at contract incepon unless it esmates that certain performance obligaons will not be sasﬁed within one year. Addionally, the Company recognizes the incremental costs of obtaining a contract as an expense when incurred if the amorzaon period of the asset that the Company otherwise would have recognized is one year or less. Product Revenue, Net The Company recognizes product revenues on sales of Auryxia primarily aributable to a limited number of customers, including wholesale distributors as well as certain specialty pharmacy providers, in the U.S., which accounts for the largest poron of the Company's total revenue. These customers resell the Company’s product to health care providers and paents. In addion to distribuon agreements with customers, the Company enters into arrangements with health care providers and payors that provide for government-mandated and/or privately-negoated rebates, chargebacks and discounts with respect to the purchase of the Company’s product. The Company’s payment terms are consistent with prevailing pracce in the respecve markets in which the Company does business. Most of the Company’s customers make payments based on contract terms, which are not aﬀected by conngent events that could impact the transacon price. Payment terms fall within the one-year guidance for the praccal expedient, which allows the Company to forgo adjustment of the contractual payment amount of consideraon for the eﬀects of a signiﬁcant ﬁnancing component. Akebia Therapeucs, Inc. | Form 10-K | Page 137 Table of Contents The Company recognizes revenue on product sales when the customer obtains control of the Company’s product, which occurs at a point in me, typically upon receipt of the product by the Company's customer. The Company expenses incremental costs of obtaining a contract, such as sales commissions, as and when incurred, if the expected amorzaon period of the asset that it would have recognized is one year or less. Sales commissions are recorded in selling, general and administrave expense in the statements of operaons and comprehensive loss. Revenue from product sales is recorded at the net sales price, or Transacon Price, which includes esmates of variable consideraon for which reserves are established and which result from discounts, returns, chargebacks, rebates, co-pay assistance and other allowances oﬀered within contracts between the Company and its customers, health care providers, payors and other indirect customers relang to the Company’s sales of its products. When appropriate, these esmates take into consideraon a range of possible outcomes which are probability-weighted in accordance with the expected value method in ASC 606 for relevant factors such as the Company’s historical experience, current contractual and statutory requirements, speciﬁc known market events and trends, industry data and forecasted customer buying and payment paerns. The amount of variable consideraon that is included in the Transacon Price may be constrained, and is included in the net sales price only to the extent that it is probable that a signiﬁcant reversal in the amount of the cumulave revenue recognized will not occur in a future period. Actual amounts of consideraon ulmately received may diﬀer from the Company’s esmates. The reserves are classiﬁed as reducons to accounts receivable, net of payable, if the trade discount and/or allowance will be credited to the customer or accrued expenses and other current liabilies or other long-term liabilies, if payable to a third-party in the consolidated balance sheets. Trade Discounts and Allowances—The Company generally provides customers with prompt pay discounts and pay fees for distribuon services, such as fees for certain data that customer's provide to the Company. Trade discounts and allowances are recorded as a reducon of revenue within the consolidated statements of operaons and comprehensive loss in the period the related product revenue is recognized. The Company esmates that, based on its experience, its customers will earn these discounts and fees, and the Company will deduct the full amount of these discounts and fees from its gross product revenues and accounts receivable at the me such revenues are recognized. Product Returns—Consistent with industry pracce, subject to certain caps for certain customers, the Company generally oﬀers customers a limited right of return which allows for the product to be returned when the product expiry is within an allowable window, when the quanty delivered is diﬀerent than quanty ordered, the product is damaged in transit prior to receipt by the customer or is subject to a recall. This right of return generally lapses once the product is provided to a paent or generally, if the bole has been opened. The Company esmates the amount of its product sales that may be returned and records this esmate as a reducon of revenue in the period the related product revenue is recognized. The Company currently esmates product return reserve using available industry data and its own historical return informaon, including its visibility into the esmated inventory remaining in the distribuon channel. Provider Chargebacks and Discounts—Chargebacks for fees and discounts to providers represent the esmated obligaons resulng from contractual commitments to sell products to qualiﬁed healthcare providers at prices lower than the list prices charged to customers who directly purchase the product from the Company. Customers charge the Company for the diﬀerence between what they pay for the product and the ulmate selling price to the qualiﬁed healthcare providers. These reserves are established in the same period that the related revenue is recognized, resulng in a reducon of product revenue and accounts receivable. Chargeback amounts are generally determined at the me of resale to the qualiﬁed healthcare provider by customers, and the Company generally issues credits for such amounts within a few weeks of the customer’s resale of the product. Reserves for chargebacks consist of credits that the Company expects to issue for units that remain in the distribuon channel at each reporng period end that the Company expects will be sold to qualiﬁed healthcare providers, and chargebacks that customers have claimed but for which the Company has not yet issued a credit. Commercial and Medicare Part D Rebates—The Company contracts with various commercial payor organizaons, primarily health insurance companies and pharmacy beneﬁt managers, for the payment of rebates with respect to ulizaon of its products. The Company esmates the rebates for commercial and Medicare Part D payors based upon (i) its contracts with the payors and (ii) informaon obtained from its customers and other third pares regarding the payor mix for Auryxia. The Company esmates these rebates and records such esmates in the same period the related revenue is recognized, resulng in a reducon of product revenue and the establishment of an accrued liability. Other Government Rebates—The Company is subject to discount obligaons under state Medicaid programs and other government programs. The Company esmates its Medicaid and other government programs rebates based upon a range of possible outcomes that are probability-weighted for the esmated payor mix. These reserves are recorded in the same period the related revenue is recognized, resulng in a reducon of product revenue and the establishment Akebia Therapeucs, Inc. | Form 10-K | Page 138 Table of Contents of a current liability which is included in accrued expenses and other current liabilies in the consolidated balance sheets. For Medicare, the Company also esmates the number of paents in the prescripon drug coverage gap for whom the Company will owe an addional liability under the Medicare Part D program. The Company’s liability for these rebates consists of invoices received for claims from prior quarters that have not been paid or for which an invoice has not yet been received, esmates of claims for the current quarter, and esmated future claims that will be made for product that has been recognized as revenue, but which remains in the distribuon channel at the end of each reporng period. Other Incenves—The Company oﬀers a voluntary paent co-pay assistance program, which provides ﬁnancial assistance to qualiﬁed commercially insured paents with prescripon drug co-payments required by payors. The calculaon of the accrual for co-pay assistance is based on actual claims processed during a given period plus an esmate of the amount the Company expects to pay based on historical ulizaon rates for the product that has been recognized as revenue but is esmated to be remaining in in the distribuon channel at the end of each reporng period. License, Collaboraon and Other Revenues The Company enters into license and collaboraon agreements within the scope of ASC 606, under which it licenses certain rights to its product candidates to third pares. The terms of these arrangements typically include the following: (i) non-refundable, up front licenses fees associated with the licensing of intellectual property; (ii) development, regulatory and commercial milestone payments; (iii) drug product the Company supplies in connecon with certain license and collaboraon agreements and (iv) royales earned on net sales of licensed products. In determining the appropriate amount of revenue to be recognized as the Company fulﬁlls its obligaons under each of its agreements, the Company implements the ﬁve-step model noted above. As part of the accounng for these arrangements, the Company develops assumpons that require judgment to determine whether the individual promises should be accounted for as separate performance obligaons or as a combined performance obligaon, and to determine the stand-alone selling price for each performance obligaon idenﬁed in the contract. A deliverable represents a separate performance obligaon if both of the following criteria are met: (i) the customer can beneﬁt from the good or service either on its own or together with other resources that are readily available to the customer, and (ii) the enty’s promise to transfer the good or service to the customer is separately idenﬁable from other promises in the contract. The Company uses key assumpons to determine the stand-alone selling price, which may include forecasted revenues, development melines, reimbursement rates for personnel costs, discount rates and probabilies of technical and regulatory success. Licenses of Intellectual Property If the license to the Company’s intellectual property is determined to be disnct from the other performance obligaons idenﬁed in the arrangement, the Company recognizes revenue from non-refundable, up-front fees allocated to the license when the license is transferred to the customer and the customer is able to use and beneﬁt from the license. For licenses that are bundled with other promises, the Company ulizes judgment to assess the nature of the combined performance obligaon to determine whether the combined performance obligaon is sasﬁed over me or at a point in me and, if over me, the appropriate method of measuring progress for purposes of recognizing revenue from non-refundable, up-front fees. The Company evaluates the measure of progress each reporng period and, if necessary, adjust the measure of performance and related revenue recognion. Milestone Payments At the incepon of each arrangement that includes development milestone payments, the Company evaluates whether the milestones are considered probable of being reached and esmates the amount to be included in the transacon price using the most likely amount method. The Company evaluates factors such as the scienﬁc, clinical, regulatory, commercial and other risks that must be overcome to assess the milestone as probable of being achieved. There is considerable judgement involved in determining whether a milestone is probable of being reached at each speciﬁc reporng period. Milestone payments that are not within the control of the Company or the customer, such as regulatory approvals, are not considered probable of being achieved unl those approvals are received. If it is probable that a signiﬁcant revenue reversal would not occur, the associated milestone value is included in the transacon price. The transacon price is then allocated to each performance obligaon on a relave stand-alone selling price basis, for which the Company recognizes revenues as, or when, the performance obligaons under the contract are sasﬁed. At the end of each subsequent reporng period, the Company re- evaluates the probability of achievement of such development milestones and any related constraint, and if necessary, adjusts its esmate of the overall transacon price. Any such adjustments are recorded on a cumulave catch-up basis, which would aﬀect collaboraon revenue in the period of adjustment. Akebia Therapeucs, Inc. | Form 10-K | Page 139 Table of Contents Drug Product Supply Collaboraon and license arrangements that include a promise for future supply of drug substance or drug product for either clinical development or commercial supply at the licensee’s discreon are generally considered as opons. The Company assesses if these opons provide a material right to the licensee and if so, they are accounted for as a separate performance obligaon. If the Company is entled to addional payments when the licensee exercises these opons, any payments are recorded in license, collaboraon and other revenues when the licensee obtains control of the goods, which is generally upon delivery. Royales The Company will recognize sales-based royales, including milestone payments based on the level of net sales, at the later of (i) when the related sales occur, or (ii) when the performance obligaon to which some or all of the royalty has been allocated has been sasﬁed (or parally sasﬁed). Collaborave Arrangements The Company records the elements of its collaboraon agreements that represent joint operang acvies in accordance with ASC Topic 808, Collaborave Arrangements, or ASC 808. Accordingly, the elements of the collaboraon agreements that represent acvies in which both pares are acve parcipants and to which both pares are exposed to the signiﬁcant risks and rewards that are dependent on the commercial success of the acvies are recorded as collaborave arrangements. The Company considers the guidance in ASC 606-10-15, Revenue from Contracts with Customers – Scope and Scope Excepons, in determining the appropriate treatment for the transacons between the Company and its collaborave partners and the transacons between the Company and third pares. Generally, the classiﬁcaon of transacons under the collaborave arrangements is determined based on the nature and contractual terms of the arrangement along with the nature of the operaons of the parcipants. To the extent product revenue is generated from the collaboraon, the Company recognizes its share of the net sales on a gross basis if the Company is deemed to be the principal in the transacons with customers, or on a net basis if the Company is instead deemed to be the agent in the transacons with customers, consistent with the guidance in ASC 606. Cost of Goods Sold Cost of goods sold, or COGS, includes costs closely correlated or directly related to the costs to manufacture commercial drug product for Auryxia, including costs paid to the Company's contract manufacturing organizaons, or CMOs, as well as indirect costs. Direct and indirect costs include fees for packaging, shipping, insurance and quality assurance, idle capacity charges, roune tesng costs, roune ongoing eﬀorts to improve exisng commercial products, reserves for excess inventory, write-oﬀs for inventory that fails to meet speciﬁcaons or is otherwise no longer suitable for commercial sale, including scrap, changes in ﬁrm purchase commitment liability and royales due to the licensor of Auryxia related to U.S. and Japan product sales recognized during the period. In addion, COGS includes the amorzaon of development product rights for the Auryxia intangible asset. The Company also includes personnel- related costs, including salaries and bonuses, employee beneﬁts and stock-based compensaon aributable to employees in parcular funcons and associated directly with the manufacturing of our commercial products. Further, the Company includes in COGS costs to manufacture drug product provided to customers for which we have a license agreement. Cost of goods sold for a newly launched product may not include the full cost of manufacturing unl the inial pre-launch inventory is depleted, and addional inventory is manufactured and sold. Unl the Company receives regulatory approval for vadadustat, the Company records expenses incurred for the manufacture of pre-launch inventory that could potenally support a U.S. launch as R&D expense. The costs associated with the pre-launch inventory for the Medice Territory was expensed to R&D through April 2023 when markeng authorizaon was received. The costs incurred to manufacturer vadadustat for the Medice Territory aer the markeng approval in the Medice Territory is capitalized in inventory. Therefore, the pre-launch inventory costs are not included in COGS. Research and Development Expenses R&D costs are expensed as incurred. Internal R&D expenses are comprised of costs incurred in providing R&D acvies, including salaries and bonuses, employee beneﬁts, stock-based compensaon for personnel engaged in R&D acvies. In addion, they include facility costs, including the laboratory and an allocaon of oﬃce space for ulizaon by R&D staﬀ, depreciaon expense on the laboratory equipment as well as other direct costs such as lab supplies and equipment. External R&D costs include development of potenal new manufacturing processes and methods for both commercial and non-commercial products, conceptual formulaon and design of possible product and process alternaves, research compounds and clinical manufacturing costs, costs incurred for consultants and other outside services, such as data Akebia Therapeucs, Inc. | Form 10-K | Page 140 Table of Contents management and stascal analysis support and materials and supplies used in support of the clinical and preclinical programs and costs paid to clinical resource organizaons, or CRO, including invesgave sites that conduct the Company's clinical trials. Non-refundable advance payments for goods and services for both Auryxia and vadadustat are recorded in prepaid and other current assets in the consolidated balance sheets and expensed when the acvity is performed or when the goods are received. In addion, the costs associated with pre-launch inventory, including the cost of raw materials, costs paid to contract manufacturers for inventory manufacturing, freight and custom charges for vadadustat are expensed as R&D prior to regulatory approval. For the years ended December 31, 2023 and 2022, material and producon related costs of pre-approval inventory recorded to R&D was $6.4 million and $7.6 million, respecvely. Selling, General and Administrave Expenses Selling, general and administrave, or SG&A, expenses consist primarily of compensaon for personnel, including stock-based compensaon related to commercial, markeng, execuve, ﬁnance and accounng, informaon technology, corporate and business development and human resource funcons. Other SG&A expenses include costs for markeng iniaves for the Company's commercial products, market research and analysis on the Company's commercial and product and potenal product candidates, conferences and trade shows, travel expenses, professional services fees (including legal, patent, accounng, audit, tax, and consulng fees), insurance costs, general corporate expenses and allocated facilies-related expenses, including rent and maintenance of facilies. Costs associated with adversing are expensed in the period incurred and are included in selling, general and administrave expenses. For the years ended December 31, 2023 and 2022, adversing expenses totaled $1.0 million and $6.7 million, respecvely, all related to the Company's U.S. sales of its commercial product Auryxia. Patent Costs All patent-related costs incurred in connecon with the ﬁling and prosecung patent applicaons are expensed as incurred due to the uncertainty about the recovery of the expenditure. Such amounts incurred are classiﬁed as SG&A expenses in the accompanying consolidated statements of operaons and comprehensive loss. Stock-Based Compensaon The Company’s stock-based compensaon program allows for grants of common stock opons, restricted stock awards, performance-based restricted stock units, or PSUs, stock appreciaon rights, or SARs and restricted stock units. Grants are awarded to employees and non-employees, including directors. The Company accounts for its stock-based compensaon awards in accordance with ASC Topic 718, Compensaon—Stock Compensaon, or ASC 718. ASC 718 requires all stock-based payments to employees and non-employees, including modiﬁcaons to exisng stock awards, to be recognized in the statements of operaons and comprehensive loss based on their fair values. The Company esmates the fair value of opons granted using the Black-Scholes opon pricing model, or Black-Scholes. The Company uses the market price at the me of grant to determine the fair value of restricted stock awards and performance- based restricted stock awards. The Black-Scholes opon pricing model requires the input of certain subjecve assumpons, including (a) the expected stock price volality, (b) the calculaon of expected term of the award, (c) the risk-free interest rate and (d) expected dividends. Prior to 2017, due to the lack of company-speciﬁc historical and implied volality data for trading the Company’s stock in the public market, the Company had based its esmate of expected volality on the historical volality of a group of similar companies that are publicly traded. The historical volality was calculated based on a period of me commensurate with the expected term assumpon. The Company uses the simpliﬁed method as prescribed by the Securies and Exchange Commission, or SEC, Staﬀ Accounng Bullen No. 107, Share-Based Payment, to calculate the expected term for opons granted to employees as it does not have suﬃcient historical exercise data to provide a reasonable basis upon which to esmate the expected term. The expected term is applied to the stock opon grant group as a whole, as the Company does not expect substanally diﬀerent exercise or post-vesng terminaon behavior among its employee populaon. For opons granted to non-employees, the Company ulizes the contractual term of the arrangement as the basis for the expected term assumpon. The risk-free interest rate is based on U.S. Treasury securies with a maturity date commensurate with the expected term of the associated award. The expected dividend yield is assumed to be zero as the Company has never paid dividends and has no current plans to pay any dividends on its common stock. The Company recognizes forfeitures as they occur. The Company’s stock-based awards are subject to either service or performance-based vesng condions. Compensaon expense related to awards to employees and non-employees with service-based vesng condions is recognized on a straight-line basis based on the grant date fair value over the associated service period of the award, which is generally the vesng term, and is adjusted for pre-vesng forfeitures in the period in which the forfeitures occur. Compensaon expense related to awards to employees and non-employees with performance-based vesng condions is recognized based on the grant date Akebia Therapeucs, Inc. | Form 10-K | Page 141 Table of Contents fair value over the requisite service period using the accelerated aribuon method to the extent achievement of the performance condion is probable. For awards with performance condions in which the award does not vest unless the performance condion is met, the Company recognizes expense if, and to the extent that, the Company esmates that achievement of the performance condion is probable. If the Company concludes that vesng is probable, it recognizes expense from the date it reaches this conclusion through the esmated vesng date. Income Taxes Income taxes are recorded in accordance with FASB Topic 740, Income Taxes, or ASC 740, which provides for deferred taxes using an asset and liability approach. The Company recognizes deferred tax assets and liabilies for the expected future tax consequences of events that have been included in the ﬁnancial statements or tax returns. Deferred tax assets and liabilies are determined based on the diﬀerence between the ﬁnancial statement and tax bases of assets and liabilies using enacted tax rates in eﬀect for the year in which the diﬀerences are expected to reverse. Valuaon allowances are provided, if, based upon the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized. All deferred taxes as of December 31, 2023 and 2022 are classiﬁed as non-current within the income tax provision. See Note 15, Income Taxes, for further informaon. The Company accounts for uncertain tax posions in accordance with the provisions of ASC 740. When uncertain tax posions exist, the Company recognizes the tax beneﬁt of tax posions to the extent that the beneﬁt will more likely than not be realized. The determinaon as to whether the tax beneﬁt will more likely than not be realized is based upon the technical merits of the tax posion, as well as consideraon of the available facts and circumstances. As of December 31, 2023 and 2022, the Company does not have any signiﬁcant uncertain tax posions. The Company recognizes interest and penales related to uncertain tax posions in income tax expense. Net Loss per Share Basic net loss per share is calculated by dividing net loss by the weighted-average shares outstanding during the period, without consideraon for common stock equivalents. Diluted net loss per share is calculated by adjusng weighted-average shares outstanding for the diluve eﬀect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For purposes of the diluted net loss per share calculaon common stock opons, stock appreciaon rights, warrants and RSUs as well as restricted stock, if the Company was to issue any, are considered to be common stock equivalents, but have been excluded from the calculaon of diluted net loss per share, as their eﬀect would be an-diluve for all periods presented. Therefore, basic and diluted net loss per share were the same for all periods presented. Diluted net income per share is calculated by dividing the net income by the weighted-average common shares outstanding for the period, including any diluve eﬀect from outstanding opons, warrants, restricted stock and RSUs using the treasury stock method. Segment Informaon Operang segments are deﬁned as components of an enterprise about which separate discrete informaon is available for evaluaon by the chief operang decision maker, or CODM, or decision-making group, in deciding how to allocate resources and in assessing performance. The Company operates its business in a single segment and as one reporng unit, which is how its chief operang decision maker (who is the Company's president and chief execuve oﬃcer) reviews ﬁnancial performance and allocates resources. The Company views its operaons as and manages its business in one operang segment. Recent Accounng Pronouncements Not Yet Adopted In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures. ASU 2023-09 requires public companies to annually (i) disclose speciﬁc categories in the rate reconciliaon and (ii) provide addional informaon for reconciling items that meet a quantave threshold (if the eﬀect of those reconciling items is equal to or greater than 5 percent of the amount computed by mulplying pretax income or loss by the applicable statutory income tax rate). ASU 2023-09 will be eﬀecve for the annual reporng periods in ﬁscal years beginning aer December 15, 2024. The Company is currently evaluang ASU 2023-09 and does not expect it to have a material eﬀect on the Company’s consolidated ﬁnancial statements. In November 2023, the FASB issued ASU 2023-07, Improvements to Reportable Segment Disclosures. ASU 2023-07 requires disclosure of signiﬁcant segment expenses that are regularly provided to the CODM and included within the segment measure of proﬁt or loss, an amount and descripon of its composion for other segment items to reconcile to segment proﬁt or loss, and the tle and posion of the enty’s CODM. ASU 2023-07 will be applied retrospecvely and is eﬀecve for annual reporng periods in ﬁscal years beginning aer December 15, 2023, and interim reporng periods in ﬁscal years beginning aer December 31, 2024. The Company is currently reviewing the impact that the adopon of ASU 2023-07 may have on its consolidated ﬁnancial statements and disclosure. Akebia Therapeucs, Inc. | Form 10-K | Page 142 Table of Contents 3. FAIR VALUE MEASUREMENTS The tables below present certain assets and liabilies measured at fair value categorized by the level of input used in the valuaon of each asset and liability (in thousands): Cash equivalents: Money market funds Cash equivalents: Money market funds Long-term liability: Embedded debt derivave Level 1 Level 2 Level 3 Total December 31, 2023 1,504 — — $ 1,504 Level 1 Level 2 Level 3 Total December 31, 2022 52,442 — — — $ — $ 52,442 760 $ 760 $ $ Cash and cash equivalents —Money market funds included within cash and cash equivalents are classiﬁed within Level 1 of the fair value hierarchy because they are valued using quoted market prices in acve markets. Embedded debt derivave —As described in Note 7, Indebtedness, the Company’s prior Loan Agreement with Pharmakon contained certain provisions that change the underlying cash ﬂows of the debt instrument, including the acceleraon of the obligaons under the Pharmakon Loan Agreement under certain events of default, and under certain circumstances, the applicaon of a default interest rate on all outstanding obligaons during the occurrence and connuance of an event of default. The Company concluded that these features of the Pharmakon Loan Agreement represent a single compound embedded debt derivave required to be bifurcated from the debt host instrument and re-measured at fair value on a quarterly basis. The Company classiﬁed the embedded debt derivave as a non-current liability in its consolidated balance sheets. The esmated fair value of the derivave liability on both December 31, 2023 and 2022 was determined using a scenario-based approach and discounted cash ﬂow model that includes principal and interest payments under various cash ﬂow assumpons. Should the Company’s assessment of the probabilies around these scenarios change, including for changes in market condions, there could be a change to the fair value of the embedded debt derivave. The determinaon of the fair value of the embedded debt derivave includes inputs not observable in the market and as such, represents Level 3 measurement. The methodology ulized requires inputs based on certain subjecve assumpons, speciﬁcally, probabilies of acceleraon of the obligaons under the Pharmakon Loan Agreement by Pharmakon under certain events of default. The following table reconciles the fair value of the embedded debt derivave (in thousands): Balance at December 31, 2022 Change in fair value, recorded as other income Balance at December 31, 2023 4. INVENTORIES AND PREPAID MANUFACTURING $ $ 760 (760) — Akebia Therapeucs, Inc. | Form 10-K | Page 143 Table of Contents Inventories consists of the following (in thousands): Inventories, current: Work-in-process Finished goods Inventories, current Long-term inventories included in other long-term assets: Raw materials Work-in-process Inventories, long-term Total inventories December 31, 2023 2022 $ $ $ $ 4,297 $ 11,394 15,691 $ 1,143 8,260 9,403 $ 25,094 $ 7,892 13,676 21,568 610 — 610 22,178 For the period ended December 31, 2023 and 2022, inventories consisted primarily of inventories related to the Company's commercial product, Auryxia. As of December 31, 2023, the Company had $0.5 million of prepaid manufacturing costs for Auryxia drug substance and manufacturing costs. The Company did not have any prepaid manufacturing related to Auryxia as of December 31, 2022. Inventory wrien down for Auryxia as a result of excess, obsolescence, scrap or other reasons charged to cost of product and other revenue in the consolidated statements of operaons and comprehensive loss totaled approximately $1.6 million and $30.2 million during the years ended December 31, 2023 and 2022, respecvely. For the year ended December 31, 2023, the Company recorded $4.3 million of lowered cost of product and other revenue due to the Company's ability to commercially sell inventory previously wrien down to zero, its then net realizable value. As of December 31, 2023, the Company has an addional $12.3 million of inventory previously wrien down inventory to its then net realizable value of zero for drug product that may be salable in future periods. Pre-Launch Inventory The Company records advance payments for vadadustat acve pharmaceucal ingredient, or API, or drug substance (raw materials) it expects to use for the potenal U.S. launch and Medice Territory as prepaid manufacturing costs. Upon the quality release of the vadadustat batches and transfer of tle to the Company from the CMO, the cost of the pre-launch inventory, including the manufacturing costs is expensed to R&D. As of December 31, 2023, the Company had $14.0 million of prepaid manufacturing costs for vadadustat drug substance expected to be used in the potenal U.S. launch of vadadustat included in prepaid expenses and other current assets on the consolidated balance sheet. See Note 6, Addional Balance Sheet Detail, for further informaon. 5. INTANGIBLE ASSET AND GOODWILL Intangible Asset Intangible asset, net of accumulated amorzaon, prior impairments and adjustments as of December 31, 2023 and 2022 consisted of the following (in thousands): Intangible asset: December 31, 2023 December 31, 2022 Gross Carrying Value Accumulated Amorzaon Net Book Value Net Book Value Developed product rights for Auryxia $ 214,705 $ (178,663) $ 36,042 $ 72,084 Esmated Useful Life 6 years The Company recorded $36.0 million in amorzaon expense during each of the years ended December 31, 2023 and 2022 related to the developed product rights for Auryxia. Goodwill As of December 31, 2023 and 2022, the Company had goodwill of $59.0 million recorded in connecon with the December 2018 merger with Keryx. The Company has not idenﬁed any goodwill impairment to date. 6. ADDITIONAL BALANCE SHEET DETAIL Prepaid expenses and other current assets are as follows (in thousands): Akebia Therapeucs, Inc. | Form 10-K | Page 144 Table of Contents Descripon Prepaid manufacturing Other Total prepaid expenses and other current assets See Note 4, Inventories, for further informaon on prepaid manufacturing expenses. Accrued expenses and other current liabilies are as follows (in thousands): Descripon Product revenue allowances Product return reserves, current poron Compensaon and related beneﬁts Accrued manufacturing costs BioVectra terminaon fees, current poron Operang lease liabilies, current poron Royales due to Panion Liability related to sale of future royales, current poron Professional fees Clinical trial costs Restructuring costs, current poron Other Total accrued expenses and other current liabilies Other long-term assets are as follows (in thousands): Descripon Long-term inventories Restricted cash Other Total other long-term assets December 31, 2023 2022 14,489 $ 5,754 20,243 $ 15,615 17,249 32,864 December 31, 2023 2022 22,940 $ 5,420 8,216 5,555 7,500 4,491 3,989 2,048 1,909 328 737 4,602 67,735 $ December 31, 2023 2022 9,403 $ 1,654 1,366 12,423 $ 26,268 7,789 11,894 4,310 — 4,744 3,804 — 1,886 5,755 2,751 6,576 75,777 610 2,703 2,059 5,372 $ $ $ $ $ $ See Note 4, Inventories, for further informaon on long-term inventories. 7. INDEBTEDNESS Entry into BlackRock Loan Facility On January 29, 2024, the Closing Date, the Company entered into the Agreement for the Provision of a Loan Facility, or the BlackRock Credit Agreement, with Kreos Capital VII (UK) Limited, or Kreos, which are funds and accounts managed by BlackRock Inc., collecvely, BlackRock, and provides for a senior secured term loan facility in the aggregate principal amount of up to $55.0 million, or the Term Loan Facility. The Term Loan Facility is available in three tranches (i) Tranche A — $37.0 million was funded on the Closing Date and used to repay the Pharmakon Term Loans; (ii) Tranche B — $8.0 million is available in a single draw through December 31, 2024, and (ii) Tranche C — $10.0 million is available in a single draw through December 31, 2024, collecve the Term Loans. Tranche B and C are available subject to certain condions, including the Company's receipt of markeng approval for vadadustat from the FDA and in the case of Tranche C, receipt of a certain amount of cumulave gross cash proceeds aer the Closing Date in the form of equity or equity linked securies in one or more series of transacons. The BlackRock Term Loan Facility has an inial maturity date of March 31, 2025, which will be automacally extended to January 29, 2028, if Company receives FDA approval for vadadustat on or prior to June 30, 2024, or the BlackRock Maturity Date. The Company is required to make interest-only payments unl December 31, 2026, aer which the Company will begin paying equal monthly principal on the ﬁrst calendar day of each month, or the BlackRock Interest Only Period. In the event of certain prespeciﬁed events, the repayment schedule will be accelerated. For example, if FDA approval of vadadustat is not Akebia Therapeucs, Inc. | Form 10-K | Page 145 Table of Contents obtained on or prior to June 30, 2024, the BlackRock Interest Only Period will automacally terminate on October 1, 2024, and the Company will be required to repay the Term Loans in seven equal monthly payments (comprised of principal and interest), commencing on October 1, 2024 and ending on the BlackRock Maturity Date. The Term Loan Facility will accrue interest at a ﬂoang annual rate equal to the sum of (i) term Secured Overnight Financing Rate, or SOFR, for a tenor of one month (subject to a ﬂoor of 4.25% per annum) plus (ii) a margin of 6.75% per annum (subject to an overall cap of 15.00% per annum on the all-in interest rate). During the connuance of any payment event of default under the BlackRock Credit Agreement, the interest rate on such overdue sum will automacally increase by an addional 3.0% per annum, and may be subject to an addional late fee of 2.0% of such overdue sum. The Term Loan Facility also includes transacon fees ranging from 1.00% to 1.25% of the draw down amount as well exit fees of 0.75% of the amount funded to the relevant tranche. If the Company prepays the outstanding loan prior to maturity, it will be required to pay a prepayment fee ranging from 1.0% to 4.0% of the amount prepaid. If prepayment is made during the ﬁrst year, the Company also is required to pay the amount of otherwise due interest payments for the twelve-month period following prepayment. The BlackRock Term Loan Facility is secured by substanally all of the exisng and aer-acquired assets of the Company, including intellectual property. The BlackRock Credit Agreement requires the Company to (i) maintain a minimum aggregate cash balance of $15.0 million in one or more controlled accounts or (ii) trailing twelve-month revenue of $150.0 million, both of which are measured monthly. The BlackRock Credit Agreement contains various aﬃrmave and negave covenants that limit the Company's ability to enter into certain transacons. On the Closing Date, Kreos Capital VII Aggregator SCSp, an aﬃliate of Kreos, or the Warrant Holder, received a warrant to purchase 3,076,923 shares of the Company’s common stock, at an exercise price per share of $1.30, and upon borrowing of Tranche C, the Company will become obligated to issue addional warrants to purchase 1,153,846 shares of the Company’s common stock at an exercise price per share of $1.30 . Each warrant shall be exercisable for eight years from the date of issuance. The Company's net proceeds from the Tranche A Loan were approximately $34.5 million, aer deducng debt issuance costs, fees and expenses. The amounts classiﬁed on the consolidated balance sheet as of December 31, 2023, are reﬂecve of the current and long-term porons due under the repayment schedule due to Blackrock. Other Agreements Accounted for as Debt The Company has a liability related to the sale of future liabilies which is accounted for as a debt arrangement. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for further informaon. The Company has a refund liability with Vifor (Internaonal) Ltd. (now a part of CSL Limited), or CSL Vifor, which is also accounted for as a debt arrangement. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for further informaon. Pharmakon Term Loan (Exnguished January 29, 2024) On November 11, 2019, the Company, with Keryx as guarantor, entered into a loan agreement, or the Pharmakon Loan Agreement, with BioPharma Credit PLC as collateral agent and a lender, or the Collateral Agent, and BioPharma Credit Investments V (Master) LP as a lender, and a Guaranty and Security Agreement with the Collateral Agent. BioPharma Credit PLC subsequently transferred its interest in the loans, solely in its capacity as a lender, to its aﬃliate, BPCR Limited Partnership. The Collateral Agent and the lenders are collecvely referred to as Pharmakon. The Pharmakon Loan Agreement, as amended, consisted of a secured term loan facility in an aggregate amount of up to $100.0 million, or Pharmakon Term Loans, which was made available under two tranches: (i) Tranche A — $80.0 million and (ii) Tranche B —the second tranche of $20.0 million. On November 25, 2019, the Company drew $77.3 million on Tranche A, net of fees and expenses of $2.7 million. On December 10, 2020, the Company drew $20.0 million on Tranche B, net of immaterial lender expenses and issuance costs. On July 15, 2022, or Second Amendment Eﬀecve Date, the Company prepaid $25.0 million of the then outstanding principal, $5.0 million on Tranche A and $20.0 million on Tranche B as well as a $0.5 million prepayment fee under the terms of the Pharmakon Loan Agreement. During the year ended December 31, 2022, the Company recorded a debt exnguishment loss of $0.9 million. As of December 31, 2023, the Company had $35.0 million of principal outstanding. The Pharmakon Term Loans, as amended, bore interest through maturity at a variable rate based on the three month SOFR plus a SOFR adjustment of 0.30% plus 7.50%. The SOFR interest rate was capped at 3.35% through October 31, 2023, the date of the Fourth Amendment to the Pharmakon Loan Agreement, or Fourth Amendment. As of December 31, 2023, the three-month SOFR rate was no longer subject to the SOFR cap, therefore, the Company's interest rate was 13.13%. The Company recognized approximately $6.0 million and $9.5 million of interest expense related to the Pharmakon Loan Agreement during Akebia Therapeucs, Inc. | Form 10-K | Page 146 Table of Contents the years ended December 31, 2023 and 2022, respecvely. Unamorzed discount and issuance costs were $0.3 million as of December 31, 2023. The Company was required to make equal quarterly principal payments that started on the 33rd-month anniversary of the applicable Funding Date unl November 25, 2024, or Original Maturity Date. The Fourth Amendment, which the Company entered into on October 31, 2023, extended the maturity date to March 31, 2025, or New Maturity Date, and revised the principal payments to monthly principal payments starng in October 2024 on the remaining principal balance of $35.0 million. During the year ended December 31, 2023, the Company made quarterly principal payments totaling $32.0 million under the Pharmakon Term Loans. The Pharmakon Loan Agreement was secured by a ﬁrst priority lien on certain assets of the Company, including Auryxia and certain related assets, cash and certain equity interests held by the Company. The Pharmakon Loan Agreement contained various aﬃrmave and negave covenants, including that limit the Company's ability to engage in speciﬁed types of transacons and require the Company to maintain one or more controlled cash accounts. In addion, the Pharmakon Loan Agreement, as amended, required the Company to (i) report quarterly minimum net Auryxia sales for the trailing twelve-month period of $85.0 million, (ii) in certain instances maintain an annual minimum liquidity threshold and (iii) not be subject to any qualiﬁcaon as to going concern in its Annual Reports on Form 10-K. If an event of default occurred, including a qualiﬁcaon as a going concern, and was connuing under the Pharmakon Loan Agreement, the Collateral Agent would have been entled to take enforcement acon, including acceleraon of amounts due under the Pharmakon Loan Agreement. Under certain circumstances, a default interest rate would have applied on all outstanding obligaons during the occurrence and connuance of an event of default. As of December 31, 2023 and 2022, the Company was in compliance with the covenants under the Pharmakon Loan Agreement. Future principal payments pursuant to the contractual terms of the Pharmakon Loan Agreement, as amended, as of December 31, 2023 were as follows (in thousands): Years ended December 31, 2024 2025 Total before unamorzed discount and issuance costs Less: unamorzed discount and issuance costs Total term loans $ $ Amounts 17,500 17,500 35,000 (317) 34,683 As it relates to the Pharmakon Loan Agreement, the Company concluded the conngent put and call features that could require mandatory repayment upon the occurrence of an event of default, default interest rates to be payable and certain other events represent an embedded derivave required to be bifurcated from the debt host instrument and accounted for separately and re-measured at fair value on a quarterly basis. The fair value of the derivave liability related to the Company’s Pharmakon Loan Agreement was $0 and $0.8 million as of December 31, 2023 and 2022, respecvely. During the years ended December 31, 2023 and 2022, the Company recognized a $0.8 million and $1.1 million gain, respecvely, in other income in the consolidated statements of operaons and comprehensive loss related to the decrease in the fair value of the embedded debt derivave. On January 29, 2024, using the proceeds from the BlackRock Credit Agreement, the Company paid the then current outstanding principal balance under the Pharmakon Term Loan of $35.0 million, plus the outstanding interest and a prepayment fee of $0.2 million. 8. DEFERRED REVENUE, REFUND LIABILITY AND LIABILITY RELATED TO SALE OF FUTURE ROYALTIES CSL Vifor License Agreement Summary of Agreement On February 18, 2022, the Company entered into a Second Amended and Restated License Agreement, or the Vifor Agreement, with CSL Vifor which amended and restated the License Agreement dated as of May 12, 2017, or the Original License Agreement. The Vifor Agreement grants CSL Vifor an exclusive license to sell vadadustat to Fresenius Kidney Care Group LLC, an aﬃliate of Fresenius Medical Care North America, or FMCNA, and its aﬃliates, including Fresenius Kidney Care Group LLC, to certain third-party dialysis organizaons approved by the Company, to independent dialysis organizaons that are members of certain group purchasing organizaons and certain non-retail specialty pharmacies, collecvely, the Supply Group, in the U.S., or Vifor Territory. The Company plans to market vadadustat in the U.S., if approved, including to the Supply Group, and sell vadadustat directly to organizaons outside the Supply Group. CSL Vifor has agreed that it would not sell or otherwise supply vadadustat unl the FDA has granted regulatory approval for vadadustat for the treatment of anemia due to Akebia Therapeucs, Inc. | Form 10-K | Page 147 Table of Contents CKD in adult paents with DD-CKD in the Vifor Territory and unl CSL Vifor has entered a supply agreement with the applicable member of the Supply Group. The Vifor Agreement is structured as a proﬁt share arrangement between the Company and CSL Vifor in which the Company will receive approximately 66% of the proﬁt, net of certain pre-speciﬁed costs. In addion, CSL Vifor made an upfront payment to the Company of $25.0 million in February 2022 in connecon with the amendment and restatement of the Vifor Agreement, which was recorded as long-term deferred revenue in the accompanying consolidated balance sheet. Unless earlier terminated, the Vifor Agreement will expire upon the later of the expiraon of all patents that claim or cover vadadustat or expiraon of markeng or regulatory exclusivity for vadadustat in the Vifor Territory. CSL Vifor may terminate the Vifor Agreement in its enrety upon thirty months' prior wrien noce aer the ﬁrst anniversary of the receipt of regulatory approval, if approved from the FDA for vadadustat for dialysis-dependent CKD paents. The Company may terminate the Vifor Agreement in its enrety for convenience, following the earlier of a certain period of me elapsing or following certain speciﬁed regulatory events, and upon six months’ prior wrien noce. If the Company so terminates for convenience, subject to speciﬁed excepons, the Company will pay a terminaon fee to CSL Vifor. In addion, either party may, subject to a cure period, terminate the Vifor Agreement in the event of the other party’s uncured material breach or bankruptcy. Investment Agreements In connecon with the Original License Agreement, in May 2017, the Company sold an aggregate of 3,571,429 shares of the Company’s common stock, or 2017 Shares, to CSL Vifor at a price per share of $14.00 for a total of $50.0 million. In February 2022, in connecon with the Vifor Agreement, the Company sold an aggregate of 4,000,000 shares of its common stock, or 2022 Shares, to CSL Vifor for a price per share of $5.00 for a total of $20.0 million. The $18.3 million represenng the premium over the closing stock price, or $4.7 million for the 2017 Shares and $13.6 million for the 2022 Shares, represent consideraon related to the Vifor Agreement. CSL Vifor agreed to a lock-up restricon to not sell or otherwise dispose of the 2017 Shares or the 2022 Shares for a period of me, which restricons have expired with respect to both the 2017 Shares and the 2022 Shares. The 2017 Shares and 2022 Shares are subject to standsll agreement and are subject to vong agreements. The 2017 Shares and 2022 Shares have not been registered pursuant to the Securies Act of 1933, as amended, or the Securies Act, and were issued and sold in reliance upon the exempon from registraon contained in Secon 4(a)(2) of the Securies Act and Rule 506 promulgated thereunder as the transacon did not involve any public oﬀering within the meaning of Secon 4(a)(2) of the Securies Act. Deferred Revenue Recognion The Company evaluated the elements of the Vifor Agreement in accordance with the provisions of ASC 606 and concluded that the contract counterparty, CSL Vifor, is a customer. The Company idenﬁed one performance obligaon under the Vifor Agreement at incepon, which is the non-sublicensable, non- transferrable license under certain of the Company’s intellectual property to (i) sell vadadustat solely to the Supply Group, (ii) sell vadadustat to Designated Wholesalers solely for resale to members of the Supply Group, (iii) conduct medical aﬀairs with respect to vadadustat in the Vifor Territory in the ﬁeld during the term of the Vifor Agreement and (iv) use the Akebia Trademark solely in connecon with the sale of vadadustat. The transacon price of $43.3 million was comprised of the up-front payment of $25.0 million and the premiums paid by CSL Vifor on the First Investment Agreement and Second Investment Agreement of $4.7 million and $13.6 million, respecvely. Pursuant to the Vifor Agreement, these payments are non- refundable and non-creditable against any other amount due to the Company. However, if the Centers for Medicare & Medicaid Services, or CMS, determines that vadadustat is excluded from the Transional Drug Add-on Payment Adjustment, or TDAPA, the Company can terminate the Vifor Agreement and will be required to repay the up-front payment and the premiums paid by CSL Vifor on the First Investment Agreement and the Second Investment Agreement. Given the uncertainty associated with a potenal future approval of vadadustat by the FDA, and whether, if approved, vadadustat would be included in certain reimbursement bundles by CMS, the Company constrained the enre transacon price at incepon. Unl the license is delivered, the transacon price of $43.3 million will remain in long-term deferred revenue in the accompanying consolidated balance sheets. (see Note 12, License, collaboraon and other revenue for further informaon) Refund Liability to Customer/Working Capital Fund Pursuant to the Vifor Agreement, CSL Vifor contributed $40.0 million to a working capital fund, or Working Capital Fund, established to fund approximately 50% of the Company’s costs of purchasing vadadustat from its contract manufacturers for the supply of vadadustat for the Vifor Territory already delivered or to be delivered to the Company through the end of 2023. The amount of the Working Capital Fund will be reviewed at speciﬁed intervals and is adjusted based on a number of factors including outstanding supply commitments for vadadustat for the Vifor Territory and agreed upon vadadustat inventory levels held by the Company for the Vifor Territory. Upon terminaon or expiraon of the Vifor Agreement for any reason other than Akebia Therapeucs, Inc. | Form 10-K | Page 148 Table of Contents convenience by CSL Vifor (including following receipt of the CRL for vadadustat), the Company will be required to refund the outstanding balance of the Working Capital Fund on the date of terminaon or expiraon. The Company has determined that the working capital fund does not represent an obligaon to transfer goods or services to CSL Vifor in the future and thus under ASC 606 was recorded as a refund liability. The refund liability is considered a debt arrangement with zero coupon interest and the Company imputes interest on the refund liability at a rate of 15.0% per annum, which was determined based on certain factors, including the Company's credit rang, comparable securies yield and the expected repayment period. On March 18, 2022, when the $40.0 million was received from CSL Vifor, the Company recorded an inial discount on the refund liability to the customer and a corresponding deferred gain to the refund liability to customer in the consolidated balance sheet. The discount on the note payable is being amorzed to interest expense using the eﬀecve interest method over the expected term of the Vifor Agreement. The deferred gain is being amorzed to interest income on a straight-line basis over the expected term of the Vifor Agreement. The amorzaon of the discount was $3.1 million and $3.4 million for the years ended December 31, 2023 and 2022, respecvely. The amorzaon of the deferred gain was $4.0 million and $2.4 million for the years ended December 31, 2023 and 2022, respecvely. As of December 31, 2023, the $40.1 million total refund liability is classiﬁed as a long-term liability based on management's esmated ming of the repayment of the refund liability to Vifor exceeding one year. Liability Related to Sale of Future Royales In February 2021, the Company entered into a royalty interest acquision agreement with HealthCare Royalty Partners IV, L.P., or HCR, or Royalty Agreement, pursuant to which the Company sold to HCR its right to receive royales and sales milestones for vadadustat in Japan and certain other Asian countries, such countries collecvely, the MTPC Territory, and such payments collecvely the Royalty Interest Payments, in each case, payable to the Company under the MTPC Agreement. The Royalty Interest Payments are subject to an annual maximum “cap” of $13.0 million, aer which the Company will receive 85% of the Royalty Interest Payments for the remainder of that year. The Royalty Interest Payments are also subject to an aggregate maximum “cap” of $150.0 million, aer which the Royalty Interest Payments will revert back to the Company. The Company was eligible to receive an addional $5.0 million in each year from 2021 through 2023 under the Royalty Agreement if speciﬁed annual sales milestones were achieved for vadadustat in the MTPC Territory, subject to the sasfacon of certain customary condions. The sales milestones for vadadustat in the MTPC Territory were not achieved for 2023, 2022 or 2021. The Company retains the right to receive all potenal future regulatory milestones for vadadustat under the MTPC Agreement. The Royalty Agreement will terminate on the earlier of the date on which HCR has received (i) the last Royalty Interest Payment or (ii) payment by the Company of an amount equal to the Aggregate Cap minus the aggregate amount of all Royalty Interest Payments actually received by HCR. At the transacon date, the Company recognized the proceeds received from HCR of $44.8 million (net of certain transacon expenses) as a liability and is amorzing it using the eﬀecve interest method over the life of the arrangement. The liability related to sale of future royales and the debt amorzaon are based on the Company’s current esmates of future royales expected to be paid over the life of the arrangement. To the extent the Company’s esmates of future royalty payments are greater or less than previous esmates or the esmated ming of such payments is materially diﬀerent than previous esmates, the Company will adjust the eﬀecve interest rate and recognize related non-cash interest expense on a prospecve basis. In the event the Company's esmates of future royales are less than the proceeds from the sale of future royales, the Company will not recognize related non-cash interest expense. On a quarterly basis, the Company assesses the expected royalty payments. The annual eﬀecve interest rate as of December 31, 2023 was 0% and, therefore the Company did not recognize any non-cash interest expense in the consolidated statements of operaons and comprehensive loss. As a result of the Company's ongoing involvement in the cash ﬂows related to the royales and sales milestones in the MTPC Territory, the Company will connue to account for the royales received as non-cash royalty revenue which is reﬂected within license, collaboraon and other revenue in the consolidated statements of operaons and comprehensive loss. During the year ended December 31, 2023 and 2022, the Company paid $2.0 million and $1.8 million of royales to HCR and as of year end the balances were is thousands): follows (in as Liability related to the sale of future royales: Current poron (included in accrued expenses and other current liabilies) Long-term poron Total liability related to sale of future royales December 31, 2023 2022 $ $ 2,048 54,013 56,061 $ $ — 57,484 57,484 The Royalty Agreement requires the Company to take certain acons, including acons with respect to the Royalty Interest Payments, the MTPC Agreement, and the Company's intellectual property. The Royalty Agreement also contains certain representaons and warranes, covenants, indemniﬁcaon obligaons, events of default and other provisions that are Akebia Therapeucs, Inc. | Form 10-K | Page 149 Table of Contents customary for a royalty monezaon transacon of this nature. In addion, the Company granted HCR a precauonary security interest in connecon with the Royalty Interest Payments. MTPC Supply Agreement See Note 12, License, Collaboraon and Other Revenues, for further informaon on short-term deferred revenue as of December 31, 2022 that was recognized during the year ended December 31, 2023. 9. LEASES Cambridge Leases Under the Cambridge Lease, the Company leases approximately 65,167 square feet of oﬃce, storage and laboratory space in Cambridge, Massachuses, which are non-cancelable operang leases. 5,951 square feet of the laboratory space is set to expire on January 31, 2025, with an extension opon for one addional period through September 11, 2026 and 59,216 oﬃce and storage space are set to expire on September 11, 2026, with one ﬁve-year extension opon available. In addion to rent, certain leases require the Company to pay addional amounts for taxes, insurance, maintenance, and other operang expenses. All of the Company's leases are classiﬁed as operang leases. The renewal opon in this real estate lease was not included in the calculaon of the operang lease asset and operang lease liability as the renewal is not reasonably certain. The lease agreements do not contain residual value guarantees. The components of lease right-of-use assets and lease liabilies are included in the consolidated balance sheets. Operang lease liabilies are based on the net present value of the remaining lease payments over the remaining lease term. In determining the present value of lease payments, the Company used its incremental borrowing rate when measuring operang lease liabilies. In arriving at the operang lease liabilies, the Company applied incremental borrowing rates ranging from 6.65% to 6.94%, which were based on the remaining lease term at either the date of adopon of ASC 842, Leases, or the eﬀecve date of any subsequent lease term extensions. As of December 31, 2023, the remaining lease term for the Cambridge Leases was 2.70 years. Operang lease costs were $5.7 million and $7.1 million for the years ended December 31, 2023 and 2022, respecvely. Cash paid for amounts included in the measurement of operang lease liabilies were $5.9 million and $7.2 million for the years ended December 31, 2023 and 2022, respecvely. The security deposit in connecon with the Cambridge Lease is $1.7 million in the form of a leer of credit, which is included as restricted cash in other long-term assets in the Company's consolidated balance sheet as of December 31, 2023. Sublease and Former Boston Lease Previously, the Company leased 27,924 square feet of oﬃce space in Boston, Massachuses, or the Boston Lease, under a non-cancelable operang lease that was set to expire in July 2031. The Company subleased the enre Boston Lease, eﬀecve October 2019 through February 2023. The Company recorded $0.3 million and $1.8 million in rental income as other income in the consolidated statements of operaons and comprehensive loss during the years ended December 31, 2023 and 2022, respecvely. In May 2023, pursuant to a Lease Assignment Agreement, or the Lease Assignment Agreement, the Company assigned all of its rights, tle, and interest in, to, and under the Boston Lease to LG Chem Life Sciences Innovaon Center, Inc., or LG Chem, and made a payment to LG Chem of $1.3 million. As of May 2023, LG Chem assumed all of the rights and obligaons of the Company under the Boston Lease and the Company has no further obligaons for rent or other payments under the Boston Lease. In accordance with ASC 842, Leases, the Company wrote oﬀ the right-of-use asset and lease liability associated with the Boston Lease, and recognized the diﬀerence between the right-of-use asset and the lease liability oﬀset by the $1.3 million payment as a loss on lease terminaon in the consolidated statements of operaons and comprehensive loss of $0.5 million. Under the terms of the Lease Assignment Agreement the Company was entled to, and received back, its security deposit of $1.0 million which had been recorded as restricted cash in other long-term assets in the Company's consolidated balance sheet as of December 31, 2022. Akebia Therapeucs, Inc. | Form 10-K | Page 150 Table of Contents Future Lease Commitments Future commitments under non-cancelable Cambridge Leases are as follows (in thousands): 2024 2025 2026 Total lease commitments Less: present value adjustment Current and long-term operang lease liabilies 10. COMMITMENTS AND CONTINGENCIES Manufacturing and Uncondional Purchase Commitment Agreements Siegfried Manufacturing Operang Leases 5,261 5,819 3,613 14,693 (1,255) 13,438 $ $ $ The Company's contractual obligaons include a commercial supply agreement with Siegfried Evionnaz, or Siegfried, to supply commercial drug substance for Auryxia. The Company and Siegfried entered into a Master Manufacturing Services and Supply Agreement, most recently amended in February 2023, or the Siegfried Agreement, under which the Company has agreed to purchase a minimum quanty of drug substance of Auryxia, annually at a predetermined price. As of December 31, 2023, the Company had a minimum total commitment of approximately $29.6 million through the end of 2026. The term of the Siegfried Agreement was set to expire on December 31, 2024, subject to the Company’s opon to extend the term through December 31, 2026. The Company provided Siegfried with wrien noce of its elecon to extend the term of the Siegfried Agreement through December 31, 2026. The Siegfried Agreement provides the Company and Siegfried with certain early terminaon rights. In connecon with the extension of the Siegfried Agreement and the related increase in contractual purchase commitments, the Company recorded an excess ﬁrm purchase commitment liability in other long-term liabilies of $1.5 million and corresponding expense to cost of product and other revenue during the year ended December 31, 2023. Patheon Manufacturing In March 2020, the Company entered into a Supply Agreement with Patheon Inc., or Patheon, or the Patheon Agreement, under which Patheon will manufacture vadadustat drug product for commercial use under a volume-based pricing structure through June 30, 2025, renewing annually unless either party gives the other party eighteen months' prior wrien noce. Under the Patheon Agreement, the Company agreed to purchase from Patheon a certain percentage of the esmated global demand for vadadustat drug product based on certain quarterly and annual forecasts provided by the Company. As of December 31, 2023, the Company had no minimum commitment with Patheon, however, as esmated global demand ﬂuctuates, the Company may have future obligaons under the Patheon Agreement. WuXi STA Manufacturing In April 2020, the Company entered into a Supply Agreement with STA Pharmaceucal Hong Kong Limited, a subsidiary of WuXi AppTec, or WuXi STA, or, as amended, the WuXi STA DS Agreement. Under the WuXi STA DS Agreement, WuXi STA will manufacture vadadustat drug substance for commercial use under a volume-based pricing structure through April 2, 2024. Pursuant to the WuXi STA DS Agreement, the Company has agreed to purchase a certain percentage of the global demand for vadadustat drug substance from WuXi STA. As of December 31, 2023, the Company has commied to purchase $13.4 million of vadadustat drug substance from WuXi STA through the end of 2024. On February 10, 2021, the Company entered into a Supply Agreement with WuXi STA, or the WuXi STA DP Agreement, under which WuXi STA will manufacture and supply vadadustat drug product for commercial purposes under a volume-based pricing structure through February 10, 2025. The vadadustat drug product price is reviewed annually by the Company and WuXi STA. The Company also reimburses WuXi STA for certain reasonable expenses. Pursuant to the WuXi STA DP Agreement, the Company has agreed to purchase a certain percentage of global demand for vadadustat drug product from WuXi STA. The WuXi STA DP Agreement may be renewed or extended by mutual agreement of the Company and WuXi STA with at least eighteen months’ prior wrien noce. The WuXi STA DP Agreement allows the Company to terminate the relaonship on 180 calendar days’ prior wrien noce to WuXi STA for any reason. In addion, each party has the ability to terminate the WuXi STA DP Agreement upon the occurrence of certain condions. Akebia Therapeucs, Inc. | Form 10-K | Page 151 Table of Contents Esteve - Assigned Supply Agreement On April 9, 2019, the Company and Esteve Química, S.A., or Esteve, entered into a Supply Agreement, or the Esteve Agreement, which included the terms and condions under which Esteve would manufacture vadadustat drug substance for commercial use under a volume-based pricing structure. On December 16, 2022, the Company, MTPC, and Esteve executed the Esteve Assignment Agreement, pursuant to which the Esteve Agreement was assigned to MTPC. The Esteve Assignment Agreement transferred the rights and obligaons of the Esteve Agreement to MTPC, speciﬁcally including the obligaons under certain purchase orders issued by the Company and accepted by Esteve. As such, the Company will have no further obligaon to take delivery of or pay for product delivered by Esteve under the transferred Esteve Agreement. BioVectra - Former Manufacturing and Uncondional Purchase Commitments Under the Manufacture and Supply Agreement with BioVectra and the Amended and Restated Product Manufacture and Supply and Facility Construcon Agreement with BioVectra, the Company agreed to purchase minimum quanes of Auryxia drug substance annually at predetermined prices as well as reimburse BioVectra for certain costs in connecon with construcon of a new facility for the manufacture and supply of Auryxia drug substance. On December 22, 2022, the Company and BioVectra entered into a terminaon agreement, under which the pares agreed, among other things, to terminate, eﬀecve immediately, any and all exisng agreements entered into between the pares in connecon with the manufacture and supply, by BioVectra to the Company, of Auryxia drug substance. In the terminaon agreement, the Company and BioVectra released one another from all exisng and future claims and liabilies and the return of certain materials and documents. In addion, the Company agreed to pay BioVectra a total of $32.5 million consisng of (i) an upfront payment of $17.5 million and (ii) six quarterly payments of $2.5 million commencing in April 2024, totaling $15.0 million. The upfront payment of $17.5 million was made during the quarter ended December 31, 2022 and was recorded in cost of product and other revenue. In accordance with ASC 420, Exit or Disposal Cost Obligaons, the Company recognized a liability and corresponding expense for the remaining terminaon fees based on esmated fair value as of December 22, 2022. The Company imputed interest on the liability for the remaining terminaon fees at a rate of 17.0% per annum, which was determined based on certain factors, including the Company's credit rang, comparable securies yield and expected repayment period of the remaining terminaon fees. The Company recorded an inial discount on the remaining terminaon fees in the consolidated balance sheet on the date of the terminaon. This resulted in the recording of a liability and corresponding charge to cost of goods sold of $11.2 million during the quarter ended December 31, 2022. The discount on the liability balance is being amorzed to interest expense using the eﬀecve interest rate method over the term of the liability. The amorzaon of the discount was $1.9 million for the year ended December 31, 2023. In-Licensing - Panion License Agreement On April 17, 2019, the Company and Panion & BF Biotech, Inc., or Panion, entered into a second amended and restated license agreement, or Panion Amended License Agreement, which amended and restated in full the license agreement between the Company and Panion. The Panion Amended License Agreement provides the Company with an exclusive license under Panion-owned know-how and patents covering the rights to sublicense, develop, make, use, sell, oﬀer for sale, import and export ferric citrate worldwide, excluding certain Asian-Paciﬁc countries, or the Licensor Territory. The Panion Amended License Agreement also provides Panion with an exclusive license under Company-owned patents covering the rights to sublicense (with the Company’s wrien consent), develop, make, use, sell, oﬀer for sale, import and export ferric citrate in certain countries in the Licensor Territory. Under the Panion Amended License Agreement, Panion is eligible to receive from the Company or any sublicensee royalty payments based on a mid-single digit percentage of sales of ferric citrate in the Company’s licensed territories. The Company is eligible to receive from Panion or any sublicensee royalty payments based on a mid-single digit percentage of net sales of ferric citrate in Panion’s licensed territories. The Panion Amended License Agreement terminates upon the expiraon of each of the Company’s and Panion’s obligaons to pay royales thereunder. In addion, the Company may terminate the Panion Amended License Agreement (i) in its enrety or (ii) with respect to one or more countries in the Company’s licensed territory, in either case upon ninety days’ noce. The Company and Panion also each have the right to terminate the Panion Amended License Agreement upon the occurrence of a material breach of the Panion Amended License Agreement by the other party, subject to certain cure provisions, or certain insolvency events. The Panion Amended License Agreement also provides that, on a country-by-country basis, unl the second anniversary of the expiraon of the obligaon of the Company or Panion, as applicable, to pay royales in a country in which such party has ferric citrate for sale on the date of such expiraon, neither the other party nor its aﬃliates will, directly or indirectly, sell, distribute or otherwise commercialize or supply or cause to supply ferric citrate to a third party for sale or distribuon in such country. The Panion Amended License Agreement includes customary terms relang to, among others, indemniﬁcaon, conﬁdenality, remedies, and representaons and warranes. In addion, the Panion Amended License Agreement provides that each of the Company and Panion has the right, but not the obligaon, to conduct ligaon against any infringer of certain patent rights under the Panion Amended License Agreement in certain territories. Akebia Therapeucs, Inc. | Form 10-K | Page 152 Table of Contents During the years ended December 31, 2023 and 2022, the Company incurred approximately $10.0 million and $13.8 million, respecvely, in royalty payments due to Panion relang to the Company’s sales of Auryxia in the U.S. and JT and Torii’s net sales of Riona in Japan. Other Third Party Contracts The Company contracts with various organizaons to conduct R&D acvies with remaining contract costs to the Company of approximately $44.7 million at December 31, 2023. The scope of the services under these R&D contracts can be modiﬁed and the contracts cancelled by the Company upon wrien noce. In some instances, the contracts may be cancelled by the third party upon wrien noce. Ligaon and Related Maers The Company is involved from me to me in various legal proceedings arising in the normal course of business. Loss conngency provisions are recorded for probable and esmable losses at our best esmate of a loss or, when a best esmate cannot be made, at our esmate of the minimum loss. These esmates are oen developed prior to knowing the amount of the ulmate loss, require the applicaon of signiﬁcant judgment and are reﬁned as addional informaon becomes known. Accordingly, we are oen inially unable to develop a best esmate of loss and therefore the esmated minimum loss amount, which could be zero, is recorded. Changes in the Company’s esmates could have a material impact. Although the outcomes of potenal legal proceedings are inherently diﬃcult to predict, the Company does not expect the resoluon of current legal proceedings to have a material adverse eﬀect on its ﬁnancial posion, results of operaons or cash ﬂows of the Company. Guarantees and Indemniﬁcaons As permied under Delaware law, the Company may indemnify its oﬃcers, directors and employees for certain events or occurrences that happen by reason of their relaonship with, or posion held at, the Company. The Company may also be subject to indemniﬁcaon obligaons by law with respect to the acons of its employees under certain circumstances and in certain jurisdicons. The Company maintains director and oﬃcer liability insurance coverage that is intended to cover a poron of amounts that may be due with respect to indemniﬁcaon aer a deducble is met. Further, the Company is a party to a variety of agreements in the ordinary course of business under which it may be obligated to indemnify third pares with respect to certain maers. For the years ended December 31, 2023 and 2022, the Company did not experience any losses related to these indemniﬁcaon obligaons, and no claims were outstanding as of December 31, 2023. The Company does not have any claims related to these indemniﬁcaon obligaons and consequently concluded that the fair value of these obligaons is negligible and no related accruals were recorded. 11. PRODUCT REVENUE AND RESERVES FOR VARIABLE CONSIDERATION To date, the Company’s only source of product revenue has been from the U.S. sales of Auryxia. Total net product revenue was $170.3 million and $176.9 million for the years ended December 31, 2023 and 2022, respecvely. Product revenue allowance and reserve categories were as follows: (in thousands) Balance at December 31, 2021 Current provisions related to sales in current year Adjustments related to prior year sales Credits/payments made Balance at December 31, 2022 Current provisions related to sales in current year Adjustments related to prior year sales Credits/payments made Balance at December 31, 2023 Chargebacks and Discounts Rebates, Fees and other Deducons Returns Total $ $ $ 1,047 $ 11,412 (9) (11,191) 1,259 $ 11,138 (304) (10,486) 1,607 $ 24,478 $ 89,095 401 (87,722) 26,252 $ 79,648 (1,506) (81,403) 22,991 $ 10,065 $ 5,603 (26) (4,719) 10,923 $ 6,181 1,648 (11,836) 6,916 $ 35,590 106,110 366 (103,632) 38,434 96,967 (162) (103,725) 31,514 Chargebacks, discounts and esmated product returns are recorded as a reducon of revenue in the period the related product revenue is recognized in the consolidated statements of operaons and comprehensive loss. Chargebacks are recorded as a reducon to accounts receivable while discounts, rebates, fees and other deducons are recorded with a corresponding increase to accrued expenses and other current liabilies or accounts payable in the consolidated balance sheets. Esmated product returns on product sales that are not expected to be returned within one year are recorded as other long-term liabilies in the consolidated balance sheets. Akebia Therapeucs, Inc. | Form 10-K | Page 153 Table of Contents Accounts receivable, net related to product sales was approximately $35.9 million and $37.3 million as of December 31, 2023 and 2022, respecvely. 12. LICENSE, COLLABORATION AND OTHER REVENUE The Company recognized the following revenues from its license, collaboraon and other revenue agreements (in thousands): Enty Medice MTPC JT and Torii Otsuka Descripon License and Product Supply of Vadadustat in EU License and Product Supply of Vadadustat in Japan License and royales related to the sale of Riona in Japan Terminated U.S. and Internaonal Agreements Total License, Collaboraon and Other Revenue Years Ended December 31, 2022 2023 10,968 $ 5,735 5,394 2,225 24,322 $ — 17,968 5,291 92,276 115,535 $ $ The following table presents changes in the Company’s contract assets and liabilies related to license, collaboraon and other revenue agreements (in thousands): Contract assets: Accounts receivable Prepaid expenses and other current assets (1) Contract liability: Deferred revenue (current and long-term) Contract assets: Accounts receivable Prepaid expenses and other current assets (1) Contract liabilies: Deferred revenue (current and long-term) Accounts payable Twelve Months Ended December 31, 2023 Balance at Beginning of Period Addions Deducons Balance at End of Period 1,901 $ 781 $ 10,088 $ — $ (8,656) $ (781) $ 3,333 — 47,034 $ — $ (3,738) $ 43,296 Twelve Months Ended December 31, 2022 Balance at Beginning of Period Addions Deducons Balance at End of Period 19,094 $ 4,309 $ 42,380 $ 3,171 $ 94,515 $ 9,550 $ 70,044 $ — $ (111,708) $ (13,078) $ (65,390) $ (3,171) $ 1,901 781 47,034 — $ $ $ $ $ $ $ (1) Excludes accounts receivable from product sales of Auryxia which are included in the accompanying consolidated balance sheets as of December 31, 2023 and 2022. During the years ended December 31, 2023 and 2022, the Company recognized the following revenues as a result of changes in the contract asset and contract liability balances in the respecve periods (in thousands): Revenue Recognized in the Period from: Deferred revenue - beginning of the period Performance obligaons sasﬁed in previous periods Medice License Agreement Years Ended December 31, 2022 2023 $ $ 3,738 $ — $ 29,574 — On May 24, 2023, or Medice Eﬀecve Date, the Company and MEDICE Arzneimiel Püer GmbH & Co. KG, or Medice, entered into a License Agreement, or the Medice License Agreement, pursuant to which the Company granted to Medice an exclusive license to develop and commercialize vadadustat for the treatment of anemia in adult paents with chronic kidney disease in European Economic Area, the UK, Switzerland and Australia, or the Medice Territory. Akebia Therapeucs, Inc. | Form 10-K | Page 154 Table of Contents Under the Medice License Agreement, the Company received an up-front payment of $10.0 million and is eligible to receive the following payments: (i) commercial milestone payments up to an aggregate of $100.0 million, and (ii) ered royales ranging from 10% to 30% of Medice's annual net sales of vadadustat in the Medice Territory, subject to reducon in certain circumstances. The royales will expire on a country-by-country basis upon the latest to occur of (a) the date of expiraon of the last-to-expire valid claim of any Company, Medice or joint patent that covers vadadustat in such country in the Medice Territory, (b) the date of expiraon of data or regulatory exclusivity for vadadustat in such country in the Medice Territory and (c) the date that is twelve years from ﬁrst commercial sale of vadadustat in such country in the Medice Territory. Under the Medice License Agreement, the Company retains the right to develop vadadustat for non-dialysis paents with anemia due to chronic kidney disease in the Medice Territory. If the Company develops vadadustat for non-dialysis paents and vadadustat receives markeng approval in the Medice Territory, Medice will commercialize vadadustat for both indicaons in the Medice Territory. In this instance, the Company would receive 70% of the net product margin of any sales of vadadustat in the non-dialysis paent populaon, unless Medice requests to share the cost of the development necessary to gain approval to market vadadustat for non-dialysis paents in the Medice Territory and the pares agree on alternave ﬁnancial terms. If the Company develops vadadustat for non-dialysis paents, the Company has determined that the acvies under the Medice License Agreement represent joint operang acvies in which both pares are acve parcipants and of which both pares are exposed to signiﬁcant risks and rewards that are dependent on the success of the acvies. Accordingly, if the Company develops vadadustat for non-dialysis paents the Company will account for the joint acvies in accordance with ASC No. 808, Collaborave Arrangements, or ASC 808. Addionally, the Company has determined that in the context of the development of vadadustat for non-dialysis paents, Medice does not represent a customer as contemplated by ASC 606-10-15, Revenue from Contracts with Customers – Scope and Scope Excepons. As a result, the acvies conducted pursuant to development acvies for vadadustat for non-dialysis paents will be accounted for as a component of the related expense in the period incurred. The Medice License Agreement expires on the date of expiraon of all payment obligaons due thereunder with respect to vadadustat in the last country in the Medice Territory, unless earlier terminated in accordance with the terms of the Medice License Agreement. Either party may, subject to a cure period, terminate the Medice License Agreement in the event of the other party's uncured material breach. Medice has the right to terminate the Medice License Agreement in its enrety for convenience upon twelve months' prior wrien noce delivered on or aer the date that is twelve months aer the Medice Eﬀecve Date. The Medice License Agreement provides that the Company and Medice will enter into a supply agreement pursuant to which the Company will supply vadadustat to Medice for commercial use in the Medice Territory. As of December 31, 2023, the Company and Medice have not yet entered into a supply agreement. The Company evaluated the elements of the Medice License Agreement in accordance with the provisions of ASC 606 and concluded Medice is a customer. The Company idenﬁed one performance obligaon in connecon with its obligaons under the Medice License Agreement, which is the license, or License Performance Obligaon. The transacon price at incepon was comprised of the up-front payment of $10.0 million, of which the Company received $8.6 million during the quarter ended June 30, 2023. The remaining $1.4 million was withheld by the German Federal Tax Oﬃce and is included in other long-term assets in the consolidated balance sheet as of December 31, 2023. Pursuant to the terms of the Medice License Agreement, the up-front payment of $10.0 million is non-refundable and non-creditable against any other amount due to the Company and was allocated to the License Performance Obligaon, which was sasﬁed as of the Medice Eﬀecve Date. As such, the Company recognized the $10.0 million up-front payment as License, collaboraon and other revenue in the consolidated statement of operaons and comprehensive loss during the year ended December 31, 2023. In accordance with ASC 606, the Company will recognize sales-based royales and milestone payments at the later of when the performance obligaon is sasﬁed or the related sales occur. Medice Leer Agreement On December 6, 2023, the Company and Medice entered into a leer agreement, or the Medice Leer Agreement, pursuant to which the Company agreed to sell to Medice a paral batch of vadadustat in order to achieve packaging validaon for the Medice Territory. The Company recognizes revenue under this arrangement when risk of loss passes to Medice and delivery has occurred. During the year ended December 31, 2023, the Company recognized $1.0 million in collaboraon revenue under the Medice Side Leer. As of December 31, 2023, there was $0.9 million in accounts receivable and no contract assets, payables or deferred revenue recorded in connecon with the Medice Leer Agreement. Akebia Therapeucs, Inc. | Form 10-K | Page 155 Table of Contents MTPC Collaboraon Agreement On December 11, 2015, the Company and Mitsubishi Tanabe Pharma Corporaon, or MTPC, entered into the MTPC Agreement, providing MTPC with exclusive development and commercializaon rights to vadadustat in Japan and certain other Asian countries, collecvely, the MTPC Territory, which was amended eﬀecve as of December 2, 2022. In addion, the Company supplies vadadustat to MTPC for both clinical and commercial use in the MTPC Territory. In February 2021, the Company entered into the Royalty Agreement with HCR, whereby the Company sold its right to receive royales and sales milestones under the MTPC Agreement, subject to certain caps and other terms and condions. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for more informaon. Unless earlier terminated, the MTPC Agreement will connue in eﬀect on a country-by-country basis unl the later of the following: expiraon of the last-to- expire patent covering vadadustat in such country in the MTPC Territory; expiraon of markeng or regulatory exclusivity in such country in the MTPC Territory; or ten years aer the ﬁrst commercial sale of vadadustat in such country in the MTPC Territory. MTPC may terminate the MTPC Agreement upon twelve months’ noce at any me aer the second anniversary of the eﬀecve date of the MTPC Agreement. Either party may terminate the MTPC Agreement upon the material breach of the other party that is not cured within a speciﬁed me period or upon the insolvency of the other party. Under the MTPC Agreement, MTPC is required to make certain milestone payments to the Company aggregang up to approximately $225.0 million upon the achievement of speciﬁed development, regulatory and commercial events. The Company has received $10.0 million in development milestone payments. Of the $40.0 million in regulatory milestone payments the Company is eligible for, the Company received $10.0 million in relaon to the Japanese NDA ﬁling in the third quarter of 2019 and $15.0 million following regulatory approval of vadadustat in Japan in the third quarter of 2020. The Company is also entled to receive up to $175.0 million in commercial milestone payments associated with aggregate sales of all products. In consideraon for the exclusive license and other rights contained in the MTPC Agreement, MTPC made a $20.0 million upfront payment as well as a $20.5 million payment for Phase 2 studies in Japanese paents completed by the Company and reimbursed by MTPC. Addionally, the Company is entled to receive ered royalty payments ranging from 13% to 20% on annual net sales of vadadustat in the MTPC Territory, subject to reducon in certain circumstances. The Company evaluated the elements of the MTPC Agreement in accordance with the provisions of ASC 606 and concluded that the contract counterparty, MTPC, is a customer. The Company idenﬁed two performance obligaons in connecon with its material promises under the MTPC Agreement as follows: (i) License, Research and Clinical Supply Performance Obligaon and (ii) Rights to Future Know-How Performance Obligaon. The transacon price was comprised of: (i) the up-front payment of $20.0 million, (ii) the cost for the Phase 2 studies of $20.5 million, (iii) the cost of all clinical supply provided to MTPC for the Phase 3 studies, (iv) $10.0 million in development milestones received, (v) $25.0 million in regulatory milestones received and (vi) $5.0 million in royales from net sales of Vafseo. The Company re-evaluates the transacon price in each reporng period and as uncertain events are resolved or other changes in circumstances occur. As of December 31, 2023, all development milestones and $25.0 million in regulatory milestones have been achieved. No other regulatory milestones or commercial milestones have been assessed as probable and have been fully constrained unl the period in which they are achieved. The Company allocates the transacon price to each performance obligaon based on the Company’s best esmate of the relave standalone selling price. The Company developed a best esmate of the standalone selling price for the Rights to Future Know-How Performance Obligaon primarily based on the likelihood that addional intellectual property covered by the license conveyed will be developed during the term of the arrangement and determined it is immaterial. As such, the Company did not develop a best esmate of standalone selling price for the License, Research and Clinical Supply Performance Obligaon and allocated the enre transacon price to this performance obligaon. Revenue for the License, Research and Clinical Supply Performance Obligaon for the MTPC Agreement is being recognized using a proporonal performance method, for which all deliverables have been completed. The Company recognizes any revenue from MTPC royales in the period in which the sales occur. The Company recognized $2.0 million and $1.8 million of revenue for royales from the net sales of Vafseo during the years ended December 31, 2023 and 2022, respecvely. As noted above, in February 2021, the Company entered into the Royalty Agreement, whereby the Company sold its right to receive these royales and sales milestones under the MTPC Agreement, subject to certain caps and other condions. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for more informaon. The revenue is classiﬁed as collaboraon revenue in the accompanying consolidated statements of operaons and comprehensive loss. As of December 31, 2023, there were no accounts receivable, contract assets, payables or deferred revenue recorded in connecon with the MTPC Agreement. Akebia Therapeucs, Inc. | Form 10-K | Page 156 Table of Contents Supply of Drug Product to MTPC On July 15, 2020, the Company and MTPC entered into a supply agreement, or the MTPC Supply Agreement, under which the Company supplies vadadustat drug product to MTPC for commercial use in Japan and certain other Asian countries, as contemplated by the MTPC Agreement. The term of the MTPC Supply Agreement extends throughout the term of the MTPC Agreement, and the terminaon provisions of the MTPC Agreement govern terminaon of the MTPC Supply Agreement. The Company does not recognize revenue under this arrangement unl risk of loss on the drug product passes to MTPC and delivery has occurred and MTPC has accepted the product. On December 16, 2022, the Company, MTPC and Esteve Química, S.A., or Esteve, executed an Assignment of Supply Agreement, or Esteve Assignment Agreement, pursuant to which the Supply Agreement between the Company and Esteve, or Esteve Agreement was assigned to MTPC. The Esteve Assignment Agreement transferred the rights and obligaons of the Company under the Esteve Agreement to MTPC. The Company has no further obligaon to take delivery of, or pay for, product delivered by Esteve. See Note 10, Commitments and Conngencies, for more informaon. During the years ended December 31, 2023 and 2022, the Company recognized $3.7 million and $16.2 million, respecvely, of revenue under the MTPC Supply Agreement. Due to the Esteve Agreement, the Company no longer records accounts receivable, deferred revenue or other current liabilies relang to the MTPC Supply Agreement. JT and Torii Sublicense Agreement The Company has an Amended and Restated Sublicense Agreement, which was amended in June 2013, with JT and Torii, or JT and Torii Sublicense Agreement, under which JT and Torii obtained the exclusive sublicense rights for the development and commercializaon of ferric citrate hydrate in Japan. JT and Torii are responsible for the future development and commercializaon costs in Japan. The Company is eligible to receive royalty payments based on a ered low double-digit percentage of net sales of Riona in Japan inclusive of amounts that the Company must pay to Panion on JT and Torii's net sales of Riona under the Panion License Agreement subject to certain reducons upon expiraon or terminaon of the Amended and Restated License Agreement between the Company and Panion, pursuant to which Company in-licensed the exclusive worldwide rights, excluding certain Asian-Paciﬁc countries, for the development and commercializaon of ferric citrate. The Company is entled to receive up to an addional $55.0 million upon the achievement of certain annual net sales milestones. The sublicense under the JT and Torii Sublicense Agreement terminates upon the expiraon of all underlying patent rights. Also, JT and Torii may terminate the JT and Torii Sublicense Agreement with or without cause upon at least six months' prior wrien noce to the Company. Addionally, either party may terminate the JT and Torii Sublicense Agreement for cause upon 60 days’ prior wrien noce aer the breach of any uncured material provision of the JT and Torii Sublicense Agreement, or aer certain insolvency events. The Company evaluated the elements of the JT and Torii Sublicense Agreement in accordance with the provisions of ASC 606 and concluded that the contract counterparty, JT and Torii, is a customer. The Company idenﬁed two performance obligaons in connecon with its obligaons under the JT and Torii Sublicense Agreement: (i) License and Supply Performance Obligaon and (ii) Rights to Future Know-How Performance Obligaon. The Company developed a best esmate of the standalone selling price for the Rights to Future Know-How Performance Obligaon primarily based on the likelihood that addional intellectual property covered by the license conveyed will be developed during the term of the arrangement and determined it immaterial. As such, the Company did not develop a best esmate of standalone selling price for the License and Supply Performance Obligaon and allocated the enre transacon price to this performance obligaon. Addionally, as of the consummaon of the Merger, the services associated with the License and Supply Performance Obligaon were completed and JT and Torii had secured their own source to manufacture ferric citrate hydrate. As such, any inial license fees as well as any development-based milestones and manufacturing fee revenue were received and recognized prior to the Merger. The Company determined that the remaining consideraon that may be payable to the Company under the terms of the sublicense agreement are either quarterly royales on net sales or payments due upon the achievement of sales-based milestones. In accordance with ASC 606, the Company recognizes sales-based royales and milestone payments based on the level of sales, when the related sales occur as these amounts have been determined to relate predominantly to the license granted to JT and Torii and therefore are recognized at the later of when the performance obligaon is sasﬁed, or the related sales occur. During the years ended December 31, 2023 and 2022, the Company recognized $5.4 million and $5.3 million, respecvely, in license revenue related to royales earned on net sales of Riona in Japan. The Company records the associated mid-single digit percentage of net sales royalty expense due to Panion, the licensor of Riona, in the same period as the royalty revenue from JT and Torii is recorded. Akebia Therapeucs, Inc. | Form 10-K | Page 157 Table of Contents Prior Collaboraon and License Agreements U.S. Collaboraon and License Agreement with Otsuka Pharmaceucal Co. Ltd. On December 18, 2016, the Company entered into a collaboraon and license agreement, or Otsuka U.S. Agreement, with Otsuka Pharmaceucal Co. Ltd, or Otsuka. The collaboraon was focused on the development and commercializaon of vadadustat in the U.S. The Company was responsible for leading the development of vadadustat, for which it submied an NDA to the FDA in March 2021, and for which it received the CRL in March 2022. Under the terms of the Otsuka U.S. Agreement, the Company granted to Otsuka a co-exclusive, non-sublicensable license under certain intellectual property controlled by the Company solely to perform medical aﬀairs acvies and to conduct non-promoonal and commercializaon acvies related to vadadustat in accordance with the associated plans. The co-exclusive license related to acvies that would be jointly conducted by the Company and Otsuka under the Otsuka U.S. Agreement. The Company evaluated the elements of the Otsuka U.S. Agreement in accordance with the provisions of ASC 606 and concluded that the contract counterparty, Otsuka, was a customer. The Company idenﬁed three performance obligaons in connecon with its obligaons under the Otsuka U.S. Agreement as follows: (i) License and Development Services Combined (License Performance Obligaon); (ii) Rights to Future Intellectual Property (Future IP Performance Obligaon) and (iii) Joint Commiee Services (Commiee Performance Obligaon). The Company allocated the transacon price to each performance obligaon based on the Company’s best esmate of the relave standalone selling price. No amounts were allocated to the Future IP Performance Obligaon because the associated best esmate of standalone selling price was determined to be immaterial. Due to the similar performance period and recognion paern between the License Performance Obligaon and the Commiee Performance Obligaon, the transacon price was allocated to the License Performance Obligaon and the Commiee Performance Obligaon on a combined basis. The Company recognized revenue on a proporonal performance basis as the underlying services were performed. Pursuant to the Otsuka U.S. Agreement, the Company received: (i) the up-front payment of $125.0 million, (ii) the cost share payment with respect to amounts incurred by the Company through December 31, 2016 of $33.8 million, and (iii) the net cost share consideraon received with respect to amounts incurred by the Company under the global development plan of approximately $319.2 million with respect to amounts incurred by the Company subsequent to December 31, 2016. On May 12, 2022, the Company received noce from Otsuka that Otsuka had elected to terminate the Otsuka U.S. Agreement and the April 25, 2017 collaboraon and license agreement with Otsuka, or Otsuka Internaonal Agreement. On June 30, 2022, the Company and Otsuka entered into the Terminaon and Selement Agreement, or Otsuka Terminaon Agreement, pursuant to which, among other things, the Company and Otsuka agreed to terminate the Otsuka U.S. Agreement and the Otsuka Internaonal Agreement as of June 30, 2022. During the year ended December 31, 2023, the Company recognized $2.2 million in collaboraon revenue in connecon with the Packaging Validaon Transfer Agreement entered into with Otsuka on April 20, 2023. Under the Packaging Validaon Transfer Agreement, the pares agreed that responsibility for all remaining packaging validaon acvies would be transferred from Otsuka to the Company in consideraon of payments made by Otsuka to the Company. The Company evaluated the agreement under ASC 606 and concluded it was closely ed to the prior collaboraon revenue agreements and under ASC 606 recognized collaboraon revenue in the current year. During the year ended December 31, 2022, the Company recognized collaboraon revenue totaling approximately $86.8 million with respect to the Otsuka U.S. Agreement. The Company accounted for the joint medical aﬀairs, commercializaon and non-promoonal acvies elements of the Otsuka U.S. Agreement in accordance with ASC No. 808, Collaborave Arrangements (ASC 808). Furthermore, these acvies were recognized for as a component of the related expense in the period incurred. During the year ended December 31, 2023, the Company incurred no costs related to the cost-sharing provisions of the Otsuka U.S. Agreement. During the year ended December 31, 2022, the Company incurred approximately $7.6 million of costs related to the cost-sharing provisions of the Otsuka U.S. Agreement of which approximately $3.8 million were reimbursable by Otsuka and recorded as a reducon to R&D expense during the year ended December 31, 2022. Internaonal Collaboraon and License Agreement with Otsuka Pharmaceucal Co. Ltd. On April 25, 2017, the Company entered into a collaboraon and license agreement with Otsuka, or the Otsuka Internaonal Agreement. The collaboraon was focused on the development and commercializaon of vadadustat in Europe, Russia, China, Canada, Australia, the Middle East and certain other territories, collecvely, the Otsuka Internaonal Territory. As discussed above, the Otsuka Internaonal Agreement was terminated on June 30, 2022 pursuant to the Otsuka Terminaon Agreement. The Company has accounted for the Otsuka Internaonal Agreement separately from the collaboraon arrangement with Otsuka with respect to the U.S. due to the lack of interrelaonship and interdependence of the elements and payment terms within each of the contracts as they related to the respecve territories. Accordingly, the Company applied the guidance in ASC 606 solely in reference to the terms and condions of the Otsuka Internaonal Agreement, while the Otsuka U.S. Akebia Therapeucs, Inc. | Form 10-K | Page 158 Table of Contents Agreement connued to be accounted for as a discrete agreement in its own right. The Company evaluated the Otsuka Internaonal Agreement in accordance with the provisions of ASC 606 and concluded that the contract counterparty, Otsuka, was a customer. The Company idenﬁed three performance obligaons in connecon with its obligaons under the Otsuka Internaonal Agreement as follows: (i) License and Development Services Combined (License Performance Obligaon); (ii) Rights to Future Intellectual Property (Future IP Performance Obligaon) and (iii) Joint Commiee Services (Commiee Performance Obligaon). The Company allocated the transacon price to each performance obligaon based on the Company’s best esmate of the relave standalone selling price. No amounts were allocated to the Future IP Performance Obligaon because the associated best esmate of standalone selling price was determined to be immaterial. Due to the similar performance period and recognion paern between the License Performance Obligaon and the Commiee Performance Obligaon, the transacon price was allocated to the License Performance Obligaon and the Commiee Performance Obligaon on a combined basis. The Company recognized revenue on a proporonal performance basis as the underlying services were performed. Pursuant to the Otsuka Internaonal Agreement, the Company received: (i) the up-front payment of $73.0 million, (ii) the cost share payment with respect to amounts incurred by the Company during the quarter ended March 31, 2017 of $0.2 million, and (iii) the net cost share consideraon received with respect to amounts incurred by the Company subsequent to March 31, 2017 of $216.7 million. During the year ended December 31, 2023, the Company recognized no revenue with respect to the Otsuka Internaonal Agreement. During the year ended December 31, 2022, the Company recognized revenue totaling approximately $5.5 million with respect to the Otsuka Internaonal Agreement. The revenue is classiﬁed as collaboraon revenue in the accompanying consolidated statements of operaons and comprehensive loss. 13. CAPITAL STOCK Authorized and Outstanding Capital Stock On June 5, 2020, the Company ﬁled a Cerﬁcate of Amendment to its Ninth Amended and Restated Cerﬁcate of Incorporaon, or its Charter, to increase the number of authorized shares of common stock from 175,000,000 to 350,000,000. As of December 31, 2023, the authorized capital stock of the Company included 350,000,000 shares of common stock, par value $0.00001 per share, of which 194,582,539 and 184,135,714 shares were issued and outstanding at December 31, 2023 and 2022, respecvely; and 25,000,000 shares of undesignated preferred stock, par value $0.00001 per share, of which no shares were issued and outstanding at December 31, 2023 and 2022. At-the-Market Facility On April 7, 2022, the Company entered into an at-the-market, or ATM, sales agreement with Jeﬀeries LLC, or Jeﬀeries, as the Company's sales agent, under which the Company may oﬀer and sell from me to me up to $26.0 million of shares of the Company's common stock in negoated transacons or transacons that are deemed to be an ATM oﬀering. During the year ended December 31, 2023, the Company sold 6,189,974 shares of common stock under this program for gross proceeds of $6.8 million ($6.7 million, net of oﬀering expenses). During January and February 2024, the Company sold 13,261,311 shares of its common stock under the ATM sales agreement with gross proceeds of $19.2 million, ($18.7 million, net of oﬀering expenses). The Company paid the Agent commissions for its services of acng as agent of up to 3.0% of the gross proceeds from the sale of the common stock pursuant to the ATM. Prior At-the-Market Facility On March 1, 2022, the Company ﬁled a prospectus supplement relang to the Company's sales agreement with Cantor Fitzgerald & Co., or Prior Sales Agreement, pursuant to which it was authorized to oﬀer and sell up to $25.3 million of its common stock at current market prices from me to me. On March 16, 2022, the Company terminated the Prior Sales Agreement. During the year ended December 31, 2022, the Company sold 404,600 shares of common stock under this program with net proceeds (aer deducng commissions and other oﬀering expenses) of $0.8 million. Unregistered Common Stock In connecon with the Vifor Agreement, CSL Vifor owns 7,571,429 shares of common stock that are unregistered under the Securies Act. See Note 8, Deferred Revenue, Refund Liability and Liability Related to Sale of Future Royales, for more informaon. Warrants to Purchase Common Stock In connecon with the BlackRock Credit Agreement, described in more detail in Note 7, Indebtedness, the Company issued a warrant to purchase 3,076,923 shares of the Company’s common stock, at an exercise price per share of $1.30, and upon borrowing of Tranche C, the Company will become obligated to issue addional warrants to purchase 1,153,846 shares of the Company’s common stock at an exercise price per share of $1.30. Each warrant shall be exercisable for eight years from date Akebia Therapeucs, Inc. | Form 10-K | Page 159 Table of Contents of issuance. The warrants and the common stock issuable upon the exercise of such warrants were not registered under the Securies Act of 1933. Accordingly, the holder thereof may only sell common stock issued upon exercise of such warrants pursuant to an eﬀecve registraon statement under the Securies Act covering the resale of those shares, an exempon under Rule 144 under the Securies Act or another applicable exempon under the Securies Act. 14. STOCK-BASED COMPENSATION AND EMPLOYEE RETIREMENT PLANS Stock-Based Compensaon Plans The Company incurred stock-based compensaon expenses of $9.3 million and $17.8 million for the years ended December 31, 2023 and 2022, respecvely. Equity Incenve Plans The following table contains informaon about the Company's equity incenve plans: Title of Plan (1)(2) Keryx Equity Plans (2) Akebia Therapeucs, Inc. Amended and Restated 2008 Equity Incenve Plan (the 2008 Plan) Akebia Therapeucs, Inc. 2014 (2) (3) Incenve Plan, as amended (the 2014 Plan) (replaces 2008 Plan) Akebia Therapeucs, Inc. 2023 Stock Incenve Plan (the 2023 Plan) (replaces 2014 Plan) (3) December 31, 2023 December 31, 2022 Group Eligible Employees, directors and consultants Employees, directors and consultants Type of Award Granted (or to be Granted) Common stock opons and RSUs Common stock opons and RSUs Awards Outstanding 232,203 — Addional Awards Available for Grant Awards Outstanding Addional Awards Available for Grant — — 387,976 419 — — Employees, directors, consultants and advisors Common stock opons, RSUs, SARs and performance awards Employees, oﬃcers, directors, consultants and advisors Common stock opons, SARs, restricted stock, unrestricted stock, RSUs, performance awards, other share-based awards and dividend equivalents 15,311,501 — 17,018,832 5,498,984 1,712,400 17,382,722 — — (1) The Keryx Equity Plans consist of the Keryx Biopharmaceucals, Inc. 1999 Share Opon Plan, Keryx Biopharmaceucals, Inc., as amended, the 2004 Long-Term Incenve Plan, as amended, the Keryx Biopharmaceucals, Inc. 2007 Incenve Plan, the Keryx Biopharmaceucals Inc. Amended and Restated 2013 Incenve Plan and the Keryx Biopharmaceucals, Inc. 2018 Equity Incenve Plan. (2) New awards are no longer being granted under these plans. (3) This table includes the following inducement awards that are subject to the terms and condions of the applicable plan but were granted as inducement awards consistent with Nasdaq Lisng Rule 5635(c)(4) and not under the applicable plan: 1,616,019 opons outstanding under the 2014 Plan and 794,000 opons outstanding under the 2023 Plan as of December 31, 2023 and 2,513,512 opons outstanding under the 2014 Plan as of December 31, 2022. Common Stock Opons and Stock Appreciaon Rights During the year ended December 31, 2023, the Company granted 2,489,500 opons to employees under the 2014 Plan and 315,000 opons to directors under the 2023 Plan. During the year ended December 31, 2023, the Company granted 635,313 stock appreciate rights, or SARs, to one execuve under the 2014 Plan. Opons and SARs granted by the Company generally vest over periods of between 12 and 48 months, subject, in each case, to the individual’s connued service through the applicable vesng date. Opons and SARs generally vest either 100% on the ﬁrst anniversary of the grant date or in installments of (i) 25% at the one year anniversary and (ii) 12 equal quarterly installments beginning aer the one year anniversary of the grant date, subject to the individual’s connuous service with the Company. Opons and SARs generally expire ten years aer the date of grant. The Company also maintains an inducement award program with a share pool that is separate from the Company's equity plans under which inducement awards may be granted consistent with Nasdaq Lisng Rule 5635(c)(4). During the year ended December 31, 2023, the Company granted 845,000 opons to purchase shares of the Company’s common stock to new hires as inducements to such employees entering into employment with the Company, of which 842,000 opons remained outstanding at December 31, 2023. Akebia Therapeucs, Inc. | Form 10-K | Page 160 Table of Contents The Company grants annual service-based stock opons to employees and directors and SARs to certain execuves under the 2023 and 2014 Plans. In addion, the Company issues common stock opons to directors, new hires and occasionally to other employees not in connecon with the annual grant process. Finally, the Company grants performance-based stock opons which generally vest in connecon with the achievement of speciﬁed commercial, regulatory and corporate milestones. The performance-based stock opons also generally feature a me-based vesng component. The expense recognized for these awards is based on the grant date fair value of the Company’s common stock mulplied by the number of opons granted and recognized over me based on the probability of meeng such commercial, regulatory and corporate milestones. The Company did not grant any performance-based stock opons under the 2023 Plan or the 2014 Plan during the year ended December 31, 2023. The Company granted 400,000 performance-based opons during the year ended December 31, 2022. The Company had 400,000 performance-based opons outstanding at December 31, 2023 and 2022. The combined stock opon acvity for the year ended December 31, 2023, is as follows: Outstanding, December 31, 2022 Granted Exercised Expired Canceled and forfeited Outstanding at December 31, 2023 Exercisable at December 31, 2023 Vested and expected to vest at December 31, 2023 Stock Opons Weighted-Average Exercise Price 11,775,411 $ 4,284,813 $ (2,250) $ (528,099) $ (2,217,040) $ 13,312,835 $ 7,354,561 $ 13,312,835 $ 5.82 0.84 0.37 5.16 6.06 4.20 6.37 4.20 Weighted-Average Contractual Life (years) Aggregate Intrinsic Value (in thousands) 7.26 years $ 180 7.27 years $ 6.05 years $ $ 2,680 792 2,680 There was immaterial intrinsic value of opons exercised during the years ended December 31, 2023 and 2022, as the value of opons exercised in 2023 and 2022 was immaterial. The fair value of opons that vested during the years ended December 31, 2023 and 2022 were $6.4 million and $8.4 million, respecvely. As of December 31, 2023, there was approximately $5.2 million of unrecognized compensaon cost related to common stock opons outstanding under the Company’s 2023 Plan or the 2014 Plan or made pursuant to the Company's inducement award program, which is expected to be recognized over a weighted average period of 2.19 years. Restricted Stock Units Generally, RSUs, granted by the Company vest in one of the following ways: (i) 100% of each RSU grant vests on the ﬁrst anniversary of the grant date, (ii) one third of each RSU grant vests on the ﬁrst, second and third anniversaries of the grant date, (iii) 50% of each RSU grant vests on the ﬁrst anniversary and 25% of each RSU grant vests every six months aer the one year anniversary of the grant date, or (iv) one third of each RSU grant vests on the ﬁrst anniversary of the grant date and the remaining two thirds vests in eight substanally equal quarterly installments beginning aer the one year anniversary, subject, in each case, to the individual’s connued service through the applicable vesng date. The grant-date fair value of the RSUs is recognized as expense on a straight-line basis. The Company determines the fair value of the RSUs based on the closing price of the common stock on the date of the grants. The Company also periodically grants performance-based restricted stock units, or PSUs, to employees under the 2023 Plan and previously granted PSUs under the 2014 Plan. The PSUs granted by the Company generally vest in connecon with the achievement of speciﬁed commercial, regulatory and corporate milestones. The PSUs also generally feature a me-based vesng component. The expense recognized for these awards is based on the grant date fair value of the Company’s common stock mulplied by the number of units granted and recognized over me based on the probability of meeng such commercial, regulatory and corporate milestones. The Company did not grant any PSUs under the 2023 Plan or the 2014 Plan during the year ended December 31, 2023. The Company granted 400,000 PSUs during the year ended December 31, 2022. RSU and PSU acvity is as follows: Akebia Therapeucs, Inc. | Form 10-K | Page 161 Table of Contents Unvested as of December 31, 2022 Granted Vested Forfeited and canceled Unvested as of December 31, 2023 2014 Plan 2023 Plan Number of Shares Weighted Average Grant Date Fair Value Number of Shares Weighted Average Grant Date Fair Value 5,674,406 2,759,675 (4,047,676) (1,046,536) 3,339,869 $2.10 $0.68 $2.06 $1.06 $1.30 — 603,400 — — 603,400 $— $1.48 $— $— $1.48 The total fair value of RSUs and PSUs that vested during 2023 and 2022 (measured on the date of vesng) was $8.4 million and $11.2 million, respecvely. As of December 31, 2023, there was approximately $3.0 million of unrecognized compensaon cost related to RSUs and PSUs, which is expected to be recognized over a weighted average period of 1.65 years. Employee Stock Purchase Plan On June 6, 2019, the Company’s stockholders approved the Amended and Restated 2014 Employee Stock Purchase Plan, or ESPP. Under the ESPP substanally all employees may voluntarily enroll to purchase shares of the Company’s common stock through payroll deducons at a price equal to 85% of the lower of the fair market values of the stock as of the beginning or the end of the six-month oﬀering period. An employee's payroll deducons under the ESPP are limited to 15% of the employee's compensaon, and an employee may not purchase more than $25,000 worth of stock during any calendar year. In addion, an employee may not purchase more than 1,500 shares in any six-month oﬀering period. As of December 31, 2023 and 2022, a total of 4,637,801 and 4,837,995 shares of the Company's common stock were available for future issuance under the ESPP, respecvely. The Company issued 200,194 shares during the year ended December 31, 2023. Stock-Based Compensaon Expense The Black-Scholes opon pricing model is used to esmate the fair value of the common stock opons. The weighted-average assumpons used in calculang the fair values of the rights to acquire stock under the 2023 Plan, the 2014 Plan and inducement awards were as follows: Common Stock Opons Risk-free interest rate Expected volality Expected term (years) Expected dividend yield Weighted average grant date fair value 3.54% 100.97% 5.51 2023 - - - —% $0.69 Years ended December 31, 4.81% 111.71% 6.25 1.69% 79.77% 5.51 4.17% 91.57% 6.25 2022 - - - —% $1.27 The Company has classiﬁed stock-based compensaon in its consolidated statements of operaons and comprehensive loss as follows (in thousands): Cost of goods sold Research and development Selling, general and administrave Restructuring Total Years ended December 31, 2023 2022 267 $ 1,964 6,456 630 9,317 $ 448 3,378 10,826 3,197 17,849 $ $ Stock-based compensaon by type of award was as follows (in thousands): Akebia Therapeucs, Inc. | Form 10-K | Page 162 Table of Contents Stock opons Restricted stock units Performance RSUs Employee stock purchase plan Total Employee Rerement Plan Years ended December 31, 2023 2022 5,310 $ 3,637 297 73 9,317 $ 8,968 8,619 116 146 17,849 $ $ In 2008, the Company established a rerement plan, or the Plan, authorized by Secon 401(k) of the Internal Revenue Code, or IRC. In accordance with the Plan, all employees who have aained the age of 21 are eligible to parcipate in the Plan as of the ﬁrst Entry Date, as deﬁned, following their date of employment. Each employee can contribute a percentage of compensaon up to a maximum of the statutory limits per year. Company contribuons are discreonary and contribuons in the amount of approximately $1.7 million and $2.6 million were made during the years ended December 31, 2023 and 2022, respecvely. 15. INCOME TAXES The Company’s income tax provision was computed based on the federal statutory rate and the state statutory rates, net of the related federal beneﬁt. There was no current or deferred income tax expense or beneﬁt for the years ended December 31, 2023 and 2022 due to the Company’s net losses and increases in its valuaon allowance against its deferred tax assets. The Company's eﬀecve income tax rate diﬀers from the statutory federal income tax rate as follows for the years ended December 31, 2023 and 2022: Federal tax at statutory rate State and local tax at statutory rate Research and development tax credits Change in valuaon allowance Other permanent diﬀerences Stock opon cancellaons Stock opon shoralls Eﬀect of rate changes Provision to return adjustment Other Eﬀecve tax rate Years Ended December 31, 2023 2022 21.0 % 2.7 0.3 (9.1) (2.0) (3.7) (1.7) (7.7) (0.3) 0.5 — % 21.0 % 2.5 — (19.3) (1.0) (2.5) (1.6) 0.6 0.3 — — % Deferred income taxes reﬂect the net tax eﬀects of temporary diﬀerences between the carrying amounts of assets and liabilies for ﬁnancial reporng purposes and the amounts used for income tax purposes. When realizaon of the deferred tax asset is more likely than not to occur, the beneﬁt related to the deducble temporary diﬀerences aributable to operaons is recognized as a reducon of income tax expense. A valuaon allowance is recorded against deferred tax assets if it is more likely than not that some or all of the deferred tax assets will not be realized. The Company cannot be certain that future taxable income will be suﬃcient to realize its deferred tax assets. Accordingly, the Company has recorded a valuaon allowance against the Company’s otherwise recognizable net deferred tax assets. The Company connues to maintain the underlying tax beneﬁts to oﬀset future taxable income and to monitor the need for a valuaon allowance based on the proﬁtability of its future operaons. The valuaon allowance increased by approximately $4.7 million and $18.2 million during the years ended December 31, 2023 and 2022, respecvely. Signiﬁcant components of the Company’s deferred tax assets and liabilies are as follows (in thousands): Akebia Therapeucs, Inc. | Form 10-K | Page 163 Table of Contents Deferred tax assets: Accrued expenses and other current liabilies Deferred revenue Sale of royalty Stock-based compensaon R&D credits Capitalized R&D costs Other non-current liabilies Net operang loss carryforward ASC 842 lease liability Inventories reserve Return reserve Refund liability Other Total deferred tax assets Less valuaon allowance Total deferred tax assets, net of valuaon allowance Deferred tax liabilies: Intangible assets 481(a) adjustments ROU asset (ASC 842) Other Total deferred tax liabilies Net deferred tax liability December 31, 2023 2022 $ 1,411 $ 9,534 12,346 6,183 4,843 18,295 3,434 288,939 2,959 4,537 1,624 8,829 14,036 376,970 (365,330) 11,640 (6,868) (1,924) (2,734) (114) (11,640) $ — $ 2,924 1,250 13,291 8,317 4,827 13,825 2,754 288,842 8,032 17,411 — 9,478 13,159 384,110 (360,621) 23,489 (15,981) — (7,426) (82) (23,489) — At December 31, 2023 and 2022, the Company had no start-up expenses capitalized for income tax purposes (aer amorzaon of $1.9 million) and $0.1 million of start-up expenses capitalized for income tax purposes (aer amorzaon of $1.7 million), respecvely, with amorzaon available to oﬀset future federal, state and local income tax. As of December 31, 2023 and 2022, the Company had approximately $1,230.4 million and $1,230.7 million, respecvely, of federal net operang losses, or NOLs, carry-forwards which expire through 2037. Included in the $1,230.4 million of federal NOLs are losses of $648.3 million that will carry forward indeﬁnitely as a result of the Tax Cuts and Jobs Act. Addionally, at December 31, 2023 and 2022, the Company had approximately $1,807.8 million and $1,808.5 million, respecvely, of state NOL carry-forwards, which expire through 2043. The Company also has approximately $2.7 million of federal research and development tax credit carryforwards which expire through 2040 and $2.7 million of state R&D tax credit carryforwards which expire through 2036. Under the provisions of the IRC, the NOLs and tax credit carry-forwards are subject to review and possible adjustment by the Internal Revenue Service and state tax authories. NOLs and tax credit carryforwards may become subject to an annual limitaon under IRC Secons 382 and 383 if there is more than a 50% change in ownership of the stockholders that own 5% or more of the Company’s outstanding stock over a three-year period. The Company completed an evaluaon of its ownership changes and concluded that an ownership change did occur on December 12, 2018 for both Akebia and Keryx in connecon with the Merger. As a consequence of this ownership change, the Company’s NOLs and tax credit carryforwards allocable to the tax periods preceding the ownership change became subject to limitaon under Secon 382 of the IRC. The Company reduced its associated deferred tax assets by $44.9 million as a result of the limitaon. The Company completed an evaluaon of its ownership changes as of March 31, 2022 and concluded that an ownership change had not occur since the previous evaluaon done through December 12, 2018. The Company may experience ownership changes in the future as a result of subsequent shis in our stock ownership, some of which may be outside the Company’s control. As a result, the Company’s ability to ulize these aributes to oﬀset taxable income may be subject to limitaons. The Company has not conducted a full study of it’s research and development credit carryforwards. A study may result in an adjustment to the Company’s research and development credit carryforwards; however, unl a study is completed, and any adjustment is known, no amounts will be presented as an uncertain tax posion. A full valuaon allowance has been provided Akebia Therapeucs, Inc. | Form 10-K | Page 164 Table of Contents against the Company’s research and development credit carryforwards and, if an adjustment is required, this adjustment would be oﬀset by an adjustment to the valuaon allowance. Thus, there would be no impact to the balance sheet or statement of operaons at this me, if an adjustment were required. The Company ﬁles income tax returns in the U.S. federal and various state and local jurisdicons. For federal and state income tax purposes, the 2022, 2021 and 2020 tax years remain open for examinaon under the normal three-year statute of limitaons. The statute of limitaons for income tax audits in the U.S. will commence upon ulizaon of NOLs and will expire three years from the ﬁling of the tax return the loss was ulized on. A reconciliaon of the beginning and ending amounts of unrecognized tax beneﬁts for the years ending December 31, 2023 and 2022 are as follows (in thousands): Balance at December 31, 2021 Addions based on tax posions of current years Balance at December 31, 2022 Reducons based on tax posions of current years Balance at December 31, 2023 $ $ 2,513 184 2,697 (2,697) — The Company does not believe there will be a material change in its unrecognized tax posions over the next twelve months. All of the unrecognized tax beneﬁts, if recognized, would be oﬀset by the valuaon allowance. 16. NET LOSS PER SHARE Potenally diluve securies, common stock opons, RSUs and SARs have been excluded from the calculaon of diluted net loss per share as their eﬀects would be an-diluve. For periods in which the Company reports a net loss, the weighted average number of shares outstanding used to calculate both basic and diluted net loss per share were the same. The shares in the table below were excluded from the calculaon of diluted net loss per share, prior to the use of the treasury stock method, due to their an-diluve eﬀect: Outstanding common stock opons Unvested restricted stock units Stock appreciaon rights Total 17. RESTRUCTURING Years Ended December 31, 2022 2023 11,726,090 12,690,624 5,681,137 3,930,167 — 635,313 17,407,227 17,256,104 On April 4, 2022, the Company restructured its operaons and executed a Board approved reducon of workforce by approximately 42% across all areas of the Company (47% inclusive of the closing of the majority of open posions) following the receipt of the CRL from the FDA to the Company’s NDA for vadadustat for the treatment of anemia due to CKD in adult paents. On May 5, 2022, the Company laid oﬀ several members of management. As a result of the restructuring, during the year ended December 31, 2022, the Company recognized $14.5 million of restructuring charges in the consolidated statement of operaons and comprehensive loss, including $11.3 million of one-me terminaon beneﬁts and contractual terminaon beneﬁts for severance, healthcare and related beneﬁts and $3.2 million of non-cash stock-based compensaon expense. On November 7, 2022, the Company further reduced its workforce by approximately 14% of the then current headcount primarily focused on the commercial organizaon as a result of the Company’s decision to shi to a strategic account management focused model for its commercial eﬀorts. This shi in approach supported the Company’s strategic pillars to drive Auryxia revenue while also connuing to decrease operang costs. During the year ended December 31, 2022, the Company recognized $1.4 million of restructuring charges in the consolidated statement of operaons and comprehensive loss, including one-me terminaon beneﬁts and contractual terminaon beneﬁts for severance, healthcare and related beneﬁts and non-cash stock-based compensaon expense. The workforce reducons were completed as of December 31, 2022, and the Company has incurred all related charges. Akebia Therapeucs, Inc. | Form 10-K | Page 165 Table of Contents The following table is a reconciliaon of the beginning and ending restructuring liability for the year ended December 31, 2023 and 2022 respecvely (in thousands): Beginning balance Restructuring accrual and adjustments Cash payments Ending balance December 31, 2023 2022 3,758 $ (521) (2,230) 1,007 $ — 12,735 (8,977) 3,758 $ $ As of December 31, 2023, $0.7 million and $0.3 million of the accrued severance, beneﬁts and associated costs are reﬂected in accrued expenses and other current liabilies and other non-current liabilies, respecvely. As of December 31, 2022, $2.8 million and $1.0 million of the accrued severance, beneﬁts and associated costs are reﬂected in accrued expenses and other current liabilies and other non-current liabilies, respecvely. 18. SUBSEQUENT EVENTS The Company has evaluated events and transacons occurring aer the balance sheet date through the date of the Company's consolidated ﬁnancial statements were issued and concluded that there were no events or transacons occurring during this period that required recognion or disclosure in the Company's consolidated ﬁnancial statements, except for maers described in Note 7, Indebtedness, related to the entering into the BlackRock Credit Agreement and the terminaon of the Pharmakon Term Loans and Note 13, Capital Stock, related to warrants issued in connecon with the BlackRock Credit Agreement and the oﬀerings under the At-the-Market facility. Item 9. Changes in and Disagreements with Accountants on Accounng and Financial Disclosure None. Item 9A. Controls and Procedures Management’s Evaluaon of our Disclosure Controls and Procedures “Disclosure controls and procedures”, as deﬁned in Rules 13a-15(e) and 15d-15(e) under the Securies Exchange Act of 1934, as amended, or the Exchange Act, are controls and other procedures that are designed to ensure that informaon required to be disclosed in our reports ﬁled or submied under the Exchange Act is recorded, processed, summarized and reported within the me periods speciﬁed in the U.S. Securies and Exchange Commission, or the SEC, rules and forms. Disclosure controls and procedures include, without limitaon, controls and procedures designed to ensure that informaon required to be disclosed in company reports ﬁled or submied under the Exchange Act is accumulated and communicated to our management, including our principal execuve and principal ﬁnancial oﬃcers, as appropriate to allow mely decisions regarding required disclosure. As required by Rules 13a-15 and 15d-15 under the Exchange Act, our management, with the parcipaon of our principal execuve oﬃcer and principal ﬁnancial oﬃcer, carried out an evaluaon of our disclosure controls and procedures as of December 31, 2023. Based upon their evaluaon, our principal execuve oﬃcer and principal ﬁnancial oﬃcer concluded that as of December 31, 2023, our disclosure controls and procedures were not eﬀecve because of a material weakness in the design of our internal control over ﬁnancial reporng related to our accounng for inventories and inventory related transacons which is described in more detail below. Management’s Annual Report on Internal Control Over Financial Reporng Our management, with the parcipaon of our principal execuve oﬃcer and principal ﬁnancial oﬃcer, is responsible for establishing and maintaining adequate internal control over ﬁnancial reporng. Internal control over ﬁnancial reporng is deﬁned in Rule 13a-15(f) or 15d-15(f) promulgated under the Exchange Act as a process designed by, or under the supervision of, our principal execuve oﬃcer and principal ﬁnancial oﬃcer and eﬀected by our board of directors, management and other personnel to provide reasonable assurance regarding the reliability of our ﬁnancial reporng and the preparaon of ﬁnancial statements for external purposes in accordance with accounng principles generally accepted in the United States of America. Our management conducted the assessment of the eﬀecveness of our internal control over ﬁnancial reporng as of December 31, 2023, based on criteria established in Internal Control— Integrated Framework issued by the Commiee of Sponsoring Organizaons of the Treadway Commission in 2013. As a result of this assessment, our management has concluded that, as of December 31, 2023, our internal control over ﬁnancial reporng was ineﬀecve due to the material weakness described below. Akebia Therapeucs, Inc. | Form 10-K | Page 166 Table of Contents Material Weakness - Inventories As of December 31, 2023, our management concluded that we did not design and maintain eﬀecve controls over the completeness and accuracy of accounng for inventory and inventory related transacons, including inventory reconciliaons, calculaon of overheads, presentaon of inventories in our balance sheet between short-term and long-term and our liabilies related to the calculaon of ﬁrm purchase commitment liability. A material weakness is a deﬁciency, or combinaon of deﬁciencies, in internal control over ﬁnancial reporng, such that there is a reasonable possibility that a material misstatement of a company’s annual or interim consolidated ﬁnancial statements will not be prevented or detected on a mely basis. Speciﬁcally, we did not maintain eﬀecve controls related to (i) the review of inventory reconciliaons, (ii) the validaon of the inventory cosng, (iii) the classiﬁcaon of inventory within the balance sheet and cost of product and other revenue related costs in the statement of operaons, (iv) the calculaon of esmated excess ﬁrm purchase commitment liability and (v) the veriﬁcaon that the existence of all inventories subject to physical inventory counts were accurately counted. Remediaon Eﬀorts of the Material Weakness - Inventories The control deﬁciencies described above resulted in certain accounng errors, including in our internal preliminary consolidated ﬁnancial statements for the year ended December 31, 2023, that were corrected prior to the issuance of such annual consolidated ﬁnancial statements. Our management has taken, plans to connue to take, acons to remediate the deﬁciency in our internal control over ﬁnancial reporng and has implemented new processes, procedures and controls designed to address the underlying causes associated with the material weakness. For example, we are in the process of: (i) implemenng and documenng new processes and controls to help ensure the completeness and accuracy of our inventory reconciliaons, (ii) engaging addional third-party subject maer experts and accounng personnel with U.S. GAAP experience speciﬁc to inventory accounng, (iii) enhancing the accuracy of key reports used to calculate the ﬁrm purchase commitment liability; and (iv) establishing eﬀecve monitoring and oversight controls to help to ensure the completeness and accuracy of inventory included in our ﬁnancial statements and related disclosures. These control deﬁciencies did not have any material impact on our current or prior period consolidated annual or interim ﬁnancial statements, but could have resulted in material misstatements of our annual or interim ﬁnancial statements that would not have been prevented or detected on a mely basis. Accordingly, our management has concluded that the control deﬁciencies were a material weakness in the Company’s internal control over ﬁnancial reporng. As management connues to evaluate and work to improve our internal control over ﬁnancial reporng, management may determine it is necessary to take addional measures to address the material weakness. Unl the controls have been operang for a suﬃcient period of me and management has concluded, through tesng, that these controls are operang eﬀecvely, the material weakness described above will connue to exist. Remediaon of Previously Idenﬁed Material Weakness - Product Return Reserves As disclosed in our 2022 Annual Report on Form 10-K/A, our management idenﬁed a material weakness in our internal control over ﬁnancial reporng relang to product return reserves. Management is commied to maintaining a strong internal control environment. In response to the material weakness previously idenﬁed, management, with the oversight of the Audit Commiee of the Board of Directors, took comprehensive acons to remediate the material weakness in internal control over ﬁnancial reporng relang to our product return reserves, including; (i) designed controls to address the completeness and accuracy of key reports ulized in the execuon of internal controls related product return reserve calculaons, (ii) engaged addional third party subject maer experts with U.S. GAAP experience speciﬁc to product returns accounng and (iii) established eﬀecve monitoring and oversight controls to help to ensure the completeness and accuracy of our accrued product returns included in our ﬁnancial statements and related disclosures as well as connued to engage an outside ﬁrm to assist management with performing suﬃcient tesng throughout the year to validate the operang eﬀecveness of certain controls over ﬁnancial reporng. These remediaon eﬀorts also enhanced our overall ﬁnancial reporng control environment related to product return reserves. As of December 31, 2023, we determined that our previously reported material weakness related to product return reserves has been remediated. Akebia Therapeucs, Inc. | Form 10-K | Page 167 Table of Contents Changes in Internal Control over Financial Reporng Except for the remediaon eﬀorts as noted “—Remediaon Eﬀorts of the Material Weakness – Inventory” and “—Remediaon of Previously Idenﬁed Material Weakness – Returns” above, there have been no changes in our internal control over ﬁnancial reporng during the year ended December 31, 2023, as deﬁned in Rules 13a-15(f) and 15(d)-15(f) promulgated under the Exchange Act, that have materially aﬀected, or are reasonably likely to materially aﬀect, our internal control over ﬁnancial reporng. Limitaons of Eﬀecveness of Controls and Procedures In designing and evaluang our disclosure controls and procedures, management recognizes that any controls and procedures, no maer how well designed and operated, can provide only reasonable assurance of achieving their objecves and management necessarily applies its judgment in evaluang the cost- beneﬁt relaonship of possible controls and procedures. Report of Independent Registered Public Accounng Firm To the Stockholders and the Board of Directors of Akebia Therapeucs, Inc. Opinion on Internal Control Over Financial Reporng We have audited Akebia Therapeucs, Inc.’s internal control over ﬁnancial reporng as of December 31, 2023, based on criteria established in Internal Control —Integrated Framework issued by the Commiee of Sponsoring Organizaons of the Treadway Commission (2013 framework) (the COSO criteria). In our opinion, because of the eﬀect of the material weakness described below on the achievement of the objecves of the control criteria, Akebia Therapeucs, Inc. (the “Company”) has not maintained eﬀecve internal control over ﬁnancial reporng as of December 31, 2023, based on the COSO criteria. A material weakness is a deﬁciency, or combinaon of deﬁciencies, in internal control over ﬁnancial reporng, such that there is a reasonable possibility that a material misstatement of the company’s annual or interim ﬁnancial statements will not be prevented or detected on a mely basis. The following material weakness has been idenﬁed and included in management’s assessment. Management has idenﬁed a material weakness in controls related to the Company’s inventory process. We also have audited, in accordance with the standards of the Public Company Accounng Oversight Board (United States) (PCAOB), the consolidated balance sheets of the Company as of December 31, 2023 and 2022, the related consolidated statements of operaons and comprehensive loss, stockholders’ (deﬁcit) equity and cash ﬂows for each of the two years in the period ended December 31, 2023, and the related notes. This material weakness was considered in determining the nature, ming and extent of audit tests applied in our audit of the 2023 consolidated ﬁnancial statements, and this report does not aﬀect our report dated March 14, 2024, which expressed an unqualiﬁed opinion thereon. Basis for Opinion The Company’s management is responsible for maintaining eﬀecve internal control over ﬁnancial reporng and for its assessment of the eﬀecveness of internal control over ﬁnancial reporng included in the accompanying Management’s Annual Report on Internal Control over Financial Reporng. Our responsibility is to express an opinion on the Company’s internal control over ﬁnancial reporng based on our audit. We are a public accounng ﬁrm registered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securies laws and the applicable rules and regulaons of the Securies and Exchange Commission and the PCAOB. We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about whether eﬀecve internal control over ﬁnancial reporng was maintained in all material respects. Our audit included obtaining an understanding of internal control over ﬁnancial reporng, assessing the risk that a material weakness exists, tesng and evaluang the design and operang eﬀecveness of internal control based on the assessed risk, and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion. Deﬁnion and Limitaons of Internal Control Over Financial Reporng A company’s internal control over ﬁnancial reporng is a process designed to provide reasonable assurance regarding the reliability of ﬁnancial reporng and the preparaon of ﬁnancial statements for external purposes in accordance with generally accepted accounng principles. A company’s internal control over ﬁnancial reporng includes those policies and procedures Akebia Therapeucs, Inc. | Form 10-K | Page 168 Table of Contents that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reﬂect the transacons and disposions of the assets of the company; (2) provide reasonable assurance that transacons are recorded as necessary to permit preparaon of ﬁnancial statements in accordance with generally accepted accounng principles, and that receipts and expenditures of the company are being made only in accordance with authorizaons of management and directors of the company; and (3) provide reasonable assurance regarding prevenon or mely detecon of unauthorized acquision, use, or disposion of the company’s assets that could have a material eﬀect on the ﬁnancial statements. Because of its inherent limitaons, internal control over ﬁnancial reporng may not prevent or detect misstatements. Also, projecons of any evaluaon of eﬀecveness to future periods are subject to the risk that controls may become inadequate because of changes in condions, or that the degree of compliance with the policies or procedures may deteriorate. /s/ Ernst & Young LLP Boston, Massachuses March 14, 2024 Item 9B. Other Informaon Rule 10b5-1 - Director and Oﬃcer Trading Arrangements From me to me, the Company's directors and oﬃcers (as deﬁned in Rule 16a-1(f) under the Securies Exchange Act of 1934, as amended, or the Exchange Act, engage in open-market transacons with respect to Company securies, including to sasfy tax withholding obligaons when equity awards vest or are exercised, and for diversiﬁcaon or other personal reasons. Transacons in Company securies by directors and oﬃcers are required to be made in accordance with the Company’s insider trading policy, which requires that the transacons be in accordance with applicable U.S. federal securies laws that prohibit trading while in possession of material nonpublic informaon. Rule 10b5-1 under the Exchange Act provides an aﬃrmave defense that enables directors and oﬃcers to prearrange transacons in the Company’s securies in a manner that avoids concerns about iniang transacons while in possession of material nonpublic informaon. The following table describes, for the fourth quarter of 2023, each trading arrangement for the sale or purchase of Company securies adopted or terminated by our directors and oﬃcers that is either (1) a contract, instrucon or wrien plan intended to sasfy the aﬃrmave defense condions of Rule 10b5-1(c) (a “Rule 10b5-1 trading arrangement”) or (2) a “non-Rule 10b5-1 trading arrangement” (as deﬁned in Item 408(c) of Regulaon S-K): Name (Title) John P. Butler (President and Chief Execuve Oﬃcer) Ellen Snow (Senior Vice President, Chief Financial Oﬃcer and Treasurer) Steven K. Burke, M.D. (Senior Vice President, Research & Development and Chief Medical Oﬃcer) Acon Taken (Date of Acon) December 1, 2023 November 20, 2023 November 17, 2023 Type of Trading Arrangement Durable Rule 10b5-1 trading arrangement for sell-to-cover transacons relang to all equity awards that have or may be granted Durable Rule 10b5-1 trading arrangement for sell-to-cover transacons relang to all equity awards that have or may be granted Durable Rule 10b5-1 trading arrangement for sell-to-cover transacons relang to all equity awards that have or may be granted Nature of Trading Arrangement Duraon of Trading Arrangement Aggregate Number of Securies Sale Sale Sale Unl ﬁnal selement of any RSUs Indeterminable (1) Unl ﬁnal selement of any RSUs Indeterminable (1) Unl ﬁnal selement of any RSUs Indeterminable (1) Akebia Therapeucs, Inc. | Form 10-K | Page 169 Table of Contents Michel Dahan (Senior Vice President, Chief Operang Oﬃcer) Nicole R. Hadas (Senior Vice President, Chief Legal Oﬃcer and Corporate Secretary) December 3, 2023 November 14, 2023 Durable Rule 10b5-1 trading arrangement for sell-to-cover transacons relang to all equity awards that have or may be granted Durable Rule 10b5-1 trading arrangement for sell-to-cover transacons relang to all equity awards that have or may be granted Sale Sale Unl ﬁnal selement of any RSUs Indeterminable (1) Unl ﬁnal selement of any RSUs Indeterminable (1) (1) The number of shares subject to RSUs that will be sold to sasfy applicable tax withholding obligaons upon vesng is unknown as the number will vary based on the extent to which vesng condions are sasﬁed, the market price of the Company’s common stock at the me of selement and the potenal future grant of addional RSUs subject to this arrangement. This trading arrangement, which applies to RSUs whether vesng is based on the passage of me and/or the achievement of performance goals, provides for the automac sale of shares that would otherwise be issuable on each selement date of a RSU in an amount suﬃcient to sasfy the applicable tax withholding obligaon, with the proceeds of the sale delivered to the Company in sasfacon of the applicable tax withholding obligaon. Item 9C. Disclosure Regarding Foreign Jurisdicons that Prevent Inspecons Not applicable. Item 10. Director, Execuve Oﬃcers and Corporate Governance PART III The informaon required by this Item 10 will be included in our Deﬁnive Proxy Statement to be ﬁled with the Securies and Exchange Commission, or SEC, with respect to our 2024 Annual Meeng of Stockholders and is incorporated herein by reference. Item 11. Execuve Compensaon The informaon required by this Item 11 will be included in our Deﬁnive Proxy Statement to be ﬁled with the SEC with respect to our 2024 Annual Meeng of Stockholders and, other than the informaon required by Item 402(v) of Regulaon S-K, is incorporated herein by reference. Item 12. Security Ownership of Certain Beneﬁcial Owners and Management and Related Stockholder Maers The informaon required by this Item 12 will be included in our Deﬁnive Proxy Statement to be ﬁled with the SEC with respect to our 2024 Annual Meeng of Stockholders and is incorporated herein by reference. Item 13. Certain Relaonships and Related Transacons, and Director Independence The informaon required by this Item 13 will be included in our Deﬁnive Proxy Statement to be ﬁled with the SEC with respect to our 2024 Annual Meeng of Stockholders and is incorporated herein by reference. Item 14. Principal Accountant Fees and Services The informaon required by this Item 14 will be included in our Deﬁnive Proxy Statement to be ﬁled with the SEC with respect to our 2024 Annual Meeng of Stockholders and is incorporated herein by reference. Akebia Therapeucs, Inc. | Form 10-K | Page 170 Table of Contents PART IV Item 15. Exhibits and Financial Statement Schedules (a) Documents ﬁled as part of this Annual Report on Form 10-K. (b) Consolidated Financial Statements Report of Independent Registered Public Accounng Firm Consolidated Balance Sheets Consolidated Statements of Operaons and Comprehensive Loss Consolidated Statements of Stockholders’ (Deﬁcit) Equity Consolidated Statements of Cash Flows Notes to Consolidated Financial Statements (2) Schedules Schedules have been omied as all required informaon has been disclosed in the consolidated ﬁnancial statements and related footnotes. (3) Exhibits The Exhibits listed below are ﬁled as part of this Annual Report on Form 10-K. Akebia Therapeucs, Inc. | Form 10-K | Page 171 Table of Contents Exhibit Number 2.1** 2.2 3.1 3.2 3.3 4.1 4.2 4.3# 4.4# 4.5! 4.6 4.7* 10.1† 10.2 10.3 10.4 Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date 8-K 001-36352 2.1 June 28, 2018 Descripon of Exhibit Agreement and Plan of Merger, dated as of June 28, 2018, by and among Akebia Therapeucs, Inc., Alpha Therapeucs Merger Sub, Inc., and Keryx Biopharmaceucals, Inc. First Amendment to Agreement and Plan of Merger, dated as of October 1, 2018, by and among Akebia Therapeucs, Inc., Alpha Therapeucs Merger Sub, Inc. and Keryx Biopharmaceucals, Inc. Ninth Amended and Restated Cerﬁcate of Incorporaon Cerﬁcate of Amendment of Ninth Amended and Restated Cerﬁcate of Incorporaon of Akebia Therapeucs, Inc. Second Amended and Restated Bylaws of Akebia Therapeucs, Inc. 8-K 8-K 8-K 8-K 001-36352 001-36352 001-36352 001-36352 Form of Common Stock Cerﬁcate S-1/A 333-193969 Fourth Amended and Restated Investors’ Rights Agreement, dated March 5, 2014 10-K 001-36352 Amendment No. 1 to Fourth Amended and Restated Investors’ Rights Agreement, dated June 28, 2017 10-K 001-36352 Investment Agreement between Akebia Therapeucs, Inc. and Vifor (Internaonal) Ltd., dated May 12, 2017 10-Q 001-36352 Investment Agreement between Akebia Therapeucs, Inc. and Vifor (Internaonal) Ltd., dated February 18, 2022 10-K 001-36352 Descripon of Registrant’s Securies 10-K 001-36352 Form of Warrant 2.1 3.1 3.1 3.1 4.1 4.4 4.5 4.1 4.5 4.6 October 1, 2018 March 28, 2014 June 9, 2020 April 28, 2023 March 4, 2014 March 4, 2015 March 12, 2018 August 8, 2017 March 1, 2022 February 25, 2021 Form of Director and Oﬃcer Indemniﬁcaon Agreement 10-K 001-36352 10.1 March 12, 2018 Oﬃce Lease Agreement Between MA-Riverview/245 First Street, L.L.C. and Akebia Therapeucs, Inc., dated December 3, 2013 S-1 333-193969 10.2 February 14, 2014 First Amendment to Oﬃce Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeucs, Inc., dated December 15, 2014 Second Amendment to Oﬃce Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeucs, Inc., dated November 23, 2015 10-K 001-36352 10.3 March 4, 2015 10-K 001-36352 10.4 March 14, 2016 Akebia Therapeucs, Inc. | Form 10-K | Page 172 Table of Contents Exhibit Number 10.5 Descripon of Exhibit Third Amendment to Oﬃce Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeucs, Inc., dated July 25, 2016 Incorporated by Reference Schedule/ Form File No. 10-Q 001-36352 Exhibit 10.1 Filed Date/ Period End Date November 9, 2016 10.6 10.7 10.8 10.9 10.10 10.11 10.12 10.13† 10.14† 10.15† 10.16† 10.17† 10.18† 10.19† 10.20† Fourth Amendment to Oﬃce Lease Agreement Between CLPF-Cambridge Science Center, LLC and Akebia Therapeucs, Inc., dated May 1, 2017 10-K 001-36352 10.6 March 12, 2018 Fih Amendment to Oﬃce Lease Agreement Between CLPF-Cambridge Science Center, LLC and Akebia Therapeucs, Inc. dated April 9, 2018 10-Q 001-36352 10.1 August 8, 2018 Sixth Amendment to Oﬃce Lease Agreement Between CLPF-Cambridge Science Center, LLC and Akebia Therapeucs, Inc. dated November 30, 2020 One Marina Park Drive Oﬃce Lease dated April 29, 2015, by and between Keryx Biopharmaceucals, Inc. and Fallon Cornerstone One MPD LLC First Amendment to One Marina Park Drive Oﬃce Lease, dated February 24, 2022, by and between Keryx Biopharmaceucals, Inc. and CLPF One Marina Park Drive LLC (successor-in-interest to Fallon Cornerstone One MPD LLC) Assignment and Assumpon Agreement, dated February 24, 2022, by and between Keryx Biopharmaceucals, Inc. and Akebia Therapeucs, Inc. 10-K 001-36352 10.8 February 25, 2021 10-K 000-30929 10.29 March 1, 2017 10-K 001-36352 10.10 March 1, 2022 10-K 001-36352 10.11 March 1, 2022 Sublease, dated as of September 9, 2019, by and between Keryx Biopharmaceucals, Inc. and Foundaon Medicine, Inc. 10-Q 001-36352 10.1 November 12, 2019 Amended and Restated 2008 Equity Incenve Plan Amendment No. 1 to Amended and Restated 2008 Equity Incenve Plan Execuve Employment Agreement with John P. Butler, dated September 16, 2013 S-1 S-1 S-1 333-193969 333-193969 10.5 10.6 February 14, 2014 February 14, 2014 333-193969 10.7 February 14, 2014 Oﬀer Leer to David Spellman, dated as of June 13, 2020 10-Q 001-36352 10.1 August 10, 2020 Form of Non-Statutory Stock Opon Agreement for Oﬃcers S-1/A 333-193969 10.24 March 4, 2014 Form of Non-Statutory Stock Opon Agreement for Non-Employee Directors S-1/A 333-193969 10.25 March 4, 2014 Amended and Restated Non-Employee Director Compensaon Program, eﬀecve April 27, 2023 10-Q 001-36352 10.1 May 8, 2023 Second Amended and Restated Non-Employee Director Compensaon Program, eﬀecve June 6, 2023 10-Q 001-36352 10.8 August 28, 2023 Akebia Therapeucs, Inc. | Form 10-K | Page 173 Table of Contents Exhibit Number 10.21†* 10.22† 10.23† 10.24† 10.25† Descripon of Exhibit Third Amended and Restated Non-Employee Director Compensaon Program, eﬀecve January 1, 2024 Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date Form of Execuve Severance Agreement for Oﬃcers S-1/A 333-193969 10.27 March 4, 2014 2014 Incenve Plan Amendment No. 1 to the Akebia Therapeucs, Inc. 2014 Incenve Plan S-1 S-8 333-193969 10.29 March 4, 2014 333-229366 4.4 January 25, 2019 Amended and Restated 2014 Employee Stock Purchase Plan DEF 14A 001-36352 Appendix A April 26, 2019 10.26† Amended and Restated Cash Incenve Plan, eﬀecve January 19, 2022 10-K 001-36352 10.28 March 1, 2022 10.27† 10.28† 10.29† 10.30† 10.31† 10.32† 10.33† 10.34† Form of Oﬃcer Restricted Stock Unit Award Agreement under 2014 Incenve Plan 10-K 001-36352 10.18 March 12, 2018 Form of Oﬃcer Restricted Stock Unit Award Agreement under 2014 Incenve Plan 10-K 001-36352 10.29 March 26, 2019 Form of Oﬃcer Inducement Award Non-Statutory Stock Opon Agreement Form of Inducement Award Non-Statutory Stock Opon Agreement for Non-Oﬃcers S-8 S-8 333-222728 333-222728 4.4 4.5 January 26, 2018 January 26, 2018 Form of Oﬃcer Performance-Based Stock Opon Award, under the Company's 2014 Incenve Plan, as amended 10-Q 001-36352 10.1 November 4, 2021 Form of Oﬃcer Performance-Based Stock Restricted Stock Unit Award, under the Company's 2014 Incenve Plan, as amended 10-Q 001-36352 10.2 November 4, 2021 Form of Oﬃcer Restricted Stock Unit Award Agreement under 2014 Incenve Plan (Retenon Awards) 10-Q 001-36352 10.6 August 4, 2022 Form of Oﬃcer Non-Statutory Stock Opon Agreement under 2014 Incenve Plan (Retenon Awards) 10-Q 001-36352 10.7 August 4, 2022 10.35†! Form of Oﬃcer Cash Bonus Leer Agreement 10-Q 001-36352 10.3 November 4, 2021 10.36† Form of Oﬃcer Stock Appreciaon Rights Award Agreement under 2014 Incenve Plan 10-Q 001-36352 10.3 May 8, 2023 10.37† Akebia Therapeucs, Inc. 2023 Stock Incenve Plan S-8 333-272453 99.1 June 6, 2023 10.38† Form of Non-Employee Director Stock Opon Agreement under 2023 Stock Incenve Plan 10-Q 001-36352 10.10 August 28, 2023 Akebia Therapeucs, Inc. | Form 10-K | Page 174 Table of Contents Exhibit Number 10.39† Descripon of Exhibit Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date Form of Non-Employee Director Restricted Stock Unit Agreement under 2023 Stock Incenve Plan 10-Q 001-36352 10.12 August 28, 2023 10.40† Form of Oﬃcer Stock Opon Agreement under 2023 Stock Incenve Plan 10-Q 001-36352 10.11 August 28, 2023 10.41† 10.42† 10.43*† 10.44*† 10.45*† 10.46*† 10.47*† 10.48† 10.49† 10.50† 10.51† 10.52† 10.53† 10.54† 10.55† Form of Oﬃcer Restricted Stock Unit Agreement under 2023 Stock Incenve Plan 10-Q 001-36352 10.13 August 28, 2023 Form of Oﬃcer Inducement Award Stock Opon Agreement under 2023 Stock Incenve Plan 10-Q 001-36352 10.14 August 28, 2023 Form of Oﬃcer Execuve Severance Agreement (Reﬂecng Clawback Policy) Form of Oﬃcer Cash Bonus Agreement (Reﬂecng Clawback Policy) Form of Oﬃcer Stock Opon Agreement under 2023 Stock Incenve Plan (Reﬂecng Clawback Policy) Form of Oﬃcer Restricted Stock Unit Agreement under 2023 Stock Incenve Plan (Reﬂecng Clawback Policy) Form of Oﬃcer Inducement Award Stock Opon Agreement under 2023 Stock Incenve Plan (Reﬂecng Clawback Policy) Keryx Biopharmaceucals, Inc. 1999 Stock Opon Plan 10-Q 001-30929 10.2 March 21, 2003 Keryx Biopharmaceucals, Inc. 2004 Long-Term Incenve Plan DEF 14A 000-30929 Annex C April 29, 2004 Amendment to the Keryx Biopharmaceucals, Inc. 2004 Long-Term Incenve Plan dated April 11, 2006 10-Q 000-30929 10.1 August 9, 2006 Keryx Biopharmaceucals, Inc. 2007 Incenve Plan DEF 14A 000-30929 Annex D April 30, 2007 Keryx Biopharmaceucals, Inc. Amended and Restated 2013 Incenve Plan Keryx Biopharmaceucals, Inc. 2018 Equity Incenve Plan 8-K S-8 000-30929 10.1 May 27, 2016 333-226005 99.1 June 29, 2018 Form of Indemniﬁcaon Agreement between Keryx Biopharmaceucals, Inc. and its Directors and Oﬃcers 10-Q 000-30929 10.1 November 9, 2016 Form of Employee Agreement (Conﬁdenality, Non-Compeon, Non- Solicitaon and Development Agreement) applicable to Oﬃcers 10-K 001-36352 10.56 March 26, 2019 Akebia Therapeucs, Inc. | Form 10-K | Page 175 Table of Contents Exhibit Number 10.56† 10.57† 10.58† Descripon of Exhibit Keryx Biopharmaceucals, Inc. Fourth Amended and Restated Directors Equity Compensaon Plan Incorporated by Reference Schedule/ Form File No. 8-K 000-30929 Exhibit 10.2 Filed Date/ Period End Date May 27, 2016 Keryx Biopharmaceucals, Inc. Third Amended and Restated Directors Equity Compensaon Plan 10-Q 000-30929 10.1 August 7, 2014 Keryx Biopharmaceucals, Inc. Director Non-Statutory Stock Opon Award Terms and Condions under the Third Amended and Restated Directors Equity Compensaon Plan 10-K 001-36352 10.59 March 26, 2019 10.59† Form of Oﬃcer Retenon Leer Agreement 10-Q 001-36352 10.6 May 9, 2022 10.60†! 10.61†! 10.62†! 10.63†! 10.64†! 10.65†! 10.66*†! 10.67*†! Form of Retenon and Separaon Agreement for Michel Dahan and Nicole R. Hadas 10-Q 001-36352 10.7 May 9, 2022 Form of Amendment to Retenon and Separaon Agreement for Michel Dahan and Nicole R. Hadas 10-Q 001-36352 10.2 November 3, 2022 Form of May 2023 Amendment to Retenon and Separaon Agreement for Michel Dahan and Nicole R. Hadas 10-Q 001-36352 10.4 August 28, 2023 July 2023 Amendment to Retenon and Separaon Agreement for Michel Dahan 10-Q 001-36352 10.5 August 28, 2023 July 2023 Amendment to Retenon and Separaon Agreement for Nicole R. Hadas 10-Q 001-36352 10.6 August 28, 2023 October 2023 Amendment to Retenon and Separaon Agreement for Nicole R. Hadas 10-Q 001-36352 10.3 November 8, 2023 February 2024 Amendment to Retenon and Separaon Agreement for Nicole R. Hadas February 2024 Amendment to Retenon and Separaon Agreement for Michel Dahan 10.68† Retenon Agreement with David Spellman, dated June 22, 2022 10-Q 001-36352 10.5 August 4, 2022 10.69† 10.70! 10.71# Separaon Agreement with David Spellman, dated June 9, 2023 and Amendment to Separaon Agreement dated July 6, 2023 10-Q 001-36352 10.7 August 28, 2023 Collaboraon Agreement between Akebia Therapeucs, Inc. and Mitsubishi Tanabe Pharma Corporaon, dated December 11, 2015 10-K 001-36352 10.49 March 1, 2022 Leer Agreement between Akebia Therapeucs, Inc. and Mitsubishi Tanabe Pharma Corporaon, dated September 26, 2017 10-Q 001-36352 10.1 November 8, 2017 Akebia Therapeucs, Inc. | Form 10-K | Page 176 Table of Contents Exhibit Number 10.72! 10.73! 10.74! 10.75! 10.76 10.77! 10.78# 10.79! 10.80# 10.81# 10.82 10.83 Descripon of Exhibit Amendment No. 1 to Collaboraon Agreement, dated December 2, 2022, by and between Akebia Therapeucs, Inc. and Mitsubishi Tanabe Pharma Corporaon Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date 10-K 001-36352 10.53 March 10, 2022 Terminaon and Selement Agreement, dated June 30, 2022, by and between the Company and Otsuka Pharmaceucal Co. Ltd. 10-Q 001-36352 10.8 August 4, 2022 Packaging Validaon Transfer Agreement, dated April 20, 2023, by and between the Company and Otsuka Pharmaceucal Co. Ltd. 10-Q 001-36352 10.3 August 28, 2023 Second Amended and Restated License Agreement, dated February 18, 2022, by and between Akebia Therapeucs, Inc. and Vifor (Internaonal) Ltd. 10-K 001-36352 10.54 March 1, 2022 Open Market Sale Agreement Akebia Therapeucs, Inc. and Jeﬀeries LLC SM , dated April 7, 2022, by and between 8-K 001-36352 1.1 April 7, 2022 Second Amended and Restated License Agreement dated April 17, 2019, by and between Akebia Therapeucs, Inc. and Panion & BF Biotech, Inc. 10-Q 001-36352 10.1 August 8, 2019 Amended and Restated Sub-License Agreement, dated June 8, 2009, as amended by the First Amendment thereto, dated June 12, 2013, by and between Keryx Biopharmaceucals, Inc., Japan Tobacco, Inc. and Torii Pharmaceucal Co., Ltd Master Manufacturing Services Agreement by and between Keryx Biopharmaceucals, Inc. and Patheon Manufacturing Services LLC and certain of its aﬃliates, dated September 27, 2016, and related Product Agreement dated September 27, 2016, and related Product Agreement dated October 12, 2016 Product Agreement, dated August 29, 2017, by and between Keryx Biopharmaceucals, Inc. and Patheon Inc. (an aﬃliate of Patheon Manufacturing Services LLC) related to the Master Manufacturing Services Agreement by and between Keryx Biopharmaceucals, Inc. and Patheon Manufacturing Services LLC and certain of its aﬃliates dated November 12, 2016 Master Manufacturing Services and Supply Agreement, dated December 20, 2017, by and between Keryx Biopharmaceucals, Inc. and Siegfried Evionnaz SA Amendment No. 1 to Master Manufacturing Services and Supply Agreement, dated as of December 21, 2020, by and between Siegfried Evionnaz SA and Keryx Biopharmaceucals, Inc. Amendment No. 2 to Master Manufacturing Services and Supply Agreement, dated as of January 29, 2021, by and between Siegfried Evionnaz SA and Keryx Biopharmaceucals, Inc. 10-Q 000-30929 10.1 November 7, 2017 10-K 001-36352 10.58 March 1, 2022 10-Q 000-30929 10.2 November 7, 2017 10-K 000-30929 10.13 February 21, 2018 10-K 001-36352 10.57 February 25, 2021 10-K 001-36352 10.58 February 25, 2021 Akebia Therapeucs, Inc. | Form 10-K | Page 177 Table of Contents Exhibit Number 10.84! 10.85 10.86! 10.87# 10.88! 10.89! 10.90! 10.91! 10.92! 10.93*! 10.94! 10.95! Descripon of Exhibit Amendment No. 3 to Master Manufacturing Services and Supply Agreement, dated as of February 11, 2021, by and between Siegfried Evionnaz SA and Keryx Biopharmaceucals, Inc. Amendment No. 4 to Master Manufacturing Services and Supply Agreement, dated as of December 17, 2021, by and between Siegfried Evionnaz SA and Keryx Biopharmaceucals, Inc. Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date 10-K 001-36352 10.59 February 25, 2021 10-K 001-36352 10.64 March 1, 2022 Amendment No. 5 to Master Manufacturing Services and Supply Agreement, dated February 28, 2023, by and between Keryx Biopharmaceucals, Inc. and Siegfried Evionnaz SA 10-Q 001-36352 10.2 May 8, 2023 Exclusive Distribuon Agreement between Keryx Biopharmaceucals, Inc. and Cardinal Health 105, Inc., dated October 16, 2014 and First Amendment to Exclusive Distribuon Agreement between Keryx Biopharmaceucals, Inc. and Cardinal Health 105, Inc., dated April 14, 2015 10-K 001-36352 10.60 March 26, 2019 Terminaon and Selement Agreement, dated December 22, 2022, by and between Keryx Biopharmaceucals, Inc. and BioVectra Inc. 10-K 001-36352 10.70 March 10, 2023 Loan Agreement, dated November 11, 2019, by and among the Company, Keryx Biopharmaceucals, Inc., Biopharma Credit plc and Biopharma Credit Investments V (Master) LP First Amendment and Waiver, dated February 18, 2022, by and among the Company, Biopharma Credit plc, BPCR Limited Partnership and Biopharma Credit Investments V (Master) LP Second Amendment and Waiver, dated July 15, 2022, by and among the Company, Biopharma Credit plc, BPCR Limited Partnership and Biopharma Credit Investments V (Master) LP Third Amendment to Loan Agreement, dated as of June 30, 2023, by and among the Company, Biopharma Credit plc, BPCR Limited Partnership and Biopharma Credit Investments V (Master) LP Fourth Amendment to Loan Agreement dated as of October 31, 2023, by and among the Company, BioPharma Credit PLC, BPCR Limted Partnership, and BioPharma Credit Investments V (Master) LP Guaranty and Security Agreement, dated November 25, 2019, by and between the Company, Keryx Biopharmaceucals, Inc. and Biopharma Credit plc 10-K 001-36352 10.62 March 12, 2020 10-K 001-36352 10.69 March 1, 2022 10-Q 001-36352 10.9 August 4, 2022 10-Q 001-36352 10.2 August 28, 2023 10-K 001-36352 10.63 March 12, 2022 Supply Agreement, dated as of March 11, 2020, by and between Akebia Therapeucs, Inc. and Patheon, Inc. 10-Q 001-36352 10.1 May 5, 2020 Akebia Therapeucs, Inc. | Form 10-K | Page 178 Table of Contents Exhibit Number 10.96! 10.97! 10.98! 10.99! 10.100! 10.101! 10.102*! 10.103* 21.1 23.1* 31.1* 31.2* 32.1* Descripon of Exhibit Supply Agreement, dated as of April 2, 2020, by and between Akebia Therapeucs, Inc. and STA Pharmaceucal Hong Kong Limited Incorporated by Reference Schedule/ Form File No. 10-Q 001-36352 Exhibit 10.2 Filed Date/ Period End Date August 10, 2020 Amendment No. 1 to the Supply Agreement, dated as of April 15, 2021, by and between Akebia Therapeucs, Inc, and STA Pharmaceucal Hong Kong Limited 10-Q 001-36352 10.1 August 5, 2021 Supply Agreement, dated February 10, 2021, by and between the Company and STA Pharmaceucal Hong Kong Limited 10-Q 001-36352 10.4 May 10, 2021 Royalty Interest Acquision Agreement, dated February 25, 2021, by and between the Company and HealthCare Royalty Partners IV, L.P. 10-Q 001-36352 10.5 May 10, 2021 License Agreement, dated December 22, 2022, by and among Akebia Therapeucs, Inc., Keryx Biopharmaceucals, Inc. and Averoa SAS 10-K 001-36352 10.81 March 10, 2023 License Agreement, dated May 24, 2023, by and between the Company and MEDICE Arzneimiel Püer GmbH & Co. KG 10-Q 001-36352 10.1 August 28, 2023 Agreement for the Provision of a Loan Facility dated January 29, 2024 between the Company and Kreos Capital VII (UK) Limited Warrant Agreement dated January 29, 2024 by and between the Company and Kreos Capital VII Aggregator SCSp List of Subsidiaries 10-K 001-36352 21.1 February 25, 2021 Consent of Ernst & Young LLP Cerﬁcaon of Principal Execuve Oﬃcer Required Under Rule 13a-14(a) of the Securies Exchange Act of 1934, as amended Cerﬁcaon of Principal Financial Oﬃcer Required Under Rule 13a-14(a) of the Securies Exchange Act of 1934, as amended Cerﬁcaon of Principal Execuve Oﬃcer and Principal Financial Oﬃcer Required Under Rule 13a-14(b) of the Securies Exchange Act of 1934, as amended, and 18 U.S.C. 1350 97.1†* Akebia Therapeucs, Inc. Dodd-Frank Compensaon Recovery Policy 101.INS* Inline XBRL Instance Document (the instance document does not appear in the Interacve Data File because XBRL tags are embedded within the Inline XBRL document) Akebia Therapeucs, Inc. | Form 10-K | Page 179 Table of Contents Exhibit Number Descripon of Exhibit Incorporated by Reference Schedule/ Form File No. Exhibit Filed Date/ Period End Date 101.SCH* Inline XBRL Taxonomy Extension Schema Document 101.CAL* Inline XBRL Taxonomy Extension Calculaon Linkbase Document 101.DEF* Inline XBRL Taxonomy Extension Deﬁnion Linkbase Document 101.LAB* 101.PRE* 104 Inline XBRL Taxonomy Extension Labels Linkbase Document Inline XBRL Taxonomy Extension Presentaon Linkbase Document Cover Page Interacve Data File (formaed as Inline XBRL and contained in Exhibit 101) * Filed, or submied electronically, herewith † Indicates management contract or compensatory plan # Indicates porons of the exhibit (indicated by asterisks) have been omied pursuant to a request for conﬁdenal treatment ! Indicates porons of the exhibit (indicated by asterisks) have been omied pursuant to Item 601(b)(10)(iv) of Regulaon S-K ** The schedules to the Agreement and Plan of Merger have been omied pursuant to Item 601(b)(2) of Regulaon S-K. The Company will furnish copies of such schedules to the Securies and Exchange Commission upon request by the Commission Item 16. Form 10-K Summary None. Akebia Therapeucs, Inc. | Form 10-K | Page 180 Table of Contents Pursuant to the requirements of Secon 13 or 15(d) of the Securies Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized. SIGNATURES Date: March 14, 2024 AKEBIA THERAPEUTICS, INC. By: /s/ John P. Butler John P. Butler President and Chief Execuve Oﬃcer Pursuant to the requirements of the Securies Exchange Act of 1934, this report was signed by the following persons on behalf of the registrant and in the capacies and on the date indicated. Akebia Therapeucs, Inc. | Form 10-K | Page 181 Table of Contents Date: March 14, 2024 By: /s/ John P. Butler John P. Butler Director, President and Chief Execuve Oﬃcer (Principal Execuve Oﬃcer) Date: March 14, 2024 By: /s/ Ellen E. Snow Ellen E. Snow Senior Vice President, Chief Financial Oﬃcer and Treasurer (Principal Financial Oﬃcer) Date: March 14, 2024 /s/ Richard C. Malabre Richard C. Malabre Chief Accounng Oﬃcer (Principal Accounng Oﬃcer) Date: March 14, 2024 By: Date: March 14, 2024 By: Date: March 14, 2024 By: Date: March 14, 2024 Date: March 14, 2024 Date: March 14, 2024 Date: March 14, 2024 By: By: By: By: /s/ Adrian Adams Adrian Adams Chairperson and Director /s/ Ron Frieson Ron Frieson Director /s/ Steven C. Gilman Steven C. Gilman Director /s/ Michael Rogers Michael Rogers Director /s/ Cynthia Smith Cynthia Smith Director /s/ Myles Wolf Myles Wolf Director /s/ LeAnne M. Zumwalt LeAnne M. Zumwalt Director Akebia Therapeucs, Inc. | Form 10-K | Page 182 Exhibit 4.7 THE SECURITIES REPRESENTED HEREBY AND THE SECURITIES ISSUABLE UPON EXERCISE HEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AND HAVE BEEN ACQUIRED FOR INVESTMENT AND NOT WITH A VIEW TO, OR IN CONNECTION WITH, THE SALE OR DISTRIBUTION THEREOF. NO SUCH TRANSFER MAY BE EFFECTED WITHOUT AN EFFECTIVE REGISTRATION STATEMENT RELATED THERETO OR AN OPINION OF COUNSEL IN A FORM SATISFACTORY TO THE COMPANY THAT SUCH REGISTRATION IS NOT REQUIRED UNDER THE SECURITIES ACT OF 1933. WARRANT AKEBIA THERAPEUTICS, INC. 1 Warrant Shares: [_________] Issue Date: [_________] Initial Exercise Date: [____________] THIS WARRANT (the “Warrant”) certifies that, for value received, Kreos Capital VII Aggregator SCSp or its assigns (the “Holder”) 2 is entitled, upon the terms and subject to the limitations on exercise and the conditions hereinafter set forth, at any time on or after [_______] (the “Initial Exercise Date”) and on or prior to 5:00 p.m. (New York City time) on [_______] (the “Termination Date”) but not thereafter, to subscribe for and purchase from Akebia Therapeutics, Inc., a Delaware corporation (the “Company”), up to the number of Warrant Shares set forth above (as subject to adjustment hereunder, the “Warrant Shares”) of Common Stock. The purchase price of one share of Common Stock under this Warrant shall be equal to the Exercise Price, as defined in Section 2(b). 3 Section 1. Definitions. In addition to the terms defined elsewhere in this Warrant, the following terms have the meanings indicated in this Section 1: “Affiliate” means any Person that, directly or indirectly through one or more intermediaries, controls or is controlled by or is under common control with a Person, as such terms are used in and construed under Rule 405 under the Securities Act. “Bid Price” means, for any date, the price determined by the first of the following clauses that applies: (a) if the Common Stock is then listed or quoted on a Trading Market, the bid price of a share of Common Stock for the time in question (or the nearest preceding date) on the Trading Market on which the Common Stock is then listed or quoted as reported by Bloomberg (based on a Trading Day from 9:30 a.m. (New York City time) to 4:02 p.m. (New York City time)), (b) if OTCQB or OTCQX is not a Trading Market, the volume weighted average per share price of the Common Stock for such date (or the nearest preceding date) on OTCQB or OTCQX as applicable, (c) if the Common Stock is not then listed or quoted for trading on OTCQB or OTCQX and if prices for the Common Stock are then reported on The Pink Open Market (or a similar organization or agency succeeding to its functions of reporting prices), the most recent bid price per share of the Common Stock so reported, or (d) in all other cases, the fair market value of a share of Common Stock as determined by an independent appraiser selected in good faith by the Holders of a majority in interest of the Warrants then outstanding and reasonably acceptable to the Company, the reasonable fees and expenses of which shall be paid by the Company. “Board of Directors” means the board of directors of the Company. “Business Day” means any day other than Saturday, Sunday or other day on which commercial banks in The City of New York are authorized or required by law to remain closed; provided, however, for clarification, commercial banks shall not be deemed to be authorized or required by law to remain closed due to “stay at home,” “shelter-in-place,” “non-essential employee” or any other similar orders or restrictions or the closure of any physical branch locations at the direction of any governmental authority so long as the electronic funds 1 To be determined pursuant to Section 2(a) of the Warrant Agreement for the Initial Warrant and Section 2(b) of the Warrant Agreement for the Tranche C Warrant. 2 To be the Issue Date. 3 To be eight years from Issue Date. transfer systems (including for wire transfers) of commercial banks in The City of New York generally are open for use by customers on such day. “Commission” means the United States Securities and Exchange Commission. “Common Stock” means the common stock of the Company, par value $0.00001 per share, and any other class of securities into which such securities may hereafter be reclassified or changed. “Common Stock Equivalents” means any securities of the Company or the Subsidiaries which would entitle the holder thereof to acquire at any time Common Stock, including, without limitation, any debt, preferred stock, right, option, warrant or other instrument that is at any time convertible into or exercisable or exchangeable for, or otherwise entitles the holder thereof to receive, Common Stock. “Exchange Act” means the Securities Exchange Act of 1934, as amended, and the rules and regulations promulgated thereunder. “Person” means an individual or corporation, partnership, trust, incorporated or unincorporated association, joint venture, limited liability company, joint stock company, government (or an agency or subdivision thereof) or other entity of any kind. “Securities Act” means the Securities Act of 1933, as amended, and the rules and regulations promulgated thereunder. “Subsidiaries” means any direct or indirect subsidiary of the Company. “Trading Day” means a day on which the Common Stock is traded on a Trading Market. “Trading Market” means any of the following markets or exchanges on which the Common Stock is listed or quoted for trading on the date in question: The Nasdaq Capital Market, The Nasdaq Global Market, The Nasdaq Global Select Market, the New York Stock Exchange or the NYSE American (or any successors to any of the foregoing). “Transfer Agent” means Continental Stock Transfer and Trust Company, the current transfer agent of the Company, and any successor transfer agent of the Company. “VWAP” means, for any date, the price determined by the first of the following clauses that applies: (a) if the Common Stock is then listed or quoted on a Trading Market, the daily volume weighted average price per share of the Common Stock for such date (or the nearest preceding date) on the Trading Market on which the Common Stock is then listed or quoted as reported by Bloomberg (based on a Trading Day from 9:30 a.m. (New York City time) to 4:02 p.m. (New York City time)), (b) if OTCQB or OTCQX is not a Trading Market, the volume weighted average price per share of the Common Stock for such date (or the nearest preceding date) on OTCQB or OTCQX as applicable, (c) if the Common Stock is not then listed or quoted for trading on OTCQB or OTCQX and if prices for the Common Stock are then reported on The Pink Open Market (or a similar organization or agency succeeding to its functions of reporting prices), the most recent bid price per share of the Common Stock so reported, or (d) in all other cases, the fair market value of a share of Common Stock as determined by an independent appraiser selected in good faith by the Holders of a majority in interest of the Warrants then outstanding and reasonably acceptable to the Company, the reasonable fees and expenses of which shall be paid by the Company. “Warrants” means this Warrant and other Common Stock purchase warrants issued by the Company pursuant in the event this Warrant is subdivided. Section 2. Exercise. a) Exercise of Warrant. Exercise of the purchase rights represented by this Warrant may be made, in whole or in part, at any time or times on or after the Initial Exercise Date and on or before the Termination Date by delivery to the Company of a duly executed PDF copy submitted by e-mail (or e-mail attachment) of the Notice of Exercise in the form attached hereto as Annex A (the “Notice of Exercise”). Within the earlier of (i) two Trading Days and (ii) the number of Trading Days comprising the Standard Settlement Period (as defined in Section 2(d)(i) herein) following the date of exercise as aforesaid, the Holder shall deliver the aggregate Exercise 2 Price for the Warrant Shares specified in the applicable Notice of Exercise by wire transfer or cashier’s check drawn on a United States bank, in either case in immediately available funds, unless the cashless exercise procedure specified in Section 2(c) below is specified in the applicable Notice of Exercise. No ink-original Notice of Exercise shall be required, nor shall any medallion guarantee (or other type of guarantee or notarization) of any Notice of Exercise be required. The Company shall have no obligation to inquire with respect to or otherwise confirm the authenticity of the signature(s) contained on any Notice of Exercise nor the authority of the person so executing such Notice of Exercise. Notwithstanding anything herein to the contrary, the Holder shall not be required to physically surrender this Warrant to the Company until the Holder has purchased all of the Warrant Shares available hereunder and the Warrant has been exercised in full, in which case, the Holder shall surrender this Warrant to the Company for cancellation within three Trading Days of the date on which the final Notice of Exercise is delivered to the Company. Partial exercises of this Warrant resulting in purchases of a portion of the total number of Warrant Shares available hereunder shall have the effect of lowering the outstanding number of Warrant Shares purchasable hereunder in an amount equal to the applicable number of Warrant Shares purchased. The Holder and the Company shall maintain records showing the number of Warrant Shares purchased and the date of such purchases. The Company shall deliver any objection to any Notice of Exercise within one Trading Day of receipt of such notice. The Holder and any assignee, by acceptance of this Warrant, acknowledge and agree that, by reason of the provisions of this paragraph, following the purchase of a portion of the Warrant Shares hereunder, the number of Warrant Shares available for purchase hereunder at any given time may be less than the amount stated on the face hereof. b) Exercise Price. The exercise price per share of Common Stock under this Warrant shall be $1.30, subject to adjustment hereunder (the “Exercise Price”). c) Cashless Exercise. If at the time of exercise hereof there is no effective registration statement registering, or the prospectus contained therein is not available for the issuance of the Warrant Shares by the Holder, or if otherwise elected by the Holder at any time, then this Warrant may also be exercised, in whole or in part, at such time by means of a “cashless exercise” in which the Holder shall be entitled to receive a number of Warrant Shares equal to the quotient obtained by dividing [(A-B) (X)] by (A), where: (A) = as applicable: (i) the VWAP on the Trading Day immediately preceding the date of the applicable Notice of Exercise if such Notice of Exercise is (1) both executed and delivered pursuant to Section 2(a) hereof on a day that is not a Trading Day or (2) both executed and delivered pursuant to Section 2(a) hereof on a Trading Day prior to the opening of “regular trading hours” (as defined in Rule 600(b) of Regulation NMS promulgated under the Exchange Act) on such Trading Day, (ii) at the option of the Holder, either (y) the VWAP on the Trading Day immediately preceding the date of the applicable Notice of Exercise or (z) the Bid Price of the Common Stock on the principal Trading Market as reported by Bloomberg L.P. (“Bloomberg”) as of the time of the Holder’s execution of the applicable Notice of Exercise if such Notice of Exercise is executed during “regular trading hours” on a Trading Day and is delivered within two hours thereafter (including until two hours after the close of “regular trading hours” on a Trading Day) pursuant to Section 2(a) hereof or (iii) the VWAP on the date of the applicable Notice of Exercise if the date of such Notice of Exercise is a Trading Day and such Notice of Exercise is both executed and delivered pursuant to Section 2(a) hereof after the close of “regular trading hours” on such Trading Day; (B) = the Exercise Price of this Warrant, as adjusted hereunder; and (X) = the number of Warrant Shares that would be issuable upon exercise of this Warrant in accordance with the terms of this Warrant if such exercise were by means of a cash exercise rather than a cashless exercise. If Warrant Shares are issued in such a cashless exercise, the parties acknowledge and agree that in accordance with Section 3(a)(9) of the Securities Act, the Warrant Shares shall take on the registered characteristics of the Warrants being exercised. The Company agrees not to take any position contrary to this Section 2(c). 3 d) Mechanics of Exercise. i. Delivery of Warrant Shares Upon Exercise. The Company shall cause the Warrant Shares purchased hereunder to be transmitted by the Transfer Agent to the Holder by crediting the account of the Holder’s or its designee’s balance account with The Depository Trust Company through its Deposit or Withdrawal at Custodian system (“DWAC”) if the Company’s transfer agent is then a participant in such system and either (A) there is an effective registration statement permitting the issuance of the Warrant Shares to or resale of the Warrant Shares by the Holder, (B) the Warrant Shares are eligible for resale by the Holder without volume or manner-of-sale limitations or the requirement for current public information, in each case, pursuant to Rule 144 (assuming cashless exercise of the Warrant), or (C) pursuant to a resale on a case-by-case basis by the Holder without volume or manner-of-sale limitations pursuant to Rule 144 (assuming cashless exercise of the Warrant), and otherwise by physical delivery of a certificate, registered in the Company’s share register in the name of the Holder or its designee, for the number of Warrant Shares to which the Holder is entitled pursuant to such exercise to the address specified by the Holder in the Notice of Exercise by the date that is the earliest of (i) two Trading Days after the delivery to the Company of the Notice of Exercise, (ii) one Trading Day after delivery of the aggregate Exercise Price to the Company and (iii) the number of Trading Days comprising the Standard Settlement Period after the delivery to the Company of the Notice of Exercise (such date, the “Warrant Share Delivery Date”); provided that the Company shall have received payment of the aggregate Exercise Price (other than in the case of a cashless exercise) prior to such applicable date. Upon delivery of the Notice of Exercise, the Holder shall be deemed for all corporate purposes to have become the holder of record of the Warrant Shares with respect to which this Warrant has been exercised, irrespective of the date of delivery of the Warrant Shares, provided that the Company shall have received payment of the aggregate Exercise Price (other than in the case of a cashless exercise) within the earlier of (i) two Trading Days and (ii) the number of Trading Days comprising the Standard Settlement Period following delivery of the Notice of Exercise. The Company agrees to maintain a transfer agent that is a participant in the FAST program so long as this Warrant remains outstanding and exercisable. As used herein, “Standard Settlement Period” means the standard settlement period, expressed in a number of Trading Days, on the Company’s primary Trading Market with respect to the Common Stock as in effect on the date of the delivery of the Notice of Exercise. ii. Delivery of New Warrants Upon Exercise. If this Warrant shall have been exercised in part, the Company shall, at the request of a Holder and upon surrender of this Warrant, at the time of delivery of the Warrant Shares, deliver to the Holder a new Warrant evidencing the rights of the Holder to purchase the unpurchased Warrant Shares remaining available under this Warrant, which new Warrant shall in all other respects be identical with this Warrant. iii. Rescission Rights. If the Company fails to cause the Transfer Agent to transmit to the Holder the Warrant Shares pursuant to Section 2(d)(i) by the Warrant Share Delivery Date, then the Holder will have the right to rescind such exercise; provided, however, that the Holder shall be required to return any Warrant Shares subject to any such rescinded exercise notice concurrently with the return to Holder of the aggregate Exercise Price paid to the Company for such Warrant Shares and the restoration of Holder’s right to acquire such Warrant Shares pursuant to this Warrant (including, issuance of a replacement warrant certificate evidencing such restored right). iv. No Fractional Shares or Scrip. No fractional shares or scrip representing fractional shares shall be issued upon the exercise of this Warrant. As to any fraction of a share which the Holder would otherwise be entitled to 4 purchase upon such exercise, the Company shall, at its election, either pay a cash adjustment in respect of such final fraction in an amount equal to such fraction multiplied by the Exercise Price or round up to the next whole share. v. Charges, Taxes and Expenses. Issuance of Warrant Shares shall be made without charge to the Holder for any issue or transfer tax or other incidental expense in respect of the issuance of such Warrant Shares, all of which taxes and expenses shall be paid by the Company, and such Warrant Shares shall be issued in the name of the Holder or in such name or names as may be directed by the Holder; provided, however, that in the event that Warrant Shares are to be issued in a name other than the name of the Holder, this Warrant when surrendered for exercise shall be accompanied by the assignment form attached hereto as Annex B (the “Assignment Form”) duly executed by the Holder and the Company may require, as a condition thereto, the payment of a sum sufficient to reimburse it for any transfer tax incidental thereto. The Company shall pay all Transfer Agent fees required for same-day processing of any Notice of Exercise and all fees to the Depository Trust Company (or another established clearing corporation performing similar functions) required for same-day electronic delivery of the Warrant Shares. vi. Closing of Books. The Company will not close its stockholder books or records in any manner which prevents the timely exercise of this Warrant, pursuant to the terms hereof. e) Beneficial Ownership Limitations. The Company shall not effect any exercise of this Warrant, and a Holder shall not have the right to exercise any portion of this Warrant, pursuant to Section 2 or otherwise, to the extent that after giving effect to such issuance after exercise as set forth on the applicable Notice of Exercise, the Holder (together with the Holder’s Affiliates, and any other Persons acting as a group together with the Holder or any of the Holder’s Affiliates (such Persons, “Attribution Parties”)), would beneficially own in excess of the Beneficial Ownership Limitation (as defined below). For purposes of the foregoing sentence, the number of shares of Common Stock beneficially owned by the Holder and its Affiliates and Attribution Parties shall include the number of shares of Common Stock issuable upon exercise of this Warrant with respect to which such determination is being made, but shall exclude the number of shares of Common Stock which would be issuable upon (i) exercise of the remaining, nonexercised portion of this Warrant beneficially owned by the Holder or any of its Affiliates or Attribution Parties and (ii) exercise or conversion of the unexercised or nonconverted portion of any other securities of the Company (including, without limitation, any other Common Stock Equivalents) subject to a limitation on conversion or exercise analogous to the limitation contained herein beneficially owned by the Holder or any of its Affiliates or Attribution Parties. Except as set forth in the preceding sentence, for purposes of this Section 2(e), beneficial ownership shall be calculated in accordance with Section 13(d) of the Exchange Act and the rules and regulations promulgated thereunder, it being acknowledged by the Holder that the Company is not representing to the Holder that such calculation is in compliance with Section 13(d) of the Exchange Act and the Holder is solely responsible for any schedules required to be filed in accordance therewith and the calculations required under this Section 2(e). To the extent that the limitation contained in this Section 2(e) applies, the determination of whether this Warrant is exercisable (in relation to other securities owned by the Holder together with any Affiliates and Attribution Parties) and of which portion of this Warrant is exercisable shall be in the sole discretion of the Holder, and the submission of a Notice of Exercise shall be deemed to be the Holder’s determination of whether this Warrant is exercisable (in relation to other securities owned by the Holder together with any Affiliates and Attribution Parties) and of which portion of this Warrant is exercisable, in each case subject to the Beneficial Ownership Limitation, and the Company shall have no obligation to verify or confirm the accuracy of such determination. In addition, a determination as to any group status as contemplated above shall be determined in accordance with Section 13(d) of the Exchange Act and the rules and regulations promulgated thereunder. For purposes of this Section 2(e), in determining the number of outstanding shares of Common Stock, a Holder may rely on the number of outstanding shares of Common Stock as reflected in (A) the Company’s most recent periodic or annual report filed with the Commission, as the case may be, (B) a more recent public announcement by the Company or (C) a more recent 5 written notice by the Company or the Transfer Agent setting forth the number of shares of Common Stock outstanding. Upon the written or oral request of a Holder, the Company shall within one Trading Day confirm orally and in writing to the Holder the number of shares of Common Stock then outstanding. In any case, the number of outstanding shares of Common Stock shall be determined after giving effect to the conversion or exercise of securities of the Company, including this Warrant, by the Holder or its Affiliates or Attribution Parties since the date as of which such number of outstanding shares of Common Stock was reported. The “Beneficial Ownership Limitation” shall be 4.99% (or, upon election by a Holder prior to the issuance of any Warrants, 9.99% or 19.99%) of the number of shares of the Common Stock outstanding immediately after giving effect to the issuance of shares of Common Stock issuable upon exercise of this Warrant. The Holder, upon notice to the Company, may increase or decrease the Beneficial Ownership Limitation provisions of this Section 2(e), provided that the Beneficial Ownership Limitation in no event exceeds 19.99% of the number of shares of the Common Stock outstanding immediately after giving effect to the issuance of shares of Common Stock upon exercise of this Warrant held by the Holder and the provisions of this Section 2(e) shall continue to apply. Any increase in the Beneficial Ownership Limitation will not be effective until the 61 day after such notice is delivered to the Company. The provisions of this Section 2(e) shall be construed and implemented in a manner otherwise than in strict conformity with the terms of this Section 2(e) to correct this Section 2(e) (or any portion hereof) which may be defective or inconsistent with the intended Beneficial Ownership Limitation herein contained or to make changes or supplements necessary or desirable to properly give effect to such limitation. The limitations contained in this Section 2(e) shall apply to a successor holder of this Warrant. This provision shall not restrict the number of shares of Common Stock which the holder of this Warrant may receive or beneficially own in order to determine the amount of securities or other consideration that such Holder may receive in the event of a Fundamental Transaction. This restriction may not be waived without stockholder approval. st Section 3. Certain Adjustments. a) Stock Dividends and Splits. If the Company, at any time while this Warrant is outstanding: (i) pays a stock dividend or otherwise makes a distribution or distributions on shares of its Common Stock or any other equity or equity equivalent securities payable in shares of Common Stock (which, for avoidance of doubt, shall not include any shares of Common Stock issued by the Company upon exercise of this Warrant), (ii) subdivides outstanding shares of Common Stock into a larger number of shares, (iii) combines (including by way of reverse stock split) outstanding shares of Common Stock into a smaller number of shares, or (iv) issues by reclassification of shares of the Common Stock any shares of capital stock of the Company, then in each case the Exercise Price shall be multiplied by a fraction of which the numerator shall be the number of shares of Common Stock (excluding treasury shares, if any) outstanding immediately before such event and of which the denominator shall be the number of shares of Common Stock outstanding immediately after such event, and the number of shares issuable upon exercise of this Warrant shall be proportionately adjusted such that the aggregate Exercise Price of this Warrant shall remain unchanged. Any adjustment made pursuant to this Section 3(a) shall become effective immediately after the record date for the determination of stockholders entitled to receive such dividend or distribution and shall become effective immediately after the effective date in the case of a subdivision, combination or re-classification. b) Subsequent Rights Offerings. In addition to any adjustments pursuant to Section 3(a) above, if at any time while this Warrant is outstanding the Company grants, issues or sells any Common Stock Equivalents or rights to purchase stock, warrants, securities or other property pro rata to the record holders of any class of shares of Common Stock (the “Purchase Rights”), then the Holder will be entitled to acquire, upon the terms applicable to such Purchase Rights, the aggregate Purchase Rights which the Holder could have acquired if the Holder had held the number of shares of Common Stock acquirable upon complete exercise of this Warrant (without regard to any limitations on exercise hereof, including without limitation, the Beneficial Ownership Limitation) immediately before the date on which a record is taken for the grant, issuance or sale of such Purchase Rights, or, if no such record is taken, the date as of which the record holders of shares of Common Stock are to be determined for the grant, issue or sale of such Purchase Rights (provided, however, that, to the extent that the Holder’s right to participate in any such Purchase Right would result in the Holder exceeding the Beneficial Ownership 6 Limitation, then the Holder shall not be entitled to participate in such Purchase Right to such extent (or beneficial ownership of such shares of Common Stock as a result of such Purchase Right to such extent) and such Purchase Right to such extent shall be held in abeyance for the Holder until such time, if ever, as its right thereto would not result in the Holder exceeding the Beneficial Ownership Limitation); provided, that such Purchase Right shall terminate on, and shall not be held in abeyance for any period subsequent to the Termination Date. c) Pro Rata Distributions. During such time as this Warrant is outstanding, if the Company shall declare or make any dividend or other distribution of its assets (or rights to acquire its assets) to holders of shares of Common Stock, by way of return of capital or otherwise (including, without limitation, any distribution of cash, stock or other securities, property or options by way of a dividend, spin off, reclassification, corporate rearrangement, scheme of arrangement or other similar transaction) (a “Distribution”), at any time after the issuance of this Warrant, then, in each such case, the Holder shall be entitled to participate in such Distribution to the same extent that the Holder would have participated therein if the Holder had held the number of shares of Common Stock acquirable upon complete exercise of this Warrant (without regard to any limitations on exercise hereof, including without limitation, the Beneficial Ownership Limitation) immediately before the date of which a record is taken for such Distribution, or, if no such record is taken, the date as of which the record holders of shares of Common Stock are to be determined for the participation in such Distribution (provided, however, that to the extent that the Holder’s right to participate in any such Distribution would result in the Holder exceeding the Beneficial Ownership Limitation, then the Holder shall not be entitled to participate in such Distribution to such extent (or in the beneficial ownership of any shares of Common Stock as a result of such Distribution to such extent) and the portion of such Distribution shall be held in abeyance for the benefit of the Holder until such time, if ever, as its right thereto would not result in the Holder exceeding the Beneficial Ownership Limitation); provided, that such Purchase Right shall terminate on, and shall not be held in abeyance for any period subsequent to the Termination Date. d) Fundamental Transaction. If, at any time while this Warrant is outstanding, (i) the Company (and all of its Subsidiaries, taken as a whole), directly or indirectly, in one or more related transactions effects any merger or consolidation of the Company with or into another Person (other than for the purpose of changing the Company’s name and/or the jurisdiction of incorporation of the Company or a holding company for the Company), (ii) the Company, directly or indirectly, effects any sale, lease, license, assignment, transfer, conveyance or other disposition of all or substantially all of its assets in one or a series of related transactions, (iii) any, direct or indirect, purchase offer, tender offer or exchange offer (whether by the Company or another Person) is completed pursuant to which holders of Common Stock are permitted to sell, tender or exchange their shares for other securities, cash or property and has been accepted by the holders of 50% or more of the outstanding Common Stock or 50% or more of the voting power of the common equity of the Company, (iv) the Company, directly or indirectly, in one or more related transactions effects any reclassification, reorganization or recapitalization of the Common Stock or any compulsory share exchange pursuant to which the Common Stock is effectively converted into or exchanged for other securities, cash or property, or (v) the Company, directly or indirectly, in one or more related transactions consummates a stock or share purchase agreement or other business combination (including, without limitation, a reorganization, recapitalization, spin-off, merger or scheme of arrangement) with another Person or group of Persons whereby such other Person or group acquires 50% or more of the outstanding shares of Common Stock or 50% or more of the voting power of the common equity of the Company (each a “Fundamental Transaction”), then this Warrant shall be deemed to have been automatically converted pursuant to Section 2(c), and thereafter the Holder shall be entitled to participate in the Fundamental Transaction on the same terms as other holders of the same class of securities of the Company; provided, however, that if the VWAP of the Warrant Shares on the date of the closing of such Fundamental Transaction is less than the aggregate Exercise Price, then this Warrant shall terminate without exercise or conversion immediately prior, and subject, to the closing of such Fundamental Transaction. e) Calculations. All calculations under this Section 3 shall be made by the Company to the nearest cent or the nearest 1/100th of a share, as the case may be. For purposes of this Section 3, the number of shares of Common Stock deemed to be issued and outstanding as of a 7 given date shall be the sum of the number of shares of Common Stock (excluding treasury shares, if any) issued and outstanding. f) Notice to Holder. i. Adjustment to Exercise Price. Whenever the Exercise Price is adjusted pursuant to any provision of this Section 3, the Company shall promptly deliver to the Holder by email a notice setting forth the Exercise Price after such adjustment and any resulting adjustment to the number of Warrant Shares and setting forth a brief statement of the facts requiring such adjustment. ii. Notice to Allow Exercise by Holder. If (A) the Company shall declare a dividend (or any other distribution in whatever form) on the Common Stock, (B) the Company shall declare a special nonrecurring cash dividend on or a redemption of the Common Stock, (C) the Company shall authorize the granting to all holders of the Common Stock rights or warrants to subscribe for or purchase any shares of capital stock of any class or of any rights, (D) the approval of any stockholders of the Company shall be required in connection with any reclassification of the Common Stock, any consolidation or merger to which the Company (and all of its Subsidiaries, taken as a whole) is a party, any sale or transfer of all or substantially all of the assets of the Company, or any compulsory share exchange whereby the Common Stock is converted into other securities, cash or property, or (E) the Company shall authorize the voluntary or involuntary dissolution, liquidation or winding up of the affairs of the Company, then, in each case, the Company shall cause to be delivered by email to the Holder at its last email or other address as it shall appear upon the Warrant Register of the Company, at least 20 calendar days prior to the applicable record or effective date hereinafter specified, a notice stating (x) the date on which a record is to be taken for the purpose of such dividend, distribution, redemption, rights or warrants, or if a record is not to be taken, the date as of which the holders of the Common Stock of record to be entitled to such dividend, distributions, redemption, rights or warrants are to be determined or (y) the date on which such reclassification, consolidation, merger, sale, transfer or share exchange is expected to become effective or close, and the date as of which it is expected that holders of the Common Stock of record shall be entitled to exchange their shares of the Common Stock for securities, cash or other property deliverable upon such reclassification, consolidation, merger, sale, transfer or share exchange; provided that the failure to deliver such notice or any defect therein or in the delivery thereof shall not affect the validity of the corporate action required to be specified in such notice. To the extent that any notice provided in this Warrant constitutes, or contains, material, non-public information regarding the Company or any of the Subsidiaries, the Company shall simultaneously file such notice with the Commission pursuant to a Current Report on Form 8-K. The Holder shall remain entitled to exercise this Warrant during the period commencing on the date of such notice to the effective date of the event triggering such notice except as may otherwise be expressly set forth herein. Section 4. Transfer of Warrant. a) Restricted Securities. The Holder understands that neither this Warrant nor the Warrant Shares have been registered under the Securities Act, by reason of a specific exemption from the registration provisions of the Securities Act. The Holder understands that the Warrant and the Warrant Shares are “restricted securities” under applicable U.S. federal and state securities laws and that, pursuant to these laws, the Holder must hold the Warrant or the Warrant Shares indefinitely unless they are registered with the Commission and qualified by state authorities, or an exemption from such registration and qualification requirements is available. The Holder understands that this Warrant and the Warrant Shares and any securities issued in respect of or exchange for such securities, may bear one or all of the following legends (in substantially the form set forth below): 8 “THE SECURITIES REPRESENTED HEREBY AND THE SECURITIES ISSUABLE UPON CONVERSION HEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), AND HAVE BEEN ACQUIRED FOR INVESTMENT AND NOT WITH A VIEW TO, OR IN CONNECTION WITH, THE SALE OR DISTRIBUTION THEREOF. NO SUCH TRANSFER MAY BE EFFECTED WITHOUT AN EFFECTIVE REGISTRATION STATEMENT RELATED THERETO OR AN OPINION OF COUNSEL IN A FORM SATISFACTORY TO THE COMPANY THAT SUCH REGISTRATION IS NOT REQUIRED UNDER THE SECURITIES ACT.” and, any legend required by the securities laws of any state to the extent such laws are applicable to the Securities represented by the certificate so legended. b) Transferability. Subject to the restrictions of Section 4(a), this Warrant and all rights hereunder (including, without limitation, any registration rights) are transferable, in whole or in part, upon surrender of this Warrant at the principal office of the Company or its designated agent, together with a written assignment of this Warrant substantially in the form attached hereto duly executed by the Holder or its agent or attorney and funds sufficient to pay any transfer taxes payable upon the making of such transfer. Upon such surrender and, if required, such payment, the Company shall execute and deliver a new Warrant or Warrants in the name of the assignee or assignees, as applicable, and in the denomination or denominations specified in such instrument of assignment, and shall issue to the assignor a new Warrant evidencing the portion of this Warrant not so assigned, and this Warrant shall promptly be cancelled. Notwithstanding anything herein to the contrary, the Holder shall not be required to physically surrender this Warrant to the Company unless the Holder has assigned this Warrant in full, in which case, the Holder shall surrender this Warrant to the Company within three Trading Days of the date on which the Holder delivers a duly executed Assignment Form to the Company assigning this Warrant in full. The Warrant, if properly assigned in accordance herewith, may be exercised by a new holder for the purchase of Warrant Shares without having a new Warrant issued. c) New Warrants. This Warrant may be divided or combined with other Warrants upon presentation hereof at the aforesaid office of the Company, together with a written notice specifying the names and denominations in which new Warrants are to be issued, signed by the Holder or its agent or attorney. Subject to compliance with Section 4(a), as to any transfer which may be involved in such division or combination, the Company shall execute and deliver a new Warrant or Warrants in exchange for the Warrant or Warrants to be divided or combined in accordance with such notice. All Warrants issued on transfers or exchanges shall be dated the initial issuance date of this Warrant and shall be identical with this Warrant except as to the number of Warrant Shares issuable pursuant thereto. d) Warrant Register. The Company shall register this Warrant, upon records to be maintained by the Company for that purpose (the “Warrant Register”), in the name of the record Holder hereof from time to time. The Company may deem and treat the registered Holder of this Warrant as the absolute owner hereof for the purpose of any exercise hereof or any distribution to the Holder, and for all other purposes, absent actual notice to the contrary. Section 5. Piggyback Registration Rights. If during the six-month period following the date of this Warrant the Company proposes to file a registration statement on Form S-1 or Form S-3 under the Securities Act providing for shelf registration of the Common Stock of any other person pursuant to “piggyback” registration rights of such other person, the Company shall promptly give notice to the Holder of this Warrant and, upon the request of such Holder, use its reasonable best efforts to also cause to be registered for the resale thereof the Warrant Shares on such registration statement for any remaining portion of the six-month period following the date of this Warrant. It shall be a condition precedent to the obligations of the Company to take any action pursuant to this Section 5 with respect to the Warrant Shares that the Holder shall furnish to the Company such information regarding itself, the Warrant Shares held by it, the intended 9 method of disposition of such securities and any other information as is reasonably required to effect the registration of such Warrant Shares. Section 6. Miscellaneous. a) No Rights as Stockholder Until Exercise; No Settlement in Cash. This Warrant does not entitle the Holder to any voting rights, dividends or other rights as a stockholder of the Company prior to the exercise hereof as set forth in Section 2(d)(i), except as expressly set forth in Section 3. Without limiting any rights of a Holder to receive Warrant Shares on a “cashless exercise” pursuant to Section 2(c) or to receive cash payments pursuant to Section 2(d)(i) and Section 2(d)(iv) herein, including if the Company is for any reason unable to issue and deliver Warrant Shares upon exercise of this Warrant as required pursuant to the terms hereof, in no event shall the Company be required to net cash settle an exercise of this Warrant or cash settle in any other form. b) Loss, Theft, Destruction or Mutilation of Warrant. The Company covenants that upon receipt by the Company of evidence reasonably satisfactory to it of the loss, theft, destruction or mutilation of this Warrant or any stock certificate relating to the Warrant Shares, and in case of loss, theft or destruction, of indemnity or security reasonably satisfactory to it (which, in the case of the Warrant, shall not include the posting of any bond), and upon surrender and cancellation of such Warrant or stock certificate, if mutilated, the Company will make and deliver a new Warrant or stock certificate of like tenor and dated as of such cancellation, in lieu of such Warrant or stock certificate. c) Saturdays, Sundays, Holidays, etc. If the last or appointed day for the taking of any action or the expiration of any right required or granted herein shall not be a Trading Day, then such action may be taken or such right may be exercised on the next succeeding Trading Day. d) Authorized Shares. The Company covenants that during the period the Warrant is outstanding, it will reserve from its authorized and unissued Common Stock a sufficient number of shares to provide for the issuance of the Warrant Shares upon the exercise of any purchase rights under this Warrant. The Company further covenants that its issuance of this Warrant shall constitute full authority to its officers who are charged with the duty of issuing the necessary Warrant Shares upon the exercise of the purchase rights under this Warrant. The Company will take such reasonable action as may be necessary to assure that such Warrant Shares may be issued as provided herein without violation of any applicable law or regulation, or of any requirements of the Trading Market upon which the Common Stock may be listed. The Company covenants that all Warrant Shares which may be issued upon the exercise of the purchase rights represented by this Warrant will, upon exercise of the purchase rights represented by this Warrant and payment for such Warrant Shares in accordance herewith, be duly authorized, validly issued, fully paid and nonassessable and free from all taxes, liens and charges created by the Company in respect of the issue thereof (other than taxes in respect of any transfer occurring contemporaneously with such issue). Except and to the extent as waived or consented to by the Holder, the Company shall not by any action, including, without limitation, amending its certificate of incorporation or through any reorganization, transfer of assets, consolidation, merger, dissolution, issue or sale of securities or any other voluntary action, avoid or seek to avoid the observance or performance of any of the terms of this Warrant, but will at all times in good faith assist in the carrying out of all such terms and in the taking of all such actions as may be necessary or appropriate to protect the rights of Holder as set forth in this Warrant against impairment. Without limiting the generality of the foregoing, the Company will (i) not increase the par value of any Warrant Shares above the amount payable therefor upon such exercise immediately prior to such increase in par value, (ii) take such action as may be necessary or appropriate in order that the Company may validly and legally issue fully paid and nonassessable Warrant Shares upon the exercise of this Warrant and (iii) use commercially reasonable efforts to obtain all such authorizations, exemptions or consents from any public regulatory body having jurisdiction thereof, as may be, necessary to enable the Company to perform its obligations under this Warrant. 10 Before taking any action which would result in an adjustment in the number of Warrant Shares for which this Warrant is exercisable or in the Exercise Price, the Company shall obtain all such authorizations or exemptions thereof, or consents thereto, as may be necessary from any public regulatory body or bodies having jurisdiction thereof. e) Jurisdiction. All questions concerning the construction, validity, enforcement and interpretation of this Warrant shall be governed by and construed and enforced in accordance with the internal laws of the State of New York, without regard to the principles of conflicts of law thereof. The Company and, by accepting this Warrant, the Holder each agrees that all legal proceedings concerning the interpretations, enforcement and defense of the transactions contemplated by this Warrant (whether brought against the Company or the Holder or their respective affiliates, directors, officers, stockholders, partners, members, employees, or agents) shall be commenced exclusively in the state and federal courts sitting in the City of New York. The Company and, by accepting this Warrant, the Holder each hereby irrevocably submits to the exclusive jurisdiction of the state and federal courts sitting in the City of New York, Borough of Manhattan for the adjudication of any dispute hereunder or in connection herewith or with any transaction contemplated hereby or discussed herein, and hereby irrevocably waives, and agrees not to assert in any suit, action or proceeding, any claim that it is not personally subject to the jurisdiction of any such court, that such suit, action or proceeding is improper or is an inconvenient venue for such proceeding. The Company and, by accepting this Warrant, the Holder each hereby irrevocably waives personal service of process and consents to process being served in any such suit, action or proceeding by mailing a copy thereof via registered or certified mail or overnight delivery (with evidence of delivery) to it at the address in effect for notices to it under this Warrant and agrees that such service shall constitute good and sufficient service of process and notice thereof. Nothing contained herein shall be deemed to limit in any way any right to serve process in any other manner permitted by law. If the Company or the Holder shall commence an action, suit or proceeding to enforce any provisions of this Warrant, the prevailing party in such action, suit or proceeding shall be reimbursed by the other party for their reasonable attorneys’ fees and other costs and expenses incurred with the investigation, preparation and prosecution of such action or proceeding. f) Restrictions. The Holder acknowledges that the Warrant Shares acquired upon the exercise of this Warrant, if not registered, and the Holder does not utilize cashless exercise, will have restrictions upon resale imposed by state and federal securities laws. g) Nonwaiver and Expenses. No course of dealing or any delay or failure to exercise any right hereunder on the part of Holder shall operate as a waiver of such right or otherwise prejudice the Holder’s rights, powers or remedies. Without limiting any other provision of this Warrant, if the Company willfully and knowingly fails to comply with any provision of this Warrant, which results in any material damages to the Holder, the Company shall pay to the Holder such amounts as shall be sufficient to cover any costs and expenses including, but not limited to, reasonable attorneys’ fees, including those of appellate proceedings, incurred by the Holder in collecting any amounts due pursuant hereto or in otherwise enforcing any of its rights, powers or remedies hereunder. h) Notices. Any and all notices or other communications or deliveries to be provided by the Holder hereunder including, without limitation, any Notice of Exercise, shall be in writing and delivered personally, by email or sent by a nationally recognized overnight courier service, addressed to the Company, at 245 First Street, Cambridge, MA 02142, Attention: Chief Financial Officer and Chief Legal Officer, email address: legal@akebia.com or such other email address or address as the Company may specify for such purposes by notice to the Holder with a copy (which shall not constitute notice) to Latham & Watkins LLP, 200 Clarendon Street, Boston, MA 02116, Attention: Wesley C. Holmes, email address: Wesley.Holmes@LW.com. Any and all notices or other communications or deliveries to be provided by the Company hereunder shall be in writing and delivered personally, by email, or sent by a nationally recognized overnight courier service addressed to the Holder at the email address or address of the Holder appearing on the books of the Company with a copy (which shall not constitute notice) to 1 Boulevard de la Foire, 1528, Luxembourg, Attention: Sonia Benhamida, Guy Arbib, Alexander Babulevich, address: Sonia.Benhamida@blackrock.com, Guy.Arbib@blackrock.com, Alexander.Babulevich@blackr email 11 ock.com. Any notice or other communication or deliveries hereunder shall be deemed given and effective on the earliest of (i) the time of transmission, if such notice or communication is delivered via email at the email address set forth in this Section prior to 5:30 p.m. (New York City time) on any date, (ii) the next Trading Day after the time of transmission, if such notice or communication is delivered via email at the email address set forth in this Section on a day that is not a Trading Day or later than 5:30 p.m. (New York City time) on any Trading Day, (iii) the second Trading Day following the date of mailing, if sent by U.S. nationally recognized overnight courier service, or (iv) upon actual receipt by the party to whom such notice is required to be given. To the extent that any notice provided by the Company hereunder constitutes, or contains, material, non-public information regarding the Company or any subsidiaries, the Company shall simultaneously file such notice with the Commission pursuant to a Current Report on Form 8-K. i) Limitation of Liability. No provision hereof, in the absence of any affirmative action by the Holder to exercise this Warrant to purchase Warrant Shares, and no enumeration herein of the rights or privileges of the Holder, shall give rise to any liability of the Holder for the purchase price of any Common Stock or as a stockholder of the Company, whether such liability is asserted by the Company or by creditors of the Company. j) Remedies. The Holder, in addition to being entitled to exercise all rights granted by law, including recovery of damages, will be entitled to specific performance of its rights under this Warrant. The Company agrees that monetary damages would not be adequate compensation for any loss incurred by reason of a breach by it of the provisions of this Warrant and hereby agrees to waive and not to assert the defense in any action for specific performance that a remedy at law would be adequate. k) Successors and Assigns. Subject to applicable securities laws, this Warrant and the rights and obligations evidenced hereby shall inure to the benefit of and be binding upon the successors and permitted assigns of the Company and the successors and permitted assigns of Holder. The provisions of this Warrant are intended to be for the benefit of any Holder from time to time of this Warrant and shall be enforceable by such Holder. l) Amendment. This Warrant may be modified or amended or the provisions hereof waived with the written consent of the Company and the holders of at least a majority of the Common Stock issuable upon the exercise of the then outstanding Warrants (determined without giving effect to Section 2(e) of the Warrants); provided such modification, amendment or waiver applies to all of the then outstanding Warrants. m) Severability. Wherever possible, each provision of this Warrant shall be interpreted in such manner as to be effective and valid under applicable law, but if any provision of this Warrant shall be prohibited by or invalid under applicable law, such provision shall be ineffective to the extent of such prohibition or invalidity, without invalidating the remainder of such provisions or the remaining provisions of this Warrant. n) Headings. The headings used in this Warrant are for the convenience of reference only and shall not, for any purpose, be deemed a part of this Warrant. o) Electronic Signatures. Electronically scanned and transmitted signatures, including by email attachment, shall be deemed originals for all purposes of this Warrant. p) Withholding. The Company shall be entitled to deduct and withhold, or cause to be deducted and withheld, taxes on all payments and distributions (or deemed distributions) with respect to this Warrant (or upon the exercise thereof) to the extent required by applicable law; provided, however, prior to deducting or withholding any such amounts, the Company shall use commercially reasonable efforts to inform the Holder in writing of its intent to withhold or deduct such amounts and to cooperate with the Holder to reduce or eliminate the requirement to withhold or deduct such amounts. To the extent that any amounts are so deducted or withheld, such amounts shall be treated for all purposes of this Warrant as having been paid to the Person in respect of which such deduction or withholding was made. In the event the Company previously remitted any amounts to a governmental authority on account of taxes required to be deducted or withheld in respect of any payment or distribution (or deemed distribution) with respect to this Warrant or upon the exercise thereof, the Company shall be 12 entitled (i) to offset any such amounts against any amounts otherwise payable in respect of this Warrant, any Warrant Shares otherwise required to be issued upon the exercise of this Warrant or any amounts otherwise payable in respect of Warrant Shares received upon the exercise of this Warrant, or (ii) to require the Person in respect of whom such deduction or withholding was made to reimburse the Company for such amounts (and such Person shall promptly so reimburse the Company upon demand). (Remainder of page left blank | Signature page follows) 13 IN WITNESS WHEREOF, the Company has caused this Warrant to be executed by its officer thereunto duly authorized as of the date first above indicated. AKEBIA THERAPEUTICS, INC. By:____________________________________ Name: Title: 14 TO: AKEBIA THERAPEUTICS, INC. NOTICE OF EXERCISE (1) The undersigned hereby elects to purchase ________ Warrant Shares of the Company pursuant to the terms of the attached Warrant (only if exercised in full), and tenders herewith payment of the exercise price in full, together with all applicable transfer taxes, if any. Annex A (2) Payment shall take the form of (check applicable box): in lawful money of the United States; or if permitted the cancellation of such number of Warrant Shares as is necessary, in accordance with the formula set forth in subsection 2(c), to exercise this Warrant with respect to the maximum number of Warrant Shares purchasable pursuant to the cashless exercise procedure set forth in subsection 2(c). (3) Please issue said Warrant Shares in the name of the undersigned or in such other name as is specified below: _______________________________ The Warrant Shares shall be delivered to the following DWAC Account Number: _______________________________ _______________________________ _______________________________ [SIGNATURE OF HOLDER] Name of Investing Entity: ________________________________________________________________________ Signature of Authorized Signatory of Investing Entity: _________________________________________________ Name of Authorized Signatory: ___________________________________________________________________ Title of Authorized Signatory: ____________________________________________________________________ Date: ________________________________________________________________________________________ ASSIGNMENT FORM (To assign the foregoing Warrant, execute this form and supply required information. Do not use this form to exercise the Warrant to purchase shares.) FOR VALUE RECEIVED, the foregoing Warrant to purchase shares of Akebia Therapeutics, Inc., a Delaware corporation, and all rights evidenced thereby are hereby assigned to Annex B Name: Address: Phone Number: Email Address: Dated: _______________ __, ______ Holder’s Signature: Holder’s Address: (Please Print) (Please Print) ______________________________________ ______________________________________ Exhibit 10.21 AKEBIA THERAPEUTICS, INC. THIRD AMENDED AND RESTATED NON-EMPLOYEE DIRECTOR COMPENSATION PROGRAM Effective January 1, 2024 Non-employee members of the Board of Directors (the “Board”) of Akebia Therapeutics, Inc. (the “Company”) shall be eligible to receive cash and equity compensation as set forth in this Third Amended and Restated Non-Employee Director Compensation Program (this “Program”). The cash and equity compensation described in this Program shall be paid or be made, as applicable, automatically and without further action of the Board, to each member of the Board who is not an employee of the Company or any parent or subsidiary of the Company (each, a “Non-Employee Director”) who is eligible to receive such cash or equity compensation, unless such Non-Employee Director declines the receipt of such cash or equity compensation by written notice to the Company. This Program shall remain in effect until it is revised or rescinded by further action of the Board. This Program shall be reviewed by the Board periodically and may be amended, modified or terminated by the Board at any time in its sole discretion and nothing herein should be construed as a guarantee to any Non-Employee Director of any particular level of cash or equity compensation. The terms and conditions of this Program shall supersede any prior cash and/or equity compensation arrangements for service as a member of the Board between the Company and any of its Non-Employee Directors. This Program shall become effective on the date set forth above (the “Effective Date”). 1. Cash Compensation. for service on the Board, effective as of January 1, 2024. (a) Annual Retainers. Each Non-Employee Director shall be eligible to receive an annual retainer of $50,000 Non-Employee Director shall be eligible to receive the following annual retainers: (b) Additional Annual Retainers. In addition to the annual retainer payable pursuant to Section 1(a) above, a (i) Chairperson of the Board. A Non-Employee Director serving as Chairperson of the Board shall be eligible to receive an additional annual retainer of $35,000 for such service; provided, that, in the event that a Non-Employee Director is one of two concurrently serving Chairpersons of the Board, the additional annual retainer payable to such Non- Employee Director pursuant to this Section 1(b)(i) shall be $17,500. (ii) Audit Committee. A Non-Employee Director serving as Chairperson of the Audit Committee of the Board (the “Audit Committee”) shall be eligible to receive an additional annual retainer of $20,000 for such service. A Non- Employee Director serving as a member of the Audit Committee (other than the Chairperson of the Audit Committee) shall be eligible to receive an additional annual retainer of $10,000 for such service. (iii) Compensation Committee. A Non-Employee Director serving as Chairperson of the Compensation Committee of the Board (the “Compensation Committee”) shall be eligible to receive an additional annual retainer of $15,000 for such service. A Non-Employee Director serving as a member of the Compensation Committee (other than the Chairperson of the Compensation Committee) shall be eligible to receive an additional annual retainer of $7,500 for such service. Exhibit 10.21 (iv) Nominating and Corporate Governance Committee. A Non-Employee Director serving as Chairperson of the Nominating and Corporate Governance Committee of the Board (the “NCG Committee”) shall be eligible to receive an additional annual retainer of $10,000 for such service. A Non-Employee Director serving as a member of the NCG Committee (other than the Chairperson of the NCG Committee) shall be eligible to receive an additional annual retainer of $5,000 for such service. (v) Research and Development Committee. A Non-Employee Director serving as Chairperson of the Research and Development Committee of the Board (the “R&D Committee”) shall be eligible to receive an additional annual retainer of $10,000 for such service. A Non-Employee Director serving as a member of the R&D Committee (other than the Chairperson of the R&D Committee) shall be eligible to receive an additional annual retainer of $5,000 for such service. (c) Payment of Retainers. The annual retainers described in Sections 1(a) and 1(b) shall be earned on a quarterly basis based on a calendar quarter and shall be paid in cash by the Company in arrears not later than the fifteenth day following the end of each calendar quarter. In the event a Non-Employee Director does not serve as a Non-Employee Director, or in the applicable positions described in Section 1(b), for an entire calendar quarter, the retainer paid to such Non-Employee Director shall be prorated for the portion of such calendar quarter actually served as a Non-Employee Director, or in such position, as applicable. 2. Equity Compensation. Non-Employee Directors shall be granted the equity awards described below. Each award described below shall be granted under and shall be subject to the terms and provisions of the Company’s 2023 Stock Incentive Plan, as amended, or any other successor Company equity incentive plan under which awards are permitted to be made to Non- Employee Directors (the “Equity Plan”) and (i) for option awards, a non-qualified stock option award agreement, including attached exhibits, in substantially the form of award agreement applicable to Non-Employee Directors most recently approved by the Board and/or the Compensation Committee, as applicable, and (ii) for restricted stock unit awards, a restricted stock unit award agreement, including attached exhibits, in substantially the form of award agreement applicable to Non-Employee Directors most recently approved by the Board and/or the Compensation Committee, as applicable. All applicable terms of the Equity Plan apply to this Program as if fully set forth herein. For the avoidance of doubt, if there is any conflict between the terms of the Equity Plan (including the applicable award agreements thereunder) and this Program, the Equity Plan (including the applicable award agreements thereunder) shall control. (a) Initial Awards. Each Non-Employee Director who is initially elected or appointed to the Board after the Effective Date shall be eligible to receive, on the date of such initial election or appointment, an option to purchase 180,000 shares of the Company’s common stock (subject to adjustment as provided in the Equity Plan). The awards described in this Section 2(a) shall be referred to as “Initial Awards.” No Non-Employee Director shall be granted more than one Initial Award. (b) Subsequent Awards. A Non-Employee Director who (i) has been serving on the Board for at least six months as of the date of any annual meeting of the Company’s stockholders after the Effective Date and (ii) will continue to serve as a Non-Employee Director immediately following such meeting, shall be automatically granted, on the date of such annual meeting, an option to purchase 45,000 shares of the Company’s common stock (subject to adjustment as provided in the Equity Plan) and 30,000 restricted stock units of the Company. The option awards described in this Section 2(b) shall be referred to as “Subsequent Options”, the restricted stock unit awards described in this Section 2(b) shall be referred to as “Subsequent RSUs”, and the Subsequent Options and Subsequent RSUs shall together be Exhibit 10.21 referred to as the “Subsequent Awards.” For the avoidance of doubt, a Non-Employee Director elected for the first time to the Board at an annual meeting of the Company’s stockholders shall only receive an Initial Award in connection with such election, and shall not receive any Subsequent Awards on the date of such meeting as well. (c) Termination of Service of Employee Directors. Members of the Board who are employees of the Company or any parent or subsidiary of the Company who subsequently terminate their service with the Company and any parent or subsidiary of the Company and remain on the Board will not receive an Initial Award pursuant to Section 2(a) above, but to the extent that they are otherwise eligible, will be eligible to receive, after termination from service with the Company and any parent or subsidiary of the Company, Subsequent Awards as described in Section 2(b) above. (d) Terms of Awards Granted to Non-Employee Directors. (i) Purchase Price. The per share exercise price of each option granted to a Non-Employee Director shall equal the fair market value (as determined pursuant to the Equity Plan) of a share of the Company’s common stock on the date the option is granted. (ii) Vesting. Each Initial Award shall vest and become exercisable in accordance with the following schedule, subject to the Non-Employee Director remaining in continuous employment or other service relationship with the Company (“Service”) through each such vesting date: 33 1/3% of the Initial Award shall vest on the one-year anniversary of the date of grant and 66 2/3% shall vest ratably on the first day of each calendar quarter between the one-year anniversary of the date of grant and the third anniversary of the date of grant. Each Subsequent Option shall vest and become exercisable in full on the first anniversary of the date of grant (or, if earlier, immediately prior to the first annual meeting of the Company’s stockholders occurring after the date of grant), subject to the Non-Employee Director remaining in continuous Service through such vesting date. Each Subsequent RSU shall vest in full on the first anniversary of the date of grant (or, if earlier, immediately prior to the first annual meeting of the Company’s stockholders occurring after the date of grant), subject to the Non-Employee Director remaining in continuous Service through such vesting date. Each Initial Award and Subsequent Award that is then-outstanding shall vest and become exercisable in full upon a change in control of the Company or termination of the Non-Employee Director’s Service due to the Non-Employee Director’s death or Disability. For purposes of the Program, “Disability” means Executive’s inability by reason of physical or mental impairment to perform his/her job duties for a period exceeding twelve (12) consecutive weeks. from the date the option is granted. (iii) Term. The term of each option granted to a Non-Employee Director shall be ten (10) years 3. Non-Employee Director Compensation Limit. Notwithstanding anything herein to the contrary, the cash compensation and equity compensation that each Non-Employee Director is entitled to receive under this Program shall be subject to any limits set forth in the applicable Equity Plan with respect to limits on awards to Non-Employee Directors. 4. Reimbursements. The Company shall reimburse each Non-Employee Director for all reasonable, documented, out- of-pocket travel and other business expenses incurred by such Non-Employee Director in the performance of such Non- Employee Director’s duties to the Company in accordance with the Company’s applicable expense reimbursement policies and procedures, as in effect from time to time. To the extent that any reimbursement under this Program provides for a deferral of compensation under Section 409A of the Internal Revenue Code of 1986, as amended: (a) the amount eligible for reimbursement in one calendar year may not affect the amount eligible for reimbursement in any other calendar year; (b) the right to Exhibit 10.21 reimbursement is not subject to liquidation or exchange for another benefit; and (c) any such reimbursement of an expense must be made on or before the last day of the calendar year following the calendar year in which the expense was incurred. EXECUTIVE SEVERANCE AGREEMENT Exhibit 10.43 This EXECUTIVE SEVERANCE AGREEMENT (the “Agreement”) is entered into by and between Akebia Therapeutics, Inc., a Delaware corporation (“Akebia” or the “Company”), and _________________, a resident of _________________________________ (the “Executive”), and is effective as of ____________ (the “Effective Date”). WHEREAS, Executive is a valued employee of the Company; and WHEREAS, the Company desires to provide certain severance benefits to Executive according to, and contingent upon, the terms and conditions stated herein (the “Severance Benefits”). NOW, THEREFORE, in consideration of the foregoing and the mutual promises contained herein, and of other good and valuable consideration, including the compensation to be received by Executive from the Company from time to time, the receipt and sufficiency of which are hereby acknowledged, the parties hereto, intending legally to be bound, hereby agree as follows: 1. Definitions. (a) Cause. For purposes of this Agreement, and in each case as determined by the Compensation Committee of the Company’s Board of Directors (the “Compensation Committee”) in its sole and reasonable discretion, the following will constitute “Cause”: (i) indictment or conviction for either any felony offense or any other crime involving dishonesty; of its subsidiaries; (ii) participation in any fraud, theft, embezzlement or other misconduct or act of dishonesty involving the Company or any (iii) intentional damage to any property of the Company or any of its subsidiaries; (iv) breach of the holder’s duties of good faith and fair dealing that are owed to the Company or any of its subsidiaries; limitation, any employment, confidentiality, non-competition, non-solicitation or assignment of inventions agreement; (v) breach or violation of any agreement between Executive and the Company or any of its subsidiaries, including, without to serve; (vi) conduct which in the good faith and reasonable determination of the Board of Directors demonstrates gross unfitness Company that have been approved by the Board of Directors or its authorized delegate, (vii) failure to comply with the code of conduct of the Company or any of its subsidiaries or any other policies of the President of the Company; or (viii) insubordination or failure to follow the directions of the Board of Directors or of the Chief Executive Officer or Company or any of its subsidiaries. (ix) any other conduct by Executive that could be expected to be harmful to the business, interests or reputation of the Executive shall have thirty (30) days after notice from the Company to cure the deficiency leading to the Cause determination (except with respect to Sections 1(a)(i) and 1(a)(ii) above, for which no notice is required) if, in the sole and reasonable discretion of the Compensation Committee, such deficiency is curable. 1 (b) Good Reason. For purposes of this Agreement the following will constitute “Good Reason” for Executive to terminate his/her employment with the Company. For the avoidance of doubt, Executive shall not be considered to have terminated his/her employment for Good Reason unless Executive has (A) reasonably determined in good faith that a Good Reason condition has occurred; (B) not consented to the occurrence that s/he alleges constitutes Good Reason; (C) given the Company written Notice of Termination for Good Reason not more than sixty (60) days after the initial existence of the alleged condition giving rise to Good Reason; (D) given the Company at least thirty (30) days after receipt of such notice to cure the alleged deficiency; and (E) terminated his/her employment within sixty (60) days following the Company’s receipt of such notice: (i) a material reduction in the nature or status of Executive’s responsibilities, authority, position or duties (unless arising directly or indirectly in connection with a documented and significant performance issue in Executive’s then-current position, as determined by the Compensation Committee in its sole and reasonable discretion). Notwithstanding the foregoing, neither of the following shall constitute Good Reason: (A) a reassignment of Executive to a position within the Company of substantially equivalent level or status with respect to Executive’s responsibilities and duties existing immediately prior to such reassignment, or (B) a change in reporting structure; a material adverse reduction in the amount of aggregate cash compensation provided to Executive or failure by the Company to pay such compensation, except where such reduction occurs contemporaneously with the implementation of a firm-wide cost- reduction program affecting comparable executives (a “Reduction Program”); (ii) (iii) the failure by the Company to continue in effect any incentive compensation plan in which Executive participates, unless an equitable alternative compensation arrangement has been provided, except that to the extent that participation in such plans has been reduced or eliminated for all other eligible executives, in which case the failure to continue Executive in any such plan shall not constitute Good Reason; or Massachusetts; provided, that Executive primarily provides services in Cambridge at the time of such establishment. (iv) establishment of the Company’s primary operations in any place beyond a fifty (50) mile radius of Cambridge, In all respects, the definition of Good Reason shall be interpreted to comply with Code Section 409A, and any successor statute, regulation and guidance thereto. (c) Change in Control. For purposes of this Agreement, a “Change in Control” means the occurrence of any of the following events other than in connection with the consummation of an initial public offering of the Company’s securities: (i) any “person” (as such term is used in Sections 13(d) and 14(d) of the Securities Exchange Act of 1934, as amended) who is not a shareholder of the Company as of the date of this Agreement or an affiliate thereof is or becomes the “beneficial owner” (as defined in Rule 13d-3 under said Act), directly or indirectly, of securities of the Company representing 50% or more of the total voting power represented by the Company’s then outstanding voting securities; (ii) a change in the composition of the Board occurring within a two-year period, as a result of which less than a majority of the directors are Incumbent Directors. “Incumbent Directors” will mean directors who either (A) are directors of the Company as of the date hereof, or (B) are elected, or nominated for election, to the Board with the affirmative votes of at least a majority of the remaining Incumbent Directors at the time of such election or nomination (but will not include an individual whose election or nomination is in connection with an actual or threatened proxy contest relating to the election of directors to the Company); (iii) the date of the consummation of a merger, scheme of arrangement or consolidation of the Company with any other corporation that has been approved by the stockholders of the Company, other than a merger, scheme of arrangement or consolidation which would result in the 2 voting securities of the Company outstanding immediately prior thereto continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity) more than fifty percent (50%) of the total voting power represented by the voting securities of the Company or such surviving entity outstanding immediately after such merger or consolidation; or assets. (iv) the date of the consummation of the sale or disposition by the Company of all or substantially all the Company’s Notwithstanding the foregoing, a transaction will not constitute a Change in Control if: (a) its sole purpose is to change the domicile of the Company’s incorporation; or (b) its sole purpose is to create a holding company that will be owned in substantially the same proportions by the persons who held the Company’s securities immediately before such transaction. In all respects, the definition of Change in Control shall be interpreted to comply with Code Section 409A, and any successor statute, regulation and guidance thereto. (d) Notice of Termination. For purposes of this Agreement, a “Notice of Termination” means a notice which, if applicable, sets forth the specific “cause” or “good reason” provision of this Section 1 and sets forth the effective date of termination. (e) Disability. For purposes of this Agreement, “Disability” means Executive’s inability by reason of physical or mental impairment to perform his/her job duties for a period exceeding twelve (12) consecutive weeks. 2. Termination of Agreement. This Agreement will terminate automatically upon (a) Executive’s termination for Cause; (b) mutual agreement between the Company and Executive; (c) Executive’s death, or (d) Executive’s Disability. Upon termination of this Agreement, Executive or his/her heirs or estate (as applicable) only will be entitled to payments required by law or agreement and benefits afforded under the Company’s employee benefit plans existing at the time of termination and in which the Executive participates. 3. Severance Benefits Upon Termination of Executive’s Employment. If Executive’s employment is terminated, then s/he may be entitled to certain monetary and non-monetary compensation and benefits as set forth below (the “Severance Benefits”): (a) Termination by the Company for Cause; Executive’s Death or Disability. If Executive’s employment is terminated by the Company for Cause or on account of the Executive’s Disability, or if Executive’s employment is terminated due to the Executive’s death, then the Company shall pay Executive all amounts earned or accrued but not paid as of the effective date of such termination, including (i) Executive’s then-current base salary; (ii) legitimate business expenses incurred by Executive in the performance of his/her duties to the Company in accordance with the Company’s normal policies and practices; (iii) vacation pay in accordance with applicable law and the Company’s normal policies and practices; and (iv) any earned or accrued bonus or incentive compensation with respect to the calendar year ended prior to the year in which the termination became effective (collectively, “Accrued Compensation”). (b) Termination by Executive without Good Reason. If Executive terminates his/her employment without Good Reason, then the Company will pay Executive all Accrued Compensation earned through the date of such resignation. Nothing herein shall prohibit the Company, in its discretion, from effectuating Executive’s resignation sooner than the date set forth in Executive’s Notice of Termination. (c) Termination by the Company without Cause or by Executive for Good Reason (No Change in Control). If Executive’s employment is terminated by the Company without Cause or by the Executive for Good Reason where there has not been a Change in Control, and provided that the Executive has satisfied all conditions precedent as set forth herein, then the Company shall: (i) pay Executive all Accrued Compensation; 3 (ii) continue paying Executive’s then-base salary for a period of twelve (12) months payable in accordance with the normal payroll practices of the Company for its executives generally, with the first such payment to be made on the first payroll date that occurs after the day that is sixty (60) days after the date of termination, retroactive to the date of Executive’s termination, or such other method of payment as determined by the Company; and (iii) provided that Executive appropriately and timely completes all required elections, the Company shall reimburse (on a taxable basis) premiums paid by Executive for health and dental insurance premiums (for himself/herself and all eligible dependents) under the Consolidated Omnibus Budget Reconciliation Act (“COBRA”) at the same amount and to the same extent it would if Executive still was employed by the Company until the earliest of (A) the last day of the month which falls twelve (12) months from the date of Executive’s termination (or such other period as required by applicable law); (B) the date that Executive and eligible dependents are no longer eligible to receive continuation coverage under COBRA; or (C) the date Executive becomes eligible to receive health or dental care coverage pursuant to the health or dental care plan of a new employer. In the event that the Company terminates Executive’s employment without Cause as set forth in this Section 3(c), but the Company determines within one (1) year of such termination that the Company had the right to terminate Executive’s employment for Cause pursuant to Sections 1(a) and 3(a) above, the Company may terminate the payment of any amounts still owed to Executive pursuant to this Section 3(c). (d) Termination by the Company without Cause or by Executive for Good Reason (Change in Control). If Executive’s employment is terminated by the Company without Cause or by Executive for Good Reason, and provided that such termination occurs within twelve (12) months after the occurrence of such qualifying event giving rise to the Change in Control; then the Company shall: (i) pay Executive all Accrued Compensation; (ii) continue paying Executive’s then-base salary for a period of twelve (12) months payable in accordance with the normal payroll practices of the Company for its executives generally, with the first such payment to be made on the first payroll date that occurs after the day that is sixty (60) days after the date of termination, retroactive to the date of Executive’s termination, or such other method of payment as determined by the Company; (iii) pay Executive an amount equal to fifty percent (50%) of his/her annual target bonus for the year in which the termination occurs, pro-rated to reflect the month in which the termination occurs, such amount to be payable in a lump-sum on the date that is the day that is sixty (60) days after the date of termination; and (iv) provided that Executive appropriately and timely completes all required elections, the Company shall reimburse (on a taxable basis) premiums paid by Executive for health and dental insurance premiums (for himself/herself and all eligible dependents) under COBRA at the same amount and to the same extent it would if Executive still was employed by the Company until the earliest of (A) the last day of the month which falls twelve (12) months from the date of Executive’s termination (or such other period as required by applicable law); (B) the date that Executive and eligible dependents are no longer eligible to receive continuation coverage under COBRA; or (C) the date Executive becomes eligible to receive health or dental care coverage pursuant to the health or dental care plan of a new employer. In the event that the Company terminates Executive’s employment without Cause as set forth in this Section 3(d), but the Company determines within one (1) year of such termination that the Company had the right to terminate Executive’s employment for Cause pursuant to Sections 1(a) and 3(a) above, the Company may terminate the payment of any amounts still owed to Executive pursuant to this Section 3(d). (e) Notice of Termination Required. Any purported termination by the Company or by Executive must be communicated by a written Notice of Termination to the other party. For purposes of 4 this Agreement, no purported termination of employment will be effective without a Notice of Termination. (f) Timing of Payments. The Accrued Compensation payable to Executive as provided in this Section 3 will be paid pursuant to applicable state law or within ten (10) business days after the effective date of Executive’s employment termination, whichever period is shorter. Any other compensation provided for in this Section 3 will be paid as set forth above, subject to Section 9 below. (g) Payroll Taxes and Withholdings. All Severance Benefits provided for in this Section 3 shall, to the extent required, be subject to ordinary and required payroll taxes, deductions and income tax withholding. (h) Reemployment. If Executive becomes reemployed by the Company prior to the end of the period in which Executive is entitled to receive Severance Benefits, Executive will no longer be entitled to receive such Severance Benefits (except for any Accrued Compensation) as of the effective date of such reemployment. (i) Benefit Plans. Executive’s entitlement to any other compensation or benefits upon termination of his/her employment shall be determined in accordance with the Company’s employee benefit plans and other applicable programs and practices then in effect. 4. Conditions Precedent to Receipt of Severance Benefits. Executive shall not be entitled to receive (or continue to receive) any Severance Benefits, except for Accrued Compensation, and shall not be entitled to any continued vesting of outstanding equity awards pursuant to Section 5(b) below unless: (a) Executive executes (prior to the deadline established by the Company), does not revoke and complies with a general release of all claims against the Company and its officers, directors and employees upon terms and in a form reasonably acceptable to the Company; (b) Executive executes (and does not rescind such acceptance within seven (7) business days after such execution) and complies fully with a new agreement to be entered into between Executive and the Company containing post-termination restrictive covenants (including, without limitation, covenants of non-disclosure, non-solicitation and non-competition, and covenants regarding the assignment of intellectual property) with the same scope, duration and conditions as any post-termination restrictive covenants previously agreed to between Executive and the Company at any time during Executive’s employment with the Company; and (c) Executive complies fully with Section 7 hereof. 5. Accelerated Vesting of Equity. (a) Upon a Change in Control. One hundred percent (100%) of Executive’s outstanding unvested options, restricted shares, restricted stock units or other equity-based awards shall immediately vest upon a Change in Control. The exercisability of stock options (or other awards requiring exercise) shall be extended, to the extent feasible and to the extent consistent with applicable law and the terms of the Company’s equity plans or programs (each, as in effect from time to time, a “Company Equity Plan” and, together, the “Company Equity Plans”) and the award agreements issued thereunder, beyond any lockup or similar restrictive period set forth in any documents executed in connection with a Change in Control. The Compensation Committee may determine in its reasonable discretion whether it is advisable or feasible to amend a Company Equity Plan or Plans and/or any equity agreements issued thereunder between the Company and Executive in order to effect the extended period of exercise contemplated by this Section 5(a). For the avoidance of doubt, no amendment shall be made by the Compensation Committee in furtherance of this Section 5(a) other than in accordance with Section 409A of Internal Revenue Code of 1986, as amended (the “Code”) and the regulations and guidance issued thereunder. (b) Upon Termination by the Company without Cause or by Executive for Good Reason. Executive’s outstanding unvested options, restricted shares, restricted stock units or other equity-based awards shall remain outstanding and continue to vest in accordance with the terms of the applicable equity agreement(s) for the period of time during which Executive continues to receive Severance 5 Benefits, as if he or she remained employed during such time, in accordance with Section 3(c)(ii) hereof. The Compensation Committee may determine in its reasonable discretion whether it is advisable or feasible to amend a Company Equity Plan or Plans and/or any equity agreements issued thereunder existing between the Company and Executive in order to effect the extended period of vesting contemplated by this Section 5(b). For the avoidance of doubt, no amendment shall be made by the Compensation Committee in furtherance of this Section 5(b) other than in accordance with Code Section 409A and the regulations and guidance issued thereunder. 6. Cooperation. During employment and after the termination of Executive’s employment for any reason, Executive agrees to cooperate with, and at the request of, the Company in the defense or prosecution of any legal matter or claim in which the Company, any of its affiliates, or any of their past or present employees, agents, officers, directors, attorneys, successors or assigns, may be or become involved and which arises or arose during Executive’s employment, to the extent such cooperation does not unreasonably interfere with Executive’s personal or professional schedule. Executive will be reimbursed for any reasonable out-of-pocket expenses incurred thereby. 7. Non-Disparagement. Executive agrees that during his/her employment and for the greater of (A) one (1) year following the termination of his/her employment (regardless of the reason for termination) or (B) the period during which Executive receives Severance Benefits hereunder, Executive will not make any statements that are disparaging about or adverse to the business interests of the Company or which are intended to harm the reputation of the Company including, but not limited to, any statements that disparage any product, service, finances, employees, officers, directors, capabilities or any other aspect of the Company’s business, products or services. 8. Successors and Assigns. (a) Assignment by Company. The Company may, without the consent of Executive, assign this Agreement or delegate its obligations hereunder to any firm, entity, company or person (collectively, a “Person”) in the event that the Company shall hereafter effect a reorganization, consolidate with, or merge into, such Person or transfer all or substantially all of its properties or assets to such Person. (b) Assignment by Executive. Neither this Agreement nor any right or interest hereunder will be assignable or transferable by Executive, his/her beneficiaries or legal representatives, except by will or by the laws of descent and distribution. All payments under this Agreement will inure to the benefit of and be enforceable by Executive’s legal personal representative(s). 9. Tax Consequences. (a) The Company does not guarantee the tax treatment or tax consequences associated with Severance Benefits received by Executive hereunder. (b) Parachute Payments. To the extent consistent with applicable law, the payment of any amounts or the provision of any benefits under this Agreement including, without limitation, the payment of Severance Benefits pursuant to Section 3 above or the accelerated vesting of equity pursuant to Section 5 above, will be reduced or adjusted to avoid triggering the excise tax imposed by Section 4999 of the Code, if such adjustment would result in the provision of a greater total benefit, on a net after-tax basis (after taking into account taking any applicable federal, state and local income taxes and the excise tax imposed by Section 4999), to Executive. (c) Section 409A. The provisions of this Agreement are intended to comply with the requirements of Code Section 409A or with the conditions for an exemption from such requirements, and shall be construed accordingly. Notwithstanding any provision of this Agreement to the contrary, if at the time of Executive’s separation from service (as defined below) Executive is a specified employee (as defined below), as determined by the Company, any and all amounts payable in connection with such separation from service that constitute deferred compensation subject to Code Section 409A, as determined by the Company, and that would otherwise be payable within six (6) months following such separation from service, shall instead be paid on the date that follows the date of such separation from service by six (6) months (or, if earlier, upon the Executive’s death). For purposes of this Agreement, all references to “termination of employment” and correlative phrases shall be construed to require a “separation from service” (as defined in Section 1.409A-1(h) of the Treasury regulations after giving 6 effect to the presumptions contained therein), and the term “specified employee” means an individual determined by the Company to be a specified employee under Treasury regulation Section 1.409A-1(i). Each payment made under this Agreement shall be treated as a separate payment and the right to a series of installment payments under this Agreement is to be treated as a right to a series of separate payments. Any reimbursement for expenses that would constitute nonqualified deferred compensation subject to Section 409A shall be subject to the following additional rules: (i) no reimbursement of any such expense shall affect Executive’s right to reimbursement of any such expense in any other taxable year; (ii) reimbursement of the expense shall be made, if at all, promptly, but not later than the end of the calendar year following the calendar year in which the expense was incurred; and (iii) the right to reimbursement shall not be subject to liquidation or exchange for any other benefit. 10. Notices. All notices, requests, demands, and other communications called for hereunder will be in writing and will be deemed given (a) on the date of delivery if delivered personally, (b) one (1) day after being sent overnight by a well-established commercial overnight service, or (c) four (4) days after being mailed by registered or certified mail, return receipt requested, prepaid and addressed to the parties or their successors at the following addresses, or at such other addresses as the parties may later designate in writing: If to the Company: Akebia Therapeutics, Inc. Attention: Chief Legal Officer 245 First Street Cambridge, Massachusetts 02142 If to Executive: at the last residential address known by the Company 11. Non-Exclusivity of Rights. Nothing in this Agreement will prevent or limit Executive’s continuing or future participation in any benefit, bonus, incentive or other plan or program provided by the Company or any of its subsidiaries and for which Executive may qualify, nor will anything herein limit or reduce such rights as Executive may have under any other agreements with the Company or any of its subsidiaries. Amounts which are vested benefits or which Executive is otherwise entitled to receive under any plan or program of the Company or any of its subsidiaries will be payable in accordance with such plan or program, except as explicitly modified by this Agreement. 12. Amendments. No provision of this Agreement may be modified, waived or discharged unless such waiver, modification or discharge is agreed to in writing and signed by Executive and the Chief Executive Officer of the Company. 13. No Waiver. No waiver by either party hereto at any time of any breach by the other party hereto of, or compliance with, any condition or provision of this Agreement to be performed by such other party will be deemed a waiver of similar or dissimilar provisions or conditions at the same or at any prior or subsequent time. 14. Governing Law. This Agreement will be governed by and construed and enforced in accordance with the laws of the Commonwealth of Massachusetts, without giving effect to the conflict of law principles thereof. 15. Dispute Resolution/Jurisdiction/Venue. Any dispute concerning this Agreement shall be heard by a court of competent jurisdiction within Massachusetts. The parties hereby acknowledge that they are subject to the personal jurisdiction of the Massachusetts courts in any county where the Company has operations or facilities and/or Executive resides. 7 16. Expenses. To the extent Executive elects to have independent legal counsel review and or negotiate the terms of this Agreement or any release required by this Agreement, Executive shall be solely responsible for all associated costs and fees, including but not limited to attorneys’ fees. 17. Severability. The provisions of this Agreement will be deemed severable and the invalidity or unenforceability of any provision will not affect the validity or enforceability of the other provisions hereof. 18. Effect on Other Agreements. The terms of this Agreement replace and supersede the terms in all other and prior agreements between Executive and the Company that relate to (i) post-separation severance and other post-separation benefits and (ii) equity acceleration in connection with a change of control, whether written or oral or express or implied, and no representations, promises, assurances or agreements have been made regarding the subject matter of this Agreement, except such as has been stated in this Agreement. For the avoidance of doubt, (a) the terms of any existing employment agreement or other agreement between Executive and the Company regarding assignment of intellectual property, confidentiality and non-disclosure, non-competition and non-solicitation between Executive and the Company shall remain in full force and effect and (b) all other terms in offer letters, employment agreements or any other agreements between Executive and the Company that do not relate to (1) post-separation severance or other post-separation benefits or (2) equity acceleration in connection with a change of control, will remain in full force and effect. 19. Clawback Policy. Notwithstanding any other provision of this Agreement, Executive agrees and acknowledges that they are and remain subject to, and bound by, the terms and conditions of Akebia Therapeutic Inc.’s Compensation Recovery Policy (as it may be amended, restated, supplemented or otherwise modified from time to time, the “Policy”). In the event it is determined in accordance with the Policy that any compensation or compensatory award granted, earned or paid to Executive must be forfeited or reimbursed to the Company, Executive will promptly take any action necessary to effectuate such forfeiture and/or reimbursement as determined by the Company. THE COMPANY AND EXECUTIVE ACKNOWLEDGE THAT (A) EACH HAS CAREFULLY READ THIS AGREEMENT, (B) EACH UNDERSTANDS ITS TERMS, (C) ALL UNDERSTANDINGS AND AGREEMENTS BETWEEN THE COMPANY AND EXECUTIVE RELATING TO THE SUBJECTS COVERED IN THIS AGREEMENT ARE CONTAINED IN IT, AND (D) EACH HAS ENTERED INTO THIS AGREEMENT VOLUNTARILY AND NOT IN RELIANCE ON ANY PROMISES OR REPRESENTATIONS BY THE OTHER, OTHER THAN THOSE CONTAINED IN THIS AGREEMENT ITSELF. IN WITNESS WHEREOF, the Company has caused this Agreement to be executed by its duly authorized person and Executive has executed this Agreement effective as of the day and year first above written. EXECUTIVE By: Name: Title: 8 AKEBIA THERAPEUTICS, INC. By: John P. Butler, Chief Executive Officer Exhibit 10.44 [Date] Personal and Conﬁdenal [First Name Last name] [Address] Re: ELT Special Bonus Program Dear [First Name Last name]: I am pleased to oﬀer you the opportunity to earn addional bonus payments related to your important work on the vadadustat program (the “ELT Special Bonus Program”) in recognion of your signiﬁcant value to Akebia Therapeucs, Inc. (“Akebia” or the “Company”) and in ancipaon of the important contribuons you will make in the next year and beyond. The purpose of this leer agreement (the “Agreement”) is to outline the terms and condions associated with the bonus payments (“Bonus Payments”) oﬀered to you by Akebia. These Bonus Payments are in addion to your annual bonus payment. If you accept the terms of this Agreement, please return a signed Agreement to [Name] no later than [Date]. 1. Special Bonus Payment. Subject to the terms and condions set forth below, and in recognion of your contribuons to the vadadustat program to date, the Company will provide you with a lump sum payment of $[●], less all required taxes, withholdings and deducons, payable within ﬁeen (15) days of the date hereof (the “Special Bonus Payment”). 2. Retenon Cash Incenve Award. Subject to the terms and condions set forth below and the terms of the Company’s Cash Incenve Plan, the Company will provide you with the following: (a) lump sum payment of $[●], less all required taxes, withholdings and deducons (“Incenve Payment 1”) upon [●] (“Event 1”), payable within ﬁeen (15) days of Event 1. (b) lump sum payment of $[●], less all required taxes, withholdings and deducons (“Incenve Payment 2” and together with Incenve Payment 1, the “Incenve Payments”) upon [●] (“Event 2”), payable within ﬁeen (15) days of Event 2. In order to be eligible for any Incenve Payment, you must remain an employee of the Company in good standing (i.e., meeng the requirements of your posion) through the date of the corresponding event. 3. Repayment of Special Bonus Payment Upon Terminaon. If you voluntarily terminate your employment with the Company within twelve (12) months aer you receive the Special Bonus Payment, then you shall repay $[●] within thirty (30) days aer the eﬀecve date of such terminaon. Should you become obligated to repay to the Company the Special Bonus Payment as set forth herein, you hereby authorize the Company to deduct any owed amount from your ﬁnal, accrued wages (including, without limitaon, any accrued but unused paid me oﬀ). You acknowledge and agree that any such deducons would constute permissible, valid oﬀsets under the Massachuses 1 Payment of Wages Act, M.G.L. c. 149 § 148 et seq. You further agree that should your ﬁnal, accrued wages be insuﬃcient to sasfy your enre repayment obligaon, you will repay any outstanding amount by personal check. You agree that you will be responsible for paying the Company’s costs of collecon, if any (including aorneys’ fees and other expenses), should the Company be required to resort to legal acon to collect any such then-outstanding amount. 4. Prior Agreements. Upon your acceptance of the terms and condions of this Agreement, the Employee Agreement (Conﬁdenality, Non-Solicitaon, Non-Compeon and Developments Agreement) last executed by you in connecon with your employment with Akebia and the Execuve Severance Agreement between you and the Company will remain in full force and eﬀect in accordance with their terms, and by your signature below are conﬁrmed, raﬁed and incorporated herein. 5. At-Will Employment. Nothing in this Agreement should be taken as a guarantee of connued employment, a speciﬁc term of employment and/or a contract of employment, and at all mes you will be expected to meet Company performance standards and abide by all Company policies and procedures. Your employment remains at will and you and the Company agree that this Agreement does not in any way modify the at-will nature of your employment by the Company. Accordingly, your employment, as well as the terms and condions thereof (except for this Agreement), may be modiﬁed or terminated with or without Cause or noce. For purposes of this Agreement, the deﬁnion of “Cause” shall be the same deﬁnion of “Cause” included in your Execuve Severance Agreement. 6. Conﬁdenality. The terms and condions of this Agreement, the existence of the ELT Special Bonus Program, and the Bonus Payments are strictly conﬁdenal except as required by applicable law. To the extent permied by applicable law, you shall not discuss or reveal any informaon concerning this Agreement to any past or present employee of the Company or any third person or enty other than the individual who presented you with this Agreement, an Akebia Human Resources representave, counsel and members of your immediate family. 7. Complete Agreement; Miscellaneous. This Agreement, together with the Cash Incenve Plan and the Execuve Severance Agreement, sets forth the complete agreement between you and the Company with respect to your eligibility for, and the payment to you of, the Bonus Payments. The provisions of this Agreement will not supersede or modify the provisions of the Employee Agreement, and nothing herein shall preclude the connued validity of the Employee Agreement which shall remain in full force and eﬀect. You agree that each provision and the subparts of each provision in this Agreement shall be treated as separate and independent clauses, and the unenforceability of any one clause shall in no way impair the enforceability of any of the other clauses of this Agreement. In the event of any dispute, this Agreement will be construed as a whole, will be interpreted in accordance with its fair meaning, and will not be construed strictly for or against either you or the Company. This Agreement may not be changed, amended, modiﬁed, altered or rescinded except upon the express wrien consent of both you and an authorized Company oﬃcer, subject to the terms of the Cash Incenve Plan, as applicable. Any waiver of any provision of this Agreement by the Company shall not constute a waiver of any other provision of this Agreement unless the Company expressly so indicates otherwise. This Agreement shall be governed by and construed in accordance with the laws of the Commonwealth of Massachuses without regard to conﬂicts of laws principles thereof. Both pares agree that any dispute under this Agreement shall be heard by a court of competent jurisdicon within Massachuses. The pares hereby acknowledge that they are subject to the personal jurisdicon of the 2 Massachuses courts in any county where the Company has operaons or facilies and/or you reside. 8. Assignment. Except as otherwise provided herein, this Agreement shall be binding upon, inure to the beneﬁt of and be enforceable by the Company and you and their respecve heirs, legal representaves, successors and assigns. If the Company shall be merged into or consolidated with another enty, the provisions of this Agreement shall be binding upon and inure to the beneﬁt of the enty surviving such merger or resulng from such consolidaon. 9. Clawback Policy. In accepng these payments, you agree and acknowledge that you are subject to, and bound by, the terms of any clawback policy that the Company has in place or may adopt in the future, including without limitaon Akebia Therapeuc Inc.’s Compensaon Recovery Policy adopted in accordance with stock exchange lisng requirements. You agree that in the event it is determined in accordance with any such policy that any compensaon or compensatory award granted, earned or paid to you including these payments or pursuant to any other compensaon arrangement must be forfeited or reimbursed to the Company, you will promptly take any acon necessary to eﬀectuate such forfeiture and/or reimbursement as determined by the Company. We are pleased to be able to oﬀer you parcipaon in the ELT Special Bonus Program, and we look forward to your connuing commitment and focus on fulﬁlling your responsibilies. Please feel free to reach out to me should you have any quesons. Sincerely, [First Name, Last name] [Title] 3 AGREED AND ACCEPTED: I acknowledge and agree that I have read the foregoing Agreement and the Cash Incenve Plan, have had the opportunity to consult with counsel and that I have freely and voluntarily entered into this Agreement. ________________________________ [First Name, Last name] Dated: _______________ 4 AKEBIA THERAPEUTICS, INC. STOCK OPTION AGREEMENT FOR OFFICERS 2023 STOCK INCENTIVE PLAN Akebia Therapeutics, Inc. (the “Company”) hereby grants the following stock option pursuant to its 2023 Stock Incentive Plan (the “Plan”). The terms and conditions attached hereto are also a part hereof. Notice of Grant Exhibit 10.45 Name of optionee (the “Participant”): Grant Date: Incentive Stock Option or Nonstatutory Stock Option: Number of shares of the Company’s Common Stock subject to this option (“Shares”): 1 Option exercise price per Share: Number, if any, of Shares that vest immediately on the grant date: Shares that are subject to vesting schedule: Vesting Start Date: 2 Final Exercise Date: Vesting Schedule: Vesting Date: Number of Options that Vest: All vesting is dependent on the Participant remaining an Eligible Participant, as provided herein. This option satisfies in full all commitments that the Company has to the Participant with respect to the issuance of stock, stock options or other equity securities. 1 This must be at least 100% of the Grant Date Fair Market Value (as defined in the Plan) of the Common Stock on the date of grant (110% in the case of a Participant that owns more than 10% of the total combined voting power of all classes of stock of the Company or its parent or subsidiary (a “10% Shareholder”) when the option is intended to qualify as an incentive stock option (an “ISO”) under Section 422 of the Internal Revenue Code). 2 The Final Exercise Date must be no more than 10 years (5 years in the case of a 10% Shareholder for an option intended to qualify as an ISO) from the date of grant. The correct approach to calculate the final exercise date is to use the day immediately prior to the date ten years out from the date of the stock option award grant (or 5 years, as applicable). Signature of Participant Street Address City/State/Zip Code Akebia Therapeutics, Inc. By: Name of Officer Title: Akebia Therapeutics, Inc. Stock Option Agreement for Officers Incorporated Terms and Conditions 1. Grant of Option. This agreement evidences the grant by the Company, on the grant date (the “Grant Date”) set forth in the Notice of Grant that forms part of this agreement (the “Notice of Grant”), to the Participant of an option to purchase, in whole or in part, on the terms provided herein and in the Company’s 2023 Stock Incentive Plan (the “Plan”), the number of Shares set forth in the Notice of Grant of common stock, $0.00001 par value per share, of the Company (“Common Stock”), at the exercise price per Share set forth in the Notice of Grant. Unless earlier terminated, this option shall expire at 5:00 p.m., Eastern time, on the Final Exercise Date set forth in the Notice of Grant (the “Final Exercise Date”). The option evidenced by this agreement is intended to be an incentive stock option as defined in Section 422 of the Internal Revenue Code of 1986, as amended, and any regulations promulgated thereunder (the “Code”) to the maximum extent permitted by law, solely to the extent designated as an incentive stock option in the Notice of Grant. Except as otherwise indicated by the context, the term “Participant”, as used in this option, shall be deemed to include any person who acquires the right to exercise this option validly under its terms. 2. Vesting Schedule. (a) General. Subject to this Agreement and the terms of any Executive Severance Agreement or other written agreement between the Participant and the Company, this option will become exercisable (“vest”) in accordance with the vesting schedule set forth in the Notice of Grant. (b) Change in Control. (1) Treatment of Option in a Change in Control. The option, to the extent outstanding immediately prior to a Change in Control but not then vested in full, shall automatically become fully vested and exercisable upon such Change in Control. (2) Definitions. (i) “Change in Control” means the occurrence of any of the following events other than in connection with the consummation of an initial public offering of the Company’s securities: (A) any “person” (as such term is used in Sections 13(d) and 14(d) of the Securities Exchange Act of 1934, as amended) who is not a shareholder of the Company as of the date of this Agreement or an affiliate thereof is or becomes the “beneficial owner” (as defined in Rule 13d-3 under said Act), directly or indirectly, of securities of the Company representing 50% or more of the total voting power represented by the Company’s then outstanding voting securities; (B) a change in the composition of the Board occurring within a two-year period, as a result of which less than a majority of the directors are Incumbent Directors; (C) the date of the consummation of a merger, scheme of arrangement or consolidation of the Company with any other corporation that has been approved by the stockholders of the Company, other than a merger, scheme of arrangement or consolidation which would result in the voting securities of the Company outstanding immediately prior thereto continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity) more than fifty percent (50%) of the total voting power represented by the voting securities of the Company or such surviving entity outstanding immediately after such merger or consolidation; or (D) the date of the consummation of the sale or disposition by the Company of all or substantially all the Company’s assets. Notwithstanding the foregoing, a transaction will not constitute a Change in Control if: (I) its sole purpose is to change the domicile of the Company’s incorporation; or (II) its sole purpose is to create a holding company that will be owned in substantially the same proportions by the persons who held the Company’s securities immediately before such transaction. In all respects, the definition of Change in Control shall be interpreted to comply with Section 409A of the Code, and any successor statute, regulation and guidance thereto. “Incumbent Directors” means directors who either (A) are directors of the Company as of the date (ii) hereof, or (B) are elected, or nominated for election, to the Board with the affirmative votes of at least a majority of the remaining Incumbent Directors at the time of such election or nomination (but will not include an individual whose election or nomination is in connection with an actual or threatened proxy contest relating to the election of directors to the Company). (c) Exercisability. The right of exercise shall be cumulative so that to the extent the option is not exercised in any period to the maximum extent permissible it shall continue to be exercisable, in whole or in part, with respect to all Shares for which it is vested until the earlier of the Final Exercise Date or the termination of this option under Section 3 hereof or the Plan. 3. Exercise of Option. (a) Form of Exercise. Each election to exercise this option shall be in writing, in the form of the Stock Option Exercise Notice attached as Annex A, signed by the Participant, and received by the Company at its principal office, accompanied by this agreement, or in such other form (which may be electronic) as is approved by the Company, together with payment in full in the manner provided in the Plan. The Participant may purchase less than the number of shares covered hereby, provided that no partial exercise of this option may be for any fractional share or for fewer than ten whole shares. (b) Continuous Relationship with the Company Required. Except as otherwise provided in this Section 3, this option may not be exercised unless the Participant, at the time he or she exercises this option, is, and has been at all times since the Grant Date, an employee, officer, or director of, or consultant or advisor to, the Company or any other entity the employees, officers, directors, consultants, or advisors of which are eligible to receive option grants under the Plan (an “Eligible Participant”). (c) Termination of Relationship with the Company. If the Participant ceases to be an Eligible Participant for any reason, then, except as provided in this paragraph or in paragraphs (d) and (e) below, the right to exercise this option shall terminate three months after such cessation (but in no event after the Final Exercise Date), provided that this option shall be exercisable only to the extent that the Participant was entitled to exercise this option on the date of such cessation; and, provided, further, that to the extent the Participant is a party to an Executive Severance Agreement or other written agreement with the Company that provides for the option to remain outstanding and continue to vest during a specified period of time following the Participant’s cessation of status as an Eligible Participant (such period, the “Severance Period”), the option shall remain outstanding and shall continue to vest in accordance with the terms of this Agreement during the Severance Period as if the Participant had remained an Eligible Participant during such period, subject to any conditions on continued vesting as may be contained in such Executive Severance Agreement or other written agreement. Any portion of this option that vests during such Severance Period will remain exercisable until the earlier of (A) the date that is three (3) months following the date that is the last day of such Severance Period, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c) will thereupon immediately terminate. For the avoidance of doubt, any portion of the option that fails to vest during the Severance Period will immediately be forfeited on the last day of such period. Notwithstanding the foregoing, if the Participant, prior to the Final Exercise Date, violates the restrictive covenants (including, without limitation, the non-competition, non-solicitation, or confidentiality provisions) of any employment contract, any non- competition, non-solicitation, confidentiality or assignment agreement to which the Participant is a party, or any other agreement between the Participant and the Company, the right to exercise this option shall terminate immediately upon such violation. (d) Exercise Period Upon Death. If the Participant dies prior to the Final Exercise Date while he or she is an Eligible Participant and the Company has not terminated such relationship for “cause” as specified in paragraph (e) below, this option shall be exercisable, within the period of one year following the date of death of the Participant, by an authorized transferee of the Participant, provided that this option shall be exercisable only to the extent that this option was exercisable by the Participant on the date of his or her death, and further provided that this option shall not be exercisable after the Final Exercise Date. (e) Termination for Cause. If, prior to the Final Exercise Date, the Participant’s employment, consulting, director or advisor relationship with the Company is terminated by the Company for Cause (as defined below), the right to exercise this option shall terminate immediately upon the effective date of such termination. If, prior to the Final Exercise Date, the Participant is given notice by the Company of the termination of his or her service by the Company for Cause, and the effective date of such termination is subsequent to the date of delivery of such notice, the right to exercise this option shall be suspended from the time of the delivery of such notice until the earlier of (i) such time as it is determined or otherwise agreed that the Participant’s service shall not be terminated for Cause as provided in such notice or (ii) the effective date of such termination (in which case the right to exercise this option shall, pursuant to the preceding sentence, terminate upon the effective date of such termination). If the Participant is a party to an Executive Severance Agreement or other written agreement with the Company, in any case which agreement contains a definition of “cause” for termination of service, “Cause” shall have the meaning ascribed to such term in such agreement. Otherwise, “Cause” shall mean willful misconduct by the Participant or willful failure by the Participant to perform his or her responsibilities to the Company (including, without limitation, breach by the Participant of any fiduciary duty or of any provision of any employment, consulting, advisory, nondisclosure, non-competition or other similar agreement between the Participant and the Company), as determined by the Company, which determination shall be conclusive. The Participant shall be considered to have been terminated for Cause if the Company determines, within 30 days after the Participant’s resignation, that termination for Cause was warranted. 4. Tax Matters. (a) Withholding. No Shares will be issued pursuant to the exercise of this option unless and until the Participant pays to the Company, or makes provision satisfactory to the Company for payment of, any federal, state or local withholding taxes required by law to be withheld in respect of this option. (b) Disqualifying Disposition. If this option is an incentive stock option and the Participant disposes of Shares acquired upon exercise of this option within two years from the Grant Date or one year after such Shares were acquired pursuant to exercise of this option, the Participant shall notify the Company in writing of such disposition. 5. Transfer Restrictions; Clawback. (a) This option may not be sold, assigned, transferred, pledged, encumbered or otherwise disposed of by the Participant, either voluntarily or by operation of law, except by will or the laws of descent and distribution, and, during the lifetime of the Participant, this option shall be exercisable only by the Participant. (b) In accepting this option, the Participant agrees to be bound by any clawback policy that the Company has in place or may adopt in the future. 6. Provisions of the Plan. This option is subject to the provisions of the Plan (including the provisions relating to amendments to the Plan), a copy of which is furnished to the Participant with this option. Notwithstanding the foregoing, to the extent the Participant has entered in to an Executive Severance Agreement with the Company, for so long as such Executive Severance Agreement remains in effect, the terms of such Executive Severance Agreement as they relate to the option shall control in the event of a conflict with this Agreement or the Plan. 7. Clawback Policy. In accepting this option, the Participant agrees and acknowledges that the Participant is subject to, and bound by, the terms of any clawback policy that the Company has in place or may adopt in the future, including without limitation Akebia Therapeutic Inc.’s Compensation Recovery Policy adopted in accordance with stock exchange listing requirements. The Participant agrees that in the event it is determined in accordance with any such policy that any compensation or compensatory award granted, earned or paid to the Participant including this option or pursuant to any other compensation arrangement must be forfeited or reimbursed to the Company, the Participant will promptly take any action necessary to effectuate such forfeiture and/or reimbursement as determined by the Company. ANNEX A Akebia Therapeutics, Inc. 245 First Street Cambridge, MA 02142 Dear Sir or Madam: Akebia Therapeutics, Inc. Stock Option Exercise Notice I, (the “Participant”), hereby irrevocably exercise the right to purchase shares of the Common Stock, $0.00001 par value per share (the “Shares”), of Akebia Therapeutics, Inc. (the “Company”) at $ per share pursuant to the Company’s 2023 Stock Incentive Plan and a stock option agreement with the Company dated (the “Option Agreement”). Enclosed herewith is a payment of $ , the aggregate purchase price for the Shares. The Shares should be registered in my name as it appears below or, if so indicated below, jointly in my name and the name of the person designated below, with right of survivorship. Dated: Signature Print Name: Address: Name and address of persons in whose name the Shares are to be jointly registered (if applicable): AKEBIA THERAPEUTICS, INC. RESTRICTED STOCK UNIT AGREEMENT FOR OFFICERS 2023 STOCK INCENTIVE PLAN Exhibit 10.46 Akebia Therapeutics, Inc. (the “Company”) hereby grants the following restricted stock units pursuant to its 2023 Stock Incentive Plan (the “Plan”). The terms and conditions attached hereto are also a part hereof. Notice of Grant Name of recipient (the “Participant”): Grant Date: Number of restricted stock units (“RSUs”) granted: Vesting Start Date: Vesting Schedule: Vesting Date: Number of RSUs that Vest: All vesting is dependent on the Participant remaining an Eligible Participant, as provided herein. This grant of RSUs satisfies in full all commitments that the Company has to the Participant with respect to the issuance of stock, stock options or other equity securities. Signature of Participant Street Address City/State/Zip Code Akebia Therapeutics, Inc. By: Name of Officer Title: Akebia Therapeutics, Inc. Restricted Stock Unit Agreement for Officers Incorporated Terms and Conditions For valuable consideration, receipt of which is acknowledged, the parties hereto agree as follows: 1. Award of Restricted Stock Units. The Company has granted to the Participant, subject to the terms and conditions set forth in this Restricted Stock Unit Agreement (this “Agreement”) and in the Company’s 2023 Stock Incentive Plan (the “Plan”), an award with respect to the number of RSUs set forth in the Notice of Grant that forms part of this Agreement (the “Notice of Grant”). Each RSU represents the right to receive one share of common stock, $0.00001 par value per share, of the Company (the “Common Stock”) upon vesting of the RSU, subject to the terms and conditions set forth herein. 2. Vesting; Delivery. (a) General. The RSUs shall vest in accordance with the Vesting Schedule set forth in the Notice of Grant (the “Vesting Schedule”), subject to the terms of any Executive Severance Agreement or other written agreement between the Participant and the Company. Any fractional shares resulting from the application of any percentages used in the Vesting Schedule shall be rounded down to the nearest whole number of RSUs. (b) Change in Control. i. Treatment of RSUs in a Change in Control. The RSUs, to the extent outstanding immediately prior to a Change in Control but not then vested in full, will automatically and immediately become fully vested upon such Change in Control. ii. Definitions. (A) “Change in Control” means the occurrence of any of the following events other than in connection with the consummation of an initial public offering of the Company’s securities: (A) any “person” (as such term is used in Sections 13(d) and 14(d) of the Securities Exchange Act of 1934, as amended) who is not a shareholder of the Company as of the date of this Agreement or an affiliate thereof is or becomes the “beneficial owner” (as defined in Rule 13d-3 under said Act), directly or indirectly, of securities of the Company representing 50% or more of the total voting power represented by the Company’s then outstanding voting securities; (B) a change in the composition of the Board occurring within a two-year period, as a result of which less than a majority of the directors are Incumbent Directors; (C) the date of the consummation of a merger, scheme of arrangement or consolidation of the Company with any other corporation that has been approved by the stockholders of the Company, other than a merger, scheme of arrangement or consolidation which would result in the voting securities of the Company outstanding immediately prior thereto continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity) more than fifty percent (50%) of the total voting power represented by the voting securities of the Company or such surviving entity outstanding immediately after such merger or consolidation; or (D) the date of the consummation of the sale or disposition by the Company of all or substantially all the Company’s assets. Notwithstanding the foregoing, a transaction will not constitute a Change in Control if: (I) its sole purpose is to change the domicile of the Company’s incorporation; or (II) its sole purpose is to create a holding company that will be owned in substantially the same proportions by the persons who held the Company’s securities immediately before such transaction. In all respects, the definition of Change in Control shall be interpreted to comply with Section 409A of the Code, and any successor statute, regulation and guidance thereto. (B) “Incumbent Directors” means directors who either (A) are directors of the Company as of the date hereof, or (B) are elected, or nominated for election, to the Board with the affirmative votes of at least a majority of the remaining Incumbent Directors at the time of such election or nomination (but will not include an individual whose election or nomination is in connection with an actual or threatened proxy contest relating to the election of directors to the Company). (c) Delivery. Upon the vesting of the RSU, the Company will deliver to the Participant, for each RSU that becomes vested, one share of Common Stock, subject to the payment of any taxes pursuant to Section 7. The Common Stock will be delivered to the Participant as soon as practicable following each vesting date, but in any event within 30 days of such date. 3. Forfeiture of Unvested RSUs Upon Cessation of Service. In the event that the Participant ceases to be an employee, officer, or director of, or consultant or advisor to, the Company or any other entity the employees, officers, directors, consultants, or advisors of which are eligible to receive awards under the Plan (an “Eligible Participant”) for any reason or no reason, with or without cause, all of the RSUs that are unvested as of the time of such cessation shall be forfeited immediately and automatically to the Company, without the payment of any consideration to the Participant, effective as of such cessation. The Participant shall have no further rights with respect to the unvested RSUs or any Common Stock that may have been issuable with respect thereto. If the Participant provides services to a subsidiary of the Company, any references in this Agreement to provision of services to the Company shall instead be deemed to refer to service with such subsidiary. Notwithstanding the foregoing, to the extent the Participant is a party to an Executive Severance Agreement or other written employment agreement with the Company that provides for the RSUs to remain outstanding and continue to vest during a specified period of time following Participant’s cessation of status as an Eligible Participant (such period, the “Severance Period”), the RSUs will remain outstanding and will continue to vest, and the Shares will be delivered upon such vesting, in accordance with the terms of this Agreement during the Severance Period as if the Participant had continued to be an Eligible Participant during such period, subject to any conditions on the vesting and delivery as may be contained in such Executive Severance Agreement or other written agreement. For the avoidance of doubt, any portion of the RSUs that fails to vest during the Severance Period will immediately be forfeited on the last day of such period. 4. Restrictions on Transfer. The Participant shall not sell, assign, transfer, pledge, hypothecate, encumber or otherwise dispose of, by operation of law or otherwise (collectively “transfer”) any RSUs, or any interest therein. The Company shall not be required to treat as the owner of any RSUs or issue any Common Stock to any transferee to whom such RSUs have been transferred in violation of any of the provisions of this Agreement. 5. Rights as a Stockholder. The Participant shall have no rights as a stockholder of the Company with respect to any shares of Common Stock that may be issuable with respect to the RSUs until the issuance of the shares of Common Stock to the Participant following the vesting of the RSUs. 6. Provisions of the Plan. This Agreement is subject to the provisions of the Plan, a copy of which is furnished to the Participant with this Agreement. 7. Tax Matters. (a) Acknowledgments; No Section 83(b) Election. The Participant acknowledges that he or she is responsible for obtaining the advice of the Participant’s own tax advisors with respect to the award of RSUs and the Participant is relying solely on such advisors and not on any statements or representations of the Company or any of its agents with respect to the tax consequences relating to the RSUs. The Participant understands that the Participant (and not the Company) shall be responsible for the Participant’s tax liability that may arise in connection with the acquisition, vesting and/or disposition of the RSUs. The Participant acknowledges that no election under Section 83(b) of the Internal Revenue Code of 1986, as amended (the “Code”), is available with respect to RSUs. (b) Withholding. The Participant acknowledges and agrees that the Company has the right to deduct from payments of any kind otherwise due to the Participant any federal, state, local or other taxes of any kind required by law to be withheld with respect to the vesting of the RSUs. At such time as the Participant is not aware of any material nonpublic information about the Company or the Common Stock and is not prohibited from doing so by the Company’s insider trading policy or otherwise, the Participant shall execute the instructions set forth in Schedule A attached hereto (the “Durable Automatic Sell-to-Cover Instruction”) as the means of satisfying such tax obligation unless the Participant has already executed such instruction, as determined by the Company. If the Participant does not execute the Durable Automatic Sell-to-Cover Instruction prior to an applicable vesting date, then the Participant agrees that if under applicable law the Participant will owe taxes at such vesting date on the portion of the award then vested the Company shall be entitled to immediate payment from the Participant of the amount of any tax required to be withheld by the Company. The Company shall not deliver any shares of Common Stock to the Participant until it is satisfied that all required withholdings have been made. 8. Miscellaneous. (a) No Right to Continued Service. The Participant acknowledges and agrees that, notwithstanding the fact that the vesting of the RSUs is contingent upon his or her continued service to the Company, this Agreement does not constitute an express or implied promise of continued service relationship with the Participant or confer upon the Participant any rights with respect to a continued service relationship with the Company or any affiliate of the Company. (b) Section 409A. The RSUs awarded pursuant to this Agreement are intended to be exempt from or comply with the requirements of Section 409A of the Code and the Treasury Regulations issued thereunder (“Section 409A”). The delivery of shares of Common Stock on the vesting of the RSUs may not be accelerated or deferred unless permitted or required by Section 409A. (c) Participant’s Acknowledgments. The Participant acknowledges that he or she: (i) has read this Agreement; (ii) has been represented in the preparation, negotiation and execution of this Agreement by legal counsel of the Participant’s own choice or has voluntarily declined to seek such counsel; (iii) understands the terms and consequences of this Agreement; (iv) is agreeing, in accepting this award, to be bound by any clawback policy that the Company has in place or may adopt in the future; and (v) is fully aware of the legal and binding effect of this Agreement. (d) Governing Law. This Agreement shall be construed, interpreted and enforced in accordance with the internal laws of the State of Delaware without regard to any applicable conflicts of laws provisions. 9. Clawback Policy. In accepting this award, the Participant agrees and acknowledges that the Participant is subject to, and bound by, the terms of any clawback policy that the Company has in place or may adopt in the future, including without limitation Akebia Therapeutic Inc.’s Compensation Recovery Policy adopted in accordance with stock exchange listing requirements. The Participant agrees that in the event it is determined in accordance with any such policy that any compensation or compensatory award granted, earned or paid to the Participant including this award or pursuant to any other compensation arrangement must be forfeited or reimbursed to the Company, the Participant will promptly take any action necessary to effectuate such forfeiture and/or reimbursement as determined by the Company. Schedule A Durable Automatic Sell-to-Cover Instruction This Durable Automatic Sell-to-Cover Instruction (this “Instruction”), which is being delivered to Akebia Therapeutics, Inc. (the “Company”) by the undersigned on the date set forth below (the “Adoption Date”), relates to the Covered RSUs (as defined following my signature below). This Instruction provides for “eligible sell-to-cover transactions” (as described in Rule 10b5-1(c)(1)(ii)(D)(3) under the Securities Exchange Act of 1934 (the “Exchange Act”)) and is intended to satisfy the affirmative defense conditions of Rule 10b5-1(c)(1) under the Exchange Act. I acknowledge that upon vesting and settlement of any Covered RSUs in accordance with the applicable RSU’s terms, whether vesting is based on the passage of time or the achievement of performance goals, I will have compensation income equal to the fair market value of the shares of the Company’s common stock subject to the RSUs that are settled on such settlement date and that the Company is required to withhold income and employment taxes in respect of that compensation income. I desire to establish a plan and process to satisfy such withholding obligation in respect of all Covered RSUs through an automatic sale of a portion of the shares of the Company’s common stock that would otherwise be issuable to me on each applicable settlement date, such portion to be in an amount sufficient to satisfy such withholding obligation, with the proceeds of such sale delivered to the Company in satisfaction of such withholding obligation. I understand that the Company has arranged for the administration and execution of its equity incentive programs and the sale of securities by participants thereunder pursuant to a platform administered by a third party (the “Administrator”) and the Administrator’s designated brokerage partner. Upon the settlement of any of my Covered RSUs after the 30th day following the Adoption Date (or if I am an officer of the Company on the Adoption Date, after the 120th day following the Adoption Date), I hereby appoint the Administrator (or any successor administrator) to automatically sell such number of shares of the Company’s common stock issuable with respect to such RSUs that vested and settled as is sufficient to generate net proceeds sufficient to satisfy the Company’s minimum statutory withholding obligations with respect to the income recognized by me in connection with the vesting and settlement of such RSUs (based on minimum statutory withholding rates for all tax purposes, including payroll and social security taxes, that are applicable to such income), and the Company shall receive such net proceeds in satisfaction of such tax withholding obligation. I hereby appoint the Chief Executive Officer, Chief Financial Officer, General Counsel and Secretary of the Company to serve as my attorneys in fact to arrange for the sale of shares of the Company’s common stock in accordance with this Instruction. I agree to execute and deliver such documents, instruments and certificates as may reasonably be required in connection with the sale of the shares of common stock pursuant to this Instruction. Unless the last box in the definition of Covered RSUs below is checked, if I have previously adopted an automatic sale or sell-to-cover instruction relating to Covered RSUs, this Instruction shall be void ab initio. I hereby certify that, as of the Adoption Date: (i) I am not prohibited from entering into this Instruction by the Company’s insider trading policy or otherwise; (ii) I am not aware of any material nonpublic information about the Company or its common stock; and (iii) I am adopting this Instruction in good faith and not as part of a plan or scheme to evade the prohibitions of Rule 10b-5 under the Exchange Act. ________________________________ Print Name: _____________________ Date: __________________________ Covered RSUs: The following restricted stock units (“RSUs”) are covered by this Instruction. Check all applicable boxes: ☐ The first award of RSUs granted to me on or after ______________ [insert date of grant of current RSUs the grant of which is triggering the execution of this Instruction; if Instruction is being executed in advance of a grant of RSUs, insert the Adoption Date] and any RSUs that may, from time to time following such date, be granted to me by the Company, other than any future granted RSUs which by the terms of the applicable award agreement require the Company to withhold shares for tax withholding obligations in connection with the vesting and settlement of such RSUs, and therefore do not permit sell-to-cover transactions. ☐ Any outstanding RSUs that were granted to me by the Company prior to the Adoption Date that (1) are not subject to any prior automatic sale or sell-to-cover instruction and (2) for which the next vesting date is after the cooling-off period referred to above, other than any previously granted RSUs which by the terms of the applicable award agreement require the Company to withhold shares for tax withholding obligations in connection with the vesting and settlement of such RSUs, and therefore do not permit sell-to-cover transactions. ☐ With respect to any RSUs, whether or not granted to me by the Company prior to the Adoption Date, that already are subject to an automatic sale or sell-to-cover instruction (a “Prior Instruction”), I elect to have such sales effected pursuant to this Instruction and confirm that doing so does not modify or change the amount, price, or timing of such sales from those provided by the Prior Instruction (and, as a result the cooling-off period referred to above is not applicable to sales pursuant to this Instruction that were previously subject to the Prior Instruction). AKEBIA THERAPEUTICS, INC. OFFICER INDUCEMENT AWARD STOCK OPTION AGREEMENT Exhibit 10.47 Akebia Therapeutics, Inc. (the “Company”) hereby grants the following inducement non-statutory stock option award. The terms and conditions attached hereto are also a part hereof. Notice of Grant Name of optionee (the “Participant”): Grant Date: Number of shares of the Company’s Common Stock subject to this option (“Shares”): 1 Option exercise price per Share: Number, if any, of Shares that vest immediately on the grant date: Shares that are subject to vesting schedule: Vesting Start Date: 2 Final Exercise Date: Vesting Schedule: Vesting Date: Number of Options that Vest: All vesting is dependent on the Participant remaining an Eligible Participant, as provided herein. This option satisfies in full all commitments that the Company has to the Participant with respect to the issuance of stock, stock options or other equity securities. Signature of Participant Street Address City/State/Zip Code Akebia Therapeutics, Inc. By: Name of Officer Title: 1 This must be at least 100% of the Grant Date Fair Market Value (as defined in the Plan) of the Common Stock on the date of grant. 2 The Final Exercise Date must be no more than 10 years from the date of grant. The correct approach to calculate the final exercise date is to use the day immediately prior to the date ten years out from the date of the stock option award grant. Akebia Therapeutics, Inc. Officer Inducement Award Non-Statutory Stock Option Agreement Incorporated Terms and Conditions 1. Grant of Option. This agreement evidences the grant by the Company, on the grant date (the “Grant Date”) set forth in the Notice of Grant that forms part of this agreement (the “Notice of Grant”), to the Participant of an option to purchase, in whole or in part, on the terms provided herein, the number of Shares set forth in the Notice of Grant of common stock, $0.00001 par value per share, of the Company (“Common Stock”), at the exercise price per Share set forth in the Notice of Grant. Unless earlier terminated, this option shall expire at 5:00 p.m., Eastern time, on the Final Exercise Date set forth in the Notice of Grant (the “Final Exercise Date”). The option evidenced by this agreement is being granted to the Participant pursuant to the inducement grant exception under Nasdaq Stock Market Rule 5635(c)(4) as an inducement that is material to the Participant’s employment with the Company, and not pursuant to the Company’s 2023 Stock Incentive Plan (the “Plan”), or any equity incentive plan of the Company. Notwithstanding the foregoing, the option shall be subject to, and governed by, and shall be construed and administered in accordance with, the terms of the Plan, which terms and conditions are incorporated herein by reference, but any shares of Common Stock issued hereunder shall not reduce the number of shares of Common Stock available under the Plan. The option evidenced by this agreement is not intended to be an incentive stock option as defined in Section 422 of the Internal Revenue Code of 1986, as amended, and any regulations promulgated thereunder (the “Code”). Except as otherwise indicated by the context, the term “Participant”, as used in this option, shall be deemed to include any person who acquires the right to exercise this option validly under its terms. 2. Vesting Schedule. (a) General. Subject to this Agreement and the terms of any Executive Severance Agreement or other written agreement between the Participant and the Company, this option will become exercisable (“vest”) in accordance with the vesting schedule set forth in the Notice of Grant. (b) Change in Control. (1) Treatment of Option in a Change in Control. The option, to the extent outstanding immediately prior to a Change in Control but not then vested in full, shall automatically become fully vested and exercisable upon such Change in Control. (2) Definitions. (i) “Change in Control” means the occurrence of any of the following events other than in connection with the consummation of an initial public offering of the Company’s securities: (A) any “person” (as such term is used in Sections 13(d) and 14(d) of the Securities Exchange Act of 1934, as amended) who is not a shareholder of the Company as of the date of this Agreement or an affiliate thereof is or becomes the “beneficial owner” (as defined in Rule 13d-3 under said Act), directly or indirectly, of securities of the Company representing 50% or more of the total voting power represented by the Company’s then outstanding voting securities; (B) a change in the composition of the Board occurring within a two-year period, as a result of which less than a majority of the directors are Incumbent Directors; (C) the date of the consummation of a merger, scheme of arrangement or consolidation of the Company with any other corporation that has been approved by the stockholders of the Company, other than a merger, scheme of arrangement or consolidation which would result in the voting securities of the Company outstanding immediately prior thereto continuing to represent (either by remaining outstanding or by being converted into voting securities of the surviving entity) more than fifty percent (50%) of the total voting power represented by the voting securities of the Company or such surviving entity outstanding immediately after such merger or consolidation; or (D) the date of the consummation of the sale or disposition by the Company of all or substantially all the Company’s assets. Notwithstanding the foregoing, a transaction will not constitute a Change in Control if: (I) its sole purpose is to change the domicile of the Company’s incorporation; or (II) its sole purpose is to create a holding company that will be owned in substantially the same proportions by the persons who held the Company’s securities immediately before such transaction. In all respects, the definition of Change in Control shall be interpreted to comply with Section 409A of the Code, and any successor statute, regulation and guidance thereto. “Incumbent Directors” means directors who either (A) are directors of the Company as of the date (ii) hereof, or (B) are elected, or nominated for election, to the Board with the affirmative votes of at least a majority of the remaining Incumbent Directors at the time of such election or nomination (but will not include an individual whose election or nomination is in connection with an actual or threatened proxy contest relating to the election of directors to the Company). (c) Exercisability. The right of exercise shall be cumulative so that to the extent the option is not exercised in any period to the maximum extent permissible it shall continue to be exercisable, in whole or in part, with respect to all Shares for which it is vested until the earlier of the Final Exercise Date or the termination of this option under Section 3 hereof or the Plan. 3. Exercise of Option. (a) Form of Exercise. Each election to exercise this option shall be in writing, in the form of the Stock Option Exercise Notice attached as Annex A, signed by the Participant, and received by the Company at its principal office, accompanied by this agreement, or in such other form (which may be electronic) as is approved by the Company, together with payment in full in the manner provided in the Plan. The Participant may purchase less than the number of shares covered hereby, provided that no partial exercise of this option may be for any fractional share or for fewer than ten whole shares. (b) Continuous Relationship with the Company Required. Except as otherwise provided in this Section 3, this option may not be exercised unless the Participant, at the time he or she exercises this option, is, and has been at all times since the Grant Date, an employee, officer, or director of, or consultant or advisor to, the Company or any other entity the employees, officers, directors, consultants, or advisors of which are eligible to receive option grants under the Plan (an “Eligible Participant”). (c) Termination of Relationship with the Company. If the Participant ceases to be an Eligible Participant for any reason, then, except as provided in this paragraph or in paragraphs (d) and (e) below, the right to exercise this option shall terminate three months after such cessation (but in no event after the Final Exercise Date), provided that this option shall be exercisable only to the extent that the Participant was entitled to exercise this option on the date of such cessation; and, provided, further, that to the extent the Participant is a party to an Executive Severance Agreement or other written agreement with the Company that provides for the option to remain outstanding and continue to vest during a specified period of time following the Participant’s cessation of status as an Eligible Participant (such period, the “Severance Period”), the option shall remain outstanding and shall continue to vest in accordance with the terms of this Agreement during the Severance Period as if the Participant had remained an Eligible Participant during such period, subject to any conditions on continued vesting as may be contained in such Executive Severance Agreement or other written agreement. Any portion of this option that vests during such Severance Period will remain exercisable until the earlier of (A) the date that is three (3) months following the date that is the last day of such Severance Period, or (B) the Final Exercise Date, and except to the extent previously exercised as permitted by this Section 3(c) will thereupon immediately terminate. For the avoidance of doubt, any portion of the option that fails to vest during the Severance Period will immediately be forfeited on the last day of such period. Notwithstanding the foregoing, if the Participant, prior to the Final Exercise Date, violates the restrictive covenants (including, without limitation, the non-competition, non-solicitation, or confidentiality provisions) of any employment contract, any non-competition, non-solicitation, confidentiality or assignment agreement to which the Participant is a party, or any other agreement between the Participant and the Company, the right to exercise this option shall terminate immediately upon such violation. (d) Exercise Period Upon Death. If the Participant dies prior to the Final Exercise Date while he or she is an Eligible Participant and the Company has not terminated such relationship for “cause” as specified in paragraph (e) below, this option shall be exercisable, within the period of one year following the date of death of the Participant, by an authorized transferee of the Participant, provided that this option shall be exercisable only to the extent that this option was exercisable by the Participant on the date of his or her death, and further provided that this option shall not be exercisable after the Final Exercise Date. (e) Termination for Cause. If, prior to the Final Exercise Date, the Participant’s employment, consulting, director or advisor relationship with the Company is terminated by the Company for Cause (as defined below), the right to exercise this option shall terminate immediately upon the effective date of such termination. If, prior to the Final Exercise Date, the Participant is given notice by the Company of the termination of his or her service by the Company for Cause, and the effective date of such termination is subsequent to the date of delivery of such notice, the right to exercise this option shall be suspended from the time of the delivery of such notice until the earlier of (i) such time as it is determined or otherwise agreed that the Participant’s service shall not be terminated for Cause as provided in such notice or (ii) the effective date of such termination (in which case the right to exercise this option shall, pursuant to the preceding sentence, terminate upon the effective date of such termination). If the Participant is subject to an Executive Severance Agreement or other written agreement with the Company, in any case which agreement contains a definition of “cause” for termination of service, “Cause” shall have the meaning ascribed to such term in such agreement. Otherwise, “Cause” shall mean willful misconduct by the Participant or willful failure by the Participant to perform his or her responsibilities to the Company (including, without limitation, breach by the Participant of any fiduciary duty or of any provision of any employment, consulting, advisory, nondisclosure, non-competition or other similar agreement between the Participant and the Company), as determined by the Company, which determination shall be conclusive. The Participant shall be considered to have been terminated for Cause if the Company determines, within 30 days after the Participant’s resignation, that termination for Cause was warranted. 4. Tax Matters. No Shares will be issued pursuant to the exercise of this option unless and until the Participant pays to the Company, or makes provision satisfactory to the Company for payment of, any federal, state or local withholding taxes required by law to be withheld in respect of this option. 5. Transfer Restrictions; Clawback. (a) This option may not be sold, assigned, transferred, pledged, encumbered or otherwise disposed of by the Participant, either voluntarily or by operation of law, except by will or the laws of descent and distribution, and, during the lifetime of the Participant, this option shall be exercisable only by the Participant. (b) In accepting this option, the Participant agrees to be bound by any clawback policy that the Company has in place or may adopt in the future. 6. Provisions of the Plan. As described in Section 1 of this Agreement, this option is subject to the provisions of the Plan (including the provisions relating to amendments to the Plan), a copy of which is furnished to the Participant with this option. Notwithstanding the foregoing, to the extent the Participant has entered in to an Executive Severance Agreement with the Company, for so long as such Executive Severance Agreement remains in effect, the terms of such Executive Severance Agreement as they relate to the option shall control in the event of a conflict with this Agreement or the Plan. 7. Clawback Policy. In accepting this option, the Participant agrees and acknowledges that the Participant is subject to, and bound by, the terms of any clawback policy that the Company has in place or may adopt in the future, including without limitation Akebia Therapeutic Inc.’s Compensation Recovery Policy adopted in accordance with stock exchange listing requirements. The Participant agrees that in the event it is determined in accordance with any such policy that any compensation or compensatory award granted, earned or paid to the Participant including this option or pursuant to any other compensation arrangement must be forfeited or reimbursed to the Company, the Participant will promptly take any action necessary to effectuate such forfeiture and/or reimbursement as determined by the Company. ANNEX A Akebia Therapeutics, Inc. 245 First Street Cambridge, MA 02142 Dear Sir or Madam: Akebia Therapeutics, Inc. Stock Option Exercise Notice I, (the “Participant”), hereby irrevocably exercise the right to purchase shares of the Common Stock, $0.00001 par value per share (the “Shares”), of Akebia Therapeutics, Inc. (the “Company”) at $ per share pursuant to a stock option agreement with the Company dated (the “Option Agreement”). Enclosed herewith is a payment of $ , the aggregate purchase price for the Shares. The Shares should be registered in my name as it appears below or, if so indicated below, jointly in my name and the name of the person designated below, with right of survivorship. Dated: Signature Print Name: Address: Name and address of persons in whose name the Shares are to be jointly registered (if applicable): Exhibit 10.66 February 8, 2024 BY EMAIL Nicole R. Hadas [Address] Dear Nikki: Upon your execution of this Amendment, the following amendments will be made to your Separation Agreement with Akebia Therapeutics, Inc. (“Akebia”) dated May 5, 2022 (as previously amended, the “Separation Agreement”). Paragraph 1(ii) of the Separation Agreement shall be replaced in its entirety with the following: (ii) Separation Date. Unless your employment is terminated by the Company for Cause or by you for Good Reason (as those terms are deined in your Executive Severance Agreement dated March 3, 2014, the “ESA”), you will remain employed until June 14, 2024 (as may be amended from time to time, the "Separation Date"). The Separation Date may be modiied only upon mutual written agreement between you and the Company. All other terms and conditions of the Separation Agreement shall remain in full force and effect. Very truly yours, AKEBIA THERAPEUTICS, INC. Accepted and Agreed to Under Seal: /s/ John P. Butler______________________ /s/ Nicole R. Hadas__________________ President and Chief Executive Oficer Nicole R. Hadas Dated: February 8, 2024 Exhibit 10.67 February 7, 2024 BY EMAIL Michel Dahan [Address] Dear Michel: Upon your execution of this Amendment, the following amendments will be made to your Separation Agreement with Akebia Therapeutics, Inc. (“Akebia”) dated May 5, 2022 (as previously amended, the “Separation Agreement”). Paragraph 1(ii) of the Separation Agreement shall be replaced in its entirety with the following: (ii) Separation Date. Unless your employment is terminated by the Company for Cause or by you for Good Reason (as those terms are deined in your Executive Severance Agreement dated March 3, 2014, the “ESA”), you will remain employed until June 28, 2024 (as may be amended from time to time, the "Separation Date"). The Separation Date may be modiied only upon mutual agreement between you and the Company. All other terms and conditions of the Separation Agreement shall remain in full force and effect. Very truly yours, AKEBIA THERAPEUTICS, INC. Accepted and Agreed to Under Seal: /s/ John P. Butler_______________________ /s/Michel Dahan______________________ President and Chief Executive Oficer Michel Dahan Dated: February 8, 2024 Certain identified information has been excluded from the exhibit because it is both (i) not material and (ii) is the type of information that the registrant treats as private or confidential. Double asterisks denote omissions. Exhibit 10.93 Execution Version FOURTH AMENDMENT TO LOAN AGREEMENT This FOURTH AMENDMENT TO LOAN AGREEMENT (this “Amendment”), dated and effective as of October 31, 2023 (the “Fourth Amendment Effective Date”), by and among AKEBIA THERAPEUTICS, INC., a Delaware corporation (as “Borrower”), BIOPHARMA CREDIT PLC, a public limited company incorporated under the laws of England and Wales (as the “Collateral Agent”), BPCR LIMITED PARTNERSHIP, a limited partnership established under the laws of England and Wales (as a “Lender”), and BIOPHARMA CREDIT INVESTMENTS V (MASTER) LP, a Cayman Islands exempted limited partnership (as a “Lender”). Recitals A. Collateral Agent, Lenders, Borrower and the other Credit Parties thereunder have entered into that certain Loan Agreement, dated as of November 11, 2019, and amended by that certain First Amendment and Waiver, dated as of February 18, 2022, that certain Second Amendment and Waiver, dated as of July 15, 2022, and that certain Third Amendment to Loan Agreement, dated as of June 30, 2023 (the “Existing Loan Agreement”) and as further amended by this Fourth Amendment, (the “Loan Agreement”). B. In accordance with Section 11.5 of the Existing Loan Agreement, Borrower (acting for its own behalf and on behalf of the other Credit Parties other than Parent), Collateral Agent and Lenders desire to amend the Existing Loan Agreement on the terms and conditions set forth herein. Agreement Now, Therefore, in consideration of the foregoing recitals and other good and valuable consideration, the receipt and adequacy of which is hereby acknowledged, and intending to be legally bound, the parties hereto agree as follows: 1. Definitions. All capitalized terms used in this Amendment (including in the recitals hereof) and not otherwise defined herein shall have the meanings assigned to them in the Loan Agreement. The rules of interpretation set forth in the first paragraph of Section 13.1 of the Loan Agreement shall be applicable to this Amendment and are incorporated herein by this reference. 2. Amendments to Loan Agreement. With effect from and including the Third Amendment Effective Date, the Existing Loan Agreement shall be amended so that it shall be read and construed for all purposes as set forth in Schedule A attached hereto. Agreement and replacing it as follows: a. The Existing Loan Agreement shall be amended by deleting in its entirety Section 2.2(b)(i) of the Existing Loan “(i) Subject to clauses (ii) and (iii) of this clause (b), with respect to each applicable Term Loan, Borrower shall make equal monthly payments of principal of such Term Loan commencing on October 31, 2024, and continuing on a monthly basis on the last date of each month thereafter through the Term Loan Maturity Date; provided, however, that if any such day is not a Business Day, the applicable payment shall be due and payable on the first Business Day immediately preceding such payment date.” Agreement and replacing it as follows: b. The Existing Loan Agreement shall be amended by deleting in its entirety Section 2.2(b)(ii) of the Existing Loan “(ii) Notwithstanding clause (i) of this clause (b), and subject to clause (iii) of this clause (b), with respect to each applicable Term Loan, on the date on which a [**] occurs (a “[**]”), (x) Borrower shall make equal quarterly payments of principal of such Term Loan commencing on the Payment Date immediately following such [**] and continuing on a quarterly basis on each Payment Date thereafter through the Term Loan Maturity Date, provided, however, that if any such day is not a Business Day, the applicable payment shall be due and payable on the first Business Day immediately preceding such Payment Date, and (y)(1) if the [**] occurs on or before July 1, 2024, then Borrower shall repay on July 1, 2024 all unpaid principal that would have been due and payable during the period commencing on the Payment Date immediately following the Fourth Amendment Effective Date and ending on the Payment Date immediately following July 1, 2024 (including all accrued and unpaid interest thereon, if any), as if Borrower had been required hereunder to make equal quarterly payments of principal of such Term Loan commencing on the Payment Date immediately following the Fourth Amendment Effective Date, and (2) if the [**] occurs after July 1, 2024, then Borrower shall promptly, and in any event no later than [**] after such [**], repay all unpaid principal that would have been due and payable during the period commencing on the Payment Date immediately following the Fourth Amendment Effective Date and ending on the Payment Date immediately following such [**] (including all accrued and unpaid interest thereon, if any), as if Borrower had been required hereunder to make equal quarterly payments of principal of such Term Loan commencing on the Payment Date immediately following the Fourth Amendment Effective Date.” Agreement and replacing it as follows: c. The Existing Loan Agreement shall be amended by deleting in its entirety Section 2.2(b)(iii) of the Existing Loan “(iii) Notwithstanding clauses (i) and (ii) of this clause (b), with respect to each Term Loan, as applicable, in connection with a decrease in the Term Loan Maturity Date and scheduled amortization of such Term Loan pursuant to Section 5.7(c), each of the then outstanding Payment Dates on which monthly payments of principal of such Term Loan are payable shall be reduced by the number of days equal to the Amortization Reduction Days in accordance with Section 5.7(c) hereof.” Agreement and replacing it as follows: d. The Existing Loan Agreement shall be amended by deleting in its entirety Section 2.3(a)(iii) of the Existing Loan “(iii) Interest is due and payable quarterly on each Interest Date, as calculated by the Collateral Agent (which calculations shall be deemed correct absent manifest error), commencing on the Interest Date occurring from and after the Fourth Amendment Effective Date; provided, however, that if any such date is not a Business Day, the applicable interest shall be due and payable on the first Business Day immediately preceding such Interest Date.” e. Section 2.3(d) of the Existing Loan Agreement and replacing it as follows: “(d) Payments. Except as otherwise expressly provided herein, all Term Loan payments and any other payments hereunder by (or on behalf of) Borrower shall be made on the date specified herein to such bank account of each applicable Lender as such Lender (or the Collateral Agent) shall have designated in a written notice to Borrower delivered on or before the Tranche A Closing Date (which such notice may be updated by such Lender (or the Collateral Agent) by written notice to Borrower from time to time after the Tranche A Closing Date). Except as otherwise expressly provided herein, interest is payable quarterly on each Interest Date provided, however, that if any such Interest Date is not a Business Day, the applicable interest shall be due and payable on the immediately preceding Business Day. Payments of principal or interest received after [**] (New York City time) on such date (or any Payment Date) are considered received at the opening of business on the next Business Day. All payments to be made by Borrower hereunder or under any other Loan Document, including payments of principal and interest made hereunder and pursuant to any other Loan Document, and all fees, expenses, indemnities and reimbursements, shall be made without set-off, recoupment or counterclaim, in lawful money of the United States and in immediately available funds.” Agreement and replacing it as follows: f. The Existing Loan Agreement shall be amended by deleting in its entirety Section 4.21(c) of the Existing Loan “(c) Except as disclosed on Schedule 4.21(c) of the Disclosure Letter, no Credit Party or any of its Subsidiaries has received any notice, oral or written, from any party to any Manufacturing Agreement containing any indication by or intent or threat of, such party to reduce or cease, in any material respect, the supply of Product or the active pharmaceutical ingredient incorporated therein in the Territory through [**] (or such earlier date in accordance with the terms and conditions of such Manufacturing Agreement, as applicable).” Loan Agreement with a reference to [**]. g. The Existing Loan Agreement shall be amended by replacing the reference to [**] in Section 5.7(c) of the Existing Agreement and replacing it as follows: h. The Existing Loan Agreement shall be amended by deleting in its entirety Section 7.1 of the Existing Loan “7.1 Payment Default. Any Credit Party fails to (a) make any payment of any principal of the Term Loans when and as the same shall become due and payable, whether at the due date thereof (including pursuant to Section 2.2(c)) or at a date fixed for prepayment (whether voluntary or mandatory) thereof or by acceleration thereof or otherwise, or (b) within [**] after the same becomes due, any payment of interest or premium pursuant to Section 2.2, including any applicable Additional Consideration, Makewhole Amount or Prepayment Premium, or any other Obligations (which [**] cure period shall not apply to any such payments due on the Term Loan Maturity Date, such earlier date pursuant to Section 2.2(b)(y), Section 2.2(c)(ii) or Section 2.2(c)(iii) hereof or the date of acceleration pursuant to Section 8.1(a) hereof). A failure to pay any such interest, premium or Obligations pursuant to the foregoing clause (b) prior to the end of such [**]-period shall not constitute an Event of Default (unless such payment is due on the Term Loan Maturity Date, such earlier date pursuant to Section 2.2(b)(y), Section 2.2(c)(ii) or Section 2.2(c)(iii) hereof or the date of acceleration pursuant to Section 8.1(a) hereof).” Prepayment Premium” and replacing it as follows: i. The Existing Loan Agreement shall be amended by deleting in its entirety clause (c) of the definition of “Tranche A “(c) if such prepayment occurs on or after the 4 -year anniversary of the Tranche A Closing Date but prior to March 31, th 2025, 0.005.” j. The Existing Loan Agreement shall be amended by deleting in its entirety each of the definitions of Interest Date, Payment Date, Term Loan Maturity Date, and Term SOFR, in Section 13.1 of the Existing Loan Agreement and replacing them, in alphabetical order, as follows: ““Interest Date” means the last day of each calendar quarter, commencing with the last day of the calendar quarter during which the Fourth Amendment Effective Date occurs.” st th ““Payment Date” means, with respect to each Term Loan, (a) the Interest Date occurring on or immediately following each of the following dates: (i) the 34 -month anniversary of the Closing Date applicable to such Term Loan, (ii) the 36 -month anniversary of such Closing Date, (iii) the 39 -month anniversary of such Closing Date, (iv) the 42 -month anniversary of such Closing Date, (v) the 45 -month anniversary of such Closing Date, (vi) the 48 -month anniversary of such Closing Date, (vii) the 51 -month anniversary of such Closing Date, (viii) the 54 -month anniversary of such Closing Date, (ix) the 57 -month anniversary of such Closing Date, (x) the 60 -month anniversary of such Closing Date, (xi) the 63 -month anniversary of such Closing Date and (b) the Term Loan Maturity Date, as the context dictates; provided, however, that if any such date is not a Business Day, the applicable payment shall be due and payable on the first Business Day immediately preceding such Payment Date. Notwithstanding the foregoing, “Payment Date” shall be subject to further adjustment in accordance with Section nd rd th th th th th th th 2.2(b)(iii) hereof (in which case, for the avoidance of doubt, the proviso above shall apply to any such adjusted date).” ““Term Loan Maturity Date” means March 31, 2025; provided, however, that the Term Loan Maturity Date shall be decreased by the number of days equal to the Amortization Reduction Days if applicable in accordance with Section 5.7(c) hereof.” ““Term SOFR” means, for any day in any calendar month, the Term SOFR Reference Rate for a tenor of three (3) months on the day (such day, the “Periodic Term SOFR Determination Day”) that is [**] prior to the first day of such Interest Period, as such rate is published by the Term SOFR Administrator; provided, however, that if as of [**] (New York City time) on any Periodic Term SOFR Determination Day the Term SOFR Reference Rate for the applicable tenor has not been published by the Term SOFR Administrator and a Benchmark Replacement Date with respect to the Term SOFR Reference Rate has not occurred, then Term SOFR will be the Term SOFR Reference Rate for such tenor as published by the Term SOFR Administrator on the first preceding U.S. Government Securities Business Day for which such Term SOFR Reference Rate for such tenor was published by the Term SOFR Administrator so long as such first preceding U.S. Government Securities Business Day is not more than [**] prior to such Periodic Term SOFR Determination Day.” Notice” in Section 13.1 of the Existing Loan Agreement. k. The Existing Loan Agreement shall be amended by deleting in its entirety the definition of “Delayed Amortization Section 13.1 of the Existing Loan Agreement: l. The Existing Loan Agreement shall be amended by adding, in alphabetical order, each of the following definitions to ““Fourth Amendment Effective Date” means October 31, 2023.” ““[**]” means [**]” ““[**]” means: [**]” ““[**]” is defined in Section 2.2(b)(ii).” 3. Representations and Warranties; Reaffirmation; Covenant to Deliver. a. Borrower hereby represents and warrants to each Lender and the Collateral Agent as follows: i. Borrower has all requisite power and authority to enter into this Amendment and to carry out the transactions contemplated hereby. ii.This Amendment has been duly executed and delivered by Borrower and is the legally valid and binding obligation of Borrower, enforceable against Borrower in accordance with its respective terms, except as such enforceability may be limited by bankruptcy, insolvency, reorganization, moratorium or similar laws relating to or limiting creditors’ rights generally or by general principles of equity. iii. The execution, delivery and performance by Borrower of this Amendment have been duly authorized and do not: (A) contravene the terms of any of Borrower’s Operating Documents; (B) violate any Requirements of Law, except to the extent that such violation could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Change; (C) conflict with or result in any breach or contravention of, or require any payment to be made under any provision of any security issued by Borrower or of any agreement, instrument or other undertaking to which Borrower is a party or affecting Borrower or the assets or properties of Borrower or any of its Subsidiaries or any order, writ, judgment, injunction, decree, determination or award of any Governmental Authority by which Borrower or any of its assets or properties are subject, except to the extent that such conflict, breach, contravention or payment could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Change; (D) require any Governmental Approval, or other action by, or notice to, or filing with, any Governmental Authority (except such Governmental Approvals or other actions, notices and filings which have been duly obtained, taken, given or made on or before the Fourth Amendment Effective Date and are in full force and effect); (E) require any approval, consent, exemption or authorization, or other action by, or notice to, or filing with, any Person other than a Governmental Authority, including Borrower’s stockholders, members or partners, (except such approvals, consents, exemptions, authorizations, actions, notices and filings which have been or will be duly obtained, taken, given or made on or before the Fourth Amendment Effective Date and are in full force and effect), except for those approvals, consents, exemptions, authorizations or other actions, notices or filings, the failure of which to obtain or make could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Change; or (F) constitute a material breach of or a material default under (which such default has not been cured or waived) or an event of default (or the equivalent thereof, however described) under, or could reasonably be expected to give rise to the cancellation, termination or invalidation of or the acceleration of Borrower’s or any Subsidiary’s obligations under, any Material Contract. iv. Both before and immediately after giving effect to this Amendment, no Event of Default or Default has occurred and is continuing. b. Borrower hereby ratifies, confirms, reaffirms, and acknowledges its obligations under the Loan Documents to which it is a party and agrees that the Loan Documents remain in full force and effect, undiminished by this Amendment, except as expressly provided herein. By executing this Amendment, Borrower acknowledges that it has read, consulted with its attorneys regarding, and understands, this Amendment. c. Borrower hereby agrees to deliver to the Collateral Agent, within here (3) Business Days of the Fourth Amendment Effective Date, originally-signed copies of the Amended and Restated Tranche A Notes, in the form attached as Exhibit B-1 hereto, in replacement of the Tranche A Notes, dated June 30, 2023, issued by Borrower to each Lender (whereupon, the Tranche A Notes, dated June 30, 2023, issued by Borrower to the each Lender shall be treated as cancelled and of no further force or effect and the Lenders shall promptly destroy any and all copies or originals of such Tranche A Notes and confirm the same by email to Borrower), the failure of which such delivery constitutes an Event of Default for all purposes under the Loan Agreement. 4. References to and Effect on Loan Agreement. Except as specifically set forth herein, this Amendment shall not modify or in any way affect any of the terms, conditions, covenants, representations and warranties contained in the Loan Agreement, or any of the rights of the Lenders and the Collateral Agent therein, which shall remain in full force and effect and are hereby ratified and confirmed in all respects. Except as specifically set forth herein, the execution, delivery and effectiveness of this Amendment shall not directly or indirectly (i) constitute a consent or waiver of any past, present or future breaches, violations or defaults of or under any provisions of the Loan Agreement nor constitute a novation of any of the Obligations under the Loan Agreement, (ii) amend, modify or operate as a waiver of any provision of the Loan Agreement or any right, power or remedy of any Lender or the Collateral Agent, or (iii) constitute a course of dealing or other basis for altering the Loan Agreement or any other Loan Document. Except as set forth herein, each of the Lenders and the Collateral Agent reserves all of its rights, powers, and remedies under the Loan Documents and Requirements of Law. On and after the Fourth Amendment Effective Date, all references in the Loan Agreement to “this Agreement,” “hereto,” “hereof,” “hereunder,” or words of like import shall mean the Loan Agreement as amended by this Amendment. 5. Successors and Assigns. This Amendment binds and is for the benefit of Borrower, the other Credit Parties, Lenders and Collateral Agent and each of their respective successors and permitted assigns. 6. Governing Law; Venue; Jury Trial Waiver. This Amendment shall be construed in accordance with and governed by the law of the State of New York. The provisions of Section 10 (Choice of law, Venue and Jury Trial Waiver Etc.) of the Loan Agreement shall apply hereto as if more fully set forth herein as if references therein to “this Agreement” were references to this Amendment. 7. Counterparts. This Amendment may be executed in any number of counterparts and by different parties on separate counterparts, each of which, when executed and delivered, is an original, and all taken together, constitute one Amendment. Delivery of an executed counterpart of a signature page of this Amendment by facsimile or other electronic imaging means (e.g. “pdf” or “tif”) shall be effective as delivery of a manually executed counterpart of this Amendment. The words “execution,” “signed,” “signature,” and words of like import in this Amendment shall be deemed to include electronic signatures or electronic records, each of which shall be of the same legal effect, validity or enforceability as a manually executed signature or the use of a paper-based recordkeeping system, as the case may be, to the extent and as provided for under any applicable law, including the Federal Electronic Signatures in Global and National Commerce Act, the New York State Electronic Signatures and Records Act, or any other similar state laws based on the Uniform Electronic Transactions Act. 8. Conflict. In the event of any conflict between any term, covenant, or condition of this Amendment and any term, covenant or condition of the Loan Agreement, the provisions of the Loan Agreement shall control and govern. [Remainder of Page Intentionally Left Blank] IN WITNESS WHEREOF, the undersigned hereto have caused this Amendment to be executed as of the date first written above by each of their officers thereunto duly authorized. BORROWER (on its own behalf and on behalf of each other Credit Party): AKEBIA THERAPEUTICS, INC., a Delaware corporation By:/s/ Ellen Snow Name: Ellen Snow Title: Chief Financial Officer [Signature page to Fourth Amendment] BIOPHARMA CREDIT PLC, as Collateral Agent By: Pharmakon Advisors, LP, its Investment Manager By: Pharmakon Management I, LLC, its General Partner By__/s/ Pedro Gonzalez de Cosio______________ Name: Pedro Gonzalez de Cosio Title: Managing Member BPCR LIMITED PARTNERSHIP, as a Lender By: Pharmakon Advisors, LP, its Investment Manager By: Pharmakon Management I, LLC, its General Partner By__/s/ Pedro Gonzalez de Cosio______________ Name: Pedro Gonzalez de Cosio Title: Managing Member BIOPHARMA CREDIT INVESTMENTS V (MASTER) LP, as Lender By: BioPharma Credit Investments V GP LLC, its general partner By: Pharmakon Advisors, LP, its Investment Manager By__/s/ Pedro Gonzalez de Cosio______________ Name: Pedro Gonzalez de Cosio Title: CEO and Managing Member Certain identified information has been excluded from the exhibit because it is both (i) not material and (ii) is the type of information that the registrant treats as private or confidential. Double asterisks denote omissions. Exhibit 10.102 Execution Version AGREEMENT FOR THE PROVISION OF A LOAN FACILITY Dated January 29, 2024 (the “Closing Date”) Between KREOS CAPITAL VII (UK) LIMITED, and AKEBIA THERAPEUTICS, INC. Page 3 17 18 20 20 22 23 27 38 41 44 44 44 45 46 TABLE OF CONTENTS 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. DEFINITIONS INTERPRETATION LOAN FACILITY TERM REPAYMENT AND PREPAYMENT INTEREST REPRESENTATIONS AND WARRANTIES UNDERTAKINGS EVENTS OF DEFAULT FEES, EXPENSES AND TAXES INDEMNITIES [RESERVED] RELEASE OF SECURITY NOTICES GENERAL SCHEDULE A – FORM OF DRAWDOWN NOTICE SCHEDULE B – FORM OF COMPLIANCE CERTIFICATE SCHEDULE C – POST-CLOSING OBLIGATIONS SCHEDULE D – EXISTING FINANCIAL INDEBTEDNESS SCHEDULE E – EXISTING INVESTMENTS SCHEDULE F – EXISTING SECURITY INTERESTS SCHEDULE G – PERMITTED LICENSES SCHEDULE H – DISCLOSURES TO REPRESENTATIONS AND WARRANTIES EXHIBIT A-1 – FORM OF U.S. TAX COMPLIANCE CERTIFICATE EXHIBIT A-2 – FORM OF U.S. TAX COMPLIANCE CERTIFICATE EXHIBIT A-3 – FORM OF U.S. TAX COMPLIANCE CERTIFICATE EXHIBIT A-4 – FORM OF U.S. TAX COMPLIANCE CERTIFICATE i AGREEMENT FOR THE PROVISION OF A LOAN FACILITY Dated __________________ 2024 (the “Closing Date”) Between KREOS CAPITAL VII (UK) LIMITED, a company incorporated in England and Wales under registration number 13611522 whose registered office is at 25-28 Old Burlington Street, London W1S 3AN, as a Lender (the "Lender Representative", which expression shall include its permitted successors and permitted assigns); and AKEBIA THERAPEUTICS, INC., a Delaware corporation (the "Borrower Representative") and any wholly-owned domestic subsidiary of the Borrower Representative (if any) that may from time to time after the date hereof be joined to this Loan Agreement as an additional Borrower pursuant to a joinder (in form and substance reasonably acceptable to the Lender) executed by such additional Borrower and the Lender Representative (the Borrower Representative and each such wholly-owned domestic subsidiary of the Borrower Representative (if any) who so becomes a Borrower hereunder, each individually a “Borrower” and together the “Borrowers”). WHEREAS: 1. The Borrowers wish to borrow up to the Total Loan Facility (as defined below) and the Lender wishes to make the Total Loan Facility available to the Borrowers subject to the terms of this agreement (this "Loan Agreement"); and 2. Each Borrower hereby confirms that on or about the date of this Loan Agreement it (and it shall procure each relevant Subsidiary Guarantor) shall enter into the Initial Security and Guarantee Documents as security for the obligations of the Loan Parties under the Loan Documents. LOAN FACILITY TERMS: Total Loan Facility Expiry Date Advance Payments Interest and Amortization $55,000,000, to be drawn down as follows: Tranche A: $37,000,000, to be drawn in full on the Closing Date Tranche B: $8,000,000 Tranche C: $10,000,000 In relation to the ability to drawdown a Tranche, the Expiry Date with respect to each Tranche is as follows: Tranche A: the Closing Date Tranche B: December 31, 2024 Tranche C: December 31, 2024 In relation to each Tranche, the repayment amount (comprising principal and interest) for such Tranche for the last Month of the Loan Term for such Tranche as set out in the Repayment Schedule (assuming the Vadadustat FDA Approval has been obtained and 24-month amortization). During the Interest Only Period, the Borrowers shall make payments of interest on each applicable Tranche in accordance with Clause 5.1.1 and Clause 6.1. After the Interest Only Period, the Borrowers shall make payments of principal and interest on each applicable Tranche in accordance with Clause 5.1.1. Notwithstanding the foregoing: A. if the Vadadustat FDA Approval is not received on or prior to June 30, 2024, the Interest Only Period will terminate on October 1, 2024, followed by 7 equal payments of principal and interest, which shall continue to accrue and become due and payable in accordance with the terms hereof (for the avoidance of doubt, the first 6 such payments shall be due on October 1, 2024 and each Monthly Payment Date thereafter through and including March 1, 2025, with the seventh and final such payment due on the Maturity Date); and B. if a Vadadustat Withdrawal Event occurs, the Borrowers shall repay, in advance, all principal and interest in respect of each Tranche in equal payments on (1) each of the twelve immediately succeeding Monthly Repayment Dates or (2) if less than twelve Monthly Repayment Dates remain before the Maturity Date, each such Monthly Repayment Date remaining before the Maturity Date, in each case commencing with the first Monthly Repayment Date to occur after the occurrence of such Vadadustat Withdrawal Event (as an illustrative example, if, after the occurrence of such Vadadustat Withdrawal Event, five Monthly Repayment Dates remain before the Maturity Date, the Borrowers shall repay all outstanding principal and interest in five equal payments: one on each such Monthly Repayment Date). 1 Loan Term Transaction Fee End of Loan Payments Minimum Drawdown Amount 1. DEFINITIONS The Total Loan Facility will mature on March 31, 2025; provided, that if the Borrower Representative receives the Vadadustat FDA Approval on or prior to June 30, 2024, the maturity date will be automatically extended to January 29, 2028 (such applicable date, the “Maturity Date”). Tranche A: [**]% of the aggregate committed amount in respect of Tranche A, payable upon the Closing Date. Tranche B: [**]% of the aggregate committed amount in respect of Tranche B, which shall be payable as follows: (a) on the Closing Date, [**]% of the aggregate committed amount in respect of Tranche B, and (b) [**]% of the aggregate committed amount in respect of Tranche B as of the Closing Date shall be payable on the earliest to occur of (i) the date Tranche B is funded, (ii) the date that the commitments in respect of Tranche B are terminated or cancelled and (iii) the date on which the availability period of Tranche B terminates. Tranche C: [**]% of the aggregate committed amount in respect of Tranche C, which shall be payable as follows: (a) on the Closing Date, [**]% of the aggregate committed amount in respect of Tranche C, and (b) [**]% of the aggregate committed amount in respect of Tranche C as of the Closing Date shall be payable on the earliest to occur of (i) the date Tranche C is funded, (ii) the date that the commitments in respect of Tranche C are terminated or cancelled and (iii) the date on which the availability period of Tranche C terminates. In relation to each Tranche, [**]% of the amount funded pursuant to the relevant Tranche, which amount shall be due and payable in accordance with Clause 10.2. $[**] In this Loan Agreement, including the recitals set out above, unless otherwise defined: 1.1 “Acquisition Consideration Condition” means, as of any date of determination, a condition that is satisfied if (a) Cash Flow as of the last day of the month most recently ended is greater than $0 and (b) the Borrower Representative has delivered to the Lender Representative Pro Forma Projections demonstrating aggregate Cash Flow greater than $0 for the last three months of the period covered by such Pro Forma Projections (taken as a whole); 1.2 "Adjusted Term SOFR" means, for purposes of any calculation, the rate per annum equal to the greater of (a) 4.25% per annum and (b) Term SOFR for such calculation; 1.3 "Advance Payment" has the meaning given in Clause 5.3 and is in the amount set forth in the Loan Facility Terms; 1.4 "Affiliate" means, in relation to any person, (i) any other person directly or indirectly owned by or controlled by such person, including subsidiaries, or (ii) any person that directly or indirectly owns or controls such person, including holding companies (it being understood that in no event shall the Lender be deemed to be an Affiliate of Borrower or any of its Subsidiaries); 1.5 "Affected Financial Institution" means (a) any EEA Financial Institution or (b) any UK Financial Institution. 1.6 "Anti-Corruption Laws" means the UK Bribery Act 2010, the US Foreign Corrupt Practices Act 1977 and/or any other applicable anti-bribery or anti-corruption law, in each case as amended, re-enacted, consolidated or replaced; 1.7 "Anti-Money Laundering Laws" means any and all laws applicable to any Borrower or any other Group Company from time to time concerning or relating to terrorism financing or money laundering; 1.8 "Applicable Interest Rate" has the meaning given in Clause 6.2; 2 1.9 "Asset Sale" means any sale, conveyance, transfer or other disposition of assets or properties of a Group Company pursuant to clause 8.2.1(xv); 1.10 "Assignee" has the meaning given in Clause 15.5; 1.11 "Available Tenor" means, as of any date of determination and with respect to the then-current Benchmark, as applicable, (a) if such Benchmark is a term rate, any tenor for such Benchmark (or component thereof) that is or may be used for determining the length of an interest period pursuant to this Loan Agreement or (b) otherwise, any payment period for interest calculated with reference to such Benchmark (or component thereof) that is or may be used for determining any frequency of making payments of interest calculated with reference to such Benchmark pursuant to this Loan Agreement, in each case, as of such date; 1.12 “Bail-In Action” means the exercise of any Write-Down and Conversion Powers by the applicable Resolution Authority in respect of any liability of an Affected Financial Institution; 1.13 “Bail-In Legislation” means, (a) with respect to any EEA Member Country implementing Article 55 of Directive 2014/59/EU of the European Parliament and of the Council of the European Union, the implementing law, rule, regulation or requirement for such EEA Member Country from time to time which is described in the EU Bail-In Legislation Schedule, and (b) with respect to the United Kingdom, Part I of the United Kingdom Banking Act 2009 (as amended from time to time) and any other law, regulation or rule applicable in the United Kingdom relating to the resolution of unsound or failing banks, investment firms or other financial institutions or their affiliates (other than through liquidation, administration or other insolvency proceedings); 1.14 "Benchmark" means, initially, the Term SOFR Reference Rate; provided that if a Benchmark Transition Event has occurred with respect to the Term SOFR Reference Rate or the then-current Benchmark, then "Benchmark" shall mean the applicable Benchmark Replacement to the extent that such Benchmark Replacement has replaced such prior benchmark rate pursuant to Clause 6.4; 1.15 "Benchmark Floor" shall mean the benchmark rate floor provided in this Loan Agreement (as of the execution of this Loan Agreement, the modification, amendment or renewal of this Loan Agreement or otherwise) with respect to Term SOFR. As of the Closing Date the Benchmark Floor is equal to 4.25% per annum; 1.16 "Benchmark Replacement" means the sum of: (a) the alternate benchmark rate that has been selected by the Lender Representative and the Borrowers giving due consideration to (i) any selection or recommendation of a replacement rate or the mechanism for determining such a rate by the Relevant Governmental Body or (ii) any evolving or then-prevailing market convention for determining a rate of interest as a replacement to the then-current Benchmark for Dollar-denominated syndicated credit facilities and (b) the Benchmark Replacement Adjustment; provided that, if the Benchmark Replacement as so determined would be less than the Benchmark Floor on any date of determination, the Benchmark Replacement will be deemed to be the Benchmark Floor for the purposes of this Loan Agreement and the other Loan Documents; 1.17 "Benchmark Replacement Adjustment" means, with respect to any replacement of the then-current Benchmark with an Unadjusted Benchmark Replacement for each applicable Interest Period, the spread adjustment, or method for calculating or determining such spread adjustment (which may be a positive or a negative value or zero), that has been selected by the Lender Representative and the Borrowers giving due consideration to (a) any selection or recommendation of a spread adjustment, or method for calculating or determining such spread adjustment, for the replacement of such Benchmark with the applicable Unadjusted Benchmark Replacement by the Relevant Governmental Body or (b) any evolving or then-prevailing market convention for determining a spread adjustment, or method for calculating or determining such spread adjustment, for the replacement of such Benchmark with the applicable Unadjusted Benchmark Replacement for U.S. dollar- denominated syndicated credit facilities at such time; 1.18 "Benchmark Replacement Conforming Changes" means, with respect to any Benchmark Replacement, any technical, administrative or operational changes (including changes to the definition of "Business Day", timing and frequency of determining rates and making payments of interest and other administrative matters) that the Lender Representative (in consultation with the Borrower) decides may be appropriate to reflect the adoption and implementation of such Benchmark Replacement and to permit the administration thereof by the Lender Representative in a manner substantially consistent with market practice (or, if the Lender Representative (in consultation with the Borrower) decides that adoption of any portion of such market practice is not administratively feasible or if the Lender Representative (in consultation with the Borrower) determines that no market practice for the administration of the Benchmark Replacement exists, in such other manner of administration as the Lender Representative reasonably determines is necessary in connection with the administration of this Loan Agreement and the other Loan Documents); 1.19 "Benchmark Replacement Date" means the earlier to occur of the following events with respect to the then-current Benchmark: (a) in the case of clause (a) or (b) of the definition of "Benchmark Transition Event", the later of (i) the date of the public statement or publication of information referenced therein and (ii) the date on which the administrator of such Benchmark permanently or indefinitely ceases to provide such Benchmark; or (b) in the case of clause (c) of the definition of "Benchmark Transition Event", the date of the public statement or publication of information referenced therein; 1.20 "Benchmark Transition Event" means the occurrence of one or more of the following events with respect to then-current Benchmark: (a) a public statement or publication of information by or on behalf of the administrator of such Benchmark (or the published component used in the calculation thereof) announcing that such administrator has ceased or will cease to provide all Available Tenors of such Benchmark (or such component thereof), permanently or indefinitely; provided that, 3 at the time of such statement or publication, there is no successor administrator that will continue to provide any Available Tenor of such Benchmark (or such component thereof); (b) a public statement or publication of information by the regulatory supervisor for the administrator of such Benchmark (or the published component used in the calculation thereof), the Term SOFR Administrator, the U.S. Federal Reserve System, an insolvency official with jurisdiction over the administrator of such Benchmark, a resolution authority with jurisdiction over the administrator of such Benchmark (or such component) or a court or an entity with similar insolvency or resolution authority over the administrator of such Benchmark (or such component), which states that the administrator of such Benchmark (or such component) has ceased or will cease to provide all Available Tenors of such Benchmark (or such component thereof) permanently or indefinitely; provided that, at the time of such statement or publication, there is no successor administrator that will continue to provide any Available Tenor of such Benchmark (or such component thereof); or (c) a public statement or publication of information by or on behalf of the regulatory supervisor for the administrator of such Benchmark (or the published component used in the calculation thereof or the regulatory supervisor for the administrator of such Benchmark or such component thereof) announcing that all Available Tenors of such Benchmark are no longer representative; 1.21 "Benchmark Transition Start Date" means in the case of a Benchmark Transition Event, the earlier of (a) the applicable Benchmark Replacement Date and (b) if such Benchmark Transition Event is a public statement or publication of information of a prospective event, the [**] prior to the expected date of such event as of such public statement or publication of information (or if the expected date of such prospective event is fewer than [**] after such statement or publication, the date of such statement or publication); 1.22 "Benchmark Unavailability Period" means, if a Benchmark Transition Event and its related Benchmark Replacement Date have occurred with respect to the then- current Benchmark and solely to the extent that such Benchmark has not been replaced with a Benchmark Replacement in accordance with Clause 6.4, the period (a) beginning at the time that such Benchmark Replacement Date has occurred and (b) ending at the time that a Benchmark Replacement has replaced the then-current Benchmark for all purposes hereunder pursuant to Clause 6.4; 1.23 "Board" means the Board of Governors of the Federal Reserve System of the United States of America and any successor thereto; 1.24 "Business Day" means (a) any day on which banks are generally open for business in London and New York other than a Saturday or Sunday and (b) with respect to the calculation of Term SOFR, any day other than a day on which the Securities Industry and Financial Market Association recommends that the fixed income departments of its members be closed for the entire day for purposes of trading in United States government securities; 1.25 “Cash Equivalents” means: (a) direct obligations of, or obligations the principal of and interest on which are unconditionally guaranteed by, the United States of America (or by any agency thereof to the extent such obligations are backed by the full faith and credit of the United States of America), in each case maturing within two years from the date of issuance thereof; (b) investments in commercial paper maturing within 2 years from the date of issuance thereof and having, at such date of acquisition, the highest credit rating obtainable from S&P or from Moody’s; (c) investments in certificates of deposit, banker’s acceptances and time deposits maturing within two years from the date of acquisition thereof issued or offered by or guaranteed by or placed with, and money market deposit accounts issued or offered by, any domestic office of any commercial bank organized under the laws of the United States of America or any State thereof that has a combined capital and surplus and undivided profits of not less than $100,000,000 and that issues (or the parent of which issues) commercial paper rated at least “Prime 1” (or the then equivalent grade) by Moody’s or “A1” (or the then equivalent grade) by S&P; (d) fully collateralized repurchase agreements with a term of not more than 30 days for securities described in clause (a) above and entered into with a financial institution satisfying the criteria of clause (c) above; (e) corporate obligations, including intermediate-term notes rated “A2/A” or higher by Moody’s and Standard and Poor’s and commercial paper rated “P1” or higher by Moody’s and “A1” or higher by Standard and Poor’s; (f) bank sweep or deposit programs and interest bearing programs from banks with a minimum $10,000,000,000 market capitalization and whose debt ratings satisfying the criteria of clause (c) or (e) above; (g) U.S. and dollar-denominated international corporate debt as long as the issuer meets credit rating and marketability guidelines; and (h) investments in “money market funds” within the meaning of Rule 2a-7 of the Investment Company Act of 1940, as amended, substantially all of whose assets are invested in investments of the type described in clauses (a) through (g) above; 1.26 “Cash Flow” means the cash flow of the Borrower Representative and its consolidated Subsidiaries, determined in accordance with GAAP, excluding non-recurring or extraordinary events and non-cash items. 4 1.27 “Cash Interest Condition” means, on any date of determination, a condition that is satisfied if Cash Flow as of the last day of each of the immediately preceding six months was greater than $0 for each such month; 1.28 "Casualty Event" means any casualty or other insured damage to, or any taking under power of eminent domain or by condemnation or similar proceeding of, any property or asset of the Borrowers or any other Group Company; 1.29 "Change of Control" has the meaning as given in Clause 9.1.9; 1.30 "Code" means the Internal Revenue Code of 1986, as amended from time to time; 1.31 "Collateral" means all the "Collateral" as defined in any of the Security Documents and shall also include the Mortgaged Properties; 1.32 "Compliance Certificate" has the meaning given to it in Clause 8.1.9(iv); 1.33 "Confidential Information" means all information relating to any Group Company, the Loan Documents or a Loan of which the Lender becomes aware or which the Lender receives in its capacity as the Lender from any member of the Group or any of its advisers in whatever form but excludes information that: (i) is or becomes public information other than as a direct or indirect result of any breach by the Lender of this Loan Agreement; (ii) is identified in writing at the time of delivery as non-confidential by any member of the Group or any of its advisers; or (iii) is known by the Lender before the date the information is disclosed to it or is lawfully obtained by the Lender after that date, from a source which is, as far as the Lender is aware, unconnected with the Group and which, in either case, as far as the Lender is aware, has not been obtained in breach of, and is not otherwise subject to, any obligation of confidentiality; 1.34 “Connection Income Taxes” means Other Connection Taxes that are imposed on or measured by net income (however denominated) or that are franchise Taxes or branch profits Taxes. 1.35 "Contractual Currency" has the meaning given to it in Clause 5.2; 1.36 "Control" shall mean the possession, directly or indirectly, of the power to direct or cause the direction of the management or policies of a Person, whether through the ownership of voting securities, by contract or otherwise, and the terms “Controlling” and “Controlled” shall have meanings correlative thereto. 1.37 "Controlled Foreign Subsidiary" means any Subsidiary of the Borrower Representative or of any Subsidiary Guarantor that is a “ controlled foreign corporation” within the meaning of Section 957 of the Code as in effect on the date hereof. 1.38 "Default" means an Event of Default or any event or circumstance specified in Clause 9.1 which would (with the expiry of a grace period, the giving of notice, the making of any determination under the Loan Documents or any combination of the foregoing) be an Event of Default; 1.39 "Designated Jurisdiction" means, at any time, any country, region or territory which is itself the subject or target of comprehensive Sanctions (which shall include, as at the date of this Loan Agreement Cuba, Iran, North Korea, Syria, the Crimea region of Ukraine, the so-called Donetsk People’s Republic and Luhansk People’s Republic); 1.40 "Domestic Subsidiary" means any Subsidiary of the Borrower Representative that is organized under the laws of the United States, any state thereof or the District of Columbia. 1.41 "Drawdown" means the drawdown of a Tranche; 1.42 "Drawdown Account" means the deposit account ending [**] maintained with [**]; 1.43 "Drawdown Date" means, subject to Clauses 3.2.1 and 3.2.2, the date specified by the Borrower Representative in the relevant Drawdown Notice or as may be otherwise agreed in writing by the Borrower Representative and the Lender Representative; 1.44 "Drawdown Notice" means a drawdown notice served in accordance with Clause 3.2 in substantially the form attached to this Loan Agreement as Schedule A (as may be amended with the prior written consent of the Lender Representative); 1.45 “EEA Financial Institution” means (a) any credit institution or investment firm established in any EEA Member Country which is subject to the supervision of an EEA Resolution Authority, (b) any entity established in an EEA Member Country which is a parent of an institution described in clause (a) of this definition, or (c) any financial institution established in an EEA Member Country which is a subsidiary of an institution described in clause (a) or (b) of this definition and is subject to consolidated supervision with its parent. 1.46 “EEA Member Country” shall mean any of the member states of the European Union, Iceland, Liechtenstein and Norway. 1.47 “EEA Resolution Authority” shall mean any public administrative authority or any person entrusted with public administrative authority of any EEA Member Country (including any delegee) having responsibility for the resolution of any EEA Financial Institution. 5 1.48 "End of Loan Payment" means the End of Loan Payment in the amount set forth in the Loan Facility Terms; 1.49 "Environmental Law" means any applicable law or regulation which relates to pollution, protection of the environment, the conditions of the workplace (to the extent relating to exposure to Hazardous Materials) or the generation, handling, storage, use, release or spillage of Hazardous Materials; 1.50 "ERISA" means the Employee Retirement Income Security Act of 1974, as the same may be amended from time to time, and the rules and regulations promulgated thereunder; 1.51 "ERISA Affiliate" shall mean any trade or business (whether or not incorporated) that, together with the Borrower Representative, is treated as a single employer under Section 414(b) or (c) of the Code, or solely for purposes of Section 302 of ERISA and Section 412 of the Code, is treated as a single employer under Sections 414(m) or (o) of the Code; 1.52 "ERISA Event" shall mean (a) any “reportable event”, as defined in Section 4043 of ERISA or the regulations issued thereunder, with respect to a Plan (other than an event for which the 30-day notice period is waived), (b) the failure to satisfy the minimum funding standards (within the meaning of Section 412 of the Code or Section 302 of ERISA), whether or not waived or a determination that any Plan or Multiemployer Plan is, or would reasonably be expected to be, an at-risk plan or a plan in endangered or critical status within the meaning of Section 430, 431 or 432 of the Code or Section 303, 304 or 305 of ERISA, (c) the filing pursuant to Section 412(c) of the Code or Section 302(c) of ERISA of an application for a waiver of the minimum funding standard with respect to any Plan, (d) the incurrence by the Borrower Representative or any of its ERISA Affiliates of any liability under Title IV of ERISA with respect to the termination of any Plan or the withdrawal or partial withdrawal of the Borrower Representative or any of its ERISA Affiliates from any Plan or Multiemployer Plan, (e) the receipt by the Borrower Representative or any of its ERISA Affiliates from the PBGC or a plan administrator of any notice relating to the intention to terminate any Plan or Plans or to appoint a trustee to administer any Plan, (f) the failure by the Borrower Representative or any of its ERISA Affiliates to make a required contribution to any Plan that results in, or would reasonably be expected to result in, the imposition of a lien or other encumbrance or the provision of security under Section 430 of the Code or Section 303 or 4068 of ERISA, (g) the receipt by the Borrower Representative or any of its ERISA Affiliates of any notice, or the receipt by any Multiemployer Plan from the Borrower Representative or any of its ERISA Affiliates of any notice, concerning the imposition of Withdrawal Liability or a determination that a Multiemployer Plan is, or is expected to be, insolvent or in reorganization, within the meaning of Title IV of ERISA, (h) the occurrence of a non-exempt “prohibited transaction” with respect to which the Borrower Representative or any of its Subsidiaries would reasonably be expected to be liable, (i) any other event or condition with respect to a Plan or Multiemployer Plan that could result in liability of the Borrower Representative or any of its Subsidiaries or (j) a Foreign Benefit Event; 1.53 "Event of Default" means any of the events or circumstances described in Clause9.1; 1.54 "Excluded Accounts" means (1) payroll, healthcare and other employee wage and benefit accounts, (2) sales, payroll and similar tax trust accounts, (3) escrow, defeasance and redemption accounts, (4) fiduciary or trust accounts, (5) accounts located outside of the United States, (6) accounts used in connection with Medicaid and Medicare in the ordinary course of business, (7) accounts used to cash collateralize letters of credit or other obligations to the extent permitted under this Loan Agreement, (8) zero balance accounts and (9) accounts with an average daily balance of less than $[**] in the aggregate for all such accounts excluded pursuant to this clause (9); 1.55 "Excluded Subsidiary" means any direct or indirect Subsidiary of the Borrower Representative that is (a) not wholly owned by the Borrower Representative or one or more wholly-owned Subsidiaries of the Borrower Representative, (b) an Immaterial Subsidiary, (c) [reserved], (d) [reserved], (e) an MSC, (f) a Subsidiary that is prohibited by applicable law, rule or regulation from guaranteeing the Loan Facility, or which would require governmental (including regulatory) consent, approval, license or authorization to provide a guarantee unless, such consent, approval, license or authorization has been received, (g) a Subsidiary with respect to which a guarantee by it of the Loan Facility could reasonably be expected to result in material and adverse Tax consequences to the Borrower Representative and its Subsidiaries (taken as a whole) as reasonably determined by the Borrower Representative and the Lender Representative, (h) a Subsidiary that is prohibited from guaranteeing the Loan Facility by any contractual obligation (to the extent such contractual restriction was not entered into in contemplation of the guarantee of the Loan Facility by such Subsidiary), (i) not for profit subsidiary and (j) any other Subsidiary with respect to which, in the reasonable judgment of the Lender Representative and the Borrower, the cost or other consequences of guaranteeing the Loan Facility would be excessive in view of the benefits to be obtained by the Lender therefrom; provided that no Excluded Subsidiary may own any equity interests issued by any Loan Party; 1.56 "Excluded Taxes" means any of the following Taxes imposed on or with respect to a Lender or required to be withheld or deducted from a payment to a Lender, (a) Taxes imposed on or measured by net income (however denominated), franchise Taxes, and branch profits Taxes, in each case, (i) imposed as a result of such Lender being organized under the laws of, or having its principal office or, in the case of any Lender, its applicable lending office located in, the jurisdiction imposing such Tax (or any political subdivision thereof) or (ii) that are Other Connection Taxes, (b) U.S. federal withholding Taxes imposed on amounts payable to or for the account of such Lender with respect to an applicable interest in a Loan or commitment pursuant to a law in effect on the date on which (i) such Lender acquires such interest in the Loan or commitment or (ii) such Lender changes its lending office, except in each case to the extent that, pursuant to Clause 10.5, amounts with respect to such Taxes were payable either to such Lender's assignor immediately before such Lender became a party hereto or to the Lender immediately before it changed its lending office, (c) Taxes attributable to such Lender’s failure to comply with Clause 10.5.7 and (d) any withholding Taxes imposed under FATCA; 1.57 "Existing Financial Indebtedness" means the Financial Indebtedness listed on Schedule D to this Loan Agreement; 1.58 "Expiry Date" means the relevant date(s) in relation to the ability to draw down a Tranche set forth in the Loan Facility Terms; 6 1.59 "FATCA" means Sections 1471 through 1474 of the Code, as of the date of this Loan Agreement (or any amended or successor version that is substantively comparable and not materially more onerous to comply with), any current or future regulations or official interpretations thereof, any agreements entered into pursuant to Section 1471(b)(1) of the Code and any fiscal or regulatory legislation, rules or practices adopted pursuant to any intergovernmental agreement, treaty or convention among Governmental Authorities and implementing such Sections of the Code; 1.60 “Federal Funds Effective Rate” means, for any day, the weighted average of the rates on overnight Federal funds transactions with members of the Federal Reserve System, as published on the next succeeding Business Day by the Federal Reserve Bank of New York, or, if such rate is not so published for any day that is a Business Day, the average of the quotations for the day for such transactions received by the Lender from three Federal funds brokers of recognized standing selected by it; 1.61 "Financial Indebtedness" means, with respect to any person, without duplication: (i) monies borrowed and debit balances at banks or other financial institutions; (ii) finance or capital leases, other than leases that would have been considered operating leases prior to the adoption of ASC 842; (iii) receivables sold or discounted, (iv) other transactions or arrangements having the commercial effect of borrowing money; (v) the marked to market value of derivative transactions entered into in connection with protection against or benefit from fluctuation in any rate or price; (vi) counter-indemnity obligations in respect of guarantees or other instruments issued by a bank or financial institution; (vii) any acceptance under any acceptance credit or bill discounting facility, (viii) any amount of any liability under an advance or deferred purchase agreement if the primary reason is to raise finance or to finance an acquisition or construction of the asset or service in question or the agreement is in respect of the supply of assets or services, (ix) liabilities under guarantees or indemnities for any of the obligations referred to in items (i) to (viii), and (x) any shares which are redeemable (other than at the option of the issuer) before the expiry of the Loan Term (provided that (A) if such shares are issued to any employee or to any plan for the benefit of employees of the Borrower Representative or its Subsidiaries or by any such plan to such employees, such shares shall not constitute Financial Indebtedness solely because they may be required to be repurchased by the Borrower or its Subsidiaries in order to satisfy applicable statutory or regulatory obligations or as a result of such employee’s termination, death or disability and (B) any class of shares of such person that by its terms authorizes such person to satisfy its obligations thereunder by delivery of shares that are not Financial Indebtedness shall not be deemed to be Financial Indebtedness), in each case of clauses (i) through (x), to the extent that such item would appear as a liability on a balance sheet of such person prepared in accordance with GAAP; Notwithstanding the foregoing, in no event shall the following constitute Financial Indebtedness: (a) prepaid or deferred revenue arising in the ordinary course of business; (b) operating leases; (c) in connection with the purchase by a Group Company of any business, any post-closing payment adjustments to which the seller may become entitled to the extent such payment is determined by a final closing balance sheet or such payment depends on the performance of such business after the closing; provided, however, that, at the time of closing, the amount of any such payment is not determinable and such amount does not appear as a liability on the balance sheet of such Group Member prepared in accordance with GAAP; (d) any obligations in respect of workers’ compensation claims, early retirement or termination obligations, deferred compensatory or employee or director equity plans, pension fund obligations or contributions or similar claims, obligations or contributions or social security or wage taxes; (e) any Warrant Instrument or any Permitted Convertible Debt Call Transaction; or (f) the [**]. 1.62 "Financial Officer" of any person shall mean the chief executive officer, president, chief financial officer, principal accounting officer, treasurer, or similar officer of such person; 1.63 "Financial Statements" means, in relation to the Borrower Representative, the audited consolidated financial statements of the Group for the period ended December 31; 1.64 "First Monthly Repayment Date" shall mean the first Monthly Repayment Date being either (i) the first Drawdown Date (where the Drawdown Date is the first day of a calendar month); or (ii) the first day of the next calendar month following the first Drawdown Date (where the first Drawdown Date is not the first day of a calendar month); 1.65 "Foreign Benefit Event" shall mean, with respect to any Foreign Pension Plan, (a) the existence of unfunded liabilities in excess of the amount permitted under any applicable law, or in excess of the amount that would be permitted absent a waiver from a Governmental Authority, (b) the failure to make the required contributions or payments, under any applicable law, on or before the due date for such contributions or payments, (c) the receipt of a notice by a Governmental Authority relating to the intention to terminate any such Foreign Pension Plan or to appoint a trustee or similar official to administer any such Foreign Pension Plan, or alleging the insolvency of any such Foreign Pension Plan, (d) the complete or partial termination of such Foreign Pension Plan or the complete or partial withdrawal of any participating employer therein, or (e) the occurrence of any transaction that is prohibited under any applicable law; 1.66 "Foreign Pension Plan" means each employee benefit plan (within the meaning of Section 3(3) of ERISA, whether or not subject to ERISA) that is not subject to United States law and is sponsored, maintained, contributed to or required to be contributed to by Borrowers or, to the extent Borrowers would have liability in connection therewith, by an Affiliate; 7 1.67 "Foreign Subsidiary" means any Subsidiary of the Borrower Representative that is not a Domestic Subsidiary; 1.68 "GAAP" means United States generally accepted accounting principles in the United States, as in effect from time to time, or those required by government or regulatory bodies or as may be in general use by significant segments of the accounting profession that are applicable to the circumstances as of the date of determination. All references to "GAAP" used herein shall be to GAAP applied consistently with the principals used in the preparation of the financials delivered by the Borrower Representative to the Lender prior to the date of this Loan Agreement and filed with the SEC; 1.69 "Governmental Authority" means any Federal, state, local or foreign court or governmental agency, authority, instrumentality or regulatory body; 1.70 "Group" means the Borrower Representative and its direct and indirect subsidiaries (if any); 1.71 "Group Company" means any member of the Group; 1.72 "Guarantee and Collateral Agreement" means that certain Guarantee and Collateral Agreement, dated as of the Closing Date, by and among the Loan Parties and the Lender Representative; 1.73 "Hazardous Materials" means all explosive or radioactive substances or wastes and all hazardous or toxic substances, materials or wastes, including petroleum or petroleum distillates, asbestos or asbestos-containing materials, toxic mold, polychlorinated biphenyls, radon gas, infectious or medical wastes and all other toxic substances, materials or wastes of any nature regulated pursuant to any Environmental Law due to their hazardous, toxic, dangerous or deleterious properties or characteristics; 1.74 "[**]" means [**]; 1.75 "Immaterial Subsidiary" means any Subsidiary of the Borrower Representative that (a) does not own or use any Intellectual Property that is material to the business of the Group (taken as a whole), (b) does not have revenues (after eliminating intercompany obligations) in excess of [**]% of the consolidated revenue (calculated in accordance with GAAP) of the Group and (c) does not have assets (after eliminating intercompany obligations) in excess of [**]% of the consolidated total assets (calculated in accordance with GAAP) of the Group; 1.76 "Increased Cost” means (i) a reduction in the rate of return from the Loan Facility or on the Lender’s overall capital, (ii) an additional or increased cost; or (iii) a reduction of any amount due and payable under any Loan Document, which is incurred or suffered by the Lender or any of its Affiliates to the extent that it is attributable to the Lender having entered into any Loan or funding or performing its obligations under any Loan Document (in each case other than as a result of (A) Indemnified Taxes, (B) Taxes described in clauses (b) through (d) of the definition of Excluded Taxes and (C) Connection Income Taxes); 1.77 “Indemnified Taxes” means (a) Taxes, other than Excluded Taxes, imposed on or with respect to any payment made by or on account of any obligation of the Borrowers under any Loan Document and (b) to the extent not otherwise described in clause (a), Other Taxes; 1.78 “Indemnitee” has the meaning given to such term in Clause 11.1; 1.79 "Initial Security and Guarantee Documents" means the following documents: (A) the Guarantee and Collateral Agreement, (B) that certain Patent Security Agreement, dated as of the Closing Date, executed by the Loan Parties and acknowledged and agreed by the Lender Representative and (C) that certain Trademark Security Agreement, dated as of the Closing Date, executed by the Loan Parties and acknowledged and agreed by the Lender Representative; 1.80 "Intellectual Property" means copyrights and related rights (including, without limitation, rights in computer software), patents, supplementary protection certificates, utility models, trade marks, trade names, service marks, domain name registrations, registered and unregistered rights in designs, database rights, semi-conductor topography rights, plant variety rights, rights in undisclosed or confidential information (such as know how, trade secrets and inventions (whether patentable or not)), other similar intellectual property rights (whether registered or not) and applications for such rights as may exist anywhere in the world; 1.81 "Interest Only Period" means the period commencing on the Closing Date and ending on December 31, 2025 (which date may be extended at any time on or prior to December 31, 2025, at the discretion of the Borrower Representative, to December 31, 2026 by written notice from the Borrower to the Lender Representative). Notwithstanding the foregoing, if the Vadadustat FDA Approval is not received on or prior to June 30, 2024, the Interest Only Period will terminate on October 1, 2024; 1.82 "Interim Payment" means, with respect to any Drawdown Date, the payment in respect of the period from such Drawdown Date (where the Drawdown Date is not the first day of a calendar month) to the First Monthly Repayment Date calculated by dividing the first Monthly payment of interest and principal specified in the relevant Repayment Schedule by thirty (30) and multiplying that figure by the number of days between (and including) such Drawdown Date and the First Monthly Repayment Date; 1.83 "Joint Venture" means any joint venture entity, whether a company, unincorporated firm, undertaking, association, joint venture or partnership or any other entity; 8 1.84 “Kreos Affiliate” means any direct Affiliate of Kreos Capital VII (UK) Limited. 1.85 "Lender" means, collectively, Kreos Capital VII (UK) Limited, a company incorporated in England and Wales under registration number 13611522 whose registered office is at 25-28 Old Burlington Street, London W1S 3AN and the other lenders from time to time party hereto; 1.86 "Liquidity" means, as of any date of determination, the sum of the amount of cash and Cash Equivalents of the Loan Parties and each MSC as of such date; provided that Liquidity shall not include (a) any cash or Cash Equivalents that are or should be listed as “restricted” on the consolidated balance sheet of the Borrower Representative as of such date (as determined in accordance with GAAP) or (b) any cash or Cash Equivalents of a Loan Party that are held in any account that is not subject to an account control agreement in favor of the Lender Representative; provided, that at all times prior to the DACA Deadline (as defined on Schedule C), cash in all accounts of the Loan Parties shall be included in “Liquidity” even if an account control agreement is not in place; 1.87 "Loan" means any loan that is made by the Lender to the Borrower pursuant to this Loan Agreement; 1.88 "Loan Documents" means collectively this Loan Agreement, the Warrant Instrument, the Security Documents, and any other agreement designated as a "Loan Document" by the Lender Representative and the Borrower Representative; 1.89 "Loan Facility" means the loan facility set out in this Loan Agreement; 1.90 "Loan Facility Terms" means the certain terms applicable to the Loan Facility as set forth under the heading Loan Facility Terms at the beginning of this Loan Agreement; 1.91 “Loan Parties” means, collectively, the Borrowers and the Subsidiary Guarantors. 1.92 "Loan Term" means with respect to each Tranche, the period set forth in the Loan Facility Terms (or such other period as may be agreed by the Lender and the Borrower Representative in writing); 1.93 "Loan to Own Investor" means: (a) any person or entity whose principal business or material activity is in investment strategies the primary purpose of which is the purchase of distressed loans or other distressed debt securities with the intention of (or view to) owning a controlling stake of the equity or gaining control of a business (directly or indirectly) (a "loan to own strategy") (a "Principal Loan to Own Investor"); (b) any person or entity that is an Affiliate or affiliated fund of a Principal Loan to Own Investor (a "Connected Loan to Own Investor"), unless such Affiliate or affiliated fund is a financial institution which has been established for at least six months and, during that period, regularly engaged in making, purchasing or investing in loans or debt securities; does not have a loan-to-own strategy as one of its investment strategies; is managed and controlled independently from such person; and is administered by persons operating behind appropriate information barriers implemented or maintained as required by law, regulation and internal policy and, in any event, to the extent required to ensure that such administration is independent from such person's interests under the Loan Documents and any information provided under the Loan Documents is not (and is not capable of being) disclosed or otherwise made available to any person operating behind such information barrier; or (c) any Principal Loan to Own Investor which has acquired and holds loans or other debt securities in any business owned (directly or indirectly) by any Connected Loan to Own Investor of such Principal Loan to Own Investor; 1.94 "Margin Stock" has the meaning assigned to such term in Regulation U. 1.95 "Material Adverse Change" means (i) a material adverse effect on the business, operations or financial condition of the Group Companies, taken as a whole; (ii) a material adverse effect on the ability of the Loan Parties (taken as a whole) to be able to pay any portion of its payment obligations under any of the Loan Documents in full or to perform its material obligations under the Loan Documents; or (iii) a material adverse effect on the rights or remedies of the Lender (taken as a whole) under any of the Loan Documents (taken as a whole), unless caused by or related to the action or inaction of the Lender; 1.96 “Material Financial Indebtedness” means Financial Indebtedness of any Group Company with an individual outstanding principal amount in excess of $[**]. 1.97 "Material Properties" means each parcel of real property (other than a parcel with a fair market value of less than $[**]) owned in fee by a Loan Party and located in the United States, but excluding any portion of such real property that contains improvements located in an area identified by the Federal Emergency Management Agency (or any successor agency) as a “special flood hazard area”; 1.98 "Minimum Drawdown Amount" means the minimum amount permitted to be drawn down in each Tranche and is the amount set forth in the Loan Facility Terms; 1.99 "Month" and "Monthly" means, in relation to any period for the accrual of commission or fees, a period starting on one day in a calendar month and ending on the numerically corresponding day in the next calendar month; 9 1.100 "Monthly Repayment Date" means the first day of a calendar month; 1.101 “MSC” means (a) Akebia Therapeutics Securities Corporation, a Massachusetts securities corporation, and (b) any other Subsidiary of the Borrower Representative that is a securities corporation formed under the laws of the commonwealth of Massachusetts; 1.102 "Multiemployer Plan" means a multiemployer plan as defined in Section 4001(a)(3) of ERISA; 1.103 "Net Cash Proceeds" means (A) with respect to any Asset Sale or Casualty Event, the cash proceeds (including cash proceeds subsequently received (as and when received) in respect of noncash consideration initially received), net of (i) selling expenses (including broker’s fees or commissions, legal fees, transfer and similar taxes and the Borrower Representative’s good faith estimate of income taxes paid or payable in connection with such sale), (ii) amounts provided as a reserve, in accordance with GAAP, against any liabilities under any indemnification obligations or purchase price adjustment associated with such Asset Sale (provided that, to the extent and at the time any such amounts are released from such reserve, such amounts shall constitute Net Cash Proceeds) and (iii) the principal amount, premium or penalty, if any, interest and other amounts on any Financial Indebtedness (other than the obligations) which is secured by the asset sold in such Asset Sale or subject to such Casualty Event and which is required to be repaid with such proceeds (other than any such financial Indebtedness assumed by the purchaser of such asset) and (B) with respect to any incurrence of Financial Indebtedness, the cash proceeds received from such incurrence, net of taxes reasonably estimated to be payable and customary investment banking fees, underwriting discounts and commissions, premiums, accrued interest and other customary costs and expenses incurred by the Group in connection with such incurrence or issuance; 1.104 “Other Connection Taxes” means , with respect to any Lender, Taxes imposed as a result of a present or former connection between such Lender and the jurisdiction imposing such Tax (other than connections arising from such Lender having executed, delivered, become a party to, performed its obligations under, received payments under, received or perfected a security interest under, engaged in any other transaction pursuant to or enforced any Loan Document, or sold or assigned an interest in any Loan or Loan Document); 1.105 “Other Taxes” means all present or future stamp, court or documentary, intangible, recording, filing or similar Taxes that arise from any payment made under, from the execution, delivery, performance, enforcement or registration of, from the receipt or perfection of a security interest under, or otherwise with respect to, any Loan Document, except any such Taxes that are Other Connection Taxes imposed with respect to an assignment; 1.106 "Party” means a party to this Loan Agreement; 1.107 "Perfection Exceptions” has the meaning given to such term in the Guarantee and Collateral Agreement; 1.108 "Permitted Acquisition” means any purchase or other acquisition of assets, property, business units or divisions, or equity interests of any person, so long as: (i) no Default or Event of Default shall have occurred and be continuing at the time of, or would immediately result from, the consummation of such acquisition; (ii) such assets, property, business units or divisions, or person whose equity interests are being acquired, are in the biopharma business or reasonably related, ancillary or complementary businesses thereto (including reasonably related, complementary, synergistic or ancillary technologies) in which the Group is then engaged; (iii) the Loan Parties shall, to the extent applicable, comply with the requirements of (x) Clause 8.1.25 of this Loan Agreement with respect to such acquired equity interests and (y) the Guarantee and Collateral Agreement and Clause 8.1.26 of this Loan Agreement with respect to such acquired assets and property, in each case within the timeframes set forth therein; and (iv) any Financial Indebtedness or Security Interests assumed in connection with such acquisition are otherwise permitted hereunder; (v) such acquisition was not preceded by an unsolicited tender offer for such equity interests by, or proxy contest initiated by, the Borrower Representative or any of its Affiliates; (vi) the Borrowers would be in compliance with either of the financial covenants set forth in Clause 8.3 as of the most recently completed test period for such financial covenant ending prior to such transaction for which financial statements have been delivered pursuant to Clause 8.1.9 after giving pro forma effect to such transaction as if such transaction had occurred as of the first day of such test period; and (vii) the Borrower Representative shall deliver Pro Forma Projections demonstrating that Cash Flow shall not be reduced by more than [**]% in the aggregate for the last three months of the period covered by such Pro Forma Projections (taken as a whole) as compared to the last three months of the standalone (i.e. not pro forma) board-approved projections for such period (taken as a whole); provided, that (A) in the case of any acquisition of assets that will not be owned by a Loan Party, or any equity interests of a person who shall not become a Loan Party, the consideration for all such acquisitions shall not exceed $[**] in any fiscal year (or, at the election of the Borrower Representative, $[**] for any one such acquisition; provided that, if the Borrower makes such election, no Permitted Acquisition of a non-Loan Party or assets to be held by a non-Loan Party shall have occurred prior to such acquisition and no Permitted Acquisition of a non-Loan 10 Party or assets to be held by a non-Loan Party shall be permitted following such acquisition) and (B) for any Permitted Acquisition, the aggregate consideration for such Permitted Acquisition, when taken together with the aggregate consideration of all Permitted Acquisitions consummated after the Closing Date and prior to such time, shall not exceed $[**], unless in the case of this clause (B) the Acquisition Consideration Condition is satisfied at the time of the consummation of such acquisition. 1.109 "Permitted Bond Hedge Transaction" means any call or capped call option (or substantively equivalent derivative transaction) pursuant to which the Borrower Representative acquires an option requiring the counterparty thereto to deliver to the Borrower Representative (i) shares of common stock of the Borrower Representative (or other securities or property following a merger event, reclassification or other change of the common stock of the Borrower representative), (ii) the cash value thereof or (iii) a combination thereof, in each case, from time to time upon exercise of such option entered into by the Borrower Representative in connection with the conversion of any Permitted Convertible Debt; provided that the purchase price for such Permitted Bond Hedge Transaction, less the proceeds received by the Borrower Representative from the sale of any related Permitted Warrant Transaction, does not exceed the net proceeds received by the Borrower Representative from the sale of such Permitted Convertible Debt issued in connection with such Permitted Bond Hedge Transaction; 1.110 "Permitted Convertible Debt" means Financial Indebtedness that is either (i) convertible into a fixed number (subject to customary anti-dilution adjustments, “make- whole” increases and other customary changes thereto) of shares of common stock of the Borrower Representative (and cash in lieu of fractional shares) (or other securities or property following a merger event, reclassification or other change of the common stock of the Borrower Representative) or (ii) sold as units with call options, warrants or rights to purchase (or substantially equivalent derivative transactions) that are exercisable for shares of common stock of the Borrower Representative (and cash in lieu of fractional shares) (or other securities or property following a merger event or other change of the common stock of the Borrower Representative); provided that such Financial Indebtedness shall (a) not require any scheduled amortization or otherwise require payment of principal in cash or, if the Cash Interest Condition is not satisfied as of the date of the issuance of such Financial Indebtedness, cash-pay interest prior to, or have a scheduled maturity date, in each case earlier than [**] after the Maturity Date (it being understood that neither (x) any offer to purchase such Financial Indebtedness as a result of “change of control” or “fundamental change” under and as defined in any indenture governing any Permitted Convertible Debt, in each case at a price no greater than [**]% of the principal amount of such Notes repurchased plus accrued but unpaid interest to, but not including, the date of such repurchase (which for the avoidance of doubt shall not be calculated at a premium) nor (y) any early conversion of such Financial Indebtedness into shares of the Borrower’s common stock in accordance with the terms thereof, in each case, shall violate the restriction of this clause (a)), (b) be unsecured or, if secured, be (i) secured by no collateral other than Collateral securing this Loan Facility and (ii) subordinated to the obligations of the Loan Parties under the Loan Documents pursuant to terms satisfactory to the Lender Representative in its sole discretion; (c) not be guaranteed by any Subsidiary of the Borrowers, and (d) shall be Financial Indebtedness of the Borrowers and not any Subsidiary thereof; provided, further, that if any Borrower or any of its Affiliates seeks to issue any Financial Indebtedness that it intends to constitute Permitted Convertible Debt (the “Proposed Convertible Debt”), the Borrower Representative shall promptly provide written notice to the Lender specifying the material proposed terms of such Proposed Convertible Debt. Notwithstanding anything to the contrary in this Loan Agreement or any other Loan Document, all terms of an accounting or financial nature used herein shall be construed, and all computations of amounts and ratios referred to herein shall be made without giving effect to any treatment of Financial Indebtedness in respect of convertible debt instruments under Accounting Standards Codification 470-20 (or any other Accounting Standards Codification or Financial Accounting Standard having a similar result or effect) to value any such Financial Indebtedness in a reduced or bifurcated manner as described therein, and such Financial Indebtedness shall at all times be valued at the full stated principal amount thereof. For the avoidance of doubt, and without limitation of the foregoing, Permitted Convertible Debt shall at all times be valued at the full stated principal amount thereof and shall not include any reduction or appreciation in value of the shares deliverable upon conversion thereof; 1.111 "Permitted Convertible Debt Call Transaction" means any Permitted Bond Hedge Transaction and any Permitted Warrant Transaction; 1.112 "Permitted Distributions" means: (i) dividends, distributions or other payments by any wholly-owned Subsidiary on its equity interests to, or the redemption, retirement or purchase by any wholly- owned subsidiary of its equity interests from, Borrower or any other wholly-owned Subsidiary; (ii) dividends, distributions or other payments by any non-wholly-owned Subsidiary on its equity interests to, or the redemption, retirement or purchase by any non- wholly-owned Subsidiary of its equity interests from, each owner 11 of such non-wholly-owned Subsidiary’s equity interests based on their relative ownership interests of the relevant class of such equity interests; (iii) any such payments made in order to consummate a Permitted Acquisition or other Permitted Investment by Borrower or any of its Subsidiaries; (iv) the payment of dividends by Borrower solely in non-cash pay and non-redeemable capital stock (including, for the avoidance of doubt, dividends and distributions payable solely in equity interests); (v) cash payments in lieu of the issuance of fractional shares arising (A) out of stock dividends, splits or combinations or (B) in connection with the exercise of warrants, options or other securities convertible into or exchangeable for equity interests; (vi) (i) the receipt or acceptance of the return to Borrower or any of its Subsidiaries of equity interests of Borrower constituting a portion of the purchase price consideration in settlement of indemnification claims, or as a result of a purchase price adjustment (including earn-outs or similar obligations) resulting from Permitted Acquisitions or Permitted Investments and (ii) payments or distributions to equity holders pursuant to appraisal rights required under requirements of law; (vii) the distribution of rights pursuant to any shareholder rights plan or the redemption of such rights for nominal consideration in accordance with the terms of any shareholder rights plan in effect on the Closing Date; (viii) purchases of equity interests of Borrower or its Subsidiaries in connection with the exercise of stock options or warrants or similar rights by way of cashless exercise, or in connection with the satisfaction of withholding tax obligations; (ix) issuance to directors, officers, employees or contractors of Borrower of common stock of Borrower upon the exercise of options or the vesting of restricted stock, restricted stock units, or other rights to acquire common stock of Borrower pursuant to plans or agreements approved by Borrower’s Board of Directors or stockholders; (x) the repurchase, retirement or other acquisition or retirement for value of equity interests of Borrower or any of its Subsidiaries held by any future, present or former employee, consultant, officer or director (or spouse, ex-spouse or estate of any of the foregoing or trust for the benefit of any of the foregoing or any lineal descendants thereof) of Borrower or any of its Subsidiaries pursuant to any management equity plan or stock option plan or any other management or employee benefit plan or agreement, or any stock subscription or shareholder agreement or employment agreement, or as otherwise approved by the board of directors of the relevant Group Company; provided, however, that the aggregate payments made under this clause (x) do not exceed in any calendar year the sum of (i) $[**] plus (ii) [**]; and (xi) the payment of customary fees and reasonable out of pocket expenses to directors of the Group Companies and indemnities provided on behalf of directors and officers of the Group Companies, in each case, in the ordinary course of business and to the extent attributable to the operation of the Group Companies; 1.113 "Permitted Financial Indebtedness" has the meaning given to that term in Clause 8.2.2; 1.114 "Permitted Licenses" means: (i) any license, sublicense and any other agreement that grants any covenant not to sue, option or other preferential right for a license, or other similar right or immunity, under any Intellectual Property, entered into by a Group Company with a person that is not an Affiliate of any Group Company and that involves the granting by such person to such Group Company of any rights to such Intellectual Property for use in connection with the Group’s business, including for research, development, manufacture, commercialization (including commercial sales to end users), marketing, promotion, co-promotion, sales, import, export or distribution of any product or services; (ii) any license, sublicense and any other agreement that grants any covenant not to sue, option or other preferential right for a license, or other similar right or immunity, under any Intellectual Property, entered into by a Loan Party with any other Loan Party that involves the granting by such Loan Party to such other Loan Party of any rights to such Intellectual Property for use in connection with such other Loan Party’s business, including for research, development, manufacture, commercialization (including commercial sales to end users), marketing, promotion, co-promotion, sales, import, export or distribution of any product or services; (iii) any license, sublicense and any other agreement that grants any covenant not to sue, option or other preferential right for a license, or other similar right or immunity, under any Intellectual Property, entered into by a Loan Party with a Person that is not an Affiliate of any Loan Party and that involves the granting by such Loan Party to such Person of any rights to such Intellectual Property on a non-exclusive basis for any purpose; (iv) any license, sublicense and any other agreement that grants any covenant not to sue, option or other preferential right for a license, or other similar right or immunity, under any Intellectual Property other than Intellectual Property relating to vadadustat or Auryxia®, entered into by a Loan Party with a Person that is not an Affiliate of any Loan Party and that involves the granting by such Loan Party to such Person of any rights to such Intellectual Property on an exclusive basis for use in connection with such Person’s business, including research, development, manufacture, commercialization (including commercial sales to end users), marketing, promotion, co-promotion, sales import, export or distribution, of products and services; provided, that any such exclusive license that is 12 exclusive to territory within the United States shall be subject to the consultation (but not the consent) of the Lender Representative; (v) any license, sublicense and any other agreement that grants any covenant not to sue, option or other preferential right for a license, or other similar right or immunity, under any Intellectual Property relating to vadadustat or Auryxia®, entered into by a Loan Party with a Person that is not an Affiliate of any Loan Party and that involves the granting by such Loan Party to such Person of any rights to such Intellectual Property on an exclusive basis in territories where the Loan Parties currently do not have a then existing commercial partner for commercial exploitation of vadadustat or Auryxia®, for use in connection with such Person’s business, including research, development, manufacture, commercialization (including commercial sales to end users), marketing, promotion, co- promotion, sales import, export or distribution, of vadadustat or Auryxia®, as applicable, in such territories; and (vi) any licenses existing on the Closing Date as set forth on Schedule G hereto. 1.115 "Permitted Investments" has the meaning given to that term in Clause 8.2.6; 1.116 "Permitted Security Interests" has the meaning given to such term in Clause 8.2.3; 1.117 "Permitted Transfers" has the meaning given to that term in Clause 8.2.1; 1.118 “Permitted Warrant Transaction” means any call option, warrant or right to purchase (or substantively equivalent derivative transaction) relating to the Borrower Representative’s common stock (or other securities or property following a merger event, reclassification or other change of the common stock of the Borrower Representative) sold by the Borrower Representative substantially concurrently with any purchase by the Borrower Representative of a related Permitted Bond Hedge Transaction. 1.119 "Plan" means an employee pension benefit plan (other than a Multiemployer Plan) which is subject to Title IV of ERISA or subject to the minimum funding standards under Section 302 of ERISA or Section 412 of the Code and that is sponsored, maintained, contributed to or required to be contributed to by Borrowers or any ERISA Affiliate. 1.120 “Pro Forma Projections” means, with respect to any acquisition, pro forma projections for the twelve fiscal month period immediately following such transaction. 1.121 “Register” has the meaning given in Clause 15.5. 1.122 "Regulation T" means Regulation T of the Board as from time to time in effect and all official rulings and interpretations thereunder or thereof; 1.123 "Regulation U" means Regulation U of the Board as from time to time in effect and all official rulings and interpretations thereunder or thereof; 1.124 "Regulation X" means Regulation X of the Board as from time to time in effect and all official rulings and interpretations thereunder or thereof; 1.125 “Related Fund” in relation to a fund or account (the "first fund"), means: (i) a fund or account which is managed or advised by the same investment manager or investment adviser as the first fund; or (ii) if it is managed by a different investment manager or investment adviser, a fund or account whose investment manager or investment adviser is an Affiliate of the investment manager or investment adviser of the first fund; or (iii) that investment manager or investment adviser itself. 1.126 "Relevant Governmental Body" means the Term SOFR Administrator, the Federal Reserve Board or the Federal Reserve Bank of New York, or a committee officially endorsed or convene by the Federal Reserve Board or the Federal Reserve Bank of New York or any successor thereto; 1.127 "Repayment Schedule" has the meaning given in Clause 5.1.1; 1.128 "Representative" means any delegate, agent, manager, administrator, nominee, attorney, trustee or custodian; 1.129 “Resolution Authority” shall mean an EEA Resolution Authority or, with respect to any UK Financial Institution, a UK Resolution Authority. 1.130 "Sanctioned Person" means, at any time, any person, organisation or vessel that is: (i) listed on a Sanctions List; (ii) a government of a Designated Jurisdiction; (iii) an agency or instrumentality of, a government of a Designated Jurisdiction; (iv) located, organised, operating from, incorporated or resident in a Designated Jurisdiction; (v) any person 50% or greater owned or controlled by any such person or persons described in (i) - (iv) above; (vi) otherwise a target of Sanctions; or (vii) acting on behalf of any of the persons listed in paragraphs (i) - (vi) above, for the purposes of evading or avoiding, or having the intended effect of or intending to evade or avoid, or facilitating the evasion or avoidance of, any Sanctions; 13 1.131 "Sanctions" means all economic or financial sanctions, regulations, sectoral sanctions, secondary sanctions, trade embargoes or other restrictive measures enacted, implemented, imposed, administered or enforced from time to time by any Sanctions Authority; 1.132 "Sanctions Authority" means any agency or person which is duly appointed, empowered or authorised to enact, administer, implement and/or enforce Sanctions, including (without limitation): (i) the United Nations Security Council; (ii) the European Union or any of its member states; (iii) the United States government, including the United States Department of the Treasury (including the Office of Foreign Assets Control (“OFAC”)), the United States Department of State and the United States Department of Commerce; and (iv) the United Kingdom government, including HM Treasury, the Foreign, Commonwealth and Development Office and the Department for Business, Energy & Industrial Strategy, including, in each case, any successor, replacement or other governmental institution or agency of the foregoing; 1.133 "Sanctions List" means the “Specially Designated Nationals and Blocked Persons” list administered by OFAC, the EU Consolidated List of Financial Sanctions Targets, the Consolidated List of Financial Sanctions Targets issued by HM Treasury, or any similar list administered or maintained and made public by any Sanctions Authority each as amended, supplemented and/or substituted from time to time; 1.134 "Security Documents" means the Initial Security and Guarantee Documents, and any other applicable document, in the agreed form, evidencing the guarantees provided by and security over assets of any Loan Party, or any document entered into by any Loan Party creating a Security Interest or guarantee in favor of the Lender Representative or otherwise designated in writing as a Security Document; 1.135 "Security Interest" means any mortgage, charge (whether fixed or floating, legal or equitable), pledge, lien, hypothecation, assignment by way of security or otherwise, trust arrangement, title retention or encumbrance or enforceable right of a third party, any other type of security interest or preferential arrangement having a similar effect to any of the foregoing or in the nature of security of any kind whatsoever and in any jurisdiction; provided, that in no event shall an operating lease (as determined prior to the adoption of ASC 842) or an agreement to sell be deemed to constitute a Security Interest. 1.136 "Security Period" means the period commencing on the date of this Loan Agreement and ending on the date all payment obligations (other than contingent indemnification and expense reimbursement obligations for which no claim has been made) have been paid in full and all loan commitments under this Loan Agreement have expired or been terminated; 1.137 "SOFR" means, with respect to any day, the secured overnight financing rate as administered by the SOFR Administrator; 1.138 "SOFR Administrator" shall mean the Federal Reserve Bank of New York (or a successor administrator of the secured overnight financing rate); 1.139 "subsidiary" means, with respect to any Person (herein referred to as the “parent”), any corporation, partnership, limited liability company, association or other business entity (a) of which securities or other ownership interests representing more than 50% of the equity or more than 50% of the ordinary voting power or more than 50% of the general partnership interests are, at the time any determination is being made, owned, Controlled or held, or (b) that is, at the time any determination is made, otherwise Controlled, by the parent or one or more subsidiaries of the parent or by the parent and one or more subsidiaries of the parent; 1.140 "Subsidiary" means any subsidiary of the Borrower Representative; 1.141 "Subsidiary Guarantor" means any subsidiary of the Borrower Representative that is or becomes a party to the Guarantee and Collateral Agreement. As of the Closing Date, the only Subsidiary Guarantor is Keryx Biopharmaceuticals, Inc., a Delaware corporation; 1.142 "Taxes" means all present and future income, value added and other taxes, levies, imposts, duties, deductions, charges and withholdings in the nature of taxes whatsoever (including backup withholding), together with interest thereon and assessments, fees, charges or penalties with respect thereto made on or in respect thereof and "Tax" shall be construed accordingly; 1.143 "Term SOFR” means the Term SOFR Reference Rate for a tenor of one month on the day (such day, the "Periodic Term SOFR Determination Day") that is [**] prior to the first day of such calculation, as such rate is published by the Term SOFR Administrator; provided that that if as of [**]., New York City time, on any Periodic Term SOFR Determination Day the Term SOFR Reference Rate has not been published by the Term SOFR Administrator and a Benchmark Replacement Date with respect to the Term SOFR Reference Rate has not occurred, then Term SOFR will be the Term SOFR Reference Rate as published by the Term SOFR Administrator on the first preceding Business Day for which such Term SOFR Reference Rate was published by the Term SOFR Administrator so long as such first preceding Business Day is not more than [**] prior to such Periodic Term SOFR Determination Day; 1.144 "Term SOFR Administrator" shall mean CME Group Benchmark Administration Limited (or a successor administrator of the Term SOFR Reference Rate selected by the Lender Representative in its reasonable discretion); 1.145 "Term SOFR Reference Rate" means the forward-looking term rate based on SOFR; 1.146 "Total Loan Facility" means the amount set forth in the Loan Facility Terms; 14 1.147 "Tranche" means an amount drawn down out of the Total Loan Facility pursuant to this Loan Agreement (it being understood that there shall be three tranches, as set forth in the Loan Facility Terms); 1.148 "Transaction Fee" means the amount set forth in the Loan Facility Terms; 1.149 "Unpaid Sum" means any sum due and payable but unpaid by any Loan Party under any Loan Document; 1.150 "Unadjusted Benchmark Replacement" shall mean the Benchmark Replacement, excluding the related Benchmark Replacement Adjustment; 1.151 "United States" and "U.S." mean the United States of America; 1.152 “U.S. Person” means any Person that is a “United States person” as defined in Section 7701(a)(30) of the Code; 1.153 "UK Financial Institution" shall mean any BRRD Undertaking (as such term is defined under the PRA Rulebook (as amended form time to time) promulgated by the United Kingdom Prudential Regulation Authority) or any person subject to IFPRU 11.6 of the FCA Handbook (as amended from time to time) promulgated by the United Kingdom Financial Conduct Authority, which includes certain credit institutions and investment firms, and certain affiliates of such credit institutions or investment firms; 1.154 "UK Resolution Authority" shall mean the Bank of England or any other public administrative authority having responsibility for the resolution of any UK Financial Institution; 1.155 "USA PATRIOT Act" shall mean The Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001 (Title III of Pub. L. No. 107-56 (signed into law October 26, 2001)); 1.156 "Vadadustat FDA Approval" means the receipt by the Borrower Representative of notice from the United States Food and Drug Administration granting the Borrower Representative or a Subsidiary Guarantor marketing approval for vadadustat; 1.157 “Vadadustat Withdrawal Event” means the withdrawal by the United States Food and Drug Administration of the marketing approval for vadadustat pursuant to a final, non-appealable determination; 1.158 "VAT" means (i) any value added tax imposed by the United Kingdom Value Added Tax Act 1994; (ii) any tax imposed in compliance with the Council Directive of 28 November 2006 on the common system of value added tax (EC Directive 2006/112); and (iii) any other tax of a similar nature, whether imposed in the United Kingdom or in a member state of the European Union in substitution for, or levied in addition to, such tax referred to in paragraph (i) or (ii) above, or imposed elsewhere. 1.159 "[**]" means [**]; 1.160 "Warrant Instrument" means a warrant instrument, in the agreed form, pursuant to which warrants over shares in the Borrower Representative are to be issued by the Borrower Representative to Kreos Capital VII Aggregator SCSp on the date of this Loan Agreement; 1.161 Write-Down and Conversion Powers” means, (a) with respect to any EEA Resolution Authority, the write-down and conversion powers of such EEA Resolution Authority from time to time under the Bail-In Legislation for the applicable EEA Member Country, which write-down and conversion powers are described in the EU Bail-In Legislation Schedule and (b) with respect to the United Kingdom, any powers of the applicable Resolution Authority under the Bail-In Legislation to cancel, reduce, modify or change the form of a liability of any UK Financial Institution or any contract or instrument under which that liability arises, to convert all or part of that liability into shares, securities or obligations of that person or any other person, to provide that any such contract or instrument is to have effect as if a right had been exercised under it or to suspend any obligation in respect of that liability or any of the powers under that Bail-In Legislation that are related to or ancillary to any of those powers. 2. INTERPRETATION 2.1 In this Loan Agreement (unless the context requires otherwise) any reference to: 2.1.1 any law or legislative provision includes a reference to any subordinate legislation made under that law or legislative provision before the date of this Loan Agreement, to any modification, re-enactment or extension of that law or legislative provision made before that date and to any former law or legislative provision which it consolidated or re-enacted before that date; 2.1.2 any gender includes a reference to other genders and the singular includes a reference to the plural and vice versa; 2.1.3 a Clause or Schedule is to a clause or schedule (as the case may be) of or to this Loan Agreement; 2.1.4 a "person" or "Person" shall be construed as including a reference to an individual, firm, company, corporation, partnership, unincorporated body of persons or any country (or state thereof or any agency thereof); 15 2.1.5 an "amendment" includes a supplement, novation or re-enactment in writing and "amended" is to be construed accordingly; 2.1.6 "assets" includes present and future properties; 2.1.7 an "authorization" includes an authorization, consent, approval, resolution, licence, exemption, filing, registration and notarisation; 2.1.8 a "regulation" includes any regulation, rule, official directive, request or guideline (whether or not having the force of law) of any governmental, inter-governmental or supranational body, agency, department or regulatory, self-regulatory or other authority or organisation; 2.1.9 [reserved]; 2.1.10 "holding company" means, in relation to a person, any other person in respect of which it is a subsidiary; 2.1.11 [reserved]; 2.1.12 this Loan Agreement (or to any specified provision of this Loan Agreement), any other document or a provision of any other document, shall be construed as a reference to this Loan Agreement, that document or a provision of that document as in force for the time being and as amended in accordance with the terms thereof, or, as the case may be, with the agreement of the relevant parties and (where such consent is, by the terms of this Loan Agreement or the relevant document, required to be obtained as a condition to such amendment being permitted) the prior written consent of the Lender; 2.1.13 "other" and "otherwise" are not to be construed ejusdem generis with any foregoing words where a wider construction is possible and "include" and "including", "in particular", "for example" or any similar expression are to be construed as being by way of illustration or emphasis only and are not to be construed as, nor shall they take effect as, limiting the generality of any foregoing words; 2.1.14 a document being in "agreed form" is a document which is in a form reasonably acceptable to the Borrower Representative and the Lender Representative; and 2.1.15 $ is the official currency of the United States. 2.2 If a payment date in relation to any payment from the Borrowers or any other Loan Party under this Loan Agreement or the Security Documents falls on a day which is not a Business Day, the relevant payment date shall be the next Business Day in that calendar month (if there is one) or the preceding Business Day (if there is not). If the performance of any other obligation by a Group Company under the Loan Documents is stated to be due on a day which is not a Business Day, the relevant date of performance shall be the immediately succeeding Business Day. 2.3 A Default (other than an Event of Default) is continuing if it has not been remedied or waived and any reference to an Event of Default being continuing is a reference to an Event of Default that has not been waived by the Lender. 2.4 The headings in this Loan Agreement are inserted for convenience only and do not form part of this Loan Agreement and do not affect its interpretation. 2.5 If there is any conflict between the provisions of this Loan Agreement and the provisions of any other Loan Document, the provisions of this Loan Agreement shall prevail. 3. LOAN FACILITY 3.1 Lender's Commitment 3.1.1 Subject to Clause 3.5 below, the Lender shall and agrees hereby to make available to the Borrowers the Total Loan Facility under the terms of this Loan Agreement, to be drawn down as set forth in the Loan Facility Terms and in accordance with Clause 3.2. 3.1.2 The Lender shall not be under any commitment to advance any part of the Loan after the Expiry Date of the applicable part of such Loan or upon the earlier termination of the Loan Facility, or on dates other than those specified in this Loan Agreement. 3.1.3 The unutilised portion (if any) of the Loan Facility shall be cancelled after the expiry of the final period for Drawdown as set forth in the Loan Facility Terms, whereupon the Total Loan Facility shall be reduced accordingly. 3.1.4 In granting the Loan Facility, the Lender is relying on the representations and warranties contained in Clause 7. 3.1.5 Each Drawdown made under the Loan Facility shall be secured by the Security Documents. 16 3.2 Date of Advance(s) of the Loan 3.2.1 Subject to Clauses 3.1.2 and 3.2.2, (and subject to the satisfaction of the relevant conditions set forth in Clause 3.5), each Tranche shall be advanced and made available to the Borrowers on the relevant Drawdown Date to the extent the Borrower has delivered an executed Drawdown Notice to the Lender Representative at least [**] (or in the case of Tranche A, at least [**]) prior to the requested Drawdown Date (or such shorter period as the Lender Representative may reasonably agree in writing). Each Drawdown Notice in respect of Tranche B or Tranche C must be received by the Lender Representative at least [**] prior to the end of the relevant Expiry Date. No more than one Drawdown Notice may be served in respect of each Tranche. Once a Drawdown Notice has been delivered to the Lender Representative, it is irrevocable. Each Tranche requested to be advanced pursuant to a Drawdown Notice shall be in an amount equal to or greater than the Minimum Drawdown Amount. 3.2.2 If the requested Drawdown Date falls on a day which is not a Business Day, the Lender shall only be obligated to pay the relevant Tranche to the applicable Borrower on the next Business Day in that calendar month. Where there is no next Business Day in that calendar month, the Lender shall only be obligated to pay the relevant Tranche to the applicable Borrower on the first Business Day of the next calendar month. 3.3 Method of Disbursement 3.3.1 The payment by the Lender to the Drawdown Account, or to such other bank account as is agreed in writing between the Lender and the Borrower Representative, shall constitute the making of the Loan (or the relevant part thereof) and each Borrower shall thereupon become indebted, as principal and direct obligor, to the Lender in an amount equal to the Loan (or the relevant part thereof) and all interest thereon and other payments due in connection therewith under this Loan Agreement. 3.3.2 Any delay or failure by the Lender to fund any loan as a result of a disruption not under the Lender’s control, including, without limitation, due to a cyber-attack, computer hacking or similar event shall not constitute a breach by the Lender of its obligations under this Loan Agreement. 3.4 [Reserved] 3.5 Conditions Precedent requirements relative to the Advance of the Loans 3.5.1 Tranche A: The obligation of the Lender to make the initial Loan under Tranche A on the Closing Date is subject solely to the satisfaction or waiver of each of the following conditions (except for any such items for which a post-closing period for completion has been granted pursuant to Schedule C): (i) (A) the provision of copies of the articles of incorporation or formation, including all amendments thereto, of each Loan Party, certified as of a recent date by the Secretary of State of the state of its organization, and a certificate as to the good standing of each Loan Party as of a recent date from such Secretary of State and (B) a certificate of the Secretary, Financial Officer or Assistant Secretary of each Loan Party, dated the date of this Loan Agreement and certifying (I) that attached thereto is a true and complete copy of the by-laws or limited liability company agreement, as applicable, of such Loan Party as in effect on such date and at all times since a date prior to the date of the resolutions described in clause (II) below, (II) that attached thereto is a true and complete copy of resolutions duly adopted by the board of directors or other applicable governing body of such Loan Party authorizing the execution, delivery and performance of the Loan Documents to which such Person is a party and, in the case of the Borrowers, the borrowings hereunder, and that such resolutions have not been modified, rescinded or amended and are in full force and effect, (III) that the certificate or articles of incorporation or formation of such Loan Party have not been amended since the date of the last amendment thereto shown on the certificate of good standing furnished pursuant to clause (A) above, and (IV) as to the incumbency and specimen signature of each officer executing any Loan Document or any other document delivered in connection herewith on behalf of such Loan Party (which certificate shall be countersigned by another officer to certify as to the incumbency and specimen signature of the Secretary, Financial Officer or Assistant Secretary executing such certificate); (ii) the relevant Parties having executed and delivered to the Lender Representative copies of the Initial Security and Guarantee Documents and this Loan Agreement, and each other document required to be delivered on the Closing Date under the Initial Security and Guarantee Documents (including share certificates and stock transfer forms where relevant). The Lender Representative shall have a security interest in the Collateral of the type and priority described in each of the Security Documents; (iii) the Borrowers’ compliance with Clauses 10.1 and (to the extent an invoice with respect thereto has been provided to the Borrower Representative at least [**] prior to the Closing Date), 10.3.1(i); (iv) evidence of the Borrowers’ compliance with Clause 8.1.15(ii); (v) [reserved]; (vi) a customary legal opinion from Latham & Watkins LLP, dated as of the date of this Loan Agreement; (vii) to the extent requested by the Lender in writing at least [**] prior to the Closing Date, all documents, confirmations and evidence required by the Lender to satisfy its "know your customer" requirements or similar 17 identification checks (including the USA PATRIOT ACT) in order to meet its obligations under applicable money laundering, or similar, laws and regulations; (viii) receipt by the Lender of customary lien searches in the jurisdiction of organization of each Loan Party; (ix) a certificate, dated as of the date of this Loan Agreement and signed by a Financial Officer of the Borrower Representative, confirming compliance with the conditions precedent set forth in the following clauses (x) and (xi); (x) the representations and warranties set forth in Clause 7 and in each other Loan Document shall be true and correct in all material respects as of the Closing Date with the same effect as though made as of such date (except to the extent that such representations and warranties specifically refer to an earlier date, in which case they shall be true and correct in all material respects as of such earlier date); (xi) at the time of, and immediately after giving effect to the borrowing as of such Drawdown Date, no Default or Event of Default shall have occurred and be continuing; (xii) delivery to the Lender Representative of a customary solvency certificate (with “solvency” to be defined in an manner consistent with Clause 7.1.42); (xiii) delivery to Kreos Capital VII Aggregator SCSp of a duly executed copy of the Warrant Instrument; (xiv) delivery to Kreos Capital VII Aggregator SCSp of a duly executed copy of the relevant warrant certificate to be issued in accordance with the terms of the Warrant Instrument; and (xv) delivery to the Lender Representative of an executed intercompany subordination agreement (the “Intercompany Subordination Agreement”). 3.5.2 Tranche B: The obligation of the Lender to make the Loan under Tranche B is subject solely to the satisfaction or waiver of each of the following conditions: (i) receipt by the Lender Representative of an executed Drawdown Notice in accordance with Clause 3.2; (ii) the representations and warranties set forth in Clause 7 and in each other Loan Document shall be true and correct in all material respects as of the applicable Drawdown Date with the same effect as though made as of such date (except to the extent that such representations and warranties specifically refer to an earlier date, in which case they shall be true and correct in all material respects as of such earlier date); (iii) at the time of, and immediately after giving effect to the borrowing as of the applicable Drawdown Date, no Default or Event of Default shall have occurred and be continuing; and (iv) the Vadadustat FDA Approval has been received on or prior to the applicable Drawdown Date. 3.5.3 Tranche C: The obligation of the Lender to make the Loan under Tranche C is subject solely to the satisfaction or waiver of each of the following conditions: (i) receipt by the Lender Representative of an executed Drawdown Notice in accordance with Clause 3.2; (ii) Tranche B has been drawn in full prior to the applicable Drawdown Date; (iii) the representations and warranties set forth in Clause 7 and in each other Loan Document shall be true and correct in all material respects as of the applicable Drawdown Date with the same effect as though made as of such date (except to the extent that such representations and warranties specifically refer to an earlier date, in which case they shall be true and correct in all material respects as of such earlier date); (iv) at the time of, and immediately after giving effect to the borrowing as of the applicable Drawdown Date, no Default or Event of Default shall have occurred and be continuing; and (v) the Borrower Representative has raised at least $[**] in cumulative gross cash proceeds in the form of equity or equity linked securities in one or more series of transactions (including any public offering, private placement or “at-the-market” offering) after the date of the Loan Agreement (any such transaction, a “Capital Raise”). 3.6 Post-Closing Obligations 3.6.1 Within the time periods specified on Schedule C hereto (as each may be extended by the Lender Representative in its reasonable discretion), the Borrower Representative shall complete (or cause to be completed) such undertakings as are set forth on Schedule C hereto. 18 3.7 Use of Funds and Collateral 3.7.1 Unless the Lender Representative shall otherwise agree in writing, the Borrowers shall use the Loan solely for the purpose of general working capital, to repay certain existing indebtedness on the Closing Date, for other general corporate purposes and for any other purpose not prohibited by the terms of this Loan Agreement (including permitted acquisitions and investments). The Lender shall not be under any obligation to concern itself with the application of the Loan. 3.7.2 The security interest granted to the Lender Representative pursuant to the Security Documents shall form security for all monies and obligations owed to the Lender by the Borrowers or any other Loan Party pursuant to this Loan Agreement or otherwise. 4. TERM 4.1 Subject to Clause 15.1, this Loan Agreement is effective when executed and dated by the Lender and the Borrower Representative and shall continue until the later of (i) termination in accordance with its terms; and (ii) the date upon which each Borrower shall have performed and satisfied all its obligations (including making all payments) under this Loan Agreement and the Security Documents (other than contingent indemnification and expense reimbursement obligations for which no claim has been made). 5. REPAYMENT AND PREPAYMENT 5.1 Repayments and Interim Payment 5.1.1 The Borrowers shall repay to the Lender Representative, in advance, principal (and interest in accordance with Clause 6.1) in respect of each Tranche on each Monthly Repayment Date in the amounts specified in the repayment schedule issued by the Lender Representative prior to the relevant Drawdown Date and attached to the relevant Drawdown Notice as may be revised from time to time by the Lender Representative in accordance with Clause 5.1.3 (the "Repayment Schedule"), provided that all payments in relation to each Tranche shall comprise interest only for the Interest Only Period, and following the Interest Only Period, the Borrowers shall repay, in advance, all outstanding principal (and interest in accordance with Clause 6.1) in respect of each Tranche in equal payments on each Monthly Repayment Date remaining, commencing with the first Monthly Repayment Date to occur after the end of the Interest Only Period (as an illustrative example, if, after the end of the Interest Only Period, thirteen Monthly Repayment Dates remain before the Maturity Date, the Borrowers shall repay all outstanding principal and interest in thirteen equal payments: one on each such Monthly Repayment Date). 5.1.2 All payments that any Borrower makes under this Loan Agreement shall be made in full, without any deduction, set-off or counterclaim and in immediately available funds on the due date to an account which the Lender Representative shall specify to the Borrower Representative in writing at least [**] prior to the applicable Monthly Repayment Date. 5.1.3 The Lender Representative shall have the right to issue a revised Repayment Schedule from time to time if the Lender Representative, in its reasonable discretion, considers it necessary in order to correct a ministerial error or to ensure that, in respect of each Tranche, on the expiry of the relevant Loan Term there will be no amounts owing from the Borrowers to the Lender in respect of the relevant Tranche(s) (and any additional payment in respect of any prior period that is required due to such revised Repayment Schedule shall be made by the Borrowers within [**] of their receipt of such revised Repayment Schedule (or, if applicable, returned by the Lender Representative to the Borrowers within [**] of the issuance of such revised Repayment Schedule). For the avoidance of doubt, any payment of an amount shown on a then-in effect Repayment Schedule shall not result in a Default or Event of Default due to a later revision of the Repayment Schedule. 5.1.4 Each payment received by the Lender Representative in respect of any Tranche shall be applied as follows: (i) first, to discharge all outstanding fees, costs, expenses and Unpaid Sums (other than any Unpaid Sums set forth in clause (ii) or (iii) below) that are then due to the Lender in respect of such Tranche; (ii) secondly, to discharge all accrued and unpaid interest in respect of such Tranche; and (iii) thirdly, to reduce the outstanding principal balance of such Tranche. 5.1.5 Any amount repaid or prepaid may not be redrawn. 5.1.6 If any Drawdown Date is not a Monthly Repayment Date, the Borrowers shall pay to the Lender Representative, on such Drawdown Date (by way of deduction by the Lender Representative of the amount of the Tranche actually advanced to the Borrowers), the Interim Payment. 5.2 Currency of Payments Repayment of the Loan and payment of all other amounts owed to the Lender will be paid to the Lender Representative in the currency in which each Tranche has been provided (the "Contractual Currency"), i.e. in Dollars, unless otherwise agreed by the Parties in writing. The Borrowers shall bear the cost in the event of and in respect of any conversion by the Lender of an amount received by it in any currency other than the Contractual Currency. 19 5.3 Advance Payment On each Drawdown Date with respect to a Tranche, the Borrowers shall pay to the Lender Representative (by way of deduction by the Lender Representative from the amount of the Tranche advanced to the Borrowers) the advance payment as set forth under the heading Loan Facility Terms at the beginning of this Loan Agreement with respect to the applicable Tranche (the "Advance Payment") which shall be held by the Lender Representative as security for and applied in or towards the repayment amount (comprising principal and interest) for the last Month of the Loan Term of that particular Tranche unless a notice under Clause 9.2.2 has been served, in which case the Advance Payment shall be applied, at the discretion of the Lender Representative, in accordance with Clause 5.1.4. 5.4 Prepayments The Borrowers shall be entitled to prepay the Loan, in whole but not in part, subject to the following conditions: 5.4.1 the Borrower Representative shall submit to the Lender Representative a written notice of prepayment (which may be conditioned upon a specific event, in which case it may be revoked at any time prior to the proposed repayment date) at least [**] in advance, indicating the amount to be prepaid and the date of the proposed prepayment; 5.4.2 on the date of such optional prepayment (or of any acceleration), the Borrower Representative shall pay the Lender Representative an amount equal to: (i) the outstanding principal amount of the Loan; (ii) all accrued and unpaid interest; (iii) should the prepayment be made: (a) prior to the first anniversary of the Closing Date, a fee equal to the sum of (i) 4.00% of the amount repaid plus (ii) the aggregate of the Monthly interest payments scheduled to be paid by the Borrowers on each Monthly Repayment Date for each then-outstanding Tranche (as is set out in the relevant Repayment Schedule) for the period commencing on the date of prepayment and ending on the date that is twelve (12) months after the date of prepayment (the “Yield Maintenance Premium”); and/or (b) (I) on or after the first anniversary of the Closing Date, but prior to the [**], a fee equal to 4.00% of the amount repaid, (II) on or after the [**], but prior to the [**]% of the amount repaid and (III) on or after the [**], but prior to the Maturity Date, 1.00% of the amount repaid (the “Early Payment Fee”); (c) Notwithstanding anything to the contrary in this Loan Agreement or any other Loan Document, it is understood and agreed that if any Loans are accelerated (whether as a result of the occurrence and continuance of any Event of Default, by operation of law or otherwise), any Yield Maintenance Premium and any Early Payment Fee, as applicable, determined as of the date of acceleration, will also be due and payable and will be treated and deemed as though the applicable Loans were repaid as of such date and shall constitute part of the obligations for all purposes herein. Any Yield Maintenance Premium and any Early Payment Fee, as applicable, shall also be payable in the event the obligations, the Loans and this Loan Agreement are satisfied or released by foreclosure (whether by power of judicial proceeding), deed in lieu of foreclosure or by any other similar means. The Group Companies expressly waive the provisions of any present or future statute or law that prohibits or may prohibit the collection of the applicable premium in connection with any such acceleration. The parties hereto further acknowledge and agree that any Yield Maintenance Premium and any Early Payment Fee, as applicable, is not intended to act as a penalty or to punish the Group Companies for any repayment or redemption of the Loans. The Group Companies expressly agree that (i) any Yield Maintenance Premium and any Early Payment Fee, as applicable, is reasonable and is the product of an arm’s length transaction between sophisticated business people, ably represented by counsel, (ii) any Yield Maintenance Premium and any Early Payment Fee, as applicable, shall be payable notwithstanding the then prevailing market rates at the time payment is made, (iii) there has been a course of conduct between the Lender and the Group Companies giving specific consideration in this transaction for such agreement to pay any Yield Maintenance Premium and any Early Payment Fee, as applicable, (iv) the Group Companies shall be estopped hereafter from claiming differently than as agreed to in this Clause, (v) the agreement of the Group Companies to pay any Yield Maintenance Premium and any Early Payment Fee, as applicable, is a material inducement to the Lender to extend the Loans, and (vi) any Yield Maintenance Premium and any Early Payment Fee, as applicable, represents a good-faith, reasonable estimate and calculation of the lost profits or damages of the Lender and that it would be impractical and extremely difficult to ascertain the actual amount of damages to the Lender or profits lost by the Lender as a result of such prepayment or acceleration. (d) Notwithstanding anything herein to the contrary, no Yield Maintenance Premium or Early Payment Fee shall be due in connection with an optional prepayment of the Loans that is in connection with a refinancing of the Loan Facility to the extent the Lender (or any Kreos Affiliate) will be a lender under such new facility. (iv) all unpaid End of Loan Payments; (v) all unpaid fees, costs and expenses; and (vi) all other unpaid sums payable by the Borrowers to the Lender under the Loan Documents. 20 5.5 Not later than the [**] following the receipt of Net Cash Proceeds in respect of any Asset Sale or Casualty Event, in each case, in excess of $[**] per transaction (or $[**] in the aggregate per fiscal year), the Borrowers shall apply [**]% of the Net Cash Proceeds received with respect thereto to prepay outstanding Loans in accordance with Clause 5.1.4; provided, that only the amount of Net Cash Proceeds in excess of $[**] per transaction or $[**] in the aggregate per fiscal year shall be subject to prepayment pursuant to this Clause 5.5. Notwithstanding anything herein to the contrary, in lieu of making the prepayment contemplated by this Clause 5.5, the Borrower Representative may instead elect to reinvest such Net Cash Proceeds in productive assets of a kind then used or usable in the business of the Borrower Representative and its Subsidiaries (including, without limitation, through Permitted Acquisitions and Permitted Investments) or in research and development, so long as (w) such reinvestment does not materially detract from the value of the Collateral (taken as a whole) as reasonably determined by the Borrower Representative in consultation with the Lender Representative, (x) the Borrower Representative has delivered to the Lender Representative a certificate of the Borrowers’ intent to reinvest such proceeds, (y) no Default or Event of Default is continuing as of the date of delivery of the certificate referred to in clause (x), and (z) such reinvestment is made within [**] after receipt of such Net Cash Proceeds (or if a binding commitment to reinvest has been entered into within such [**] period, within [**] after the end of such [**] period). 5.6 In the event that any Group Company shall receive Net Cash Proceeds from the issuance or incurrence of Financial Indebtedness for borrowed money that is not permitted to be incurred pursuant to the terms of this Loan Agreement, the Borrowers shall, substantially simultaneously with (and in any event not later than the [**] following) the receipt of such Net Cash Proceeds, apply an amount equal to [**]% of such Net Cash Proceeds to prepay the outstanding Loans in accordance with Clause 5.1.4. 5.7 In the event that the Borrowers seek to make a prepayment in connection with a refinancing of this Loan Agreement (a “Proposed Refinancing”), (i) the Borrower Representative shall provide written notice to the Lender, (ii) the Lender and its Affiliates shall have the right (but not the obligation) to make a proposal to provide all or a portion of such Proposed Refinancing by providing written notice to the Borrower Representative within [**] after receipt of any notice of a Proposed Refinancing (such proposal, a “Financing Proposal”), which the Borrower Representative may elect to accept or decline in its sole discretion; provided that, during such [**] period, neither the Borrower Representative nor any of its Subsidiaries may enter into exclusivity with a third party with respect to the Proposed Refinancing or consummate any such Proposed Refinancing. 6. INTEREST 6.1 The Borrowers shall pay to the Lender Representative, in advance, all unpaid and accrued interest in respect of each Tranche outstanding on each Monthly Repayment Date; provided that if the Borrowers prepay any Tranche on a day other than a Monthly Repayment Date, the Lender Representative shall return to the Borrower the amount of interest paid that exceeds the amount of interest that accrued. 6.2 Interest on the principal amount of each Tranche from time to time shall accrue from day to day at a rate of Adjusted Term SOFR plus six point seven five per cent (6.75% per annum) (the “Applicable Interest Rate”), from the applicable Drawdown Date until the repayment in full of such Loan; provided that the all-in interest rate shall not exceed 15.00% per annum. Interest on the Loan and each part thereof shall be paid to the Lender Representative on each Monthly Repayment Date in the Contractual Currency in the amounts to be specified in the Repayment Schedule. 6.3 Time of payment of any sum due from the Borrowers is of the essence under this Loan Agreement. If the Borrowers fail to pay any sum to the Lender Representative on its due date for payment (after the expiration of any grace periods therefor), the Borrowers shall pay to the Lender Representative forthwith, on demand, interest on such overdue sum (compounded on a Monthly basis) from the due date (or, if later, the date of expiration of the applicable grace period) to the date of actual payment (as well after as before judgment) at a rate equal to the Applicable Interest Rate plus three per cent (3%) per annum. If the Borrowers fail to pay any sum within [**] after such sum is due and payable, the Borrowers shall pay to the Lender forthwith on demand, a one-off late payment charge of two per cent (2)% of such overdue sum, to compensate the Lender for additional administrative expense. 6.4 (i) Notwithstanding anything to the contrary herein or in any other Loan Document, upon the occurrence of a Benchmark Transition Event, the Lender Representative and the Borrower Representative may amend this Loan Agreement to replace the then-current Benchmark with a Benchmark Replacement. No replacement of the then-current Benchmark with a Benchmark Replacement pursuant to this clause (i) shall occur prior to the applicable Benchmark Transition Start Date. (ii) In connection with the use, administration, adoption or implementation of a Benchmark Replacement, the Lender Representative shall have the right (in consultation with the Borrower) to make Benchmark Replacement Conforming Changes from time to time and, notwithstanding anything to the contrary herein or in any other Loan Document, any amendments implementing such Benchmark Replacement Conforming Changes will become effective without any further action or consent of any other party to this Loan Agreement. (iii) The Lender Representative shall promptly notify the Borrower Representative of (A) any occurrence of a Benchmark Transition Event and its related Benchmark Replacement Date and Benchmark Transition Start Date, (B) the implementation of any Benchmark Replacement, (C) the effectiveness of any Benchmark Replacement Conforming Changes and (D) (x) the removal or reinstatement of any tenor of a Benchmark pursuant to clause (iv) below and (y) the commencement or conclusion of any Benchmark Unavailability Period. Any determination, decision or election that may be made by the Lender Representative pursuant to this Clause, including any determination with respect to a tenor, rate or adjustment or of the occurrence or non-occurrence of an event, circumstance or date and any decision to take or refrain from taking any action, will be conclusive and binding absent manifest error and may be made in its or their sole discretion and without consent from any other party hereto, except, in each case, as expressly required pursuant to this Clause. 21 (iv) Notwithstanding anything to the contrary herein or in any other Loan Document, at any time (including in connection with the implementation of a Benchmark Replacement), (x) if the then-current Benchmark is a term rate (including the Term SOFR Reference Rate) and either (A) any tenor for such Benchmark is not displayed on a screen or other information service that publishes such rate from time to time as selected by the Lender Representative or (B) the regulatory supervisor for the administrator of such Benchmark has provided a public statement or publication of information announcing that any tenor for such Benchmark is not or will not be representative, then the Lender Representative may modify the interest period (or any similar or analogous definition) for any Benchmark settings at or after such time to remove such unavailable or non-representative tenor and (y) if a tenor that was removed pursuant to clause (x) above either (A) is subsequently displayed on a screen or information service for a Benchmark (including a Benchmark Replacement) or (B) is not, or is no longer, subject to an announcement that it is not or will not be representative for a Benchmark (including a Benchmark Replacement), then the Lender Representative may modify the interest period (or any similar or analogous definition) for all Benchmark settings at or after such time to reinstate such previously removed tenor. (v) Upon the Borrower Representative’s receipt of notice of the commencement of a Benchmark Unavailability Period, the Borrower Representative may revoke any request for a SOFR Borrowing, conversion to or continuation of SOFR Loans to be made, converted or continued during any Benchmark Unavailability Period. 7. REPRESENTATIONS AND WARRANTIES 7.1 Each Borrower warrants and represents to the Lender, jointly and severally, that except as set forth on Schedule H, as of the date of this Loan Agreement: 7.1.1 (i) each Loan Party and each material Domestic Subsidiary is a corporation or limited liability company, as applicable, duly organized and validly existing under the laws of its state of incorporation or formation, as applicable and (ii) each material Subsidiary that is not a Domestic Subsidiary is duly organized and validly existing under the laws of its country of incorporation; 7.1.2 each Loan Party has the corporate capacity, and has taken all corporate action and obtained all corporate consents, necessary for it: (i) to execute the Loan Documents to which it is or is to be party; (ii) to borrow under this Loan Agreement and to make all the payments contemplated by, and to comply with all its other obligations under the Loan Documents to which it is or is to be party; and (iii) subject to the Perfection Exceptions, to grant the Lender Representative a first priority Security Interest in respect of the Collateral pursuant to the Security Documents to which it is or is to be party; 7.1.3 each Group Company has good, valid and marketable title to, or valid leases and licences of, and all appropriate authorizations to use, the assets necessary to carry on its business as it is being conducted, except in each case where the failure to possess the same would not reasonably be expected to have a Material Adverse Change; 7.1.4 [reserved]; 7.1.5 the Loan Documents to which any Loan Party is or is to be party, do now or, as the case may be, will, upon execution and delivery (and, where applicable, registration as provided for in the Loan Documents): (i) constitute the relevant Loan Party’s legal, valid and binding obligations enforceable against it in accordance with their respective terms; and (ii) subject to the Perfection Exceptions, create legal, valid and binding security interests enforceable in accordance with their respective terms; in each case subject to subject to the effects of bankruptcy, insolvency, fraudulent conveyance, reorganization, moratorium and other similar laws relating to or affecting creditors’ rights generally, and general equitable principles (whether considered in a proceeding in equity or at law); 7.1.6 the execution and (where applicable) registration by any Loan Party of the Loan Documents to which it is or is to be party and the performance of the transactions contemplated thereunder, and the borrowing by each Borrower of the Loan and the compliance by each Loan Party with the Loan Documents to which it is or is to be party, will not involve or lead to a contravention of: (i) any applicable material law or other material legal or regulatory requirement; (ii) the organizational documents of such Loan Party; or (iii) any material contractual or other obligation or restriction which is binding on any Borrower or any other Group Company or any of their assets; 22 7.1.7 the payment obligations under the Loan Documents of the Loan Parties rank at least pari passu with the claims of all its other unsecured and unsubordinated creditors, except for obligations mandatorily preferred by law applying to companies generally; 7.1.8 all material consents, licences, approvals and authorizations required by any Loan Party in connection with the entry into, performance, validity and enforceability of the Loan Documents to which it is or is to be party have been or (upon execution thereof) shall have been obtained by the Drawdown Date and are (or upon execution thereof shall be) in full force and effect during the life of this Loan Agreement, except in each case where the failure to obtain or possess the same would not reasonably be expected to have a Material Adverse Change; 7.1.9 all authorizations necessary for the conduct of the business, trade and ordinary activities of members of the Group have been obtained or effected and are in full force and effect, except in each case where the failure to obtain or possess the same would not reasonably be expected to have a Material Adverse Change; 7.1.10 no corporate action, legal proceeding or other procedure or circumstance (including any creditors’ process) described in Clauses 9.1.7 has been taken, or to the knowledge of the Borrower Representative, threatened in writing in relation to a member of the Group; 7.1.11 [reserved]; 7.1.12 [reserved]; 7.1.13 no financial or other written information furnished by or on behalf of any Borrower in connection with the negotiation of the Loan Documents delivered to the Lender pursuant to the Loan Documents (other than projected financial information, pro forma financial information and information of a general economic or industry nature), when taken as a whole, contains any material misstatement of fact or omits to state any material fact necessary to make the statements therein (when taken as a whole), in the light of the circumstances under which they were made, not materially misleading; provided that, with respect to projected and pro forma financial information, the Borrowers represent only that such information was prepared in good faith based upon assumptions believed to be reasonable at the time of preparation and delivery; it being understood that actual results may vary from such forecasts and that such variances may be material; 7.1.14 the Financial Statements were prepared in accordance with GAAP and consistently applied, except as expressly noted therein, and fairly represent (in conjunction with the notes thereto) in all material respects the financial condition of the Borrower Representative as at the date to which they were drawn up and the results of the Borrower Representative’s operations during the financial year then ended; 7.1.15 since November 8, 2023, there has been no Material Adverse Change in the business or financial condition of the Group; 7.1.16 [reserved]; 7.1.17 there is no litigation, action, proceeding, arbitration, investigation or claim pending or, so far as the Borrower Representative is aware, threatened in writing against any Group Company before any court or administrative agency which would reasonably be expected to have a Material Adverse Change; 7.1.18 no judgment or order of a court, arbitral body or agency which would reasonably be expected to have a Material Adverse Change has been made against it or any Group Company; 7.1.19 the Borrowers or the relevant Loan Party owns with good and marketable title all the Collateral, free from all security interests (other than Permitted Security Interests), and all the Collateral is in good operating condition and repair, and are adequate for the uses to which they are being put, and none of such Collateral are in need of maintenance or repairs except for ordinary, routine maintenance and repairs that are not material in nature or cost; 7.1.20 the Group has no Financial Indebtedness other than Permitted Financial Indebtedness; 7.1.21 the Group has not granted any security over its assets to any third party except for Permitted Security Interests; 7.1.22 no other event or circumstance is outstanding which constitutes a default under any other agreement or instrument which is binding on any Borrower or any other Group Company or to which its (or any of Group Company’s) assets are subject, in each case, which would reasonably be expected to cause a Material Adverse Change; 7.1.23 no Borrower nor any other Group Company has breached any law or regulation which breach has or would reasonably be expected to have a Material Adverse Change; 7.1.24 no labour disputes are current or, to the best of its knowledge and belief (after having made due and careful enquiry) has been threatened in writing against any Borrower or any other Group Company which has or would reasonably be expected to have a Material Adverse Change; 7.1.25 each Borrower and each other Group Company is the sole legal and beneficial owner of, or otherwise to its knowledge, holds the necessary rights to use, the Intellectual Property used in its business other than Permitted Licenses; 23 7.1.26 no material part of any Intellectual Property owned by any Borrower or a Group Company that is material to its business as of the date hereof or material to the business contemplated to be conducted in the future has been judged invalid or unenforceable, in whole or in part; 7.1.27 to the knowledge of Borrower, no Borrower or a Group Company, in carrying on its business, infringes any Intellectual Property of any third party which has caused, or would reasonably be expected to cause, a Material Adverse Change; 7.1.28 each Borrower and each other Group Company has taken all formal or procedural actions (including payment of fees) as reasonably required to: (i) maintain its material Intellectual Property; (ii) maintain the confidentiality of any trade secrets; and (iii) to register any registrable Intellectual Property that is material to its business; 7.1.29 no Borrower nor any other Group Company is aware of any current, pending or threatened (in writing) challenge or objection by any third party to its use of any Intellectual Property, or to the knowledge of Borrower, the infringement of any of its Intellectual Property by any third party, in each case where such challenge, objection or infringement has caused, or would reasonably be expected to cause, a Material Adverse Change; 7.1.30 [reserved]; 7.1.31 [reserved]; 7.1.32 no Borrower or any Subsidiary is required to be registered as an “investment company” under the Investment Company Act of 1940; 7.1.33 none of the Borrowers, any of the Group Companies, any of their respective directors or officers, nor, to the knowledge of the Borrower Representative, any of their respective employees, or any of their respective agents who act in any capacity in connection with the Loan Facility, is or are a Sanctioned Person; 7.1.34 in the past five years, each Borrower and each of the Group Companies and each of their respective directors and officers, and, to the knowledge of the Borrower Representative, each of their respective employees and agents, in connection with their activities related to the Borrower or any Group Company, have conducted their business in compliance with all applicable Anti-Corruption Laws, Anti-Money Laundering Laws and Sanctions; 7.1.35 [reserved]; 7.1.36 no loan, use of proceeds or transaction contemplated by this Loan Agreement will directly, or to the knowledge of the Borrower Representative, indirectly, violate applicable Anti-Corruption Laws, Anti-Money Laundering Laws or Sanctions; 7.1.37 each Borrower and each other Group Company have instituted and maintain in effect policies and procedures reasonably designed to promote compliance by each Borrower and each other Group Company and their respective directors, officers, employees, agents and representatives with all applicable Anti-Corruption Laws, Anti-Money Laundering Laws and Sanctions; 7.1.38 [reserved]; 7.1.39 [reserved]; 7.1.40 each Borrower and each other Group Company is in compliance in all material respects with the EU General Data Protection Regulation 2016/679, the Data Protection Act 2018 and any other analogous legislation in any applicable jurisdiction, in each case that is applicable to it and other than to the extent failure to so comply would not reasonably be expected to result in a Material Adverse Change; 7.1.41 no Borrower or any of its respective Subsidiaries is engaged principally, or as one of its important activities, in the business of extending credit for the purpose of buying or carrying Margin Stock. No part of the proceeds of any Loan will be used for any purpose that entails a violation of, or that is inconsistent with, the provisions of the Regulations of the Board, including Regulation T, U or X; 7.1.42 immediately after the consummation of the transactions to occur on the date of this Loan Agreement and immediately following the making of each Loan and after giving effect to the application of the proceeds of each Loan, (a) the aggregate fair value of the assets of the Group will exceed the aggregate debts and liabilities, subordinated, contingent or otherwise, of the Group; (b) the aggregate present fair saleable value of the property of the Group will be greater than the amount that will be required to pay the probable liability of the debts and other liabilities of the Group, subordinated, contingent or otherwise, as such debts and other liabilities become absolute and matured; (c) the Group does not believe that it will incur debts and liabilities, subordinated, contingent or otherwise, beyond its ability to pay such debts and liabilities as they become absolute and matured; and (d) the Group will not have unreasonably small capital with which to conduct the business in which it is engaged as such business is now conducted and is proposed to be conducted following the date of this Loan Agreement; 7.1.43 except as would not reasonably be expected to have a Material Adverse Change, each Borrower is in compliance with the applicable provisions of ERISA and the Code and the regulations and published interpretations thereunder. No ERISA Event has occurred or is reasonably expected to occur that, when taken together with all other such ERISA Events, would reasonably be expected to result in a material liability of any Borrower or any of its ERISA Affiliates. The present value of all benefit liabilities under each Plan (based on the assumptions used for purposes of Statement of Financial Accounting 24 Standards No. 87, as amended) did not, as of the last annual valuation date applicable thereto, exceed the fair market value of the assets of such Plan; 7.1.44 except as would not reasonably be expected to have a Material Adverse Change, each Foreign Pension Plan is in compliance with all laws applicable thereto and the respective requirements of the governing documents for such plan. With respect to each Foreign Pension Plan, no Borrower, its respective Affiliates or any of their respective directors, officers, employees or agents has engaged in a transaction which would subject any Borrower or any Subsidiary, directly or indirectly, to a tax or civil penalty which would reasonably be expected, individually or in the aggregate, to result in a Material Adverse Change. With respect to each Foreign Pension Plan, reserves have been established in the financial statements furnished to the Lender Representative in respect of any unfunded liabilities in accordance with applicable law and prudent business practice or, where required, in accordance with ordinary accounting practices in the jurisdiction in which such Foreign Pension Plan is maintained, except as would not reasonably be expected to result in a Material Adverse Change; and 7.1.45 each Borrower and its respective Subsidiaries has filed or caused to be filed all U.S. federal and state income tax returns and other material U.S. federal, state, local and foreign tax returns or materials required to have been filed by it and has paid or caused to be paid all material taxes due and payable by it and all assessments received by it, except taxes that are being contested in good faith by appropriate proceedings and for which such Borrower or such Subsidiary, as applicable, shall have set aside on its books adequate reserves. 7.1.46 The Borrowers’ representations and warranties set out in this Loan Agreement shall survive the execution and dating of this Loan Agreement. 8. UNDERTAKINGS Each Borrower undertakes to the Lender, jointly and severally, to comply with the following provisions of this Clause 8 at all times during the Security Period, except as the Lender Representative may otherwise agree in writing: 8.1 Affirmative Undertakings 8.1.1 each Borrower shall (and shall procure that each Group Company shall) comply in all respects with all laws, ordinances and regulations to which it/they may be subject, if failure so to comply has or would reasonably be expected to result in a Material Adverse Change; 8.1.2 each Borrower shall (and shall procure that each Group Company shall) obtain, effect and keep effective all permissions, licences, consents and permits which may from time to time be required to conduct its business, in each case to the extent that failure to so obtain, effect or keep effective would or would reasonably be likely to result in a Material Adverse Change. 8.1.3 each Borrower shall (and shall procure that each Group Company shall) do or cause to be done all things necessary to preserve, renew and keep in full force and effect its legal existence except in a transaction permitted under Clause 8.2.1 or 8.2.5; 8.1.4 each Borrower shall (and shall procure that each Group Company shall) comply in all respects with all laws to which it may be subject, if failure to so comply has or would reasonably be expected to result in a Material Adverse Change; 8.1.5 each Borrower shall (and shall ensure that each Group Company shall) comply with all Environmental Law and implement procedures reasonably designed to monitor compliance with and to prevent liability under any Environmental Law; 8.1.6 each Borrower shall (and to the extent any Loan Party has pledged its assets pursuant to a Security Document, each Borrower shall procure that such Loan Party shall) own only for its own account the Collateral free from all Security Interests and other interests and rights of every kind, except for Permitted Security Interests and Permitted Agreements; 8.1.7 the Borrower Representative shall provide to the Lender Representative, promptly upon becoming aware of them, the details of any litigation, arbitration or administrative proceedings which are current, threatened in writing or pending against any member of the Group and which would, if adversely determined, reasonably be expected to constitute a Material Adverse Change; 8.1.8 the Borrower Representative shall provide to the Lender Representative, promptly upon becoming aware of them, the details of any judgment or order of a court, arbitral body or agency which is made against any member of the Group and which would reasonably be expected to constitute a Material Adverse Change; 8.1.9 the Borrower Representative shall provide the Lender Representative with: (i) within [**] after the end of each fiscal year, its audited consolidated balance sheet and related audited consolidated statements of income, stockholders’ equity and cash flows showing the consolidated financial condition of the Borrower Representative and its consolidated Subsidiaries as of the close of such fiscal year and the results of its operations and the operations of such Subsidiaries during such year, together with comparative figures for the immediately preceding fiscal year, all audited by independent public accountants of recognized national standing and accompanied by an opinion of such accountants (which 25 opinion shall not include (i) an explanatory paragraph expressing substantial doubt about the ability of the Borrower Representative and its consolidated Subsidiaries to continue as a going concern or (ii) any qualification or exception as to the scope of such audit (provided that such opinion may contain exceptions, qualifications or explanatory paragraphs that are with respect to, or resulting from, (A) an upcoming maturity date under the Loan Facility or other indebtedness incurred in compliance with this Loan Agreement, (B) any actual or potential inability to satisfy a financial maintenance covenant, including the applicable financial covenant under Clause 8.3, on a future date or in a future period, (C) a “going concern” qualification or explanatory paragraph (or similar exception) with respect to liquidity or (D) an “emphasis of matter” paragraph) to the effect that such consolidated financial statements fairly present the financial condition and results of operations of the Borrower Representative and its consolidated Subsidiaries on a consolidated basis in accordance with GAAP consistently applied, together with a customary “management discussion and analysis” provision; (ii) within [**] after each of the first three fiscal quarters of each fiscal year of the Borrower Representative, its unaudited consolidated balance sheet and related unaudited consolidated statements of income, stockholders’ equity and cash flows showing the consolidated financial condition of the Borrower Representative and its consolidated Subsidiaries as of the close of such fiscal quarter and the results of its operations and the operations of such Subsidiaries during such fiscal quarter and the then elapsed portion of the fiscal year, and comparative unaudited figures for the same periods in the immediately preceding fiscal year, all certified by one of its Financial Officers as fairly presenting the financial condition and results of operations of the Borrower Representative and its consolidated Subsidiaries on a consolidated basis in accordance with GAAP consistently applied, subject to normal year-end audit adjustments, together with a customary “management discussion and analysis” provision; (iii) [reserved]; (iv) (A) concurrently with any delivery of financial statements under the foregoing clauses (i) and (ii) above and (B) within [**] after the end of each of the first two fiscal months of each fiscal quarter (commencing with the month ended February 29, 2024), a certificate of a Financial Officer in substantially the form attached as Schedule B to this Loan Agreement (a "Compliance Certificate"), (x) except with respect to any Compliance Certificate delivered pursuant to clause (B) above, certifying that no Default or Event of Default has occurred and is continuing or, if such a Default or Event of Default has occurred and is continuing, specifying the nature and extent thereof and any corrective action taken or proposed to be taken with respect thereto, (y) setting forth computations in reasonable detail satisfactory to the Lender Representative demonstrating compliance with the financial covenant contained in Clause 8.3 and (z) except with respect to any Compliance Certificate delivered pursuant to clause (B) above, including the details of any Group Company incorporated or acquired on or after the date of this Loan Agreement to the extent not previously disclosed to the Lender Representative; (v) at the request of the Lender Representative, after the date of delivery of the financial information required pursuant to the foregoing clauses (i) and (ii), the chief executive officer and/or the chief financial officer (or other applicable senior officer) of the Borrower Representative will hold and participate in a [**] conference call or teleconference at a time selected by the Borrower Representative and reasonably acceptable to the Lender Representative to (i) review such financial information with respect to the previous [**], and the financial condition of the Borrower Representative and its Subsidiaries and (ii) discuss the operating performance, clinical progress financial condition and strategy of the Group; (vi) within [**] of their approval by the relevant board of directors of such Group Company, a consolidated budget showing: (i) a projected quarterly consolidated profit and loss statement (presented in management statement format, excluding non-cash items such as depreciation, amortization, stock-compensation and non-recurring items), (ii) a projected quarterly cash forecast for the forthcoming financial year and (iii) solely to the extent available in the customary practice of the Group, a projected quarterly consolidated balance sheet, in each case in the form customarily prepared by the Borrower Representative (collectively, a "Budget"); (vii) any revised version of a Budget previously provided to the Lender Representative pursuant to clause (vi) above within [**] of the approval by the relevant board of directors of the relevant Group Company of such revised Budget; (viii) promptly after written request therefore, such further information regarding the financial condition, business and operations of any member of the Group as the Lender Representative may reasonably request; and (ix) all material documents or summaries thereof dispatched by the Borrower Representative and each other Group Company to all of its shareholders or to its secured creditors generally, promptly after the time they are delivered to the shareholders or secured creditors; provided that the Group shall not be required to disclose any such information that presents a conflict of interest, is confidential or otherwise protected by attorney-client privilege; provided, that any documents required to be delivered pursuant to Clause 8.1.9 (or to the extent any such documents are included in materials otherwise filed with the SEC) may be delivered electronically or by filing with the SEC and if so delivered or filed, shall be deemed to have been delivered on the date on which such documents are posted on the relevant internet or intranet website, if any, to which the Lender Representative has access (including EDGAR); provided that the Borrower shall notify (which may be by facsimile or electronic mail) the Lender Representative of the posting of any such documents described in clauses (i) and (ii) above and provide to 26 the Lender Representative by electronic mail electronic versions (i.e., soft copies) of such documents to the extent requested by the Lender Representative. 8.1.10 the Borrower Representative shall provide to the Lender Representative all documents, confirmations and evidence reasonably requested in writing by any Lender (through the Lender Representative) to satisfy its "know your customer" requirements or similar identification checks (including the USA PATRIOT Act) in order to meet its obligations from time to time under applicable money laundering, or similar, laws and regulations; 8.1.11 promptly upon becoming aware of a Vadadustat Withdrawal Event, the Borrower Representative shall provide notice thereof to the Lender Representative; 8.1.12 during the continuance of an Event of Default pursuant to Clause 9.1.2, 9.1.3 (solely with respect to a breach of Clause 8.3) or 9.1.7, at the written request of the Lender Representative, (x) the Lender Representative shall be entitled to have a representative attend all meetings of the Borrower Representative's (and each Group Company's) board of directors and/or any committee thereof in a non-voting observer capacity and (y) the Borrower Representative agrees to give notice of all such board and committee meetings to the Lender Representative at the same time as to its directors, and to facilitate attendance of the Lender Representative’s representative at such board and/or committee meetings; 8.1.13 each Borrower shall (and shall procure that each Loan Party shall) maintain in force and promptly obtain or renew all consents required: (i) for each Borrower and each other Loan Party to perform its obligations under the Loan Documents, as relevant; (ii) for the legality, validity, admissibility or enforceability of the Loan Documents; and (iii) for each Borrower and each other Loan Party to continue to own the Collateral (except to the extent such Collateral will cease to constitute Collateral as the result of a Permitted Transfer, Permitted Investment or other transaction expressly permitted by the terms of this Loan Agreement), and each Borrower shall, and shall procure that each Loan Party shall, comply with the terms of all such consents; 8.1.14 the Borrower Representative shall notify the Lender Representative promptly after it becomes aware of the occurrence of any Event of Default, and shall thereafter keep the Lender Representative fully up to date with all material developments as reasonably requested by the Lender Representative; 8.1.15 insurance matters: (i) the Borrower Representative shall (and shall ensure that each Group Company shall) maintain adequate risk protection through insurances on and in relation to its business and assets to the extent reasonably required on the basis of good business practice (as reasonably determined by the Borrower Representative), taking into account, inter alia, its (and any Group Company's) financial position and nature of operations. All insurances must be with reputable independent insurance companies or underwriters (as reasonably determined by the Borrower Representative); (ii) Subject to Clause 3.6, the Borrower Representative shall (A) use reasonable best efforts to ensure that the Lender Representative shall be named as (x) an additional insured with respect to the U.S. general liability insurance policies (which, for the avoidance of doubt, shall not include any directors and officers policies, workers compensation, business interruption policies or cyber policies) maintained by a Loan Party and (y) lender’s loss payee with respect to the U.S. general property insurance policies maintained by a Loan Party and (B) use commercially reasonable efforts to cause each such policy to provide that it shall not be cancelled, modified or not renewed (x) by reason of nonpayment of premium upon not less than [**] prior written notice thereof by the insurer to the Lender Representative (giving the Lender Representative the right to cure defaults in the payment of premiums) or (y) for any other reason upon not less than [**] prior written notice thereof by the insurer to the Lender Representative; provided that, unless an Event of Default shall have occurred and be continuing and the Lender Representative shall have exercised its rights pursuant to Clause 9.2 of this Loan Agreement, (1) all proceeds from insurance policies shall be paid to the applicable Loan Party, (2) to the extent any Lender receives any insurance proceeds, such Lender shall promptly turn over to the Borrower Representative such amounts received by it as an additional insured or lender’s loss payee, and (3) the Lender agrees that the Borrower Representative and/or its Subsidiaries shall have the sole right to adjust or settle any claims under such insurance; 8.1.16 subject to the Perfection Exceptions and any other exceptions, thresholds, limitations and deadlines contained in this Loan Agreement or the other Loan Documents, each Borrower shall at the request of the Lender Representative from time to time (and shall procure that each Group Company shall) promptly execute and deliver such further documents creating Security Interests in favour of the Lender Representative over such assets of the relevant Group Company and in such form as the Lender Representative may reasonably require in its discretion from time to time to: (i) secure all monies, obligations and liabilities of the Borrowers and/or any Group Company to the Lender Representative under the Loan Documents; (ii) facilitate the realisation of the Collateral (it being understood that the Collateral shall not be realized upon unless an Event of Default is continuing); and/or (iii) exercise the powers conferred on the Lender Representative or a receiver or administrator appointed under any Security Document; 27 8.1.17 each Borrower shall (and shall procure that each Group Company shall) maintain in good working order and condition (ordinary wear and tear excepted) all of its assets necessary or desirable in the conduct of its business (subject to Permitted Transfers, Permitted Investments or other transactions permitted pursuant to the terms of this Loan Agreement); 8.1.18 each Borrower shall (and it shall procure each Group Company shall): (i) preserve and maintain the subsistence and validity of all Intellectual Property material to the operation of its business; (ii) use commercially reasonable efforts to prevent, and take action against, any infringement in any material respect of the Intellectual Property necessary for its business; (iii) prosecute and maintain all applications and registrations in place in respect of material Intellectual Property which it has now or makes hereinafter and pay all registration fees and taxes necessary to maintain such Intellectual Property in full force and effect and record its interest in such Intellectual Property unless in Borrower’s reasonable judgement, such Intellectual Property is either (i) immaterial or (ii) no longer required in the ordinary course of the Group's business; and (iv) not use or permit the Intellectual Property necessary for its business to be used in a way or take any step or omit to take any step in respect of such Intellectual Property which would reasonably likely materially and adversely affect the existence or value of such Intellectual Property or imperil the right of the Group to use such Intellectual Property. 8.1.19 each Borrower shall (and shall procure that each Group Company shall) at all times comply with the requirements of all applicable Anti-Corruption Laws, Anti-Money Laundering Laws and Sanctions; 8.1.20 each Borrower shall (and shall procure that each Group Company shall) maintain in effect and enforce policies and procedures reasonably designed to promote compliance with applicable Anti-Corruption Laws, Anti-Money Laundering Laws and Sanctions; 8.1.21 each Borrower shall (and shall procure that each Group Company shall) pay and discharge all material Taxes imposed upon it or its assets within the time period allowed without incurring penalties unless and only to the extent that such payment is being contested in good faith, adequate reserves are being maintained for those Taxes and the costs required to contest them and reasonable details of which have been expressly notified to the Lender Representative in writing, and such payment can be lawfully withheld; 8.1.22 each Borrower shall (and shall procure that each Group Company shall) keep proper books of record and account in which full, true and correct entries in conformity with GAAP and all requirements of any applicable laws are made of all dealings and transactions in relation to its business and activities. 8.1.23 the Borrower Representative will, and will cause each of its Subsidiaries to, permit any representatives of the Lender Representative to visit and inspect the financial records and the properties of such person at reasonable times and as often as reasonably requested and to make extracts from and copies of such financial records, and permit any representatives designated by the Lender Representative to discuss the affairs, finances and condition of such person with the officers thereof; provided that if no Event of Default has occurred and is continuing, then the (i) the Lender Representative shall conduct no more than [**] such inspections per calendar year (in the aggregate for all such representatives) and (ii) Borrowers’ reimbursement obligations with respect to such inspections shall be limited to [**] (in the aggregate for all such representatives) per calendar year; 8.1.24 each Borrower shall (and shall procure that each Group Company shall) subordinate any existing and future loans between the Group Companies to the rights and interests hereunder pursuant to the Intercompany Subordination Agreement or another subordination agreement reasonably satisfactory to the Lender Representative; 8.1.25 if the Borrower Representative shall form or acquire any new direct or indirect Subsidiary (other than an Excluded Subsidiary) or any Subsidiary shall cease to be an Excluded Subsidiary, it shall, (i) within [**] after the acquisition, formation or cessation thereof, cause any such Subsidiary that is a Domestic Subsidiary to become a Loan Party and (ii) within [**] after the acquisition, formation or cessation thereof, cause any such Subsidiary that is a Foreign Subsidiary to become a Loan Party, in each case by delivering to the Lender Representative: (i) in the case of any such Subsidiary that is to become an additional Borrower, a duly executed joinder to this Loan Agreement in form and substance reasonably satisfactory to the Lender Representative; (ii) in the case of any such Domestic Subsidiary, a duly executed joinder to the Guarantee and Collateral Agreement, in form and substance reasonably satisfactory to the Lender Representative; (iii) in the case of any such Foreign Subsidiary, a New York law guarantee agreement and a security agreement governed by the laws of the jurisdiction of organization of such Foreign Subsidiary, in each case in form and substance reasonably satisfactory to the Lender Representative; (iv) such other duly executed Security Documents and schedules as required by the Guarantee and Collateral Agreement or applicable foreign law security agreement (including Intellectual Property security agreements, if applicable), consistent with the forms (if any) delivered on the Closing Date with respect to 28 the Borrower Representative or otherwise in form and substance reasonably satisfactory to the Lender Representative; (v) a customary certificate containing organizational documents, resolutions, a good standing certificate from the state of incorporation of such Subsidiary and an incumbency certificate, substantially consistent with the certificate delivered pursuant to Clause 3.5.1(i); and (vi) customary legal opinions from counsel to the Loan Parties (if customary in the relevant jurisdiction for such opinions to be provided by borrowers’ counsel) with respect to the above clauses (i) through (iv); and 8.1.26 if any Loan Party shall acquire any Material Property, it shall promptly notify the Lender Representative and, if reasonably requested by the Lender Representative, shall execute and deliver a customary mortgage (together with customary ancillary documents and deliverables) in favor of the Lender Representative within [**] of such request (all such properties that are subject to a mortgage, the “Mortgaged Properties”). 8.2 Negative Undertakings 8.2.1 each Borrower shall not (and shall procure that each Group Company shall not), by one or a series of transactions, whether related or not and whether at one time or over a period of time, sell, lease, convey, transfer, assign, licence or otherwise dispose of (each, a “Transfer”) any asset (including (but not limited to) by any form of sale and leaseback, invoice discounting or factoring), in each case other than the following (such following items, “Permitted Transfers”); (i) Transfers of inventory, equipment, accounts receivable, notes receivable or other current assets in the ordinary course of business (other than, for the avoidance of doubt, pursuant to factoring or receivables financing arrangements); (ii) the discount without recourse or sale or other disposition or conversion into notes receivable of unpaid and overdue accounts receivable arising in the ordinary course of business in connection with the compromise, collection or settlement thereof and not part of a financing transaction; (iii) Transfers of surplus, damaged, worn out or obsolete equipment that is, in the reasonable judgment of Borrower exercised in good faith, no longer economically practicable to maintain or useful in the ordinary course of business; (iv) the lease, assignment, license, sublicense or sublease of any real or personal property (other than Intellectual Property) in the ordinary course of business; (v) the surrender or waiver of obligations of trade creditors or customers or other contract rights that were incurred in the ordinary course of business, including pursuant to any plan of reorganization or similar arrangement upon the bankruptcy or insolvency of any trade creditor or customer or compromise, settlement, release or surrender of a contract, tort or other litigation claim, arbitration or other disputes; (vi) Transfers arising from foreclosures, condemnations, eminent domain, seizure, nationalization or any similar action with respect to assets, or dispositions of property subject to Casualty Events; (vii) Transfers of property to the extent that (i) such property is exchanged for credit against the purchase price of similar replacement property that is promptly purchased or (ii) the proceeds of such Transfer are applied to the purchase price of such replacement property (which replacement property is actually promptly purchased); (viii) the unwinding of swap contracts; (ix) Transfers that constitute Permitted Security Interests or Permitted Distributions, or that are made pursuant to the terms of any Permitted Agreement or Permitted Investment; (x) Transfers of cash and Cash Equivalents in the ordinary course of business for equivalent value and in a manner that is not prohibited by the terms of this Loan Agreement or the other Loan Documents; (xi) Transfers (A) between or among Loan Parties, (B) between or among Subsidiaries that are not Loan Parties, (C) from a Subsidiary that is not a Loan Party to a Loan Party, (D) of cash and Cash Equivalents to any MSC, so long as no Default or Event of Default is continuing (provided that such MSC may only hold such cash or Cash Equivalents in an investment account (which may not be subject to a Security Interest in favor of any other person (other than Security Interests arising as a matter of law in favor of the financial institution at which such account is located)) and invest such cash pursuant to the investment policy of the Group) and (E) from a Loan Party to a member of the Group (other than an MSC) that is not a Loan Party; provided that all such Transfers pursuant to this clause (E) shall not exceed $[**] in the aggregate in any fiscal year; (xii) (A) the sale or issuance of equity interests of any Subsidiary of Borrower to any Group Company and (B) the issuance of directors’ qualifying shares and shares issued to foreign nationals to the extent required by applicable law; 29 (xiii) any Transfer, abandonment, cancellation, non-renewal or discontinuance of use or maintenance of Intellectual Property of the Group that the Borrower Representative reasonably determines in good faith is (i) no longer useful to the business of the Group, (ii) no longer economically practicable to maintain in the ordinary course of business or (ii) is not material to the business of the Group (taken as a whole); (xiv) (i) the issuance or sale of any Permitted Convertible Debt by the Borrower Representative, (ii) the sale of any Permitted Warrant Transaction by the Borrower Representative, (iii) the purchase of any Permitted Bond Hedge Transaction by the Borrower Representative or (iv) the performance by the Borrower Representative of its obligations under any Permitted Convertible Debt, any Permitted Warrant Transaction or any Permitted Bond Hedge Transaction; and (xv) any other Transfer, provided that the fair market value of all property so Transferred pursuant to this clause (xv) shall not exceed $[**] in the aggregate in any fiscal year; 8.2.2 each Borrower shall not (and shall ensure that no Group Company shall) incur or allow to remain outstanding any Financial Indebtedness, other than the following (such following items, “Permitted Financial Indebtedness”): (i) under this Loan Agreement and the other Loan Documents; (ii) Existing Financial Indebtedness; (iii) indebtedness pursuant to intercompany arrangements permitted under Clause 8.2.6(xv); (iv) non-speculative hedging transactions in connection with protection against interest rate or currency fluctuations and forward purchase contracts, in each case, entered into in the ordinary course of business; (v) arising in the ordinary course of business with suppliers of goods or services with a maximum duration of [**] or that are being contested in good faith; (vi) customer deposits and advance payments received in the ordinary course of business from customers for goods purchased in the ordinary course of business; (vii) indebtedness arising as a result of operating leases entered into by any Group Company in the ordinary course of business; (viii) the Permitted Agreements (including any milestone payments or similar payments pursuant to the terms thereof); (ix) indebtedness not to exceed $[**] in the aggregate at any time outstanding, consisting of (i) indebtedness incurred to finance the purchase, lease, construction, installation, repair, or improvement of fixed or capital assets and (ii) capital lease obligations; (x) indebtedness of with respect to letters of credit entered into in the ordinary course of business in an amount not to exceed $[**] outstanding at any time; (xi) (i) indebtedness with respect to workers’ compensation claims, payment obligations in connection with health, disability or other types of social security benefits, unemployment or other insurance obligations, reclamation and statutory obligations or (ii) indebtedness related to employee benefit plans, including annual employee bonuses, accrued wage increases and 401(k) plan matching obligations; in each case, incurred in the ordinary course of business; (xii) indebtedness in respect of performance bonds, bid bonds, appeal bonds, surety bonds and completion guarantees and similar obligations arising in the ordinary course of business; (xiii) indebtedness in respect of (A) automated clearing house transactions and payment facilitation programs and (B) netting services, overdraft protection and other cash management services (including depository, credit, purchasing or debit card, corporate credit cards, non-card e-payable services, electronic funds transfer, treasury management services (including controlled disbursement services, return items and interstate depository network services), other demand deposit or operating account relationships, foreign exchange facilities, credit card processing services and merchant services), in each case of clauses (A) and (B), in the ordinary course of business and, in the case of clause (B), not to exceed $[**] in the aggregate outstanding at any time; (xiv) indebtedness consisting of the financing of insurance premiums in the ordinary course of business; (xv) indebtedness consisting of guarantees resulting from endorsement of negotiable instruments for collection by any Group Company in the ordinary course of business; (xvi) indebtedness created or arising under any royalty, synthetic royalty or other monetization or similar transaction and in each case incurred solely in connection with any properties or assets which do not 30 constitute Collateral under the Loan Documents; provided, however, that any such indebtedness is non-recourse to Borrower or any other Loan Party; (xvii) indebtedness consisting of (A) indemnities and purchase price adjustments and (B) obligations of a Person to pay an earn-out, milestone payment or similar contingent or deferred consideration to a counterparty incurred or created in connection with an acquisition, transfer, investment or other sale or disposition permitted under this Loan Agreement, including, with respect to any purchase price holdback in respect of a portion of the purchase price of an asset sold to that Person to satisfy unperformed obligations of the seller of such asset, any obligation to pay such seller the excess of such holdback over such obligations; provided, that any indebtedness incurred under this clause (B) shall not, when taken together with the aggregate outstanding amount of all other indebtedness incurred under this clause (B) after the Closing Date and prior to such time, exceed $[**] in the aggregate unless the Acquisition Consideration Condition is satisfied as of the date such indebtedness is incurred; (xviii) Permitted Convertible Debt; (xix) other Financial Indebtedness not to exceed $[**] in the aggregate outstanding at any time; (xx) guarantees of Permitted Financial Indebtedness incurred pursuant to clauses (i) through (xix) or (xxi); and (xxi) extensions, refinancings, modifications, amendments and restatements of Permitted Indebtedness in clauses (i) through (xx) above; provided, that the principal amount thereof is not increased (other than by any reasonable amount of premium (if any), interest (including post-petition interest), fees, expenses, charges or additional or contingent interest reasonably incurred in connection with the same and the terms thereof); 8.2.3 each Borrower shall not (and shall ensure that no other Group Company shall) create or permit to subsist any Security Interest over any of its assets, other than the following (such following items, “Permitted Security Interests”): (i) a Security Interest provided to the Lender Representative or any Lender under this Loan Agreement or any other Loan Document; (ii) any lien arising by operation of law or regulation (including landlords’, carriers’, warehousemen’s, mechanics’, materialmen’s, contractors’, suppliers of materials’, architects’ and repairmen’s Liens and other similar Liens), in each case, arising in the ordinary course of business and securing obligations that are not due and payable or are being contested in good faith; (iii) deposits to secure the performance of bids, trade contracts (other than for Indebtedness), leases (other than capital lease obligations), statutory obligations, surety and appeal bonds, performance bonds and other obligations of a like nature incurred in the ordinary course of business; (iv) Security Interests existing on the date hereof and set forth on Schedule F hereto; (v) Security Interests for material taxes, assessments or governmental charges (A) which are not yet [**] past due or payable or (B) which are being contested in good faith by appropriate proceedings and for which adequate reserves are being maintained to the extent required by GAAP; (vi) (A) pledges and deposits made in the ordinary course of business in compliance with workmen’s compensation, payroll taxes, unemployment insurance and other social security laws or regulations, (B) Security Interests made in the ordinary course of business securing liability for reimbursement or indemnification obligations of insurance carriers providing property, casualty or liability insurance to the Borrower Representative or any of its Subsidiaries, (C) Security Interests to secure performance of tenders, bids, leases, statutory or regulatory obligations, surety and appeal bonds, government contracts, performance and return-of-money bonds and other obligations of like nature, in each case other than for borrowed money and entered into in the ordinary course of business and (D) Security Interests in favor of customs and revenue authorities arising as a matter of law to secure payment of customs duties in connection with the importation and exportation of goods in the ordinary course of business; (vii) Security Interests (including the right of set-off) of a collection bank arising under Section 4-210 of the Uniform Commercial Code, or any comparable or successor provision, on items in the course of collection, and other Security Interests in favor of banks or other financial institutions incurred on deposits made in accounts held at such institutions in the ordinary course of business; provided that such Security Interests (A) are not given in connection with the incurrence of any Financial Indebtedness, (B) relate solely to obligations for administrative and other banking fees and expenses incurred in the ordinary course of business in connection with the establishment or maintenance of such accounts and (C) are within the general parameters customary in the banking industry; (viii) Security Interests arising from attachments or judgments, orders, or decrees in circumstances not constituting an Event of Default; 31 (ix) Security Interests that are contractual rights of set-off (A) relating to pooled deposit or sweep accounts of Borrower or any of its Subsidiaries to permit satisfaction of overdraft or similar obligations incurred in the ordinary course of business or (B) relating to purchase orders and other agreements entered into with customers of Borrower or any of its Subsidiaries in the ordinary course of business; (x) Security Interests solely on any cash earnest money deposits made by Borrower or any of its Subsidiaries in connection with any Permitted Acquisition, Permitted Investment or other acquisition of assets or properties not otherwise prohibited under this Loan Agreement; (xi) Security Interests on cash or Cash Equivalents securing obligations under Clause 8.2.2(x); (xii) Security Interests securing obligations under (A) Clause 8.2.2(ix), to the extent such Security Interests extend only to the assets and property the acquisition, lease, construction, installation, repair, replacement or improvement of which is financed thereby and any replacements, additions and accessions thereto and any income or profits thereof; provided, that individual financings provided by a lender may be cross collateralized to other financings provided by such lender or its affiliates or (B) Clause 8.2.2(iv); (xiii) Security Interests on specific items of inventory or other goods and proceeds of any person securing such person’s obligations in respect of bankers’ acceptances or letters of credit entered into in the ordinary course of business issued or created for the account of such person to facilitate the purchase, shipment or storage of such inventory or other goods, in an amount not to exceed $[**] in the aggregate outstanding at any time; (xiv) Security Interests disclosed by the title insurance policies delivered for any Mortgaged Property; (xv) servitudes, easements, rights-of-way, restrictions and other similar encumbrances on real property imposed by law and encumbrances consisting of zoning or building restrictions, easements, licenses, restrictions on the use of property or minor defects or other irregularities in title which, in the aggregate, are not material, and which do not in any case materially detract from the value of the property subject thereto or interfere with the ordinary conduct of the business of any Borrower or any of its Subsidiaries; (xvi) security given to a public utility or any municipality or governmental authority when required by such utility or authority in connection with the operations of a Group Company in the ordinary course of business; (xvii) to the extent constituting a Security Interest, escrow arrangements securing indemnification obligations associated with any Permitted Acquisition or Permitted Investment; (xviii) Security Interests in favor of any Loan Party; (xix) Security Interests arising from, or from Uniform Commercial Code financing statement filings regarding, operating leases or conditional sale, title retention, consignment or similar arrangements entered into by a Group Company in the ordinary course of business; (xx) Permitted Agreements; (xxi) judgment and attachment Security Interests not giving rise to an Event of Default pursuant to Clause 9.1.8 and notices of lis pendens and associated rights related to litigation being contested in good faith by appropriate proceedings and for which adequate reserves have been made; (xxii) other Security Interests not to exceed $[**] in the aggregate outstanding at any time; and (xxiii) the modification, replacement, extension or renewal of the Security Interests described in clauses (i) through (xxii) above; provided, however, that any such modification, replacement, extension or renewal must (A) be limited to the assets or properties encumbered by the existing Security Interest (and any additions, accessions, parts, improvements and attachments thereto and the proceeds thereof) and (B) not increase the principal amount of any Financial Indebtedness secured by the existing Security Interest (other than by any reasonable premium or other reasonable fees and expenses reasonably incurred in connection therewith). 8.2.4 each Borrower shall not (and shall ensure that no other Group Company shall): (i) declare, make or pay any dividend, charge, fee or other distribution (or interest on any unpaid dividend, charge, fee or other distribution) (whether in cash or in kind) on or in respect of its share capital (or any class of its share capital); (ii) repay or distribute any dividend or share premium reserve; (iii) pay any management, advisory or other fee to or to the order of any of its shareholders in their capacity as a shareholder; or 32 (iv) redeem, repurchase, defease, retire or repay any of its share capital or resolve to do so, without the prior written consent of the Lender Representative, in each case, other than Permitted Distributions. Notwithstanding the foregoing, and for the avoidance of doubt, this section shall not prohibit (i) the conversion or exchange by holders of (including any cash payment upon conversion or exchange), or required payment of any principal or premium on (including, for the avoidance of doubt, in respect of a required repurchase in connection with the redemption of Permitted Convertible Debt upon satisfaction of a condition related to the stock price of the Borrower Representative’s common stock) or required payment of any interest with respect to, any Permitted Convertible Debt in each case, in accordance with the terms of the indenture governing such Permitted Convertible Debt or (ii) the entry into (including the payment of premiums in connection therewith) or any required payment with respect to, or required early unwind or settlement of, any warrant relating to the Borrower Representative’s common stock (including, without limitation, the Warrant Instrument), Permitted Bond Hedge Transaction or Permitted Warrant Transaction, in each case, in accordance with the terms of the agreement governing such warrant relating to the Borrower Representative’s common stock (including, without limitation, the Warrant Instrument), Permitted Bond Hedge Transaction or Permitted Warrant Transaction. Notwithstanding the foregoing, Borrowers may repurchase, exchange or induce the conversion of Permitted Convertible Debt by delivery of shares of the Borrower Representative’s common stock and/or a different series of Permitted Convertible Debt; provided that, for the avoidance of doubt, substantially concurrently with, or a commercially reasonable period of time before or after, the related settlement date for the Permitted Convertible Debt that are so repurchased, exchanged or converted, Borrowers may exercise or unwind or terminate early (whether in cash, shares or any combination thereof) the portion of the Permitted Bond Hedge Transactions and Permitted Warrant Transactions, if any, corresponding to such Permitted Convertible Debt that is so repurchased, exchanged or converted; 8.2.5 each Borrower shall not (and shall procure that no other Group Company shall), enter into any amalgamation, demerger, merger or corporate reconstruction; provided that: (i) any Loan Party may merge, amalgamate or consolidate with (A) a Borrower, so long as such Borrower is the surviving entity or (B) any other Loan Party (other than a Borrower); (ii) any Group Company that is not a Loan Party may merge, amalgamate or consolidate with (i) any Loan Party, so long as such Loan Party is the surviving entity or (ii) any other Group Company that is not a Loan Party; (iii) any Group Company may liquidate or dissolve or change its legal form; provided that if such Group Company is a Loan Party, either (A) the validity, perfection and priority of the Security Interests securing the Loan Facility are not adversely affected thereby or (B) such Loan Party shall at or before the time of such liquidation or dissolution transfer its assets to another Loan Party; and (iv) any Group Company may enter into any amalgamation, demerger, merger or corporate reconstruction in order to effect a Permitted Transfer, Permitted Acquisition or other Permitted Investment; 8.2.6 each Borrower shall not (and shall procure that each Group Company shall not) (A) acquire any assets or equipment, other than in the normal course of business and upon an arm’s length basis, (B) acquire any equity interests of any third party, or any business unit or division of any third party, (C) invest in or acquire any shares, stocks, securities or other interest in any Joint Venture or transfer any assets or lend to or guarantee or give an indemnity for or give security for the obligations of a Joint Venture or maintain the solvency of or provide working capital to any Joint Venture (or agree to do any of the foregoing), or (D) be a creditor in respect of any Financial Indebtedness, in each case, other than the following (such items, “Permitted Investments”): (i) investments in Subsidiaries existing on the date hereof; (ii) investments shown on Schedule E; (iii) investments consisting of cash and Cash Equivalents; (iv) investments consisting of the endorsement of negotiable instruments for deposit or collection or similar transactions in the ordinary course of business; (v) guarantees of operating leases or of other obligations that do not constitute Financial Indebtedness, in each case, entered into in the ordinary course of business; (vi) non-cash Investments made in connection with reorganization activities otherwise permitted under this Loan Agreement or in connection with tax planning; (vii) investments that constitute Permitted Security Interests, Permitted Transfers or Permitted Distributions, or that are made in accordance with the terms of Permitted Agreements or Permitted Financial Indebtedness (including guarantees of Permitted Financial Indebtedness); (viii) investments consisting of (A) non cash loans to employees, officers or directors relating to the purchase of equity securities of the Borrower Representative pursuant to employee stock purchase plans, or agreements approved by Borrower’s Board of Directors, (B) advances or other investments to employees, 33 officers or directors to cover tax obligations in connection with the vesting of restricted stock issued to such employee, officer or director, (C) travel advances and employee relocation loans and other employee advances in the ordinary course of business in an amount not to exceed $[**] at any time outstanding, and (D) other loans to employees, officers or directors of any Group Company in an amount not to exceed, in the case of this clause (D), $[**] in the aggregate at any time outstanding; (ix) investments (including debt obligations) received in connection with the bankruptcy or reorganization of customers or suppliers and in settlement of delinquent obligations of, and other disputes with, customers or suppliers arising in the ordinary course of business; (x) investments consisting of notes receivable of, or prepaid royalties and other credit extensions, to customers, distributors, suppliers, licensors and licensees who are not Affiliates, in the ordinary course of business; (xi) Permitted Acquisitions; (xii) other investments consisting of (A) the formation of any Subsidiary for the purpose of effectuating a Permitted Acquisition, the capitalization of such Subsidiary whether by capital contribution or intercompany loans, in each case, to the extent otherwise permitted by the terms of this Loan Agreement, related investments in Subsidiaries necessary to consummate such Permitted Acquisition, and the receipt of any non-cash consideration in a Permitted Acquisition, and (B) earnest money deposits required in connection with a Permitted Acquisition or other acquisition of properties or assets not otherwise prohibited hereunder; (xiii) investments of any person that (A) becomes a Subsidiary after the date hereof, or (B) are assumed after the date hereof by any Subsidiary in connection with an acquisition of assets from such Person, in either case, in a Permitted Acquisition; (xiv) investments constituting the licensing of Intellectual Property expressly permitted under this Loan Agreement; (xv) investments by (i) any Loan Party in any other Loan Party, (ii) any Subsidiary which is not a Loan Party in any other Subsidiary which is not a Loan Party, (iii) any Subsidiary which is not a Loan Party in any Loan Party, (iv) any Loan Party in a Subsidiary which is not a Loan Party, in an amount not to exceed $[**] per fiscal year and (v) any Group Company in any MSC so long as no Default or Event of Default is continuing; (xvi) investments in connection with, and the performance of obligations under (including, for the avoidance of doubt, the entry into, payments of any premium with respect to, and the settlement of) any Permitted Bond Hedge Transactions and Permitted Warrant Transactions, in each case in accordance with its terms; and (xvii) other investments not to exceed $[**] in the aggregate per fiscal year; 8.2.7 notwithstanding any other provision of this Loan Agreement, each Borrower shall not request any Loan, and each Borrower shall not use, and shall ensure that no Group Company, its or their respective directors, officers, employees, agents and representatives shall use, the proceeds of any Loan, directly or knowingly indirectly, (i) in furtherance of an offer, payment, promise to pay, or authorization of the payment or giving of money, or anything else of value, to any person in violation of any applicable Anti-Corruption Laws, Anti-Money Laundering Laws or Sanctions, (ii) to fund, finance or facilitate any activities, business or transaction of or with any Sanctioned Person or in any Designated Jurisdiction, or (iii) in any other manner that would result in the violation by any party of any applicable Sanctions, Anti-Corruption Laws or Anti Money Laundering Laws; 8.2.8 each Borrower shall procure that no substantial change is made to the general nature of the business of the Borrower Representative or the Group from that carried on at the date of this Loan Agreement (or any business reasonably related, complementary, synergistic or ancillary thereto or reasonable extensions thereof); 8.2.9 each Borrower shall not (and shall procure that each Group Company shall not) make any distribution, whether in cash, property, securities or a combination thereof, other than regular scheduled payments of interest as and when due (to the extent not prohibited by any applicable subordination provisions) in respect of, or pay, or commit to pay, or directly or indirectly redeem, repurchase, retire or otherwise acquire for consideration, or set apart any sum for the aforesaid purposes, any Financial Indebtedness with an individual outstanding principal amount in excess of $[**] that is contractually subordinated to the Loan Facility (“Junior Debt”), or pay in cash any amount in respect of any Junior Debt that may at the obligor’s option be paid in kind or in other securities, in each case other than (i) under intercompany loans permitted to be incurred pursuant to this Loan Agreement, (ii) pursuant to the terms of any Permitted Agreement or (iii) refinancings of Permitted Financial Indebtedness to the extent such refinancing is permitted pursuant to Clause 8.2.2; 8.2.10 each Borrower shall not (and shall procure that each Group Company shall not) enter into, incur or permit to exist any agreement or other arrangement that prohibits, restricts or imposes any condition upon (A) the ability of any Borrower or any Loan Party to create, incur or permit to exist any Security Interest upon any of its property or assets, or (B) the ability of any Subsidiary to pay dividends or other distributions with respect to any of its equity interests or to make or repay loans or advances to any Borrower or any other Subsidiary or to guarantee Financial Indebtedness of any Borrower or any other Subsidiary; provided that the foregoing shall not apply to: 34 (i) restrictions in agreements listed on Schedules D, E, F or G; (ii) restrictions contained in the [**] or the [**]; (iii) restrictions and conditions imposed by law, rule, regulation or order; (iv) restrictions and conditions imposed by any Loan Document; (v) customary restrictions and conditions contained in agreements relating to the sale of a Subsidiary or any assets pending such sale, provided such restrictions and conditions apply only to the Subsidiary that is to be sold (or, in the case of an asset sale, only to the assets being sold) and such sale is permitted hereunder; (vi) restrictions or conditions imposed by any agreement relating to Permitted Agreements or secured Financial Indebtedness permitted by this Loan Agreement if such restrictions or conditions apply only to the property or assets that are the subject of such Permitted Agreement or that secures such Indebtedness; (vii) solely in the case of clause (A) above, customary provisions in leases, subleases, licenses, sublicenses and other contracts; (viii) customary provisions in leases, licenses and other contracts restricting assignment; and (ix) any restriction contained in agreements covering Permitted Financial Indebtedness; provided that (i) such restrictions contained will not materially affect the Borrowers’ ability to make anticipated principal or interest payments under this Loan Agreement (as determined by the Borrower Representative in good faith) or (ii) such restrictions taken as a whole are not materially less favorable to the Borrowers than the restrictions contained in this Loan Agreement and do not materially and adversely impair the Lender’s rights and remedies under this Loan Agreement (as determined by the Borrower Representative in good faith); 8.2.11 each Borrower shall not (and shall procure that each Group Company shall not) permit any waiver, supplement, modification, amendment, termination or release of (i) its certificate of incorporation, by-laws, operating, management or partnership agreement or other organizational documents or (ii) the [**] or the [**], in each case, that, taken as a whole, is materially adverse to the interests of the Lender in its capacity as such, other than pursuant to a transaction or action permitted by this Loan Agreement; 8.2.12 the Borrower Representative shall not change its fiscal year-end to a date other than December 31; 8.2.13 notwithstanding anything in this Loan Agreement to the contrary, the Borrower Representative and its Subsidiaries are permitted to enter into, maintain and perform their respective obligations under, the following agreements: (i) the [**], (ii) the [**], (iii) any agreement providing for the sale, financing or other monetization on commercially reasonable terms of non-U.S. royalties or milestones from the Borrowers’ proprietary products, vadadustat and Auryxia®, (iv) any agreements providing for the sale, financing or other monetization on commercially reasonable terms of U.S. royalties from vadadustat, subject to (x) a cap of [**]% royalty on net sales and (y) $[**] of total payments under any such outstanding agreements under this clause (iv) (other than any deferred compensation, milestone payments or similar arrangements) (clauses (i) through (iv), together with all documents related thereto, collectively, the “Permitted Royalty Agreements”) and (v) any Permitted License (together with the Permitted Royalty Agreements, collectively, “Permitted Agreements”); 8.2.14 notwithstanding anything in this Loan Agreement to the contrary, the Borrower Representative and its Subsidiaries are permitted to complete Capital Raise transactions and maintain and perform their respective obligations under any agreements related thereto; and 8.2.15 each Borrower shall: (i) not permit any MSC to engage in any business activities or have any assets or liabilities other than its ownership of cash and Cash Equivalents and liabilities incidental thereto; (ii) not permit any assets owned or held by any MSC or any equity interests issued by any MSC to be subject to any Security Interest (other than Security Interests arising as a matter of law in favor of the financial institution at which any account of an MSC is located); and (iii) during the continuance of an Event of Default, cause each MSC to, at the option of the Lender Representative, transfer all cash and Cash Equivalents held by such MSC to an account subject to a control agreement in favor of the Lender Representative within [**] of receipt by the Borrower Representative of a written request therefor by the Lender Representative. 8.3 Financial Covenant 8.3.1 The Borrower Representative shall ensure that, as of the last day of each fiscal month (commencing with the month ended February 29, 2024), either: 35 (i) Liquidity is greater than or equal to $15,000,000; or (ii) the consolidated revenue of the Group is greater than or equal to $150,000,000 for the 12-month period ending on such applicable test date. For the avoidance of doubt, only one of the two covenants contained in clauses (i) and (ii) is required to be satisfied, and if the Borrower shall be in compliance with one such covenant but not the other, that shall not constitute a Default or Event of Default. 9. EVENTS OF DEFAULT 9.1 An Event of Default occurs if: 9.1.1 [reserved]; 9.1.2 any Group Company fails to pay (i) any principal sum payable under any Loan Document or under any document relating to the Loan Documents when due and payable (or, if failure to pay is the result of an administrative error or technical problem, within [**] after the due date therefor), (ii) any interest payment payable under any Loan Document within [**] after the due date therefor or (iii) any other amount payable under any Loan Document within [**] after the due date therefor; provided that, in each case, if there has been a material disruption to those payment or communications systems or to those financial markets which are, in each case, required to operate in order for payments to be made in connection with this Loan Agreement and which disruption is not caused by, and is beyond the control of, any of the parties, failure to make such payment shall not result in an Event of Default so long as such payment is made within [**] after its due date; 9.1.3 any Group Company (as relevant) fails to perform any undertaking contained in Clause 8.1.3 (solely with respect to the Borrower), 8.2 or 8.3; 9.1.4 any Group Company (as relevant) fails to perform any undertaking (other than those described in Clause 9.1.2 or 9.1.3) contained in any Loan Document and such failure continues for [**] after the earlier of the date on which (i) a Financial Officer of any Group Company becomes aware of such failure and (ii) written notice thereof shall have been given to the Borrower Representative by the Lender Representative, unless the Lender Representative (at its sole discretion) notifies the Borrower Representative in writing that it is satisfied that the breach has not put any of the security for the Loan immediately at risk and that it considers that the breach is capable of remedy; 9.1.5 any representation, warranty or statement of fact made by, or by an officer of, any Group Company in any Loan Document or in the Drawdown Notice or any other notice or document relating to any Loan Document is incorrect, untrue or misleading in any material respect when it is made or deemed repeated; 9.1.6 (i) any principal or interest, regardless of amount, due in respect of any Material Financial Indebtedness is not paid when due (after the expiration of any grace periods therefor), (ii) any commitment for any Material Financial Indebtedness is cancelled by a creditor of any Group Company (other than at maturity or the stated expiration of such commitment, or any cancellation that is at the request of a Group Company), (iii) any Security Interest over any of the assets of any Group Company securing any Material Financial Indebtedness is enforced by the creditor thereof, or (iv) any other event or condition occurs that results in any Material Financial Indebtedness becoming due prior to its scheduled maturity or that enables or permits (with or without the giving of notice, but after the expiration of any grace periods therefor) the holder or holders of any Material Financial Indebtedness or any trustee or agent on its or their behalf to accelerate any Material Financial Indebtedness prior to its scheduled maturity; provided that this clause 9.1.6 shall not apply (a) to Financial Indebtedness that becomes due as a result of the sale or transfer or other disposition (including a Casualty Event) of property or assets and such Financial Indebtedness is repaid when required under the documents providing for such Indebtedness, (b) to events of default, termination events or any other similar event under the documents governing swap contracts for so long as such event of default, termination event or other similar event does not result in the occurrence of an early termination date or any acceleration or prepayment of any amounts or other Financial Indebtedness payable thereunder or (c) if the relevant breach under such Financial Indebtedness is remedied or validly waived by the creditors of such Financial Indebtedness prior to any acceleration of the Loans under this Loan Agreement pursuant to Clause 9.2; provided further, that this Clause 9.1.6 shall not apply to (x) any redemption, exchange, repurchase, conversion or settlement with respect to any Permitted Convertible Debt, or satisfaction of any condition giving rise to or permitting the foregoing, pursuant to their terms unless (i) such redemption, exchange, repurchase, conversion or settlement results from a default or event of default thereunder or an event of the type that constitutes an Event of Default, (ii) there is a failure to consummate such redemption, exchange, repurchase, conversion or settlement resulting in a default or event of default thereunder or an event of the type that constitutes an Event of Default or (iii) such redemption exchange, repurchase, conversion or settlement is not permitted under the Loan Documents, or (y) early payment requirement or unwinding or termination with respect to any Permitted Bond Hedge Transaction or Permitted Warrant Transaction, or satisfaction of any condition giving rise to or permitting the foregoing, in accordance with the terms thereof, so long as, in any such case, the Borrower Representative is not the “defaulting party” (or substantially equivalent term) under the terms of such Permitted Bond Hedge Transaction or Permitted Warrant Transaction, as applicable; 9.1.7 (i) an involuntary proceeding shall be commenced or an involuntary petition shall be filed in a court of competent jurisdiction seeking (i) relief in respect of the Borrower Representative or any Subsidiary, or of a substantial part of the property or assets of the Borrower Representative or a Subsidiary, under Title 11 of the United States Code, as now constituted or hereafter amended, or any other Federal, state, provincial, territorial or foreign bankruptcy, insolvency, receivership or similar law, (ii) the appointment of a receiver, interim receiver, receiver and manager, administrator, examiner, monitor, trustee, custodian, sequestrator, conservator or similar official for the Borrower Representative or any Subsidiary) or for a substantial part of the property or assets of the Borrower Representative 36 or a Subsidiary or (iii) the winding-up or liquidation of the Borrower Representative or any Subsidiary and, in each case, such proceeding or petition shall continue undismissed or unstayed for [**], or an order or decree approving or ordering any of the foregoing shall be entered; or (ii) the Borrower Representative or any Subsidiary shall (i) voluntarily commence any proceeding or file any petition seeking relief under Title 11 of the United States Code, as now constituted or hereafter amended, or any other Federal, state, provincial, territorial or foreign bankruptcy, insolvency, receivership or similar law, (ii) consent to the institution of, or fail to contest in a timely and appropriate manner, any proceeding or the filing of any petition described in clause (i) above, (iii) apply for or consent to the appointment of a receiver, interim receiver, receiver and manager, administrator, examiner, monitor, trustee, custodian, sequestrator, conservator or similar official for the Borrower Representative or such Subsidiary or for a substantial part of the property or assets of the Borrower Representative or such Subsidiary, or (iv) make a general assignment for the benefit of creditors; 9.1.8 any final judgment or order of a court, arbitral body or agency for the payment of money is made in relation to the Loan Documents or the transactions contemplated by the Loan Documents or against any member of the Group or its assets which have, or has, or are, or would reasonably be likely to have a Material Adverse Change (solely to the extent not covered by independent third-party insurance or indemnification as to which the insurer or indemnitor has been notified of such judgement, order or award and has affirmed coverage thereof in writing); 9.1.9 there is a Change of Control in any Group Company; for purposes of this Clause 9.1.9, a "Change of Control" shall mean any of the following events (whether in one or in a series of related transactions): (A) the sale of all or substantially all the assets of the Group to any person other than a Group Company or (B) a person or “group” (within the meaning of Rule 13d-5 under the U.S. Securities Exchange Act of 1934, as in effect on the date hereof, but excluding any employee benefit plan of such person and its subsidiaries and any person or entity acting in its capacity as trustee, agent or other fiduciary or administrator of any such plan), acquires beneficial ownership of more than [**]% of the voting stock of the Borrower Representative (determined on a fully diluted basis); provided that the Lender Representative may agree, by written notice to the Borrower Representative, that a Change of Control shall not be deemed an Event of Default, but that nevertheless the consequences set forth in Clause 9.2.1 and 9.2.2 shall apply, and in such event the Loan, all accrued interest and all other amounts accrued, owing or payable under the Loan Documents shall be due and payable simultaneously with the closing of the Change of Control transaction; 9.1.10 (i) Any material provision of the Loan Documents proves to have been or becomes invalid or unenforceable other than as permitted under the Loan Documents, (ii) subject to the Perfection Exceptions, a Security Interest created by the Security Documents over any material portion of the Collateral ceases to be a valid, perfected, first priority Security Interest in the Collateral covered thereby, other than as expressly permitted under the Loan Documents or (iii) the Borrower Representative or any other Loan Party repudiates or rescinds a Loan Document or purports in writing to repudiate or rescind a Loan Document (other than in connection with the end or termination of the Security Period), except, in each case, as a result of the failure of the Lender or the Lender Representative to (x) maintain possession of certificates actually delivered to it representing securities pledged under the Loan Documents, (y) maintain possession of instruments actually delivered to it representing indebtedness pledged under the Loan Documents or (z) file UCC continuation statements or amendments; 9.1.11 any guaranty under the Security Documents for any reason shall cease to be in full force and effect (other than in accordance with its terms or as otherwise permitted under the Loan Documents) or any guarantor shall deny in writing that it has any further liability under the Security Documents (other than as a result of the discharge of such guarantor in accordance with the terms of the Loan Documents); 9.1.12 a Material Adverse Change occurs; or 9.1.13 an ERISA Event or a Foreign Benefit Event shall have occurred that, when taken together with all other such ERISA Events and Foreign Benefit Events, would reasonably be expected to result in liability of any Borrower in an aggregate amount that would result in a Material Adverse Change. 9.2 Lender's Rights At any time during the continuance of any Event of Default, the Lender Representative may: 9.2.1 serve on the Borrower Representative a notice stating that all obligations of the Lender to the Borrower Representative under this Loan Agreement including (without limitation) the obligation to advance the Loan (or any part thereof) are terminated; 9.2.2 serve on the Borrower Representative a notice stating that, the Loan, all interest and all other amounts accrued, owing or payable under the Loan Documents are immediately due and payable; 9.2.3 serve on the Borrower Representative a notice stating that, the Loan, all interest and all other amounts accrued, owing or payable under the Loan Documents are due and payable on demand; 9.2.4 declare the Security Documents to be enforceable; and/or 9.2.5 take any other action which, as a result of the Event of Default or any notice served under Clauses 9.2.1 or 9.2.2 above, the Lender is entitled to take under the Security Documents or any applicable law. 37 9.3 End of Lender’s Obligations. At the time of service of a notice under Clause 9.2.1 and/or Clause 9.2.2, all the obligations of the Lender to the Borrower Representative to extend new Loans under this Loan Agreement shall terminate. 9.4 Acceleration (a) Other than with respect to any Event of Default occurring under Clause 9.1.7, on the service of a notice under Clause 9.2.2 the following sums shall become immediately due and payable and (b) with respect to any Event of Default occurring under 9.1.7, the following sums shall automatically become immediately due and payable, in each case without presentment, demand, protest or any other notice of any kind, all of which are hereby expressly waived by the Borrower Representative and each other Group Company: 9.4.1 the outstanding principal amount of the Loan; 9.4.2 all accrued and unpaid interest; 9.4.3 all unpaid End of Loan Payments; 9.4.4 all unpaid fees, costs and expenses; and 9.4.5 all other outstanding sums payable by the Borrowers to the Lender under the Loan Documents. 9.5 Waiver of Event of Default The Lender Representative, at its sole and absolute discretion, may waive any Default or Event of Default hereunder, prior to or after the event or events giving rise thereto, provided that such waiver may be effected only by written notice provided by the Lender Representative to the Borrower Representative to that effect (and subject further to Clause 15.3 below); it being understood and acknowledged, that if and so long as no notice of waiver of a Default or an Event of Default was so provided, such Default or Event of Default shall be deemed as having occurred and in effect for all purposes hereunder (subject to the Borrower Representative’s right to remedy or cure a Default). 10. FEES, EXPENSES AND TAXES 10.1 Transaction Fee The Transaction Fee shall be paid by the Borrower Representative to the Lender Representative upon the date of this Loan Agreement, or with respect to the portion thereof that is not payable on the date of this Loan Agreement in respect of Tranche B and Tranche C, on the earliest to occur of (i) the date Tranche B or Tranche C, as appliable, is first funded, (ii) the date that the commitments in respect of Tranche B or Tranche C, as applicable, are terminated or cancelled and (iii) the date on which the availability period of Tranche B or Tranche C, as applicable, terminates (in each case in accordance with the Loan Facility Terms). 10.2 End of Loan Payments The End of Loan Payment shall accrue on the amount of each Tranche and shall be payable in respect of each Tranche on the earlier of: (i) the date on which the Loan is prepaid in full or otherwise falls due for repayment in full (whether at maturity or by acceleration); and (ii) the date on which the final payment by the Borrowers in respect of the relevant Tranche is due for payment (whether at maturity or by acceleration). 10.3 Documentary Costs 10.3.1 The Borrowers shall promptly pay to the Lender Representative within [**] of the Lender Representative's written demand (accompanied by a reasonably detailed invoice), the reasonable and documented out-of-pocket expenses (including reasonable and documented out-of-pocket legal expenses of one external counsel and one local counsel for each applicable jurisdiction) incurred by the Lender in connection with: (i) the negotiation, execution, preparation and perfection of the Loan Documents entered into on or around the date of this Loan Agreement and the transactions contemplated hereby and thereby; (ii) the negotiation, execution, preparation and perfection of Security Documents after the date of this Loan Agreement and the transactions contemplated thereby; (iii) any amendment or supplement to the Loan Documents, or any proposal for such an amendment to be made; and (iv) any consent or waiver by the Lender concerned under or in connection with the Loan Documents or any request by the Borrower Representative for such a consent or waiver. 10.3.2 The Borrowers shall promptly pay to the Lender Representative within [**] of the Lender Representative's written demand (together with a reasonably detailed invoice), the reasonable and documented out-of-pocket expenses (including reasonable and documented out-of-pocket legal expenses of one external counsel and one local counsel for each applicable 38 jurisdiction) incurred by the Lender in connection with any step taken by the Lender with a view to the protection or enforcement of any right or Security Interest created by the Loan Documents. 10.4 Certain Taxes and Duties 10.4.1 [Reserved]. 10.4.2 Where any Borrower is required by the Loan Documents to pay, reimburse or indemnify the Lender for any cost or expense, each Borrower, at the same time as it pays, reimburses or indemnifies (as the case may be) the Lender for such cost or expense, shall also pay, reimburse or indemnify such part thereof as represents VAT, save to the extent that the Lender reasonably determines that it is entitled to a credit or repayment in respect of such VAT from the relevant Tax authority. 10.4.3 All amounts expressed to be payable under a Loan Document by any Borrower to the Lender which (in whole or in part) constitute the consideration for any supply for VAT purposes are deemed to be exclusive of any VAT which is chargeable on that supply, and accordingly, if VAT is or becomes chargeable on any supply made by the Lender to a Borrower under a Loan Document and the Lender is required to account to the relevant tax authority for the VAT, such Borrower must pay to the Lender (in addition to and at the same time as paying any other consideration for such supply) an amount equal to the amount of the VAT (subject to the Lender providing a valid VAT invoice to such Borrower). 10.4.4 In relation to any supply made by the Lender to the Borrower under a Loan Document, if reasonably requested by the Lender Representative, the Borrower must promptly provide the Lender Representative with details of the Borrower’s VAT registration and such other information as is reasonably requested in connection with the Lender’s VAT reporting requirements in relation to such supply. 10.4.5 Any reference in Clauses 10.4.2, 10.4.3, and 10.4.5 to any Party shall, at any time when such Party is treated as a member of a group for VAT purposes, include (where appropriate and unless the context otherwise requires) a reference to the representative member of such group at such time (the term "representative member" to have the same meaning as in the United Kingdom Value Added Tax Act 1994 and shall include any similar or equivalent term in any other jurisdiction). 10.5 Liability for Taxes 10.5.1 Each Borrower shall make all payments to be made by it without any Tax deduction, unless a Tax deduction is required by law. Each Borrower shall promptly upon becoming aware that it must make a Tax deduction (or that there is any change in the rate or the basis of a Tax deduction) notify the Lender Representative. 10.5.2 If any Borrower is required to make any Tax deduction by law from any payment due under the Loan Documents, such Borrower shall be entitled to make such Tax deduction, and, if such Tax is an Indemnified Tax, the payment due from such Borrower shall be increased to an amount which (after making such Tax deduction, including such Tax deduction applicable to additional sums payable under this Clause 10.5) leaves an amount equal to the amount which would have been due for payment if no Tax deduction had been required. 10.5.3 The Borrowers shall timely pay to the relevant Governmental Authority in accordance with applicable law, or at the option of the Lender Representative timely reimburse it for the payment of, any Other Taxes. 10.5.4 The Borrowers shall indemnify each Lender, within [**] after demand therefor, for the full amount of any Indemnified Taxes (including Indemnified Taxes imposed or asserted on or attributable to amounts payable under this Clause 10.5) payable or paid by such Lender or required to be withheld or deducted from a payment to such Lender and any reasonable expenses arising therefrom or with respect thereto, whether or not such Indemnified Taxes were correctly or legally imposed or asserted by the relevant Governmental Authority. A certificate as to the amount of such payment or liability delivered to the Borrower Representative by the Lender Representative shall be conclusive absent manifest error. 10.5.5 If any Borrower is required to make a Tax deduction, such Borrower shall make that Tax deduction and any payment required in connection with that Tax deduction within the time allowed and in the minimum amount required by law. 10.5.6 Within [**] of making either a Tax deduction or any payment required in connection with that Tax deduction, the Borrower Representative shall deliver to the Lender Representative evidence reasonably satisfactory to it that the Tax deduction has been made or (as applicable) any appropriate payment paid to the relevant taxing authority. 10.5.7 Each Lender shall deliver to the Borrower Representative, at the time or times reasonably requested by the Borrower Representative, such properly completed and executed documentation reasonably requested by the Borrower Representative as will permit such payments to be made without withholding or at a reduced rate of withholding. In addition, each Lender, if reasonably requested by the Borrower Representative, shall deliver such other documentation prescribed by applicable law or reasonably requested by the Borrower Representative as will enable the Borrowers to determine whether or not such Lender is subject to backup withholding or information reporting requirements. Notwithstanding anything to the contrary in the preceding two sentences, the completion, execution and submission of such documentation (other than such documentation set forth in Clause 10.5.7(i), Clause 10.5.7(ii) and Clause 10.5.7(iv)) shall not be required if in the Lender’s reasonable judgment such completion, execution or submission would subject such Lender to any material unreimbursed cost or expense or would materially prejudice the legal or commercial position of such Lender. Without limiting the generality of the foregoing, 39 (i) if a Lender is a U.S. Person, it shall deliver to the Borrower Representative on or prior to the date on which such Lender becomes a Lender under this Loan Agreement (and from time to time thereafter upon the reasonable request of the Borrower Representative), executed copies of IRS Form W-9 certifying that such Lender is exempt from U.S. federal backup withholding tax; (ii) if a Lender is not a U.S. Person, to the extent it is legally entitled to do so, it shall deliver to the Borrower Representative (in such number of copies as shall be requested by the Borrower Representative) on or prior to the date on which such Lender becomes a Lender under this Loan Agreement (and from time to time thereafter upon the reasonable request of the Borrower Representative), whichever of the following is applicable: (1) if such Lender is claiming the benefits of an income tax treaty to which the United States is a party (x) with respect to payments of interest under any Loan Document, executed copies of IRS Form W- 8BEN or IRS Form W-8BEN-E establishing an exemption from, or reduction of, U.S. federal withholding Tax pursuant to the “interest” article of such tax treaty and (y) with respect to any other applicable payments under any Loan Document, IRS Form W-8BEN or IRS Form W-8BEN-E establishing an exemption from, or reduction of, U.S. federal withholding Tax pursuant to the “business profits” or “other income” article of such tax treaty; (2) executed copies of IRS Form W-8ECI; (3) if such Lender is claiming the benefits of the exemption for portfolio interest under Section 881(c) of the Code, (x) a certificate substantially in the form of Exhibit A-1 to the effect that such Lender is not a “bank” within the meaning of Section 881(c)(3)(A) of the Code, a “10 percent shareholder” of any Borrower within the meaning of Section 871(h)(3)(B) of the Code, or a “controlled foreign corporation” related to any Borrower as described in Section 881(c)(3)(C) of the Code (a “U.S. Tax Compliance Certificate”) and (y) executed copies of IRS Form W-8BEN or IRS Form W-8BEN- E; or (4) if the Lender is not the beneficial owner, executed copies of IRS Form W-8IMY, accompanied by IRS Form W-8ECI, IRS Form W-8BEN, IRS Form W-8BEN-E, a U.S. Tax Compliance Certificate substantially in the form of Exhibit A-2 or Exhibit A-3, IRS Form W-9, or other certification documents from each beneficial owner, as applicable; provided that if such Lender is a partnership and one or more direct or indirect partners of the Lender are claiming the portfolio interest exemption, such Lender may provide a U.S. Tax Certificate substantially in the form of Exhibit A-4 on behalf of each such direct and indirect partner; (iii) if a Lender is not a U.S. Person, to the extent it is legally entitled to do so, deliver to the Borrower Representative (in such number of copies as shall be requested by the Borrower Representative) on or prior to the date on which such Lender becomes a Lender under this Loan Agreement (and from time to time thereafter upon the reasonable request of the Borrower Representative), executed copies of any other form prescribed by applicable law as a basis for claiming exemption from or a reduction in U.S. federal withholding Tax, duly completed, together with such supplementary documentation as may be prescribed by applicable law to permit the Borrowers to determine the withholding or deduction required to be made; and (iv) if a payment made to any Lender under any Loan Document would be subject to U.S. federal withholding Tax imposed by FATCA if such Lender were to fail to comply with the applicable reporting requirements of FATCA (including those contained in Section 1471(b) or 1472(b) of the Code, as applicable), such Lender shall deliver to the Borrower Representative at the time or times prescribed by law and at such time or times reasonably requested by the Borrower Representative such documentation prescribed by applicable law (including as prescribed by Section 1471(b)(3)(C)(i) of the Code) and such additional documentation reasonably requested by the Borrower Representative as may be necessary for the Borrowers to comply with their obligations under FATCA and to determine that such Lender has complied with such Lender’s obligations under FATCA or to determine the amount, if any, to deduct and withhold from such payment. Solely for purposes of this Clause 10.5.7(iv), “FATCA” shall include any amendments made to FATCA after the date of this Loan Agreement. 10.5.8 [Reserved] 10.5.9 If any Lender determines, in its sole discretion exercised in good faith, that it has received a refund of any Taxes as to which it has been indemnified pursuant to this Clause 10.5 (including by the payment of additional amounts pursuant to this Clause 10.5), it shall pay to the Borrowers an amount equal to such refund (but only to the extent of indemnity payments made under this Clause 10.5 with respect to the Taxes giving rise to such refund), net of all out-of-pocket expenses (including Taxes) of such Lender and without interest (other than any interest paid by the relevant Governmental Authority with respect to such refund). The Borrowers, upon the request of a Lender, shall repay to such Lender the amount paid over pursuant to this Clause 10.5.9 (plus any penalties, interest or other charges imposed by the relevant Governmental Authority) in the event that such Lender is required to repay such refund to such Governmental Authority. Notwithstanding anything to the contrary in this Clause 10.5.9, in no event will any Lender be required to pay any amount to the Borrowers pursuant to this Clause 10.5.9 the payment of which would place such Lender in a less favourable net after-Tax position than such Lender would have been in if the Tax subject to indemnification and giving rise to such refund had not been deducted, withheld or otherwise imposed and the indemnification payments or additional amounts with respect to such Tax had never been paid. This Clause 10.5.9 shall not be construed to require any Lender to make available its Tax returns (or any other information relating to its Taxes that it deems confidential) to the Borrowers or any other Person. 10.5.10 Each party’s obligations under this Clause 10.5 shall survive the resignation or replacement of any Lender or any assignment of rights by, or the replacement of, any Lender, the termination, expiration or cancellation of the commitments and the repayment, satisfaction or discharge of all obligations under any Loan Document. 10.5.11 If any Lender requests compensation under Clause 10.6 or requests any Borrower to pay any Indemnified Taxes or additional amounts to such Lender pursuant to Clause 10.5, then such Lender shall (at the request of the Borrower Representative) use reasonable efforts to, as applicable, designate a different lending office for funding or booking its Loans hereunder or to assign its rights and obligations hereunder to another of its offices, branches or affiliates, if, in the judgment of such Lender, such designation or assignment (i) would eliminate or reduce amounts payable pursuant to Clause 10.6 or Clause 10.5, as the case may be, in the future, and (ii) would not subject such Lender to any unreimbursed cost or expense and would not otherwise be disadvantageous to such Lender. The Borrowers hereby agree to pay all reasonable costs and out-of-pocket expenses incurred by such Lender in connection with any such designation or assignment. 40 10.6 Illegality and Increased Costs 10.6.1 If it is or becomes contrary to any law or regulation for the Lender to make available the Loan Facility or to maintain its obligations to do so or fund the Loan, the Lender shall promptly notify the Borrower Representative whereupon: (i) the Lender's obligations to make the Loan Facility available shall be terminated; and (ii) the Borrowers shall be obliged to prepay the Loan either: (a) forthwith; or (b) on a future specified date on or before the latest date permitted by the relevant law or regulation. 10.6.2 If the result of any change that occurs after the Closing Date in (or in the interpretation, administration or application of), or to the generally accepted interpretation or application of, or the introduction of, any law or regulation is to subject the Lender to any Increased Cost, then: (i) the Lender shall notify the Borrower Representative in writing of such event promptly upon its becoming aware of the same; and (ii) the Borrowers shall, within [**] of written demand (together with a reasonably detailed invoice), pay to the Lender the amount of the Increased Costs which the Lender has suffered as a result. 11. INDEMNITIES 11.1 Indemnity for Non-Scheduled Payments Without derogating from, and without prejudice to the Lender's right under, Clause 10 above, the Borrowers shall indemnify the Lender and its Affiliates and the respective partners, directors, trustees, officers, employees, members, agents, administrators, managers and representatives of the Lender and its Affiliates (the foregoing persons, each an “Indemnitee”) fully on its demand in respect of all expenses, liabilities and losses (but not lost profit) which are suffered or incurred by such Indemnitee (except for such expenses, liabilities and losses due solely to such Indemnitee’s gross negligence or willful misconduct) as a result of or in connection with: 11.1.1 any Tranche not being borrowed on the date specified in the Drawdown Notice for any reason other than a default by the Lender; 11.1.2 any failure (for whatever reason) by the Borrowers to make payment of any amount due under the Loan Documents on the due date or, if so payable, on demand; or 11.1.3 the occurrence and/or continuance of an Event of Default and/or the acceleration of repayment of the Loan under Clause 9.4. 11.2 [Reserved]. 11.3 Third Party Claims Indemnity The Borrowers shall indemnify each Indemnitee fully on its demand in respect of claims, demands, proceedings, liabilities, losses and reasonable, documented expenses of every kind, including without limitation legal fees and expenses for one external counsel (and one local counsel for each relevant jurisdiction) ("liability items") which may be made or brought against, or incurred by, such Indemnitee (except for such expenses, liabilities and losses due solely to such Indemnitee’s gross negligence or willful misconduct), in any country, in relation to: 11.3.1 any action lawfully taken, or omitted or neglected to be taken, under or in connection with the Loan Documents by such Indemnitee or by any receiver appointed under the Security Documents after the occurrence of any Event of Default; and 11.3.2 any breach or inaccuracy of any of the representations and warranties contained in Clause 7 of this Loan Agreement or in the Security Documents or any breach of any undertaking contained in Clause 8 hereof or elsewhere in the Loan Documents. Notwithstanding anything herein to the contrary, Clause 11 of this Loan Agreement shall not apply with respect to Taxes other than Taxes that represent expenses, liabilities and losses arising from any non-Tax claim. 12. [RESERVED] 13. RELEASE OF SECURITY 13.1.1 The Lender hereby irrevocably agrees that the Security Interests granted to the Lender Representative or any Lender on any Collateral shall be immediately and automatically released, in each case, without any further action by any person: (i) upon payment in full of all obligations under the Loan Documents (other than contingent indemnification obligations and expense reimbursement obligations as to which no claim has been asserted); (ii) upon the sale, disposition, distribution or other transfer of such Collateral, as part of or in connection with any transaction permitted hereunder or under each other Loan Document, in each case to a person that is not a Loan Party; (iii) that constitutes an Excluded Asset (as defined in the Guarantee and Collateral Agreement) as a result of an occurrence not prohibited under this Loan Agreement; or 41 (iv) to the extent such Collateral is owned by a Subsidiary Guarantor, upon release of such Subsidiary Guarantor from its obligations under its guaranty pursuant to clause 13.1.2 below; 13.1.2 The Lender hereby irrevocably agrees that a Subsidiary Guarantor shall be immediately and automatically released from any applicable guaranty and all other obligations under the Loan Documents if such Subsidiary Guarantor ceases to be a Subsidiary or otherwise becomes an Excluded Subsidiary as a result of a transaction permitted under this Loan Document. 13.1.3 In each case described in Clauses 13.1.1 and 13.1.2, the Lender Representative shall (at the cost of the Borrowers, to the extent required by Clause 10.3) promptly take all appropriate action, and execute and deliver to the Borrower Representative all documents, required (or reasonably requested by the Borrower Representative) to evidence the release of the Security Interest in the applicable Collateral or the release of the guaranty and other obligations of the applicable Subsidiary Guarantor (including the prompt return of possessory Collateral held by the Lender that is released from the Security Interest created by the Security Documents; provided that in the event that the Lender had previously acknowledged receipt of possessory collateral and loses or misplaces any such possessory collateral, the Lender shall provide a loss affidavit to the Borrower Representative, in a form reasonably satisfactory to the Borrower Representative). 13.1.4 In the case of Clause 13.1.3, upon the Lender Representative’s reasonable request, the Borrower Representative shall deliver to the Lender Representative a certificate certifying that the applicable transaction causing the release of Security Interests or release of the Subsidiary Guarantor has been consummated in compliance with this Loan Agreement and the other Loan Documents and that such release is permitted by this Loan Agreement (and for the avoidance of doubt, no other documentation or information shall be required to be provided by the Borrower Representative or any other Group Company). 14. NOTICES 14.1 Any notice, demand or other communication (“Notice”) to be given by any Party under, or in connection with, this Loan Agreement shall be in writing and signed by or on behalf of the Party giving it. Any Notice shall be served by sending it by email to the address set out in Clause 14.2, or delivering it by hand or by pre-paid first class post to the address set out in Clause 14.2 and in each case marked for the attention of the relevant Party set out in Clause 14.2 (or as otherwise notified from time to time in accordance with the provisions of this Clause 14). Any Notice so served by email, post or hand shall be deemed to have been duly given or made as follows: 14.1.1 if sent by email, at the time of transmission; or 14.1.2 in the case of delivery by hand, when delivered, or 14.1.3 in the case of delivery by first class post, on the second Business Day after posting, provided that in each case where delivery by hand occurs after 5pm on a Business Day (local time in the place of receipt) or on a day which is not a Business Day, service shall be deemed to occur at 9am on the next following Business Day (local time in the place of receipt). References to time in this Clause are to local time in the country of the addressee. 14.2 The addresses and email addresses of the Parties for the purpose of Clause 14 are as follows: 14.2.1 Lender: Address: Kreos Capital VII (UK) Limited, c/o BlackRock Investment Management (UK) Limited – Private Debt-EMEA Venture & Growth Lending Group 12 Throgmorton Avenue, London EC2N 2DL For the attention of: [**] Email: [**] with copies to: Email: [**] For the attention of: [**] and: The Office of the General Counsel (EMEA) (Legal Transactions Group) 42 Email: [**] For the attention of: [**] 14.2.2 Borrowers: Address 245 First Street, Cambridge, MA 02142 For the attention of: Chief Financial Officer and Chief Legal Officer Email: [**] with a copy to: Latham & Watkins LLP 555 11 Street NW, Suite 1000 th Washington, DC 20004 Attention: [**] Email: [**] 14.3 A Party may notify the other Party to this Loan Agreement of a change to its name, relevant addressee, address or email address for the purposes of this Clause 14, provided that such notice shall only be effective on: 14.3.1 the date specified in the notification as the date on which the change is to take place; or 14.3.2 if no date is specified or the date specified is less than five (5) Business Days after the date on which notice is given, the date following five (5) Business Days after notice of any change has been given. 14.4 In proving service it shall be sufficient to prove that the envelope containing such notice was properly addressed and sent or delivered to the address shown thereon or that the facsimile transmission was made and a facsimile confirmation report was received, as the case may be. 15. GENERAL 15.1 All agreements, covenants, representations, warranties and indemnities of the Borrowers contained in this Loan Agreement or in the Drawdown Notices or other documents delivered pursuant hereto or in connection herewith and continuing, shall survive and remain binding following the execution and delivery, and the expiration, cancellation or other termination of this Loan Agreement and/or the Drawdown Notice. 15.2 [Reserved]. 15.3 No failure to exercise, nor any delay in exercising, on the part of the Lender, any right or remedy hereunder shall operate as a waiver, nor shall any single or partial exercise of any right or remedy prevent any further or other exercise, or the exercise of any other right or remedy. The rights and remedies provided in this Loan Agreement are cumulative and not exclusive of any rights or remedies provided by law or in equity. Waiver by the Lender of any default shall not constitute waiver of any other default. 15.4 During the continuance of an Event of Default, the Lender may set off any matured obligation due from the Borrowers or any other Loan Party under the Loan Documents against any matured obligation owed by the Lender to that party, regardless of the place of payment, booking branch or currency of either obligation. If the obligations are in different currencies, the Lender may convert either obligation at a market rate of exchange in its usual course of business for the purpose of the set-off. 15.5 No Borrower may assign or transfer its rights, benefits or obligations under this Loan Agreement. The Lender shall have the right, in its sole discretion, to assign, sell, pledge, grant a Security Interest in or otherwise encumber its rights under the Loan Documents and/or one or more Drawdown Notices to any third party (an "Assignee"), and/or may act as an agent for any Assignee in accepting any Drawdown Notice; provided that (A) the Lender may not assign the Loan to any competitor of the Borrower or the Group (as identified in writing to the Lender Representative from time to time) or any Loan to Own Investor (collectively, "Disqualified Institutions") and (B) as long as no Event of Default has occurred and is continuing, the Lender may not assign the Loan (other than assignments made to Affiliates and Related Funds) without the prior written consent of the Borrower Representative. Each Borrower agrees that if it receives notice from the Lender that it is to make payments under this Loan Agreement and/or any Drawdown Notice to such Assignee rather than to the Lender, or that any of its other obligations under the relevant Drawdown Notice are to be owed to the named Assignee, each Borrower shall comply with any such notice (to the extent the assignment to such Assignee was made in accordance with the terms of this Loan Agreement). Subject to the foregoing, this Loan Agreement and each Drawdown Notice inures to the benefit of, and is binding upon, the successors and assigns of the Lender. The Lender, or any agent appointed by it, in either case acting solely for this purpose as an agent of the Borrowers, shall maintain a register (the “Register”) for the recordation of (i) the name and address of the Lender, and the commitments of, and principal 43 amounts (and stated interest) of the Loans owing to, the Lender pursuant to the terms thereof from time to time and (ii) any transfers. The entries in the Register shall be conclusive absent manifest error. The Register shall be available for inspection by the Borrowers and the Lender at any reasonable time and from time to time upon reasonable prior notice. The obligations of the Borrowers under the Loan Agreement and the Security Documents are registered obligations and the right, title and interest of the Lender and its Assignees in and to such obligations shall be transferable only upon notation of such transfer in the Register. This Clause 15.5 shall be construed so that such obligations are at all times maintained in “registered form” within the meaning of Sections 163(f), 871(h)(2) and 881(c)(2) of the Code and any related regulations (and any other relevant or successor provisions of the Code or such regulations). 15.6 The Lender agrees to keep all Confidential Information confidential and not to disclose it to anyone, save to the extent permitted by Clauses 15.7 to 15.9, and to ensure that all Confidential Information is protected with security measures and a degree of care that would apply to its own confidential information. 15.7 The Lender may disclose: 15.7.1 to any of its Affiliates and Related Funds, limited partners, investors and any of its or their officers, directors, employees, professional advisers, auditors, partners and Representatives such Confidential Information as the Lender shall consider appropriate if any person to whom the Confidential Information is to be given pursuant to this clause is informed in writing of its confidential nature and that some or all of such Confidential Information may be price-sensitive information except that there shall be no such requirement to so inform if the recipient is subject to professional obligations to maintain the confidentiality of the information or is otherwise bound by requirements of confidentiality in relation to the Confidential Information; 15.7.2 to any person appointed by the Lender or by a person to whom clause 15.8.1 or 15.8.2 applies to provide administration or settlement services (including sustainability service providers, valuation advisors, custodians and depositaries) in respect of one or more of the Loan Documents such Confidential Information as may be required to be disclosed to enable such service provider to provide services if the service provider to whom the Confidential Information is to be given has entered into a form of confidentiality undertaking agreed between the Borrower Representative and Lender; and 15.7.3 to any rating agency (including its professional advisers) such Confidential Information as may be required to be disclosed to enable such rating agency to carry out its normal rating activities in relation to the Loan Documents and/or the Group Companies. 15.8 The Lender may additionally disclose to any person: 15.8.1 to (or through) whom it assigns or transfers (or may potentially assign or transfer) all or any of its rights and/or obligations under the Loan Documents, and to any of that person's Affiliates, Related Funds, Representatives and professional advisers; 15.8.2 with (or through) whom it enters into (or may potentially enter into), whether directly or indirectly, any sub-participation in relation to, or any other transaction under which payments are to be made or may be made by reference to, one or more Loan Document and/or one or more Group Company and to any of that person's Affiliates, Related Funds, Representatives and professional advisers; 15.8.3 appointed by the Lender or by a person to whom clause 15.8.1 or 15.8.2 applies to receive communications, notices, information or documents delivered pursuant to the Loan Documents on its behalf; 15.8.4 who invests in or otherwise finances (or may potentially invest in or otherwise finance), directly or indirectly, any transaction referred to in clause 15.8.1 or 15.8.2 or leverage providers; 15.8.5 to whom information is required or requested to be disclosed by any court of competent jurisdiction or any governmental, banking, taxation or other regulatory authority or similar body, the rules of any relevant stock exchange or pursuant to any applicable law or regulation; 15.8.6 to whom information is required to be disclosed in connection with, and for the purposes of, any litigation, arbitration, administrative or other investigations, proceedings or disputes; 15.8.7 party to the Loan Documents; or 15.8.8 with the consent of the Borrower Representative, in each case, such Confidential Information as the Lender shall consider appropriate if: (i) in relation to Clauses 15.8.1 to 15.8.3, the person to whom the Confidential Information is to be given has entered into a Confidentiality Undertaking except that there shall be no requirement for a Confidentiality Undertaking if the recipient is a professional adviser and is subject to professional obligations to maintain the confidentiality of the Confidential Information; (ii) in relation to Clause 15.8.4, the person to whom the Confidential Information is to be given has entered into a Confidentiality Undertaking or is otherwise bound by requirements of confidentiality in relation to the Confidential Information they receive and is informed that some or all of such Confidential Information may be price-sensitive information; and (iii) in relation to Clauses 15.8.5 and 15.8.6, the person to whom the Confidential Information is to be given is informed of its confidential nature and that some or all of such Confidential Information may be price-sensitive information except that there shall be no requirement to so inform if, in the opinion of the Lender, it is not practicable so to do in the circumstances. 44 15.9 The Lender may disclose to any national or international numbering service provider appointed by it to provide identification numbering services in respect of this Loan Agreement, the Loans and/or one or more Group Company the following information: 15.9.1 the names, country of domicile and place of incorporation of the Group Companies; 15.9.2 the date of this Loan Agreement (and any amendment and restatement agreement); 15.9.3 the governing law and jurisdiction of this Loan Agreement; 15.9.4 the amount, currencies, types, ranking and term of the Loans; 15.9.5 changes to any of the information previously supplied pursuant to the above; and 15.9.6 such other information agreed between the Lender and the Borrower Representative, to enable such numbering service provider to provide its usual syndicated loan numbering identification services. 15.10 The Parties acknowledge and agree that each identification number assigned to this Loan Agreement, the Loans and/or one or more Group Companies by a numbering service provider and the information associated with each such number may be disclosed to users of its services in accordance with the standard terms and conditions of that numbering service provider. 15.11 The Borrowers and each other Group Company shall keep confidential the terms of this Loan Agreement except: (a) as may be required by law (including SEC disclosure rules and regulations, it being understood that a copy of this Loan Agreement shall be publicly filed) or a court of competent jurisdiction, or as requested or required by any governmental or regulatory authority; (b) to the extent the relevant information is already in the public domain other than by reason of improper disclosure by a Group Company in violation of any confidentiality obligations hereunder; (c) the Group Companies may disclose the terms of this Loan Agreement and the other Loan Documents to its Affiliates and to the officers, directors, agents, employees, attorneys, accountants, advisors or controlling persons (and, in each case, each of their attorneys and advisors) of any Group Company or any of its Affiliates; (d) to the extent necessary in connection with the enforcement of the Group’s rights under the Loan Documents; and (e) if the Lender Representative consents in writing to such proposed disclosure. 15.12 [Reserved]. 15.13 [Reserved]. 15.14 This Loan Agreement may not be modified except in writing executed by the Lender Representative and the Borrowers. No supplier or agent of the Lender is authorised to bind the Lender or to waive or modify any term of this Loan Agreement. 15.15 In any litigation or arbitration proceedings arising out of or in connection with a Loan Document, the entries made in the accounts maintained by the Lender are prima facie evidence of the matters to which they relate. 15.16 Any certification or determination by the Lender Representative of a rate or amount under any Loan Document is, in the absence of manifest error, conclusive evidence of the matters to which it relates. 15.17 This Loan Agreement may be executed in counterparts (including facsimile and .pdf copies), each of which shall be an original, but all such counterparts shall together constitute one and the same instrument. 15.18 Each of the parties hereto agrees and acknowledges that (a) the transaction consisting of this Loan Agreement may be conducted by electronic means, (b) it is such party’s intent that, if such party signs this Loan Agreement using an electronic signature, it is signing, adopting and accepting this Loan Agreement and that signing this Loan Agreement using an electronic signature is the legal equivalent of having placed its handwritten signature on this Loan Agreement on paper and (c) it is being provided with an electronic or paper copy of this Loan Agreement in a usable format. The words “execution,” “signed,” “signature,” and words of like import in any Loan Document or any amendment or other modification thereof (including waivers and consents) shall be deemed to include electronic signatures or the keeping of records in electronic form, each of which shall be of the same legal effect, validity or enforceability as a manually executed signature or the use of a paper-based recordkeeping system, as the case may be, to the extent and as provided for in any applicable law, including the Federal Electronic Signatures in Global and National Commerce Act, the New York State Electronic Signatures and Records Act, or any other similar state laws based on the Uniform Electronic Transactions Act. 45 15.19 THIS LOAN AGREEMENT AND THE OTHER LOAN DOCUMENTS (OTHER THAN AS EXPRESSLY SET FORTH IN OTHER LOAN DOCUMENTS) SHALL BE CONSTRUED IN ACCORDANCE WITH AND GOVERNED BY THE LAWS OF THE STATE OF NEW YORK. 15.20 This Loan Agreement shall become effective when it shall have been executed by the Borrowers and the Lender and when the Lender Representative shall have received counterparts hereof which, when taken together, bear the signatures of each of the other parties hereto. 15.21 Notwithstanding anything herein to the contrary, if at any time the interest rate applicable to any Loan, together with all fees, charges and other amounts which are treated as interest on such Loan under applicable law (collectively the “Charges”), shall exceed the maximum lawful rate (the “Maximum Rate”) that may be contracted for, charged, taken, received or reserved by the Lender or participation in accordance with applicable law, the rate of interest payable in respect of such Loan or participation hereunder, together with all Charges payable in respect thereof, shall be limited to the Maximum Rate and, to the extent lawful, the interest and Charges that would have been payable in respect of such Loan or participation but were not payable as a result of the operation of this Section shall be cumulated and the interest and Charges payable to the Lender in respect of other Loans or participations or periods shall be increased (but not above the Maximum Rate therefor) until such cumulated amount, together with interest thereon at the Federal Funds Effective Rate to the date of repayment, shall have been received by such Lender. 15.22 This Loan Agreement and the other Loan Documents constitute the entire contract between the parties relative to the subject matter hereof. Any other previous agreement among the parties with respect to the subject matter hereof is superseded by this Loan Agreement and the other Loan Documents. Nothing in this Loan Agreement or in the other Loan Documents, expressed or implied, is intended to confer upon any person (other than the parties hereto and thereto, their respective successors and assigns permitted hereunder and, to the extent expressly contemplated hereby, the related parties of the Lender) any rights, remedies, obligations or liabilities under or by reason of this Loan Agreement or the other Loan Documents. 15.23 EACH PARTY HERETO HEREBY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY RIGHT IT MAY HAVE TO A TRIAL BY JURY IN RESPECT OF ANY LITIGATION DIRECTLY OR INDIRECTLY ARISING OUT OF, UNDER OR IN CONNECTION WITH THIS LOAN AGREEMENT OR ANY OF THE OTHER LOAN DOCUMENTS. EACH PARTY HERETO (A) CERTIFIES THAT NO REPRESENTATIVE, AGENT OR ATTORNEY OF ANY OTHER PARTY HAS REPRESENTED, EXPRESSLY OR OTHERWISE, THAT SUCH OTHER PARTY WOULD NOT, IN THE EVENT OF LITIGATION, SEEK TO ENFORCE THE FOREGOING WAIVER AND (B) ACKNOWLEDGES THAT IT AND THE OTHER PARTIES HERETO HAVE BEEN INDUCED TO ENTER INTO THIS LOAN AGREEMENT AND THE OTHER LOAN DOCUMENTS, AS APPLICABLE, BY, AMONG OTHER THINGS, THE MUTUAL WAIVERS AND CERTIFICATIONS IN THIS SECTION. 15.24 In the event any one or more of the provisions contained in any Loan Document should be held invalid, illegal or unenforceable in any respect, the validity, legality and enforceability of the remaining provisions contained herein and therein shall not in any way be affected or impaired thereby (it being understood that the invalidity of a particular provision in a particular jurisdiction shall not in and of itself affect the validity of such provision in any other jurisdiction). The parties shall endeavor in good-faith negotiations to replace the invalid, illegal or unenforceable provisions with valid provisions the economic effect of which comes as close as possible to that of the invalid, illegal or unenforceable provisions. 15.25 Each party hereto irrevocably and unconditionally submits, for itself and its property, to the exclusive jurisdiction of any New York State court or Federal court of the United States of America sitting in the Borough of Manhattan in New York City, and any appellate court from any thereof, in any action or proceeding arising out of or relating to this Loan Agreement or the other Loan Documents, or for recognition or enforcement of any judgment, and each of the parties hereto irrevocably and unconditionally agrees that all claims in respect of any such action or proceeding may be heard and determined in such New York State or, to the extent permitted by law, in such Federal court. Each of the parties hereto agrees that a final judgment in any such action or proceeding shall be conclusive and may be enforced in other jurisdictions by suit on the judgment or in any other manner provided by law. Nothing in this Loan Agreement shall affect any right that the Lender may otherwise have to bring any action or proceeding relating to this Loan Agreement or the other Loan Documents against any Borrower or its properties in the courts of any jurisdiction. 15.26 Each party hereto irrevocably and unconditionally waives, to the fullest extent it may legally and effectively do so, any objection which it may now or hereafter have to the laying of venue of any suit, action or proceeding arising out of or relating to this Loan Agreement or the other Loan Documents in any New York State or Federal court. Each of the parties hereto irrevocably waives, to the fullest extent permitted by law, the defense of an inconvenient forum to the maintenance of such action or proceeding in any such court. 15.27 The Lender notifies the Borrowers that pursuant to the requirements of the USA PATRIOT Act, it is required to obtain, verify and record information that identifies the Borrowers, which information includes the name and address of the Borrowers and other information that will allow the Lender to identify the Borrowers in accordance with the USA PATRIOT Act. 15.28 Notwithstanding anything to the contrary in any Loan Document or in any other agreement, arrangement or understanding among any such parties, each party hereto acknowledges that any liability of any Affected Financial Institution arising under any Loan Document, to the extent such liability is unsecured, may be subject to the write-down and conversion powers of the applicable Resolution Authority and agrees and consents to, and acknowledges and agrees to be bound by: 46 15.28.1 the application of any Write-Down and Conversion Powers by the applicable Resolution Authority to any such liabilities arising hereunder which may be payable to it by any party hereto that is an Affected Financial Institution; and 15.28.2 the effects of any Bail-In Action on any such liability, including, if applicable: (i) a reduction in full or in part or cancellation of any such liability; (ii) a conversion of all, or a portion of, such liability into shares or other instruments of ownership in such Affected Financial Institution, its parent undertaking, or a bridge institution that may be issued to it or otherwise conferred on it, and that such shares or other instruments of ownership will be accepted by it in lieu of any rights with respect to any such liability under any Loan Document; or (iii) the variation of the terms of such liability in connection with the exercise of the write-down and conversion powers of the applicable Resolution Authority. 15.29 Each Borrower hereby irrevocably appoints the Borrower Representative, as the agent for such Borrower on its behalf, to (i) request Loans from the Lender, (ii) to give and receive notices under the Loan Documents and (iii) take all other action which the Borrower Representative or the Borrowers are permitted or required to take under this Loan Agreement (including entering into amendments to any Loan Document). Each warranty, covenant, agreement and undertaking made on behalf of a Borrower or the Borrower Representative shall be deemed for all purposes to have been made by such Borrower and shall be binding upon and enforceable against such Borrower to the same extent as if the same had been made directly by such Borrower. Each Borrower hereby agrees that such Borrower is jointly and severally liable for, and hereby absolutely and unconditionally guarantees to the Lender, the full and prompt payment (whether at stated maturity, by acceleration or otherwise) and performance of, all obligations owed or hereafter owing to the Lender by each other Borrower. [Remainder of page left blank intentionally] 47 Duly executed by the Parties on the date first set out on the first page of this Loan Agreement. BORROWER and BORROWER REPRESENTATIVE AKEBIA THERAPEUTICS, INC. By: /s/ Ellen Snow Name: Ellen Snow Title: Chief Financial Officer 48 LENDER and LENDER REPRESENTATIVE Signed For and on behalf of KREOS CAPITAL VII (UK) LIMITED Authorised signatory By: /s/ Aris Constantinides Name: Aris Constantinides Title: Director 49 Exhibit 10.103 Execution Version THIS WARRANT AGREEMENT (this “Agreement”), is made and entered into as of January 29, 2024 (the “Effective Date”), by and between Akebia Therapeutics, Inc., a Delaware corporation (the “Company”), and Kreos Capital VII Aggregator SCSp (“Holder”). WARRANT AGREEMENT Recitals In order to induce Kreos Capital VII (UK) Limited (“Lender”) to enter into that certain Loan Agreement dated as of January 29, 2024 (the “Loan Agreement”), between the Company, as borrower, and Lender, as lender, the Company has agreed to issue to Holder (an Affiliate of the Lender), upon the occurrence of certain events, Warrants (as defined below) to purchase such number of shares of Common Stock, par value $0.00001 (the “Common Stock”), of the Company (the “Warrant Shares” and, together with such Warrants and all shares of Common Stock (as defined below) or other securities, if any, issuable upon conversion of the Warrants, the “Securities”), and at such exercise price, as determined pursuant to this Agreement. Terms 1. Definitions. Terms used in this Agreement and not otherwise defined shall have the meaning given to them in the Loan Agreement. In addition to terms separately defined in this Agreement, as used in this Agreement, the following terms have the following meanings: “Affiliate” means with respect to any specified entity, any other entity that, directly or indirectly through one or more intermediaries, controls, or is controlled by, or is under common control with, the specified entity, where the term “control”, “controlled”, or “controlling” as used in this definition means the possession, directly or indirectly, of the power to direct or cause the direction of the management and policies of an entity, whether through the ownership of voting securities, by contract or otherwise. “Related Fund” in relation to a fund or account (the "first fund"), means: (i) a fund or account which is managed or advised by the same investment manager or investment adviser as the first fund; or (ii) if it is managed by a different investment manager or investment adviser, a fund or account whose investment manager or investment adviser is an Affiliate of the investment manager or investment adviser of the first fund; or (iii) that investment manager or investment adviser itself. “Warrant” means a warrant to purchase Warrant Shares issued by the Company pursuant to this Agreement and in the form set forth on Exhibit A. 2. Issuance of Warrants. 3,076,923 Warrant Shares upon the closing of the transactions contemplated by the Loan Agreement (the “Initial Issue Date”). (a) Initial Warrant. The Company shall issue a Warrant (the “Initial Warrant”) reflecting the Holder’s right to purchase Tranche C Warrant. The Company shall issue a Warrant (the “Tranche C Warrant”) reflecting the Holder’s right to purchase 1,153,846 Warrant Shares upon the first drawdown of Tranche C as contemplated by the Loan Agreement (the “Tranche C Issue Date” and together with the Initial Issue Date, as applicable, the “Issue Date”). (b) be equal to $1.30 (the “Exercise Price”). (c) Shares; Exercise Price. The Exercise Price per Warrant Share for the Initial Warrant and the Tranche C Warrant shall exchange of documents. At the Warrant Closing, the Company (d) Warrant Closings; Deliveries. The closing of a Warrant issuance (a “Warrant Closing”) shall take place remotely via shall deliver an original Warrant dated as of the date of the Warrant Closing, duly executed by an authorized officer of the Company. 3. follows: Representations and Warranties of the Company. The Company represents and warrants to, and agrees with, the Holder as (a) The Warrant Shares and all shares of Common Stock or other securities, if any, issuable upon conversion of the Warrant Shares shall, upon issuance in accordance with the terms of the applicable Warrant, be duly authorized, validly issued, fully paid and non-assessable, and free of any liens and encumbrances except for restrictions on transfer provided for herein or under applicable federal and state securities laws. The Company covenants that it shall, if applicable, at all times following an Issue Date described in Section 2(a) or Section 2(b) of this Agreement, as applicable, cause to be reserved and kept available out of its authorized and unissued capital stock such number of shares of Common Stock and other securities as will be sufficient to permit the exercise in full of the Warrant and the conversion of the Warrant Shares into Common Stock or such other securities. securities laws, the Company will use its commercially reasonable efforts to obtain such approvals or registrations as may be appropriate. (b) If the issuance of any of the Securities require approvals or registrations under applicable state “blue sky” or federal (c) Any corporate action required to be taken by the Board of Directors and/or stockholders of the Company in order to authorize the Company to enter into this Agreement and the Warrant, and to issue the applicable Securities has been taken or, with respect to the Securities, will be taken prior to the date of issuance of such Securities. All action on the part of the officers of the Company necessary for the execution and delivery of this Agreement and the Warrant and the performance of all respective obligations of the Company thereunder has been taken or, in the case of the Warrant, will be taken prior to date of issuance of the Warrant. This Agreement constitutes, and the Warrant will constitute, valid and legally binding obligations of the Company, enforceable against the Company in accordance with their respective terms except (i) as limited by applicable bankruptcy, insolvency, reorganization, moratorium, fraudulent conveyance, or other laws of general application relating to or affecting the enforcement of creditors’ rights generally and (ii) as limited by laws relating to the availability of specific performance, injunctive relief, or other equitable remedies. (d) Assuming the accuracy of the Holder’s representations and warranties in Section 4 of this Agreement, the execution, delivery and performance of the Agreement will not result in any violation or be in conflict with or constitute, with or without the passage of time and giving of notice, (i) a default under any law applicable to the Company or any instrument, judgment, order, writ, decree, contract or agreement to which the Company is a party or by which its assets are bound except such defaults as would not reasonably be expected to materially and adversely affect the Company; or (ii) an event which results in the creation of any lien, charge or encumbrance upon any assets of the Company or the suspension, revocation, forfeiture, or nonrenewal of any material permit or license applicable to the Company. 4. Representations and Warranties of Holder. Holder represents and warrants to the Company as of the date hereof, and as of the date of issuance of the Warrant, as follows: Purchase for Own Account. The applicable Securities are being acquired for investment for Holder’s account, not as a nominee or agent, and not with a view to the public resale or distribution within the meaning of the U.S. Securities Act of 1933, as amended (the “Securities Act”). Holder also represents that it has not been formed for the specific purpose of acquiring any of the Securities. (a) (b) Disclosure of Information. Holder is aware of the Company’s business affairs and financial condition and has received or has had access to all the information it considers necessary or appropriate to make an informed investment decision with respect to the acquisition of the applicable Securities. Holder further has had an opportunity to ask questions and receive answers from the Company regarding the terms and conditions of the applicable Securities and to obtain additional information (to the 2 extent the Company possessed such information or could acquire it without unreasonable effort or expense) necessary to verify any information furnished to Holder or to which Holder has access. (c) Investment Experience. Holder understands that the purchase of the Securities involves substantial risk. Holder has experience as an investor in securities of companies in the development stage and acknowledges that Holder can bear the economic risk of such Holder’s investment in the Securities and has such knowledge and experience in financial or business matters that Holder is capable of evaluating the merits and risks of its investment in the applicable Securities and/or has a preexisting personal or business relationship with the Company and certain of its officers, directors or controlling persons of a nature and duration that enables Holder to be aware of the character, business acumen and financial circumstances of such persons. under the Securities Act. (d) Accredited Investor Status. Holder is an “accredited investor” within the meaning of Regulation D promulgated (e) The Securities Act. Holder understands that the applicable Securities will not be registered under the Securities Act in reliance upon a specific exemption therefrom, which exemption depends upon, among other things, the bona fide nature of the Holder’s investment intent as expressed herein. Holder understands any Securities issued must be held indefinitely unless subsequently registered under the Securities Act and qualified under applicable state securities laws, or unless exemption from such registration and qualification are otherwise available. 5. Restrictive Legends. legend substantially similar to the following (in addition to any other legend required by applicable law): (a) Legend. Holder understands that any certificates representing the Securities shall be stamped or imprinted with a THIS WARRANT AND THE SHARES ISSUABLE HEREUNDER AND ANY SHARES ISSUABLE UPON CONVERSION THEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), OR THE SECURITIES LAWS OF ANY STATE AND MAY NOT BE OFFERED, SOLD, PLEDGED OR OTHERWISE TRANSFERRED UNLESS AND UNTIL REGISTERED UNDER SAID ACT AND LAWS OR, IN THE OPINION OF LEGAL COUNSEL IN FORM AND SUBSTANCE SATISFACTORY TO THE ISSUER, SUCH OFFER, SALE, PLEDGE OR OTHER TRANSFER IS EXEMPT FROM SUCH REGISTRATION. Instructions Regarding Transfer Restrictions. Holder consents to the Company making a notation on its records and giving instructions to any transfer agent, if applicable, in order to implement the restrictions on transfer established in Section 5(a) of this Agreement. (b) (c) Removal of Legend. The legend identified in Section 5(a) of this Agreement stamped or imprinted on any certificate evidencing any Securities and any stock transfer instructions and record notations with respect to such Securities, if applicable, shall be removed and the Company shall issue a certificate without such legend to the holder of such Securities if (i) such Securities are registered under the Securities Act, or (ii) such holder provides the Company with an opinion of counsel reasonably satisfactory to the Company and its transfer agent, if applicable, to the effect that a sale or transfer of such Securities may be made without registration or qualification. The Company agrees that it shall not require an opinion of counsel if (x) there is no material question as to the availability of Rule 144 (without restriction, including the provisions of Rule 144(c), (e) or (f)) promulgated under the Securities Act or (y) the transfer is to an Affiliate or Related Fund of Holder, provided that any such transferee is an “accredited investor” as defined in Regulation D promulgated under the Securities Act. 6. Transfer of the Securities. The Securities may not be transferred or assigned in whole or in part except in compliance with applicable federal and state securities laws by the transferor and the transferee. 7. General Provisions. 3 (a) Entire Agreement. This Agreement (including the Exhibit) constitutes the entire agreement among the parties and supersedes and cancels any prior agreements, representations, warranties, or communications, whether oral or written, among the parties relating to the subject matter of, or the transactions contemplated by, this Agreement. Neither this Agreement nor any of its provisions may be modified, changed, waived, discharged, or terminated orally. This Agreement may only be modified, changed, waived, discharged, or terminated by an agreement in writing signed by the party against whom or which the enforcement of such modification, change, waiver, discharge, or termination is sought. (b) Assignment, Successors and Assigns. The rights and obligations under this Agreement may be assigned by Holder. The terms and conditions of this Agreement shall inure to the benefit of and be binding upon the respective successors and assigns of the parties. Nothing in this Agreement, express or implied, is intended to confer upon any party other than the parties or their respective successors and assigns any rights, remedies, obligations, or liabilities under or by reason of this Agreement, except as expressly provided in this Agreement. (c) Notices. All notifications, requests, demands, and other communications required or permitted to be given under this Agreement shall be in writing and shall be deemed given when mailed (with return receipt requested), emailed, faxed (which is confirmed), or sent via a recognized overnight courier service such as Federal Express, to the parties at the addresses set forth on the signature page, or pursuant to such other instructions as may be designated in writing by the party to receive such notice. New York, without giving effect to its principles regarding conflicts of law. (d) Governing Law. This Agreement shall be governed by and construed in accordance with the laws of the State of (e) Counterparts. This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Counterparts may be delivered via facsimile, electronic mail (including PDF) or other transmission method and any counterpart so delivered shall be deemed to have been duly and validly delivered and be valid and effective for all purposes. Attorney’s Fees. If any action at law or in equity (including arbitration) is necessary to enforce or interpret the terms of this Agreement, the prevailing party in such shall be entitled to receive from the non-prevailing party the prevailing party’s reasonable attorney’s fees, costs and necessary disbursements in addition to any other relief to which it may be entitled. (f) (g) No Further Obligations. The Company acknowledges and agrees that the Holder has not made any representation, undertaking, commitment or agreement to provide or assist the Company in obtaining any financing, investment or other assistance, other than with regard to the Loan Agreement. In addition, the Company acknowledges and agrees that (i) no statements, whether written or oral, made by the Holder or its representatives on or after the date of this Agreement shall create an obligation, commitment or agreement to provide or assist the Company in obtaining any financing or investment, (ii) the Company shall not rely on any such statement by any the Holder or its representatives and (iii) an obligation, commitment or agreement to provide or assist the Company in obtaining any financing or investment may only be created by a written agreement, signed by the Holder and the Company, setting forth the terms and conditions of such financing or investment and stating that the parties intend for such writing to be a binding obligation or agreement. The Holder shall have the right, in its sole and absolute discretion, to refuse or decline to participate in any other financing of or investment in the Company, and shall have no obligation to assist or cooperate with the Company in obtaining any financing, investment or other assistance. (h) Certain Remedies. Each party acknowledges and agrees that the other party would be damaged irreparably if this Agreement is not performed in accordance with its terms or otherwise is breached and that a party will be entitled to an injunction and other equitable relief (without posting any bond or other security) to prevent breaches hereof and to enforce specifically this Agreement and its terms in addition to any other remedy to which such party may be entitled hereunder. 4 (i) Tax Treatment. The Holder and the Company intend and agree that (i) the Initial Warrant and Tranche A drawn on the Initial Issue Date pursuant to the Loan Agreement are to be treated as an “investment unit” within the meaning of Section 1273(c)(2) of the Code and Treasury Regulation Section 1.1273-2(h), (ii) the Tranche C Warrant and the first drawn portion of the Tranche C pursuant to the Loan Agreement are to be treated as an “investment unit” within the meaning of Section 1273(c)(2) of the Code and Treasury Regulation Section 1.1273-2(h), and (iii) the fair market values of the Initial Warrant, Tranche C Warrant, Tranche A and Tranche C shall be reasonably determined by the Company with the consent of the Holder (not to be unreasonably withheld, delayed or conditioned). The parties hereto agree not to take a position inconsistent with this Section 7(i) for U.S. federal and applicable state and local income tax purposes unless required by a final “determination” within the meaning of Section 1313 of the Code to the contrary. [REMAINDER OF PAGE INTENTIONALLY LEFT BLANK] 5 IN WITNESS WHEREOF, the duly authorized representatives of the parties have executed and delivered this Agreement as of the Effective Date. AKEBIA THERAPEUTICS, INC. By: /s/ Ellen Snow Name: Ellen Snow Title: Chief Financial Officer Address per Section 7(c): 245 First Street Cambridge, MA 02142 Attn: Chief Financial Officer and Chief Legal Officer Email: [**] KREOS CAPITAL VII AGGREGATOR SCSp By: /s/ Mark Collins Name: Mark Collins Title: Manager Address per Section 7(c): 1 Boulevard de la Foire 1528, Luxembourg Attn: Sonia Benhamida, Guy Arbib, Alexander Babulevich Email: [**] [Signature Page to Warrant Agreement] EXHIBIT A Form of Warrant Incorporated by reference to Exhibit 4.7 of this Annual Report on Form 10-K filed with the Securities Exchange Commission on March 14, 2024 Exhibit 23.1 We consent to the incorporaon by reference in the following Registraon Statements: Consent of Independent Registered Public Accounng Firm (1) Registraon Statement (Form S-8 No. 333-196748) pertaining to the Amended and Restated 2008 Equity Incenve Plan, the 2014 Incenve Plan, and the 2014 Employee Stock Purchase Plan of Akebia Therapeucs, Inc., (2) Registraon Statement (Form S-8 No. 333-209469) pertaining to the 2014 Incenve Plan and the 2014 Employee Stock Purchase Plan of Akebia Therapeucs, Inc., (3) Registraon Statement (Form S-8 No. 333-216475) pertaining to the 2014 Incenve Plan and the 2016 Inducement Award Program of Akebia Therapeucs, Inc., (4) Registraon Statement (Form S-8 No. 333-222728) pertaining to the 2014 Incenve Plan and the 2016 Inducement Award Program of Akebia Therapeucs, Inc., (5) Registraon Statement (Form S-8 No. 333-228772) pertaining to the 2014 Incenve Plan of Akebia Therapeucs, Inc. and the 1999 Share Opon Plan, 2004 Long-Term Incenve Plan, 2007 Incenve Plan, Amended and Restated 2013 Incenve Plan, and 2018 Equity Incenve Plan of Keryx Biopharmaceucals, Inc., (6) Registraon Statement (Form S-8 No. 333-229366) pertaining to the 2014 Incenve Plan, the 2014 Employee Stock Purchase Plan, and the Inducement Grant Awards (January 2018 – December 2018) of Akebia Therapeucs, Inc., (7) Registraon Statement (Form S-8 No. 333-233140) pertaining to the Amended and Restated 2014 Employee Stock Purchase Plan of Akebia Therapeucs, Inc., (8) Registraon Statement (Form S-8 No. 333-236060) pertaining to the 2014 Incenve Plan and the Inducement Grant Awards (January 2019 – December 2019) of Akebia Therapeucs, Inc., (9) Registraon Statement (Form S-8 No. 333-252336) pertaining to the 2014 Incenve Plan and the Inducement Grant Awards (January 2020 – December 2020) of Akebia Therapeucs, Inc., (10) Registraon Statement (Form S-8 No. 333-262392) pertaining to the 2014 Incenve Plan, as amended, and the Inducement Grant Awards (January 2021 – December 2021) of Akebia Therapeucs, Inc., (11) Registraon Statement (Form S-8 No. 333-269457) pertaining to the 2014 Incenve Plan, as amended, and the Inducement Stock Opon Awards (January 2022 – December 2022) of Akebia Therapeucs, Inc., (12) Registraon Statement (Form S-8 No. 333-272453) pertaining to the 2023 Stock Incenve Plan of Akebia Therapeucs, Inc., and (13) Registraon Statement (Form S-8 No. 333-276770) pertaining to the Inducement Stock Opon Awards (January 2023 – December 2023) of Akebia Therapeucs, Inc.; of our reports dated March 14, 2024, with respect to the consolidated ﬁnancial statements of Akebia Therapeucs, Inc. and the eﬀecveness of internal control over ﬁnancial reporng of Akebia Therapeucs, Inc. included in this Annual Report (Form 10-K) of Akebia Therapeucs, Inc. for the year ended December 31, 2023. /s/ Ernst & Young LLP Boston, Massachuses March 14, 2024 Exhibit 31.1 CERTIFICATION PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002 I, John P. Butler, certify that: 1. 2. 3. 4. I have reviewed this Annual Report on Form 10-K of Akebia Therapeutics, Inc.; Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report; The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d- 15(f)) for the registrant and have: (a) (b) (c) (d) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared; Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles; Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and 5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the Audit Committee of the registrant’s Board of Directors (or persons performing the equivalent functions): (a) (b) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting. Date: March 14, 2024 By: /s/ John P. Butler John P. Butler President, Chief Executive Officer and Director (Principal Executive Officer) Exhibit 31.2 CERTIFICATION PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002 I, Ellen E. Snow, certify that: 1. 2. 3. 4. I have reviewed this Annual Report on Form 10-K of Akebia Therapeutics, Inc.; Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report; Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report; The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d- 15(f)) for the registrant and have: (a) (b) (c) (d) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in which this report is being prepared; Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles; Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and 5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant’s auditors and the Audit Committee of the registrant’s Board of Directors (or persons performing the equivalent functions): (a) (b) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal control over financial reporting. Date: March 14, 2024 By: /s/ Ellen E. Snow Ellen E. Snow Senior Vice President, Chief Financial Officer and Treasurer (Principal Financial Officer) CERTIFICATION PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 (18 U.S.C. Section 1350) In connection with the accompanying Annual Report of Akebia Therapeutics, Inc., or the Company, on Form 10-K for the fiscal year ended December 31, 2023, or the Report, I, John P. Butler, as Chief Executive Officer and President of the Company, and I, Ellen E. Snow, as Senior Vice President, Chief Financial Officer and Treasurer of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that: 1. The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and 2. The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. Exhibit 32.1 Date: March 14, 2024 Date: March 14, 2024 By: By: /s/ John P. Butler John P. Butler President, Chief Executive Officer and Director (Principal Executive Officer) /s/ Ellen E. Snow Ellen E. Snow Senior Vice President, Chief Financial Officer and Treasurer (Principal Financial Officer) Exhibit 97.1 Akebia Therapeutics, Inc. Dodd-Frank Compensation Recovery Policy This Compensation Recovery Policy (this “Policy”) is adopted by Akebia Therapeutics, Inc. (the “Company”) in accordance with Nasdaq Listing Rule 5608 (“Rule 5608”), which implements Rule 10D-1 under the Securities Exchange Act of 1934, as amended (the “Exchange Act”) (as promulgated pursuant to Section 954 of the Dodd-Frank Wall Street Reform and Consumer Protection Act of 2010). This Policy is effective as of October 2, 2023 (the “Effective Date”). 1. Definitions (a) “Accounting Restatement” means a requirement that the Company prepare an accounting restatement due to the material noncompliance of the Company with any financial reporting requirement under the U.S. federal securities laws, including any required accounting restatement to correct an error in previously issued financial statements that is material to the previously issued financial statements, or that would result in a material misstatement if the error were corrected in the current period or left uncorrected in the current period. Changes to the Company’s financial statements that do not represent error corrections are not an Accounting Restatement, including: (A) retrospective application of a change in accounting principle; (B) retrospective revision to reportable segment information due to a change in the structure of the Company’s internal organization; (C) retrospective reclassification due to a discontinued operation; (D) retrospective application of a change in reporting entity, such as from a reorganization of entities under common control; and (E) retrospective revision for stock splits, reverse stock splits, stock dividends or other changes in capital structure. (b) “Committee” means the Compensation Committee of the Company’s Board of Directors (the “Board”). (c) “Covered Person” means a person who served as an Executive Officer at any time during the performance period for the applicable Incentive-Based Compensation. (d) “Erroneously Awarded Compensation” means the amount of Incentive-Based Compensation that was Received that exceeds the amount of Incentive-Based Compensation that otherwise would have been Received had the amount of Incentive-Based Compensation been determined based on the restated amounts, computed without regard to any taxes paid by the Covered Person or by the Company on the Covered Person’s behalf. For Incentive-Based Compensation based on stock price or total shareholder return, where the amount of Erroneously Awarded Compensation is not subject to mathematical recalculation directly from the information in an Accounting Restatement, the amount of Erroneously Awarded Compensation will be based on a reasonable estimate by the Committee of the effect of the Accounting Restatement on the stock price or total shareholder return upon which the Incentive-Based Compensation was Received. The Company will maintain documentation of the determination of that reasonable estimate and provide such documentation to Nasdaq. (e) “Executive Officer” means the Company’s officers as defined in Rule 16a-1(f) under the Exchange Act. (f) “Financial Reporting Measures” means (A) measures that are determined and presented in accordance with the accounting principles used in preparing the Company’s financial statements, and any measures that are derived wholly or in part from such measures (whether or not such measures are presented within the Company’s financial statements or 1 included in a filing made with the U.S. Securities and Exchange Commission), (B) stock price and (C) total shareholder return. Exhibit 97.1 (g) “Incentive-Based Compensation” means any compensation that is granted, earned, or vested based wholly or in part upon the attainment of a Financial Reporting Measure. (h) Incentive-Based Compensation is deemed to be “Received” in the Company’s fiscal period during which the Financial Reporting Measure specified in the applicable Incentive-Based Compensation award is attained, even if the payment or grant of the Incentive-Based Compensation occurs after the end of that period or is subject to additional time-based vesting requirements. (i) “Recovery Period” means the three completed fiscal years immediately preceding the earlier of: (A) the date the Board, a committee of the Board, or the officer or officers of the Company authorized to take such action if Board action is not required, concludes, or reasonably should have concluded, that the Company is required to prepare an Accounting Restatement; or (B) the date a court, regulator, or other legally authorized body directs the Company to prepare an Accounting Restatement. In addition, if there is a change in the Company’s fiscal year end, the Recovery Period will also include any transition period to the extent required by Rule 5608. 2. Recovery of Erroneously Awarded Compensation Subject to the terms of this Policy and the requirements of Rule 5608, if the Company is required to prepare an Accounting Restatement, the Company will attempt to recover, reasonably promptly from each Covered Person, any Erroneously Awarded Compensation that was Received by such Covered Person during the Recovery Period pursuant to Incentive-Based Compensation that is subject to this Policy. 3. Interpretation and Administration (a) Role of the Committee. This Policy will be interpreted by the Committee in a manner that is consistent with Rule 5608 and any other applicable law and will otherwise be interpreted in the business judgment of the Committee. All decisions and interpretations of the Committee that are consistent with Rule 5608 will be final and binding. (b) Compensation Not Subject to this Policy. This Policy does not apply to Incentive-Based Compensation that was Received before the Effective Date. With respect to any Covered Person, this Policy does not apply to Incentive-Based Compensation that was Received by such Covered Person before beginning service as an Executive Officer. (c) Determination of Means of Recovery. Subject to the requirement that recovery be made reasonably promptly, the Committee will determine the appropriate means of recovery, which may vary between Covered Persons or based on the nature of the applicable Incentive-Based Compensation, and which may involve, without limitation, establishing a deferred repayment plan or setting off against current or future compensation otherwise payable to the Covered Person. Recovery of Erroneously Awarded Compensation will be made without regard to income taxes paid by the Covered Person or by the Company on the Covered Person’s behalf in connection with such Erroneously Awarded Compensation. (d) Determination That Recovery is Impracticable. The Company is not required to recover Erroneously Awarded Compensation if a determination is made by the Committee that either (A) after the Company has made and documented a reasonable attempt to recover such 2 Exhibit 97.1 Erroneously Awarded Compensation, the direct expense paid to a third party to assist in enforcing this Policy would exceed the amount to be recovered or (B) recovery of such Erroneously Awarded Compensation would likely cause an otherwise tax- qualified retirement plan, under which benefits are broadly available to employees of the registrant, to fail to meet the requirements of Section 401(a)(13) or 411(a) of the Internal Revenue Code and regulations thereunder. (e) No Indemnification or Company-Paid Insurance. The Company will not indemnify any Covered Person against the loss of Erroneously Awarded Compensation and will not pay or reimburse any Covered Person for the purchase of a third- party insurance policy to fund potential recovery obligations. (f) Interaction with Other Clawback Provisions. The Company will be deemed to have recovered Erroneously Awarded Compensation in accordance with this Policy to the extent the Company actually receives such amounts pursuant to any other Company policy, program or agreement, pursuant to Section 304 of the Sarbanes-Oxley Act or otherwise. (g) No Limitation on Other Remedies. Nothing in this Policy will be deemed to limit the Company’s right to terminate employment of any Covered Person, to seek recovery of other compensation paid to a Covered Person, or to pursue other rights or remedies available to the Company under applicable law. Adopted by the Board on November 21, 2023. 3

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