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
For the fiscal year ended December 31, 2019
OR
☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Commission File Number 001-36352
AKEBIA THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
245 First Street, Cambridge, MA
(Address of principal executive offices)
20-8756903
(I.R.S. Employer
Identification No.)
02142
(Zip Code)
Registrant’s telephone number, including area code: (617) 871-2098
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Trading Symbol(s)
Name of each exchange on which registered
Common Stock, par value $0.00001 per share
AKBA
The Nasdaq Global Market
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YES ☒ NO ☐
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. YES ☐ NO ☒
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities 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 submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405
of Regulation 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 reporting company, or
an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging
growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer
☐
Accelerated filer
☒
☐
Non-accelerated filer
☐
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any
new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Smaller reporting company
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 voting and non-voting 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 28, 2019, was $565,808,424.
The number of shares of registrant’s Common Stock outstanding as of March 1, 2020 was 129,858,262.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Proxy Statement for the registrant’s 2020 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual
Report on Form 10-K.
TABLE OF CONTENTS
PART I
.................................................................................................................................................................................
Item 1.
Business .................................................................................................................................................................
Item 1A.
Risk Factors ............................................................................................................................................................
Item 1B.
Unresolved Staff Comments...................................................................................................................................
Item 2.
Item 3.
Item 4.
Properties ................................................................................................................................................................
Legal Proceedings...................................................................................................................................................
Mine Safety Disclosures .........................................................................................................................................
PART II
.................................................................................................................................................................................
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity
Securities............................................................................................................................................................
Item 6.
Item 7.
Selected Financial Data ..........................................................................................................................................
Management’s Discussion and Analysis of Financial Condition and Results of Operations.................................
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk................................................................................
Item 8.
Item 9.
Financial Statements and Supplementary Data ......................................................................................................
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure ................................
Item 9A.
Controls and Procedures .........................................................................................................................................
Item 9B.
Other Information ...................................................................................................................................................
PART III
.................................................................................................................................................................................
Item 10.
Directors, Executive Officers and Corporate Governance .....................................................................................
Item 11.
Executive Compensation ........................................................................................................................................
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters ..............
Item 13.
Certain Relationships and Related Transactions, and Director Independence .......................................................
Item 14.
Principal Accountant Fees and Services.................................................................................................................
PART IV .................................................................................................................................................................................
Item 15.
Exhibits, Financial Statement Schedules ................................................................................................................
Item 16.
Form 10-K Summary ..............................................................................................................................................
SIGNATURES ...............................................................................................................................................................................
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NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements that are being made pursuant to the provisions of the U.S.
Private Securities Litigation Reform Act of 1995 with the intention of obtaining the benefits of the “safe harbor” provisions of that
Act. All statements contained in this Annual Report on Form 10-K other than statements of historical fact are forward-looking
statements. These forward-looking statements may be accompanied by words such as “anticipate,” “believe,” “build,” “can,”
“contemplate,” “continue,” “could,” “should,” “designed,” “estimate,” “project,” “expect,” “forecast,” “future,” “goal,” “intend,”
“likely,” “may,” “plan,” “possible,” “potential,” “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:
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the potential therapeutic benefits, safety profile, and effectiveness of our product candidates, including the potential
for vadadustat to set a new standard of care in the treatment of anemia due to chronic kidney disease;
the timing, investment and associated activities involved in continued commercialization of Auryxia;
the potential indications, demand and market potential and acceptance of our product and product candidates, including
our estimates regarding the potential market opportunity for Auryxia, vadadustat or any other product candidates and the
size of eligible patient populations;
the potential therapeutic applications of the hypoxia inducible factor, or HIF, pathway;
our pipeline, including its potential, and out research and development activities;
our competitive position, including estimates, developments and projections relating to our competitors and their products
and product candidates, and our industry;
our expectations with respect to (i) the anticipated financial impact and potential benefits to us related to our merger with
Keryx Biopharmaceuticals, Inc., or Keryx, that was completed on December 12, 2018, or the Merger, (ii) integration of
the businesses subsequent to the Merger, and (iii) other matters related to the Merger;
our expectations, projections and estimates regarding our capital requirements, need for additional capital, financing our
future cash needs, costs, expenses, revenues, capital resources, cash flows, financial performance, profitability, tax
obligations, liquidity, growth, contractual obligations, the period of time our cash resources and collaboration funding will
fund our current operating plan, internal control over financial reporting and remediation of any deficiencies, and
disclosure controls and procedures;
the timing of the availability and disclosure of clinical trial data and results;
our and our collaborators’ strategy, plans and expectations with respect to the development, manufacturing,
commercialization, launch, marketing and sale of our product candidates, and the associated timing thereof;
the designs of our studies, and the type of information and data expected from our studies and the expected benefits
thereof;
the timing of or likelihood of regulatory filings and approvals, including labeling or other restrictions;
our ability to maintain any marketing authorizations we currently hold or will obtain, including our marketing
authorizations for Auryxia and our ability to complete post-marketing requirements with respect thereto;
our ability to negotiate, secure and maintain adequate pricing, coverage and reimbursement terms and processes on a
timely basis, or at all, with third-party payors for Auryxia or any other product candidate that may be approved;
the targeted timing of enrollment of our clinical trials;
the timing of initiation of our clinical trials and plans to conduct preclinical and clinical studies in the future;
the timing and amounts of payments from or to our collaborators and licensees, and the anticipated arrangements and
benefits under our collaboration and license agreements, including with respect to milestones and royalties;
our intellectual property position, including obtaining and maintaining patents; and the timing, outcome and impact of
administrative, regulatory, legal and other proceedings relating to our patents and other proprietary and intellectual
property rights, as well as Abbreviated New Drug Applications filed by generic drug manufacturers and potential U.S.
Food and Drug Administration Approval thereof, and associated patent infringement suits that we have filed or may file,
or other actions that we may take against such companies, and the timing and resolution thereof;
2
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expected reliance on third parties, including with respect to the development, manufacturing, supply and
commercialization of our product and product candidates;
accounting standards and estimates, their impact, and their expected timing of completion;
estimated periods of performance of key contracts;
our facilities, lease commitments, and future availability of facilities;
cybersecurity;
insurance coverage;
our employees, including our management team, employee compensation, employee relations, and our ability to attract
and retain high quality employees;
the implementation of our business model, current operating plan, and strategic plans for our business, product candidates
and technology, and business development opportunities including potential collaborations, alliances, mergers,
acquisitions or licensing of assets; and
the timing, outcome and impact of current and any future legal proceedings.
Any or all of these forward-looking statements in this Annual Report on Form 10-K may turn out to be inaccurate. These forward-
looking statements involve risks and uncertainties, including those that are described in Part I, Item 1A. Risk Factors included in this
Annual Report and elsewhere in this Annual Report on Form 10-K, that could cause our actual results, financial condition,
performance or achievements to be materially different from those indicated in these forward-looking statements. Given these risks
and uncertainties, you should not place undue reliance on these forward-looking statements. Forward-looking statements speak only as
of the date of this Annual Report on Form 10-K. Except as required by law, we assume no obligation to publicly update or revise these
forward-looking statements for any reason. Unless otherwise stated, our forward-looking statements do not reflect the potential impact
of any future acquisitions, mergers, dispositions, joint ventures or investments we may make.
This Annual Report on Form 10-K also contains estimates and other information concerning our industry and the markets for certain
diseases, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions.
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 parties, industry, medical and general publications, government data and
similar sources.
In this Annual Report on Form 10-K, unless otherwise stated or the context otherwise requires, references to “Akebia,” “we,” “us,”
“our,” “the Company,” and similar references refer to Akebia Therapeutics, Inc. and, where appropriate, its subsidiaries, including
Keryx.
AURYXIA®, AKEBIA® Therapeutics and their associated logos are trademarks of Akebia and/or its affiliates. All other trademarks,
trade names and service marks appearing in this Annual Report on Form 10-K are the property of their respective owners. All website
addresses given in this Annual Report on Form 10-K are for information only and are not intended to be an active link or to
incorporate any website information into this document.
3
Item 1.
Business
Overview
PART I
We are a biopharmaceutical company focused on the development and commercialization of renal therapeutics for people living with
kidney disease. Our portfolio includes a late-stage product candidate and a commercial product:
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Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor, or HIF-PHI, in global Phase 3
development for two indications: (1) anemia due to chronic kidney disease, or CKD, in adult patients on dialysis, or DD-
CKD, and (2) anemia due to CKD in adult patients not on dialysis, or NDD-CKD. We believe vadadustat has the potential
to set a new oral standard of care for patients with anemia due to CKD, subject to regulatory approval. Vadadustat is
designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower
oxygen availability with stabilization of hypoxia-inducible factor, or HIF, which can lead to red blood cell, or RBC,
production and improved oxygen delivery to tissues.
Auryxia® (ferric citrate) is approved and marketed in the United States for two indications: (1) the control of serum
phosphorus levels in adult patients with DD-CKD, or the Hyperphosphatemia Indication, and (2) the treatment of iron
deficiency anemia, or IDA, in adult patients with NDD-CKD, or the IDA Indication. Ferric citrate is also approved and
marketed in Japan as an oral treatment for the improvement of hyperphosphatemia in patients with CKD, including DD-
CKD and NDD-CKD, under the trade name Riona® (ferric citrate hydrate).
If the results of our global Phase 3 studies for vadadustat are positive, we plan to file for regulatory approval in the United States and
other regions. In connection with our plan to file for regulatory approval for vadadustat in the United States, we entered into a letter
agreement on February 14, 2020, or the Letter Agreement, with Vifor (International) Ltd., or Vifor Pharma, relating to Vifor Pharma’s
agreement with a third party to purchase a Priority Review Voucher, or the PRV, issued by the U.S. Food and Drug Administration, or
FDA, subject to satisfaction of customary closing conditions, or the PRV Purchase. A PRV entitles the holder to priority review of a
New Drug Application, or NDA, or a Biologics License Application for a new drug, which reduces the target FDA review time to six
months after official acceptance of the submission, and could lead to expedited approval. Pursuant to the Letter Agreement, we will
pay Vifor Pharma $10.0 million within fifteen business days after the closing of the PRV Purchase. Vifor Pharma is obligated to retain
all rights to, and maintain the validity of, the PRV until we and Vifor Pharma (a) enter into a definitive agreement setting forth the
financial and other terms by which Vifor Pharma will assign the PRV to us for use with our planned NDA for vadadustat for the
treatment of anemia due to CKD in both DD-CKD and NDD-CKD patients, or (b) make a mutual decision to sell the PRV and share
the proceeds based on certain terms.
We plan to commercialize vadadustat, subject to FDA approval, in the United States with our existing nephrology-focused
commercial organization, while also leveraging our collaboration with Otsuka Pharmaceutical Co. Ltd., or Otsuka, and its U.S.
commercial organization. We also granted Otsuka exclusive rights to commercialize vadadustat in Europe, China and certain other
markets, subject to marketing approvals. In Japan and certain other countries in Asia, we granted Mitsubishi Tanabe Pharma
Corporation, or MTPC, exclusive rights to commercialize vadadustat, subject to marketing approvals. In addition, we granted Vifor
Pharma an exclusive license to sell vadadustat solely to Fresenius Kidney Care Group LLC, or FKC, which manages approximately
40% of the dialysis patients in the United States, at its U.S. dialysis clinics, and to certain third party dialysis organizations in the
United States, approved by us, or Third Party Dialysis Organizations, which account for up to an additional 20% of the dialysis market
in the United States. The license granted to Vifor Pharma would be effective upon FDA approval of vadadustat in the DD-CKD
indication, the earlier of a determination by the Centers for Medicare & Medicaid Services, or CMS, that vadadustat will be included
in Medicare’s bundled reimbursement model or that vadadustat will be reimbursed using the Transitional Drug Add-On Payment
Adjustment, or TDAPA, and a milestone payment by Vifor Pharma.
We market Auryxia in the United States with our well-established, nephrology-focused commercial organization. Our Japanese
sublicensee, Japan Tobacco, Inc., or JT, and its subsidiary, Torii Pharmaceutical Co., Ltd., or Torii, commercialize Riona in Japan.
We were incorporated in 2007 under the laws of the State of Delaware. On December 12, 2018, we completed a merger, or the Merger,
with Keryx Biopharmaceuticals, Inc., or Keryx, combining a nephrology-focused commercial organization with our robust
development organization. Following the Merger, Keryx is our wholly owned subsidiary, and we are integrating our business and
Keryx’s business with the goal of positioning Akebia to realize the potential growth opportunities and synergies from the Merger.
4
Strategy
Our mission and our culture are centered around the goal of improving the lives of people impacted by kidney disease, through the
discovery, development and commercialization of innovative therapeutics. Our strategy is to execute on the following initiatives,
which we believe will create significant market opportunities for us:
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Complete the global clinical development of and successfully commercialize vadadustat for the treatment of anemia
due to CKD. We believe vadadustat has the potential to address limitations of injectable erythropoiesis-stimulating agents,
or ESAs, and set a new oral standard of care for the treatment of anemia due to CKD, subject to regulatory approval. We
are conducting a global Phase 3 clinical development program for vadadustat. Our collaboration partner, MTPC, recently
completed its Phase 3 clinical development program for vadadustat in Japan and submitted a Japanese New Drug
Application, or JNDA, in the third quarter of 2019 for the treatment of anemia due to CKD. We expect to read out top line
data from our global Phase 3 studies beginning with INNO2VATE in the second quarter of 2020, and then PRO2TECT in
mid-2020. If these results are positive, we believe that these studies will support filings for regulatory approval in the
United States and other regions. We believe we are well positioned to commercialize vadadustat in the United States with
our nephrology-focused commercial team, as well as our partnership with Otsuka, and through our agreement with Vifor
Pharma, subject to FDA approval. We plan to support Otsuka’s and MTPC’s commercialization of vadadustat in Europe,
Japan and certain other markets, subject to regulatory approvals. We retain full commercial rights to vadadustat in Latin
America, allowing us maximum flexibility in the region.
Grow adoption of Auryxia within its approved indications. We aim to continue to use our nephrology-focused
commercial organization to increase awareness, demand and adoption for Auryxia for its approved indications with key
stakeholders including nephrologists, third-party payors, dialysis organizations, patients and their families. We also
believe that reinstating Medicare coverage of Auryxia for the IDA Indication would allow for greater adoption of Auryxia
in both of its approved indications. See Part I, Item 3. Legal Proceedings for further information with respect to our
efforts.
Leverage Auryxia as a clinical catalyst and commercial beachhead for vadadustat, in CKD. In addition to bringing
meaningful clinical benefits to patients, Auryxia provides strategic value to Akebia by allowing us to leverage our existing
nephrology-focused commercial footprint and deepen key customer and prescriber relationships that we believe will be
important for the future commercialization of vadadustat, if approved, and other potential future renal products.
Expand our pipeline and portfolio of renal therapeutics to advance care for people living with kidney disease. We aim
to add to our pipeline and portfolio of renal therapeutics through internal discovery and development, and through
strategic transactions, such as in-licenses, collaborations and acquisitions. Our pipeline and portfolio expansion efforts
will be guided by our purpose to improve the lives of people impacted by kidney disease.
Our management team has extensive experience in developing and commercializing drugs for the treatment of renal and metabolic
disorders, a deep understanding of the renal space and biological pathways involved in kidney disease including HIF biology and iron
metabolism, and broad business development expertise. With this management team, fully integrated capabilities spanning research,
manufacturing, development and commercialization, a commercial revenue stream and a strong balance sheet, we are well positioned
to execute on our strategy.
Background on Kidney Disease
Kidney disease is an area of major unmet need globally, driving massive healthcare costs and with a generally poor prognosis:
eventually many patients will progress to a stage where they are dependent on dialysis, with high morbidity and a significant increase
in mortality rate.
Kidney disease can be caused by a number of distinct and concomitant factors, including cardiometabolic disorders (primarily diabetes
and hypertension), genetic kidney diseases, autoimmune disorders, and aging. Given the prevalence and growth rates of these various
underlying conditions, kidney disease prevalence is expected to continue to increase globally. In the United States, chronic kidney
disease significantly impacts the U.S. healthcare system, affecting about 37 million patients and costing Medicare over $120 billion
annually in 2017 for treating Medicare beneficiaries with CKD of end-stage renal disease. The U.S. Department of Health and Human
Services has recognized the national pandemic and partnered with the American Society of Nephrology to found the KidneyX
Innovation Accelerator, a public-private partnership to improve the lives of the 850 million people worldwide currently affected by
kidney diseases by accelerating innovation in the prevention, diagnosis and treatment of kidney diseases.
Most of the conditions covered by the term “kidney disease” may lead to dependence on dialysis or kidney transplant for survival,
causing renal failure, directly or indirectly, by accelerating the onset of CKD. Dependence on dialysis is associated with a significant
increase in mortality and hospitalizations, and a significant reduction in quality of life for patients. There is a clear need to improve the
clinical and quality of life outcomes for people living with kidney disease. It is our vision, in time, to provide or contribute to better
alternatives that improve the lives of people impacted by kidney disease.
5
As a first step towards our vision, we aim to advance care for patients with CKD, which is the current focus of our pipeline and
portfolio of approved indications.
CKD is a condition in which the kidneys are progressively damaged to the point that they cannot properly filter the blood circulating
in the body. This damage causes waste products to build up in the patient’s blood leading to other health problems, including anemia,
cardiovascular disease and bone disease. As illustrated in the table below, CKD patients are categorized in one of five stages based on
the degree of their loss of kidney function as measured by the glomerular filtration rate, or GFR, and the level of protein in the urine,
referred to as albuminuria.
Stages and Prevalence of Chronic Kidney Disease in the United States
Description
Kidney damage with normal or
increased GFR
Kidney damage with mildly
decreased GFR
Moderately decreased GFR
Severely decreased GFR
Kidney failure (includes non
dialysis, dialysis and transplant)
Stage
1
2
3
4
5
Sources:
GFR (mL/min/1.73m2)a
U.S. Prevalence Ratesb, c
Estimated Number of U.S.
Patients (millions)d, e
≥90
60-89
30-59
15-29
4.6%
3.0%
6.7%
0.4%
<15 (or dialysis)
0.3% (calculated)
11.2
7.3
16.4
1.0
0.7
a
b
c
d
e
GFR categories defined in the August 2012 Kidney Disease Improving Global Outcomes Clinical Practice Guideline for
Anemia in Chronic Kidney Disease, p. vii.
U.S. Prevalence Rates for Stages 1-4 based on averages of data from 2011-2012, 2013-2014, and 2015-2016, CDC CKD
Surveillance System, National Health and Nutrition Examination Survey, or NHANES.
U.S. Prevalence Rate for Stage 5 is based on a calculation using estimated number of U.S. patients with ESRD from 2018
U.S. Renal Data System Annual Report, as set forth in this table, and U.S. population data for people 20 years and older
from www.census.gov.
Estimated Number of U.S. Patients for Stages 1-4 based on the 2018 U.S. Prevalence rates, as set forth in this table, as
applied by Akebia to U.S. population data for people 20 years and older from www.census.gov.
Estimated Number of U.S. End-Stage Renal Disease Patients from 2018 U.S. Renal Data System Annual Report.
The prevalence and incidence of CKD is increasing in all segments of the United States population. Risk factors for the development
of CKD include concomitant diseases such as hypertension, diabetes mellitus and cardiovascular disease, lifestyle factors such as
tobacco use and inactivity, family history, aging and prenatal factors such as maternal diabetes mellitus, low birth weight and small-
for-gestational-age status. According to an article in The Lancet published in May 2013, projected worldwide population changes
suggest that the potential number of cases of CKD, specifically end-stage, will increase disproportionately in countries such as Japan,
China and India where the number of elderly people is increasing. This effect will be accelerated further if the growth in the
prevalence of hypertension and diabetes persists, along with the associated increased risk of stroke and cardiovascular disease, and
access to treatment does not improve.
The progression of CKD towards renal failure is complicated by multiple conditions which further deteriorate kidney function and the
general health of patients if left untreated. Typically the prevalence of these conditions increases as CKD progresses. For instance,
anemia is characterized by low hemoglobin levels and is typically associated with a worsening quality of life, increased
hospitalizations and increased mortality. The prevalence of anemia increases with the severity of CKD from an estimated 20% in
patients with Stage 3 NDD-CKD to an estimated 95% in patients with Stage 5 DD-CKD.
Anemia, or low hemoglobin/red blood count, in patients with CKD most commonly arises from two etiologies:
1.
Anemia due to CKD: results from inadequate levels of EPO, a protein hormone synthesized by specialized cells in the
kidney that stimulates production of red blood cells in the bone marrow. As renal function declines, the body
progressively loses the ability to produce endogenous EPO; and
2.
IDA: results from low levels of iron due to abnormal iron absorption and utilization in patients with CKD.
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Anemia due to CKD in NDD-CKD and DD-CKD patients are the two indications being investigated in Phase 3 clinical trials for
vadadustat, and IDA in adult patients with NDD-CKD is an FDA-approved indication for Auryxia.
Hyperphosphatemia is another condition associated with CKD that is characterized by elevated serum phosphorus levels and is also
typically associated with a worsening of health including increased cardiovascular risk and increased mortality. Hyperphosphatemia in
DD-CKD patients is also an FDA-approved indication for Auryxia.
In addition to these conditions that are the current focus of our pipeline and portfolio of approved indications, there are several other
disorders that have deleterious consequences on patient’s health, including hypercalcemia, hyperkalemia, hyponatremia,
hypernatremia, and hyperparathyroidism. These conditions are generally not well controlled, particularly in the later stages of CKD
and as patients transition to dialysis.
When considering the clinical and commercial opportunities in CKD, it is important to take note of the contrasting market dynamics
between DD-CKD and NDD-CKD.
DD-CKD patients receive treatment for the various complications of CKD including anemia and hyperphosphatemia. Given the
concentration of dialysis clinics in large networks, with DaVita and Fresenius Kidney Care accounting for a vast majority of the
dialysis population in the United States, treatment is usually driven by medical protocols that are rolled out across the entire 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 patient population. This is particularly true of medications covered under the End Stage Renal Disease, or ESRD, Prospective
Payment System, or PPS, in Medicare, or the ESRD Bundle, a payment structure with a flat base rate per dialysis session adjusted for
individual patient and facility characteristics. Dialysis-related drugs are included in the ESRD Bundle if they fall into functional
categories such as anemia management and bone and mineral metabolism, except that oral-only drugs are exempted from inclusion
until 2025. In a final ESRD PPS rule published in November 2018, CMS confirmed that it will expand the Transitional Drug Add-On
Payment Adjustment, or TDAPA, to all new dialysis drugs approved by the FDA after January 1, 2020. The TDAPA will provide
separate payment for new drugs for two years based on the drug’s Average Sales Price, ASP, that will be added to the base rate in
order to facilitate the adoption of innovative therapies. Although there are several details that need clarification, the rule provides
support for our assumption that new anemia treatments, including the HIF-PHI class, will be included in the ESRD Bundle and will be
eligible for separate payment initially under TDAPA.
In contrast, NDD-CKD is characterized by larger patient populations with lower treatment rates for CKD-related conditions. In
addition to improving cardiovascular risk and quality of life, unmet need includes delaying the progression of CKD and therefore the
transition to dialysis. Reimbursement in the non-dialysis setting aligns with traditional commercial and government payer
reimbursement for outpatient drugs.
Vadadustat
Overview
Vadadustat is an investigational oral HIF-PHI product candidate in global Phase 3 development for two indications: anemia due to
CKD in adult patients with DD-CKD, and anemia due to CKD in adult patients with NDD-CKD. We believe vadadustat has the
potential to set a new oral standard of care for patients with anemia due to CKD, subject to regulatory approval. Vadadustat is
designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower oxygen
availability with stabilization of HIF, which can lead to RBC production and, improved oxygen delivery to tissues. The significance of
the HIF pathway was recognized by the 2019 Nobel Prize and the 2016 Albert Lasker Basic Medical Research Award, which honored
the three physician-scientists who discovered the HIF pathway and elucidated this primary oxygen sensing mechanism that is essential
for survival.
Market Opportunity
Anemia due to Chronic Kidney Disease
Anemia is common in patients with CKD, and its prevalence increases with disease progression. Anemia due to CKD results from
inadequate EPO levels, which negatively affect RBC production. Left untreated, anemia accelerates overall deterioration of patient
health with increased morbidity and mortality. Based on third party prevalence data and company estimates, approximately 37 million
people in the United States have CKD and approximately 5.7 million of these individuals suffer from anemia. The current standard of
care for anemia due to CKD is treatment by injectable recombinant human ESAs, such as EPOGEN® (epoetin alfa) and Aranesp®
(darbepoetin alfa), or blood transfusion. Based on publicly available information on ESA sales and market data compiled by a third-
party vendor, global sales of injectable ESAs for all uses were estimated to be approximately $6.1 billion in 2018. The vast majority of
these sales are believed to have been for the treatment of anemia due to CKD.
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When administered to a patient, injectable ESAs provide supraphysiological levels of exogenous EPO to stimulate production of
RBCs. While injectable ESAs can be effective in raising hemoglobin levels, they have the potential to cause significant side effects,
and need to be injected subcutaneously or intravenously. In particular, injectable ESAs may lead to thrombosis, stroke, myocardial
infarction and death. While these safety concerns, which became evident starting in 2006, have led to a significant reduction in the use
of injectable ESAs, injectable ESAs remain the current standard of care for both NDD-CKD and DD-CKD patients with anemia.
NDD-CKD Market
Data from the U.S. Renal Data System, or USRDS, 2015 Annual Data Report indicate that the collective injectable ESA treatment rate
in NDD-CKD patients in the United States decreased by approximately half from 2009 to 2013. As a result of the safety concerns
associated with ESAs, today, a high proportion of NDD-CKD patients with anemia are either not treated or inadequately treated
despite having low hemoglobin levels. In contrast to treatment with ESAs, we believe vadadustat, subject to regulatory approval, has
the potential to expand the number of NDD-CKD patients receiving treatment by offering an alternative oral treatment for anemia due
to CKD with a differentiated safety profile.
DD-CKD Market
According to the USRDS 2019 Annual Data Report, there were approximately 524,000 patients in the United States on dialysis in
2017, of which 88% were on in-center hemodialysis and the remainder on peritoneal or home hemodialysis. ESAs are given to
approximately 90% of in-center hemodialysis patients and 75% of peritoneal dialysis patients.
There is an unmet need for treatment options for patients with anemia due to CKD that offer a differentiated and/or improved safety
profile, and such agents would have significant market potential.
Vadadustat Has the Potential to Set a New Oral Standard of Care
We believe that, based on the HIF-PHI mechanism of action and clinical data to date, vadadustat has the potential to set a new oral
standard of care for the treatment of anemia due to CKD within both the NDD and DD markets. Below is a summary of the key
clinical findings; further details are included below.
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Vadadustat stimulated endogenous EPO production. In two Phase 1 studies in normal healthy volunteers and one Phase 2
study in CKD patients, vadadustat increased serum EPO levels in a dose-dependent manner. Pre-dose EPO levels returned
to baseline levels prior to subsequent daily dose. In these studies, vadadustat stimulated endogenous EPO production
while avoiding supraphysiologic EPO levels.
Vadadustat significantly increased and maintained hemoglobin levels. Our Phase 2 studies in CKD subjects with anemia
demonstrated that vadadustat significantly increased and/or maintained hemoglobin levels. In addition and more recently,
our partner, MTPC’s, Phase 3 studies in Japanese NDD-CKD and DD-CKD patients with anemia due to CKD further
demonstrated the durability of vadadustat with data that showed that vadadustat’s effect on hemoglobin was sustained
through to 52 weeks comparable to the control arm, darbepoetin alfa.
Vadadustat was dosed orally once daily and three times weekly. Our Phase 2 studies showed that vadadustat can be orally
dosed once daily in NDD-CKD subjects with up to 20 weeks of dosing. In addition, our Phase 2 clinical study in DD-
CKD subjects demonstrated that in subjects who remained on therapy, once daily oral dosing of vadadustat maintained
stable hemoglobin levels in subjects converting from injectable ESA therapy over 16 weeks. This study also showed the
potential for three-times weekly dosing of vadadustat in DD-CKD.
Vadadustat resulted in favorable changes in iron parameters. In three Phase 2 clinical studies, treatment with vadadustat
was associated with decreases in ferritin and hepcidin and increases in total iron binding capacity. These changes are
consistent with improved iron mobilization and utilization for erythropoiesis in NDD-CKD and DD-CKD subjects.
Based on this and other data, we believe vadadustat has the potential to be a treatment for anemia due to CKD with a differentiated
safety profile compared with the current standard of care, injectable ESAs, by:
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stimulating erythropoiesis and avoiding supraphysiologic EPO levels;
increasing hemoglobin in a predictable and controlled manner; and
minimizing hemoglobin excursions and cycling.
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Based upon these key characteristics, we believe vadadustat has the potential to possibly reduce the risk of cardiovascular and
thrombotic events associated with injectable ESAs. The efficacy of vadadustat in raising/maintaining hemoglobin levels within a
target range, and the cardiovascular safety of vadadustat as compared with darbepoetin alfa, an injectable ESA, is being assessed in
our global Phase 3 clinical program for vadadustat.
Vadadustat Clinical Development Program
We believe vadadustat has the potential to address limitations of injectable ESAs and set a new oral standard of care for the treatment
of anemia due to CKD, subject to regulatory approval. We are conducting a global Phase 3 clinical development program for
vadadustat, and our collaboration partner, MTPC, recently completed its Phase 3 clinical development program for vadadustat in
Japan and submitted a JNDA in the third quarter of 2019 for vadadustat for the treatment of anemia due to CKD. We expect top line
data from our global Phase 3 programs, INNO2VATE and PRO2TECT, to read out in the second quarter of 2020 and mid-2020,
respectively. If the trial results are positive, we believe these studies will support filings for regulatory approval in the United States
and other regions.
Vadadustat Global Phase 3 Clinical Program
We are conducting a global Phase 3 clinical development program for vadadustat which includes two separate programs called
INNO2VATE and PRO2TECT. INNO2VATE studies vadadustat in DD-CKD patients with anemia due to CKD in two separate studies
and PRO2TECT studies vadadustat in NDD-CKD patients with anemia due to CKD in two separate studies. Combined, we enrolled
approximately 7,500 patients in these studies and are evaluating once daily oral dosing of vadadustat against an injectable ESA active
comparator, darbepoetin alfa.
In August 2016, the first patient was dosed in INNO2VATE. We completed enrollment in the larger of the two INNO2VATE studies,
which enrolled 3,554 patients, in February 2019, and we completed enrollment in the smaller INNO2VATE study, which enrolled 369
patients, in April 2019. We anticipate reporting top-line data for the INNO2VATE studies in the second quarter of 2020.
The first patient was dosed in PRO2TECT in December 2015. We completed enrollment of PRO2TECT correction and conversion
studies, which enrolled 1,761 and 1,752 patients, respectively, in August 2019. We anticipate reporting top-line data for the
PRO2TECT studies in mid-2020.
In both the PRO2TECT and INNO2VATE Phase 3 programs, the primary efficacy endpoint of each program is the mean change in
hemoglobin between baseline and the primary evaluation period. Non-inferiority, or NI, is achieved if the lower bound of the 95%
confidence interval for the between-group difference of the mean hemoglobin change does not fall below the pre-specified NI margin.
Both the PRO2TECT and INNO2VATE programs include the primary safety endpoint of the assessment of major adverse cardiovascular
events, or MACE, with a comparison of vadadustat to darbepoetin alfa. MACE is defined as the composite endpoint of all-cause mortality,
non-fatal myocardial infarction, or non-fatal stroke. The primary analysis for each program is based on the combined MACE events from
the two Phase 3 studies in each program (PRO2TECT and INNO2VATE). NI is achieved if the upper bound of the 95% confidence
interval for the hazard ratio of vadadustat to darbepoetin alfa does not exceed the pre-specified NI margin. We have prospectively defined
and agreed to non-inferiority margins with the United States and European regulatory authorities and have agreed with the United States
regulatory authorities on the key components of our statistical analysis plan.
In addition to our Phase 3 clinical development program, we are conducting a Phase 2 clinical study of vadadustat, FO2RWARD-2,
evaluating a modified approach to once-daily and three-times weekly dosing, including assessment of a vadadustat starting dose based
on an individual’s pre-conversion ESA dose prior to study entry and higher titration doses of vadadustat (750 mg and 900 mg). We
believe data from this and other studies could support registration of the modified approach to once daily dosing and supplemental
registration of three times weekly dosing, and further strengthen our potential commercial position if vadadustat is approved for
marketing.
We completed a series of clinical drug-drug interaction studies largely focusing on transporter pathways evaluating vadadustat as a
victim (using probe inhibitors) or perpetrator (using probe substrates) of drug interactions. No meaningful drug interactions were
observed with atorvastatin (P-gp/OATP1B1 substrate), pravastatin (OATP1B1/1B3 substrate), digoxin (P-gp substrate), furosemide
(OAT1/OAT3 substrate), adefovir (OAT1 substrate), cyclosporine (P-gp/BCRP/OATP inhibitor), probenecid (OAT3 and UGT
inhibitor), or rabeprazole (gastric acid-reducing agent). With concomitant administration of vadadustat, a mild-to-moderate interaction
was observed with simvastatin (OATP1B1/B3 substrate), and moderate drug interactions were observed with rosuvastatin
(BCRP/OATP1B1/1B3 substrate), ferrous sulfate, and sulfasalazine (BCRP substrate). In addition, in vitro drug-drug interaction
studies demonstrated a very low risk of vadadustat for drug interactions due to alteration of metabolic enzyme activities, i.e.
cytochrome P450 or UDP-glucuronosyltransferase isoforms. No clinical drug-interaction was observed with celecoxib (CYP2C9).
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MTPC’s Phase 3 Clinical Program of Vadadustat in Japan
On March 12, 2019 and November 9, 2019, we announced positive top-line results from two Phase 3 active-controlled pivotal studies
evaluating vadadustat in Japanese subjects with anemia due to CKD (J01 and J03 Studies). These studies were conducted by our
development and commercialization collaboration partner in Japan, MTPC. Each study, one in NDD-CKD patients and one in DD-
CKD patients, met its primary endpoint. In addition, results from two Phase 3 single-arm studies conducted by MTPC in peritoneal
dialysis patients and DD-CKD patients (J02 and J04 Studies) further support vadadustat’s potential in these indications. MTPC
submitted a JNDA in the third quarter of 2019 for vadadustat for the treatment of anemia due to CKD.
The Phase 3 randomized, open-label, active-controlled correction and conversion study (J01 Study) assessed the efficacy and safety of
vadadustat compared to darbepoetin alfa in 304 Japanese NDD-CKD patients with anemia, with a treatment duration of 52 weeks.
Data from the planned analysis at 24 weeks were announced in March 2019 and showed that the study met its primary endpoint: The
difference in mean hemoglobin (Hb) was -0.26 g/dL (95% CI -0.50, -0.02 g/dL), achieving the pre-specified non-inferiority criterion
of -0.75 g/dL. The mean Hb level at week 20 and week 24 were 11.66 g/dL (95% CI 11.49, 11.84 g/dL) for vadadustat-treated
subjects compared to 11.93 g/dL (95% CI 11.76, 12.10 g/dL) for darbepoetin alfa-treated subjects. The mean Hb level at week 52 was
11.51 g/dL (95% CI 11.35, 11.67 g/dL) for vadadustat-treated subjects compared to 11.58 g/dL (95% CI 11.43, 11.74 g/dL) for
darbepoetin alfa-treated subjects. The incidence of adverse events, or AEs, was 90.1% in the vadadustat-treated group compared to
92.2% in the darbepoetin alfa-treated group. The top three most common AEs reported in vadadustat-treated subjects were
nasopharyngitis (24.5%), diarrhea (11.9%), and constipation (9.3%). The incidence of serious adverse events, or SAEs, was 27.8% in
the vadadustat-treated group compared to 32.0% in the darbepoetin alfa-treated group; no SAE was considered related to study drug.
No deaths were reported in the vadadustat-treated group.
The Phase 3 randomized, double-blind, active-controlled conversion study (J03 Study) assessed the efficacy and safety of vadadustat
compared to darbepoetin alfa in 323 Japanese DD-CKD patients with anemia who had been receiving ESA therapy prior to study
screening, with a treatment duration of 52 weeks. Data from the planned analysis at 24 weeks were announced in March 2019 and
showed that the study met its primary endpoint: The difference in mean Hb was -0.05 g/dL (95% CI -0.26, 0.17 g/dL), achieving the
pre-specified non-inferiority criterion of -0.75 g/dL. The mean Hb level at week 20 and week 24 at 10.61 g/dL (95% CI 10.45, 10.76
g/dL) for vadadustat-treated subjects compared to 10.65 g/dL (95% CI 10.50, 10.80 g/dL) for darbepoetin alfa-treated subjects. The
mean Hb level at week 52 was 10.39 g/dL (95% CI 10.24, 10.54 g/dL) for vadadustat-treated subjects compared to 10.62 g/dL (95%
CI 10.48, 10.76 g/dL) for darbepoetin alfa-treated subjects. The incidence of AEs was 95.1% in the vadadustat-treated group
compared to 98.1% in the darbepoetin alfa-treated group. The top three most common AEs reported in vadadustat-treated subjects
were nasopharyngitis (45.7%), diarrhea (15.4%), and shunt stenosis (14.2%). The incidence of SAEs was 25.3% in the vadadustat-
treated group compared to 27.3% in the darbepoetin alfa-treated group; no SAE was considered related to study drug. There were two
deaths reported in the vadadustat-treated group and one death in the darbepoetin alfa-treated group and all three were assessed as not
related to either vadadustat or darbepoetin alfa.
Vadadustat Phase 1 and Phase 2 Studies
To date, we have completed twenty-four Phase 1 and Phase 2 studies of vadadustat. Findings from three Phase 2 studies demonstrated
that vadadustat administered daily raised and/or maintained hemoglobin levels within a target range and improved markers of iron
mobilization to support erythropoiesis in CKD patients. The range of doses used in these Phase 2 studies had been previously shown,
in Phase 1 studies of healthy volunteers, to stimulate endogenous EPO production while avoiding supraphysiologic EPO levels. The
results from one completed Phase 1 and two Phase 2 of these studies are summarized below.
Phase 1 Study in Normal Healthy Volunteers (CI-0002)
We completed a Phase 1 randomized, double-blind, placebo-controlled, multiple-ascending dose study to evaluate the safety,
tolerability, pharmacodynamics response, and pharmacokinetics of vadadustat administered for 10 days to healthy male
volunteers. Dose responsive increases in reticulocytes, or immature RBCs, and hemoglobin levels were demonstrated in the
study. Mean serum EPO levels increased by 36%, 48%, and 89% over baseline, at 8 to 16 hours after dosing in the vadadustat 500
mg/day, 700 mg/day, and 900 mg/day dosing groups, respectively, and returned to baseline by 24 hours after dosing. The incidence of
AEs was generally similar between the combined vadadustat dosing groups, which was 76.5%, and the placebo group, which was
78%. Gastrointestinal AEs occurred in 26.5% of subjects in the vadadustat groups and in no subjects on placebo, of which mild to
moderate diarrhea was the most frequent AE (24%), with evidence of a dose-related effect. No SAEs or deaths were reported in this
study.
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Phase 2b Study in Non-Dialysis CKD Subjects (CI-0007)
We completed a multi-center Phase 2b study of vadadustat in NDD-CKD patients with anemia. This double-blind, randomized,
placebo-controlled study evaluated the efficacy and safety of vadadustat over 20 weeks of dosing in 210 patients (138 vadadustat and
72 placebo) with CKD Stages 3 to 5. Patients were enrolled into one of three groups: (1) injectable ESA naïve with hemoglobin ≤10.5
g/dL, (2) previously treated with injectable ESA with hemoglobin ≤10.5 g/dL, or (3) actively treated with injectable ESA with
hemoglobin ≥9.5 and ≤12.0 g/dL, and were randomized at a ratio of 2 to 1 to once daily vadadustat or placebo. The primary endpoint
was the percentage of patients with either a mean hemoglobin of ≥11.0 g/dL or an increase in hemoglobin by ≥1.2 g/dL from baseline.
A protocol-defined dose adjustment algorithm was used to achieve the primary endpoint and to minimize hemoglobin excursions ≥13
g/dL.
The average age of patients was 66 years; 78% of patients had diabetes mellitus; and the mean estimated GFR was 25 mL/min/1.73m2.
54.9% of vadadustat treated patients compared to 10.3% of placebo treated patients met the primary endpoint (p=0.0001). Only 4.3%
of patients in the vadadustat group had any hemoglobin excursion ≥13.0 g/dL. Between Groups 1 and 2 (the two correction cohorts;
ESA-naïve and ESA previously treated), mean Hb increased significantly in the vadadustat group from pre-dose average to end-of-
study average (Week 19/20). In Group 3 (conversion cohorts; ESA actively treated), placebo treated patients experienced a decline in
the mean hemoglobin within the first two weeks, whereas patients randomized to vadadustat maintained a stable hemoglobin
throughout the study.
Increases in hemoglobin in the vadadustat group were preceded by an increase in reticulocytes and accompanied by an increase in
total iron binding capacity and a decrease in serum hepcidin and ferritin. There was no difference between the vadadustat and placebo
groups in vascular endothelial growth factor, or VEGF, levels during the study.
A similar percentage of patients experienced an AE in the vadadustat and placebo treatment groups (vadadustat 74.6% vs. placebo
73.6%); however, the frequency of certain AEs - diarrhea, nausea, hypertension and hyperkalemia - was greater in the vadadustat arm
compared to placebo. In the vadadustat arm, a higher number of patients reported SAEs of acute and chronic renal failure compared to
placebo (9.4% vs. 2.8%, respectively); however, none was considered drug-related by the investigator. The percentage of patients who
had an SAE resulting in dialysis initiation, considered to be a more objective measure of the severity of renal disease, was comparable
between vadadustat and placebo groups (8.0% versus 9.7%, respectively) and the number of patients who discontinued from the study
due to AEs of worsening CKD requiring dialysis was also comparable between the vadadustat (4.3%) and placebo (5.6%) groups.
One subject with multiple co-morbidities and concomitant medications, including chlorthalidone, had an SAE of liver function test, or
LFT, abnormal, considered a case of drug-induced liver injury meeting the biochemical criteria of Hy’s Law, which was assessed as
probably related to vadadustat. This subject made a complete recovery after vadadustat was discontinued. There were three deaths in
vadadustat-treated patients of which two cardiovascular deaths were considered to be unrelated to vadadustat and one death was
attributed to myocardial ischemic and considered by the investigator to be possibly related to vadadustat; no autopsy was performed.
There were no deaths in the placebo group.
In summary, vadadustat achieved the desired outcomes of raising and maintaining hemoglobin and increasing iron mobilization, while
minimizing hemoglobin excursions ≥13 g/dL. Pergola et al published the results of this study in Kidney International 2016.
Phase 2 Study in Dialysis-Dependent CKD Patients (CI-0011)
We completed a multi-center, open-label, 16-week study to assess the hemoglobin response, safety, and tolerability of vadadustat in
DD-CKD patients. The study enrolled 94 hemodialysis patients with baseline hemoglobin levels of 9-12 g/dL, who were maintained
on injectable ESAs prior to study entry. Patients were converted from injectable ESA to vadadustat, and assigned to one of three dose
cohorts: 300 mg once daily; 450 mg once daily; or 450 mg three-times weekly. For each dose cohort, the average hemoglobin level at
study entry was compared to the average hemoglobin level at weeks 7 and 8, and to the average hemoglobin level at weeks 15 and 16.
To evaluate hemoglobin response to each of the dose regimens, during the first eight weeks of this study, patients were to remain on
the prescribed starting dose, or decreased if necessary to control hemoglobin in the target range. Beginning at week 8, the dose of
vadadustat could be increased or decreased to maintain hemoglobin levels as needed. Intravenous iron use was allowed.
The underlying demographics and profiles of these CKD patients were well-balanced across the three cohorts, and reflective of the
United States DD-CKD population as reported in the literature. Average age was 58 years, with an average time on dialysis of 4.6
years. The most common cause of end-stage renal disease was diabetes mellitus and/or hypertension. Baseline hemoglobin levels were
similar at 10.4-10.6 g/dL in all three cohorts and the serum ferritin levels indicated that the patients were iron replete at study entry
and throughout the study.
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For patients in all three dosing cohorts (converted from ESA) who completed the study, the primary endpoint of maintaining stable
mean hemoglobin levels over 16 weeks was achieved. In the sensitivity analysis using last observation carried forward to account for
early discontinuations, mean Hb levels remained stable in the 300 mg daily dose cohort and modest declines were observed in the 450
mg daily and 450 mg three-times weekly dose cohorts. Post-hoc analyses indicated that baseline pre-conversion ESA dose was
inversely associated with mean change in hemoglobin. Consistent with previous studies, all three starting dose regimens suggested an
improvement in iron mobilization, as reflected by increases in total iron binding capacity and serum iron, and decreases in serum
ferritin and hepcidin levels. Only one subject in the 300 mg once daily cohort had a single hemoglobin excursion to 13.1 g/dL.
These data support further development of vadadustat daily dosing to assess its long-term safety and efficacy in patients on
hemodialysis. These data also support further investigation of three times weekly dosing of vadadustat.
Adverse events were balanced across the three cohorts with 83% of patients with at least one AE. There were no discernible trends in
the frequency of AEs or SAEs by dose cohort. The most frequently reported AEs were nausea and diarrhea, 11.7% and 10.6%,
respectively, with no apparent dose relationship. The majority of AEs were mild or moderate in severity. SAEs were reported in 13
patients, or 13.8%, including two patients with acute myocardial infarction considered not related to vadadustat by the investigator. No
SAEs were reported as related to vadadustat and no deaths occurred during the study. Haase et al published the results of this study in
Nephrology Dialysis Transplantation 2018.
Commercialization
We are in the process of preparing for a potential commercial launch of vadadustat in Japan, the United States and certain other
markets. Our ability to launch vadadustat in the United States is dependent on the successful outcome of our global Phase 3 program,
the successful filing and defense of an NDA, and approval by the FDA and other regulatory authorities.
We plan to commercialize vadadustat, subject to FDA approval, in the United States with our well-established, nephrology-focused
commercial organization, while leveraging our collaboration with Otsuka and its U.S. nephrology commercial organization. We also
granted Otsuka exclusive rights to commercialize vadadustat in Europe, China and certain other markets, subject to marketing
approvals. In Japan and certain other countries in Asia, we granted MTPC exclusive rights to commercialize vadadustat, subject to
marketing approvals. In addition, we granted Vifor Pharma an exclusive license to sell vadadustat to FKC and Third Party Dialysis
Organizations, which combined manage up to approximately 60% of the dialysis patients in the United States, which would be
effective upon FDA approval of vadadustat, vadadustat’s reimbursement under a bundled reimbursement model or that vadadustat will
be reimbursed using the TDAPA, and a milestone payment by Vifor Pharma. During the term of the license agreement, Vifor Pharma
is not permitted to sell any HIF product that competes with vadadustat in the United States to FKC or its affiliates or to any Third
Party Dialysis Organization, and we may not directly supply vadadustat to FKC or any other affiliate of FMCNA or any Third Party
Dialysis Organization. For more information about our license, collaboration and strategic agreements relating to vadadustat, see Part I,
Item 1. Business – License, Collaboration and Other Strategic Agreements – Vadadustat.
Our Commercial Product: Auryxia
Overview
Auryxia (ferric citrate) is a non-calcium, non-chewable, orally-administered tablet that was approved for marketing by the FDA in
September 2014 as a phosphate binder for the Hyperphosphatemia Indication and was commercially launched in the United States
shortly thereafter. In November 2017, Auryxia received marketing approval from the FDA for a second indication, the IDA Indication,
and was commercially launched for this indication in the United States shortly thereafter.
In January 2014, our Japanese sublicensee, JT, received approval from the Japanese Ministry of Health, Labour and Welfare to market
ferric citrate hydrate in Japan under the trade name Riona as an oral treatment for the improvement of hyperphosphatemia in patients
with CKD, including DD-CKD and NDD-CKD, and was commercially launched in Japan shortly thereafter. In July 2019, JT, and its
subsidiary, Torii, reported positive top-line results from a pivotal Phase 3 comparative study evaluating Riona for the treatment of
IDA in adult patients in Japan. Upon successful completion of its Phase 3 program, JT and Torii stated that they expect to file an
application for approval of IDA as an additional indication for Riona in Japan.
In September 2015, we received approval to market ferric citrate in the European Union under the tradename Fexeric. Pursuant to the
sunset clause under EU law, the European Commission’s approval of Fexeric in the EU was contingent on, among other things, our
commencing marketing of Fexeric within three years; although we successfully negotiated an extension to December 23, 2019, we did
not commence marketing Fexeric by such date and therefore the Fexeric approval in the EU has ceased to be valid.
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We have licensed and sublicensed certain intellectual property rights covering Auryxia from Panion & BF Biotech, Inc., or Panion.
For more information regarding our intellectual property rights to Auryxia and our license agreement with Panion see Part I, Item 1.
Business – Intellectual Property – Auryxia and Part I, Item 1. Business - License, Collaboration and Other Strategic Agreements –
License Agreement with Panion & BF Biotech, Inc. We have received Paragraph IV certification notice letters regarding Abbreviated
New Drug Applications, or ANDAs, submitted to the FDA requesting approval for generic versions of Auryxia tablets (210 mg iron
per tablet), with the first having been received on October 31, 2018. We have filed certain complaints for patent infringement relating
to such ANDAs, and have entered into a settlement and license agreement with one such ANDA filer. See Part I, Item 3. Legal
Proceedings for further information relating to the ANDAs, lawsuits and settlement.
Market Opportunity
Hyperphosphatemia
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 function, excess dietary phosphorus is removed by the kidneys and
excreted in urine. In adults with functioning 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 are the only interventions marketed for the treatment of hyperphosphatemia. According to the USRDS 2019 Annual
Data Report, there are approximately 524,000 adult patients in the United States with DD-CKD in 2017, of which approximately 87%
were treated with a phosphate binder. Phosphate binders need to be taken with meals and snacks, and it is not uncommon for DD-
CKD patients to be prescribed as many as 12 or more phosphate binder pills per day, among other medications. Patients taking
phosphate binders also experience gastrointestinal tolerability issues. As a result of the pill burden and tolerability issues associated
phosphate binders, prescribed phosphate binders are often intolerable for many patients, leading to lack of treatment adherence and
compliance.
In addition, in 2017 approximately 35% of patients 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 gastrointestinal-related 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.
Sevelamer and lanthanum-based phosphate binders are other alternatives. Lanthanum is a rare earth element and is minimally
absorbed in the gastrointestinal tract. Lower level tissue deposition, particularly in bone and liver, has been observed in animals,
however, the long-term, potentially harmful, effects due to the accumulation of lanthanum in these tissues have not been clearly
determined.
Aluminum-type phosphate binders were widely used in the past. However, the systemic absorption of aluminum from these agents and
the potential toxicity associated with their use no longer make this type of binder a viable long-term treatment option.
Iron Deficiency Anemia
Anemia is a condition 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 patients not having enough iron to manufacture healthy RBCs. Although
anyone can develop IDA, IDA is particularly common in patients with NDD-CKD. IDA is associated with fatigue, lethargy, decrease
quality of life, cardiovascular complications, hospitalizations and increased mortality.
We estimate that there are more than 500,000 adult patients in the United States with NDD-CKD diagnosed with IDA. 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 patients, which may adversely impact their effectiveness, and are associated with certain side effects, such as constipation,
diarrhea and cramping, that may adversely affect patient compliance. IV iron is viewed as an effective treatment; however, like other
intravenous medicines, it is logistically difficult to administer in an office setting, where NDD-CKD patients are more often treated.
Commercialization
We market Auryxia in the United States through our well-established, nephrology-focused sales force and commercial organization.
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Auryxia, as an oral drug, is covered by Medicare only under Part D. We have gained broad access for Auryxia in the United States in
both Medicare Part D and commercial channels. Auryxia is currently covered for the Hyperphosphatemia Indication in nine of the ten
largest Medicare Part D plans, which provide coverage for approximately 35.8 million people, and the ten largest commercial plans
and pharmacy benefit managers in the United States, which provide coverage for approximately 131.0 million people. In September
2018, the Centers for Medicare & Medicaid Services, or CMS, decided that Auryxia would not be covered by Medicare for the IDA
Indication. While this decision does not impact CMS coverage of the Hyperphosphatemia Indication, it requires all Auryxia
prescriptions for Medicare patients to undergo a prior authorization to ensure their use in the Hyperphosphatemia Indication. On
October 15, 2019, we filed a complaint in the United States District Court for the District of Massachusetts against CMS and the U.S.
Department of Health and Human Services challenging CMS’s decision that Auryxia would no longer be covered by Medicare for the
IDA Indication and CMS’s related decision that imposed a prior authorization requirement for Auryxia in the Hyperphosphatemia
Indication. See Part I, Item 3. Legal Proceedings for further information.
JT, and its subsidiary, Torii, market Riona in Japan. We receive tiered double-digit royalties from JT and Torii based on their sales in
Japan.
Manufacturing and Supply
Overview
We neither own nor operate, and currently have no plans to own or operate, any manufacturing or distribution facilities. We currently
rely on third-party contract manufacturing organizations, or CMOs, to produce all of our preclinical and clinical material and
commercial supply and third-party distributors to distribute Auryxia. We expect to continue to rely on either existing or alternative
distributors and CMOs to distribute our products and supply our ongoing and planned preclinical and clinical studies and for
commercial production.
We have established relationships with several CMOs under which the CMOs manufacture preclinical and clinical supplies of
vadadustat drug substance and drug product and clinical and commercial supply of Auryxia drug substance and drug product. All
clinical and commercial supplies are manufactured under current Good Manufacturing Practices, or cGMPs, which is a regulatory
standard for the production of pharmaceuticals that will be used in humans.
Vadadustat
We currently have redundant supply arrangements in place for the preclinical and clinical supply of vadadustat. We have entered into
supply agreements with Esteve Química, S.A. and Patheon Inc. for the manufacture of vadadustat drug substance and drug product,
respectively, for commercial use. We intend to put additional supply arrangements in place for commercial manufacturing of
vadadustat. We plan to mitigate potential commercial supply risks for vadadustat, if any, through inventory management and
redundant manufacturing arrangements for both drug substance and drug product; however, the timing of such arrangements is
uncertain and may occur following the launch of vadadustat, if approved.
Vadadustat is a small molecule. The synthesis of vadadustat is reliable and reproducible from starting materials available from
multiple 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 quantity cannot be guaranteed and we cannot ensure that we will be successful in this endeavor.
Auryxia
We have established CMO relationships for the supply of Auryxia to help ensure that we will have sufficient material for ongoing
commercial sales and clinical trials. The drug substance for Auryxia is supplied by Siegfried Evionnaz SA (two sites) and BioVectra
Inc. (one site), pursuant to supply agreements with pricing structured on a per-kilogram basis. Auryxia drug product is supplied by
Patheon Manufacturing Services LLC (Thermo Fisher) (three sites) pursuant to a Master Manufacturing Service Agreement with per-
bottle pricing structured on a tiered basis, with the price reduced as the product volume increases. These agreements require that we
satisfy certain minimum purchase requirements, but we are not obligated to use them as our sole suppliers. For more information
about our manufacturing agreements for Auryxia, see Part II, Item 7. Management’s Discussion and Analysis and Note 16 to our
consolidated financial statements in Part II, Item 8. Financial Statements and Supplementary Data.
Our CMOs have other clients and may have other priorities that could affect their ability to perform the work satisfactorily and/or on a
timely basis. Both of these occurrences would be beyond our control.
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The active pharmaceutical ingredient of Auryxia, ferric citrate, is a small molecule. The synthesis of ferric citrate is reliable and
reproducible from starting materials available from multiple 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 quantity cannot be guaranteed, and we cannot ensure that we will be successful in this
endeavor.
We utilize third parties for the commercial distribution of Auryxia, including wholesale distributors and certain specialty pharmacy
providers. We have also engaged Cardinal Health as the exclusive third-party logistics distribution agent for commercial sales of
Auryxia.
License, Collaboration and Other Strategic Agreements
Vadadustat
U.S. Collaboration with Otsuka Pharmaceutical Co. Ltd.
On December 18, 2016, we entered into a collaboration and license agreement with Otsuka, or the Otsuka U.S. Agreement, pursuant
to which we agreed to co-exclusively collaborate with Otsuka with respect to the development and commercialization of vadadustat in
the United States, subject to the approval of vadadustat by the FDA. We continue to lead the ongoing global Phase 3 development
program for vadadustat. We and Otsuka will co-commercialize vadadustat in the United States, subject to the approval of vadadustat
by the FDA.
Under the terms of the Otsuka U.S. Agreement, Otsuka paid us an upfront payment of $125.0 million and we expect Otsuka to provide
additional funding of $266.8 million or more, depending on the actual costs incurred, toward the vadadustat global Phase 3
development program. Due to the costs incurred in completing the activities under the current global development plan exceeding a
certain threshold in the second quarter of 2019, we elected to require Otsuka to increase the aggregate percentage of current global
development costs it funds under the Otsuka U.S. Agreement and the Otsuka International Agreement, as defined below, from 52.5%
to 80%, or the Otsuka Funding Option. The additional funding expected to result from having exercised the Otsuka Funding Option,
or the Additional Funding, is fully creditable against future payments due to us under the arrangement, provided that future payments
due to us may not be reduced by more than 50% in any calendar year and any remaining creditable amount above 50% in any calendar
year will be applied to subsequent future payments until fully credited. We are eligible to receive from Otsuka up to $190.0 million in
development and regulatory milestones and up to $575.0 million in specified commercial milestones.
The Otsuka U.S. Agreement establishes a profit share for the commercialization of vadadustat in the United States. The parties will
equally share all net sales of vadadustat in the United States, if approved, and generally each party will bear half of all costs in the
United States, including medical affairs, commercialization and manufacturing costs.
Under the Otsuka U.S. Agreement, we and Otsuka will jointly conduct, and will have equal responsibility for, all medical affairs and
commercialization activities pursuant to plans agreed by the parties. We will remain responsible for manufacturing vadadustat.
Additionally, the parties agreed not to promote, market or sell any competing product in the territory covered by the agreement.
International Collaboration with Otsuka Pharmaceutical Co. Ltd.
On April 25, 2017, we entered into a collaboration and license agreement with Otsuka, or the Otsuka International Agreement,
pursuant to which we granted Otsuka an exclusive license for the development and commercialization of vadadustat in certain territory
outside the United States. The territory covered by the Otsuka International Agreement includes the European Union, Russia, China,
Australia, Canada, the Middle East and certain other countries, or the Otsuka International Territory, but excludes Latin America and
previously licensed jurisdictions. Under the Otsuka International Agreement, Otsuka is responsible for certain development activities
and commercializing vadadustat in the Otsuka International Territory, while we lead the ongoing global Phase 3 development
program. Otsuka will fund a significant percentage of the costs of such global development program regardless of the total actual costs
ultimately incurred. We and Otsuka have final decision-making authority with respect to certain matters. Additionally, the parties
agreed not to promote, market or sell any competing product in the territory covered by the agreement.
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Under the terms of the Otsuka International Agreement, we expect Otsuka to pay us at least $287.2 million, comprised of $73.0
million that was paid upon execution of the Otsuka International Agreement and $214.2 million or more, depending on actual costs
incurred, of development funding. In addition, we are eligible to receive from Otsuka up to $132.0 million in development and
regulatory milestones and up to $525.0 million in commercial milestones. Otsuka also agreed to make tiered, escalating royalty
payments ranging from low double digits up to thirty percent of net sales of vadadustat within the Otsuka International Territory. In
limited circumstances, upper tier royalties may be subject to reduction if the supply price charged by us to Otsuka for vadadustat
exceeds certain agreed upon thresholds, and royalty payments may also be reduced if a generic product is launched, on a country-by-
country basis. Otsuka may elect to conduct additional studies of vadadustat in the European Union, subject to our right to delay such
studies based on our objectives outside the Otsuka International Territory. Otsuka will pay a percentage of the costs of any such
studies, and we will pay its portion of the costs in the form of a credit against future amounts due to us under the Otsuka International
Agreement.
Collaboration with Mitsubishi Tanabe Pharma Corporation
On December 11, 2015, we entered into a collaboration agreement with MTPC, or the MTPC Agreement, providing MTPC with
exclusive development and commercialization rights to vadadustat in Japan and certain other Asian countries, or the MTPC Territory.
In addition, we will supply vadadustat for both clinical and commercial use in the MTPC Territory, subject to MTPC’s option to
manufacture commercial drug product in the MTPC Territory. We plan to enter into a supply agreement with MTPC for the
commercial supply of vadadustat prior to commercial launch.
We and MTPC agreed that, instead of including Japanese patients in our global Phase 3 program for vadadustat, MTPC would be the
sponsor of a Phase 3 program for vadadustat in Japan. MTPC reported top-line data for the two Phase 3 pivotal trials and data from the
two supportive Phase 3 studies in March 2019 and 52-week data for the two Phase 3 pivotal trials in November 2019. In July 2019,
MTPC submitted a Japanese New Drug Application, or JNDA, to the Ministry of Health, Labor and Welfare in Japan for
manufacturing and marketing approval of vadadustat, as a treatment for anemia due to CKD.
Under the terms of the MTPC Agreement, MTPC will make payments to us of up to $245.0 million in the aggregate based on the
achievement of certain development, regulatory and sales milestones, as well as tiered double-digit royalty payments of up to 20% on
sales of vadadustat in the MTPC Territory, subject to reduction upon launch of a generic product on a country-by-country basis.
MTPC is responsible for the costs of the Phase 3 program for vadadustat in Japan and will make no additional funding payments for
our global Phase 3 program for vadadustat. Additionally, the development costs of approximately $20.5 million for our Phase 2
studies in Japan were reimbursed to us by MTPC.
In addition, in September 2017 we agreed to provide MTPC with an option to use data from our global Phase 3 vadadustat program to
obtain regulatory approval for vadadustat in Japan. If exercised, MTPC would make payments to us of up to $25.0 million.
Vifor Pharma License Agreement
On May 12, 2017, we entered into a License Agreement with Vifor Pharma, or the Vifor Agreement. On April 8, 2019, we entered
into an Amended and Restated License Agreement with Vifor Pharma, or the Vifor Amended Agreement, which amends and restates
in full the Vifor Agreement, pursuant to which we granted Vifor Pharma an exclusive license to sell vadadustat to FKC, an affiliate of
Fresenius Medical Care North America, and to Third Party Dialysis Organizations, in the United States, which would be effective
upon the approval of vadadustat for DD-CKD patients by the FDA, inclusion of vadadustat in a bundled reimbursement model or that
vadadustat will be reimbursed using the TDAPA, and payment by Vifor Pharma of a $25 million milestone upon the occurrence of
these two events. The Vifor Agreement is structured as a profit share arrangement between us and Vifor Pharma in which we will
receive a majority of the profit from Vifor Pharma’s sales of vadadustat to FKC and to Third Party Dialysis Organizations in the
United States. We will share the milestone payment and the revenue from the profit share with Otsuka pursuant to the Otsuka U.S.
Agreement. We retain all rights to commercialize vadadustat for use in the NDD-CKD market and in other dialysis organizations in
the United States, which will be done in collaboration with Otsuka if vadadustat is approved by the FDA.
Prior and subject to FDA approval of vadadustat, we and Vifor Pharma plan to enter into a commercial supply agreement for
vadadustat pursuant to which we would supply all of Vifor Pharma’s commercial requirements for vadadustat in the United States. In
addition, pursuant to the Vifor Agreement, Vifor Pharma will enter into supply agreements that govern the terms pursuant to which
Vifor Pharma would supply vadadustat to FKC and Third Party Dialysis Organizations for use in patients at its dialysis centers,
subject to FDA approval; however, FKC and the Third Party Dialysis Organizations are not obligated to utilize vadadustat in its
clinics. During the term of the Vifor Agreement, Vifor Pharma will not sell to FKC, its affiliates, or Third Party Dialysis
Organizations any HIF product that competes with vadadustat in the United States, and we may not directly supply vadadustat to FKC
or any other affiliate of FMCNA or any Third Party Dialysis Organization.
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Janssen Pharmaceutica NV Research and License Agreement
On February 9, 2017, we entered into a Research and License Agreement, the Janssen Agreement, pursuant to which Janssen granted
us an exclusive license under certain intellectual property rights to develop and commercialize worldwide certain HIF-PH-targeted
compounds.
Under the terms of the Janssen Agreement, Janssen granted us a license for a three-year research term to conduct research on
Janssen’s HIF compound portfolio, which research term is now expired. During the research term, we could designate one or more
compounds as candidates for development and commercialization. Once a compound was designated for development and
commercialization, we were to be solely responsible for the development and commercialization of the compound worldwide at our
own cost and expense.
Under the terms of the Janssen Agreement, we paid an upfront payment of $1.0 million in cash to Janssen and issued a warrant to
purchase 509,611 shares of our common stock, the fair value of which was approximately $3.4 million. In addition, Janssen could be
eligible to receive up to an aggregate of $16.5 million from us in specified development milestone payments on a product-by-product
basis. Janssen will also be eligible to receive up to $215.0 million from us in specified commercial milestones as well as tiered,
escalating royalties ranging from a low to mid-single digit percentage of net sales, on a product-by-product basis and subject to
reduction upon expiration of patent rights or the launch of a generic product in the territory.
Janssen also has a right of first offer to engage in exclusive negotiations with us to develop and commercialize certain products
developed by us containing compounds for the treatment of inflammatory bowel disease.
Auryxia
License Agreement with Panion & BF Biotech, Inc.
Prior to the Merger, Keryx entered into a license agreement, or the Panion License Agreement, which was amended from time to time,
with Panion & BF Biotech, Inc., or Panion, under which Keryx in-licensed the exclusive worldwide rights, excluding certain Asian-
Pacific countries, or the Licensor Territory, for the development and commercialization of ferric citrate.
On April 17, 2019, we and Panion entered into a second amended and restated license agreement, or the Panion Amended License
Agreement, which amends and restates in full the Panion License Agreement, effective as of April 17, 2019. The Panion Amended
License Agreement provides Keryx 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 the Licensor Territory. The
Panion Amended License Agreement also provides Panion with an exclusive license under Keryx-owned patents covering the rights to
sublicense (with our written 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 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 expiration of each of our and Panion’s obligations to pay royalties
thereunder. In addition, we may terminate the Panion Amended License Agreement (i) in its entirety or (ii) with respect to one or more
countries in our licensed territory, in either case upon 90 days’ notice. 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, until the second anniversary of the expiration of our or Panion’s obligation, as applicable, to pay royalties in
a country in which such party has ferric citrate for sale on the date of such expiration, 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
distribution in such country. In addition, the Panion Amended License Agreement provides that each of us and Panion has the right,
but not the obligation, to conduct litigation against any infringer of certain patent rights under the Panion Amended License
Agreement in certain territories.
During the year-ended December 31, 2019, Panion earned $10.2 million in royalty payments relating to the sales of Auryxia in the
United States and JT and Torii net sales of Riona in Japan, as we are required to pay a low double-digit percent of sublicense income
to Panion under the terms of the license agreement, excluding any income under the JT and Torii sublicense.
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Sublicense Agreement with Japan Tobacco Inc. and Torii Pharmaceutical Co., Ltd.
In September 2007, Keryx entered into a Sublicense Agreement with JT and Torii, under which JT and Torii obtained the exclusive
sublicense rights for the development and commercialization of ferric citrate in Japan. Effective June 8, 2009, Keryx 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 marketing approval of ferric citrate from the Japanese Ministry of Health,
Labour and Welfare. Ferric citrate, 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 patients with CKD, including NDD-CKD and DD-
CKD. JT and Torii are currently conducting a Phase 3 clinical program evaluating Riona for the treatment of IDA in adult patients in
Japan. JT and Torii have stated that, upon successful completion of its Phase 3 program, they expect to file an application for approval
of IDA as an additional indication 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 tiered double-digit percentage of net sales of Riona in Japan escalating up to the mid-teens,
subject to certain reductions upon expiration or termination of the Panion Amended License Agreement, and may also receive up to an
additional $55.0 million upon the achievement of certain annual net sales milestones. In accordance with our revenue recognition
policy, royalty revenues are recognized in the quarter that JT and Torii provide their written report and related information to us
regarding sales of Riona, which generally will be one quarter following the quarter in which the underlying sales by JT and Torii
occurred. We recorded $5.9 million in license revenue related to royalties earned on net sales of Riona in Japan during the twelve
months ended December 31, 2019. We record the associated mid-single digit percentage of net sales royalty expense due to Panion,
the licensor of ferric citrate, in the same period as the royalty revenue from JT and Torii is recorded.
The sublicense under the Revised Agreement terminates upon the expiration of all underlying patent rights. Also, JT and Torii may
terminate the Revised Agreement with or without cause upon at least six months prior written notice to us. Additionally, either party
may terminate the Revised Agreement for cause upon 60 days’ prior written notice after the breach of any uncured material provision
of the Revised Agreement, or after certain insolvency events.
Intellectual Property
The proprietary nature of, and protection 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 position by, among other methods, filing patent
applications related to our proprietary technology, inventions and improvements that are important to the development and
implementation of our business. We also rely on know-how, continuing technological innovation and potential in-licensing
opportunities to develop and maintain our proprietary position. Additionally, we may benefit from a variety of statutory frameworks in
the United States, Europe and other countries that provide periods of non-patent-based exclusivity for qualifying molecules. See “—
Regulatory Matters.”
Our commercial success will depend in part on obtaining and maintaining patent protection 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 parties from making, using, selling, offering to sell or
importing our products depends on the extent to which we have rights under valid and enforceable patents that cover these activities.
We cannot be sure that patents will be granted with respect to any of our pending patent applications or with respect to any patent
applications filed by us in the future, nor can we be sure that any of our existing patents or any patents that may be granted to us in the
future will be commercially useful in protecting our product candidates, discovery programs and processes. Even once patents
successfully issue, third parties 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.”
Individual patents extend for varying periods of time depending on the date of filing of the patent application or the date of patent
issuance and the legal term of patents in the countries in which they are obtained. Generally, patents issued from applications filed in
the United States are effective for 20 years from the earliest filing date of a United States non-provisional application or an
international application filed under the Patent Cooperation Treaty. In addition, in certain instances, a patent term can be extended to
recapture a portion of the term effectively lost as a result of the FDA regulatory review period, however, the restoration period cannot
be longer than five years and the total patent term including the restoration period must not exceed 14 years following FDA approval.
The duration of foreign patents varies in accordance with provisions of applicable local law, but typically is also 20 years from the
earliest international filing date. Patent term recapture for loss of term as a result of the regulatory review period is available in some
foreign jurisdictions. In the United States, a patent’s term may also be lengthened by patent term adjustment, which compensates a
patentee for administrative delays by the United States Patent and Trademark Office, or USPTO, in granting a patent, or may be
shortened if a patent is terminally disclaimed over an earlier-filed patent.
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Changes in either the patent laws or interpretations of patent laws in the United States and other countries can diminish our ability to
protect our inventions 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 pharmaceutical industries are characterized
by extensive litigation regarding patents and other intellectual property rights. Our ability to maintain and solidify our proprietary
position for our drugs and technology will depend on our success in obtaining effective claims and enforcing those claims once
granted. We do not know whether any of the patent applications that we may file or license from third parties 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 protection or
competitive advantages against competitors with similar technology. Furthermore, our competitors 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 time 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
commercialization, thereby reducing any advantage of any such patent. The patent positions for Auryxia and vadadustat are
summarized below.
Vadadustat Patent Portfolio
We hold 11 issued patents covering the composition of matter, polymorph, method of treating anemia, and pharmaceutical
compositions of vadadustat in the United States and additional patents issued or pending in many other major jurisdictions worldwide,
including Europe, Japan, China, South Korea, Brazil, Mexico, Russia, Israel and India. The expected expiration dates for these patents
are between 2027 and 2034 plus any extensions or adjustments of term available under national law.
We also hold patents and patent applications directed to processes for manufacturing vadadustat, dosing regimens, formulations, and
various other aspects relating to the treatment of anemia using vadadustat that are expected to expire between 2032 and 2040 exclusive
of possible patent term extensions or adjustments.
We have ongoing opposition and invalidity proceedings relating to vadadustat. See Part II, Item 3. Legal Proceedings for further
information relating to these matters.
Auryxia Patent Portfolio
Pursuant to Keryx’s license with Panion & BF Biotech, Inc., or Panion, we have the exclusive rights under a series of patents and
patent applications to commercialize Auryxia worldwide, excluding certain Asian-Pacific countries. These patents and patent
applications include claims directed to compositions of matter, pharmaceutical compositions, methods of treatment, as well as
methods for the manufacture of Auryxia.
Keryx’s patent rights include 15 issued U.S. patents listed in the Orange Book covering the composition of matter, method of treating
hyperphosphatemia, and pharmaceutical compositions of Auryxia. The expected expiration dates for these patents are between 2020
and 2030 plus any additional patent term extensions that may be available.
Pursuant to the sublicense with our Japanese partner, Japan Tobacco Inc., or JT, and its subsidiary, Torii Pharmaceutical 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 applications with composition of matter claims and methods of use claims covering Riona, the
trade name under which JT and Torii market ferric citrate in Japan. The expected expiration dates for these patents and pending patent
applications are between 2022 and 2027. To date, to our knowledge, no contested proceedings or third-party claims have been lodged
against any of these Japanese patents.
We have received Paragraph IV certification notice letters regarding ANDAs submitted to the FDA requesting approval for generic
versions of Auryxia tablets (210 mg iron per tablet), have filed certain complaints for patent infringement relating to such ANDAs,
and have entered into a settlement and license agreement with one such ANDA filer. We also have an ongoing appeal regarding an
opposition proceeding against a European patent covering Auryxia. See Part II, Item 3. Legal Proceedings for further information
relating to these matters.
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Other Intellectual Property Rights
We depend upon trademarks, trade secrets, know-how and continuing technological advances to develop and maintain our competitive
position. To maintain the confidentiality of trade secrets and proprietary information, we require our employees, scientific advisors,
consultants and collaborators, upon commencement of a relationship with us, to execute confidentiality agreements and, in the case of
parties other than our research and development collaborators, to agree to assign their inventions to us. These agreements are designed
to protect our proprietary information and to grant us ownership of technologies that are developed in connection with their
relationship with us. These agreements may not, however, provide protection for our trade secrets in the event of unauthorized
disclosure of such information.
In addition to patent protection, we may utilize orphan drug regulations, pediatric exclusivity or other provisions of the Food, Drug
and Cosmetic Act of 1938, as amended, or FDCA, such as new chemical entity exclusivity or new formulation exclusivity, to provide
market exclusivity for a drug candidate. In the United States, the FDA has the authority to grant additional data protection for
approved drugs where the sponsor conducts specified testing in pediatric or adolescent populations. If granted, this pediatric
exclusivity may provide an additional six months which are added to the term of data protection as well as to the term of a relevant
patent, to the extent these protections have not already expired. We may also seek to utilize market exclusivities in other territories.
We cannot assure that our drug products or any drug candidates we may acquire or in-license, will obtain such orphan drug
designation, pediatric exclusivity, new chemical entity exclusivity or any other market exclusivity in the United States, European
Union or any other territory, or that we will be the first to receive the respective regulatory approval for such drugs so as to be eligible
for any market exclusivity protection.
Know-How
In addition to patents, we rely upon unpatented know-how and continuing technological innovation to develop and maintain our
competitive position. We seek to protect our proprietary information, in part, using confidentiality agreements with our collaborators,
employees and consultants and invention assignment provisions in the confidentiality agreements with our employees. These
agreements are designed to protect our proprietary information and, in the case of the invention 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 resulting know-how and inventions.
The Hatch-Waxman Act
Orange Book Listing
In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent whose claims cover the
applicant’s product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s
Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book. Drugs listed in the
Orange Book can, in turn, be cited by potential generic competitors in support of approval of an ANDA. An ANDA provides for
marketing of a drug product that has the same active ingredients in the same strengths and dosage form as the listed drug and has been
shown through bioequivalence testing to be therapeutically equivalent to the listed drug. Other than the requirement for
bioequivalence testing, ANDA applicants are usually not required to conduct, or submit results of, nonclinical or clinical tests to prove
the safety or effectiveness of their drug product. Drugs approved in this way are commonly referred to as “generic equivalents” to the
listed drug and can often be substituted by pharmacists under prescriptions written for the original listed drug.
The ANDA applicant is required to make certain certifications to the FDA concerning any patents listed for the approved product in
the FDA’s Orange Book. Specifically, the applicant must certify that: (i) the required patent information has not been filed; (ii) the
listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent
expiration; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA applicant may also elect to
submit a Section viii statement, certifying that its proposed ANDA label does not contain or carve out any language regarding the
patented method-of-use, rather than certify to a listed method-of-use patent.
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If the applicant does not challenge the listed patents, the ANDA will not be approved until all the listed patents claiming the
referenced product have expired. A certification 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 certification. If the ANDA applicant has provided a Paragraph IV certification to
the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has
been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the
notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV
certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months from receiving the Paragraph
IV certification, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is favorable to the
ANDA applicant. Also, the ANDA will not be approved until any applicable non-patent exclusivity listed in the Orange Book for the
referenced product has expired.
Exclusivity
Upon NDA approval of a new chemical entity, or NCE, which is a drug that contains an active moiety that has not been approved by
the FDA in any other NDA, that drug receives five years of marketing exclusivity during which time the FDA cannot accept any
ANDA seeking approval of a generic version of that drug. Certain changes to a drug, such as the addition of a new indication 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 submitted one year before NCE exclusivity expires if a Paragraph IV certification is filed. If there is no listed
patent in the Orange Book, there may not be a Paragraph IV certification, and, thus, no ANDA may be filed before the expiration of
the exclusivity period.
On August 23, 2018, Keryx submitted a Citizen Petition requesting, inter alia, that FDA recognize that Auryxia is eligible for five
years of NCE exclusivity based on its novel active ingredient and for three years exclusivity for the IDA Indication. On January 19,
2019, FDA responded that Auryxia is eligible for a three-year exclusivity period for the IDA Indication, which expires on November
6, 2020. FDA, however, denied the NCE exclusivity based on its determination that Auryxia contains a previously-approved active
moiety (ferric cation). FDA’s decision on the Citizen Petition is subject to further review both within FDA and in the courts. On
February 21, 2019, Akebia filed a Petition for Reconsideration of FDA’s decision on the NCE determination for Auryxia.
Patent Term Extension
After 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 testing phase which is the
time between IND submission and NDA submission, and all of the review phase, which is the time between NDA submission and
approval, up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursue approval
with due diligence. The total patent term after the extension may not exceed 14 years.
We have filed applications 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, 5,753,706, and 8,338,642 each of which covers Auryxia for delays caused by FDA regulatory review. If granted, we can
utilize 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 expiration of these patents, competitors who obtain the requisite regulatory approval may potentially offer
products with the same composition and/or method of use as our product, so long as the competitors do not infringe any other patents
that we may own or license.
For patents that might expire before a determination 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 times.
For each interim patent extension granted, the post-approval patent extension is reduced by one 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. We have filed for and
received interim patent term extension in accordance with 35 U.S.C. § 156(e)(2) for U.S. Patent No. 5,753,706, which currently has an
expiration date of February 3, 2021.
In addition, certain jurisdictions 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 Patents
Nos. 4964585 and 4173553 will expire in November 2025 and November 2022, respectively.
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Competition
The pharmaceutical and biotechnology industries are highly competitive. Our competitors include pharmaceutical companies and
biotechnology companies, as well as universities and public and private research institutions. In addition, companies that are active in
different but related fields represent substantial competition for us. Many of our competitors have significantly greater capital
resources, larger research and development staffs and facilities and greater experience in drug development, regulation, manufacturing
and marketing than we do. These organizations also compete with us to recruit qualified personnel, attract partners for joint ventures
or other collaborations, and license technologies that are competitive with ours. To compete successfully in this industry, we must
identify novel and unique drugs or methods of treatment and then complete the development of those drugs as treatments in advance
of our competitors.
Vadadustat
If vadadustat is approved and launched commercially, competing branded drugs may include EPOGEN® (epoetin alfa) and Aranesp®
(darbepoetin alfa), both commercialized by Amgen, Procrit® (epoetin alfa) and Eprex® (epoetin alfa), commercialized by Johnson &
Johnson in the United States and Europe, respectively, and Mircera® (methoxy PEG-epoetin beta), commercialized by Vifor Pharma
in the United States and Roche Holding Ltd. outside the United States. We may also face competition from potential new anemia
therapies. There are several other HIF-PHI product candidates in various stages of active development for anemia indications that may
be in direct competition with vadadustat if and when they are approved and launched commercially. These candidates are being
developed by such companies as FibroGen, Japan Tobacco International, GlaxoSmithKline plc and Bayer HealthCare AG. FibroGen,
together with its collaboration partners, Astellas Pharma Inc. and AstraZeneca PLC, is currently in global Phase 3 clinical
development of its product candidate, roxadustat. The product has launched for DD-CKD in Japan and both DD-CKD and NDD-CKD
in China. FibroGen announced that the FDA has completed its filing review of its NDA for roxadustat for both DD-CKD and NDD-
CKD and set a Prescription Drug User Fee Act date of December 20, 2020. They have stated they expect Astellas to file a marketing
authorization application in the EU, or MAA, for both indications in the second quarter of 2020. GlaxoSmithKline plc is currently in
global Phase 3 clinical development of its product candidate, daprodustat. Japan Tobacco International and Bayer HealthCare AG are
currently in Phase 3 clinical development of their product candidates in Japan. GlaxoSmithKline plc and Japan Tobacco International
have submitted NDAs for their product candidates for the treatment of renal anemia in Japan. In addition, certain companies are
developing potential new therapies for renal-related diseases that could potentially reduce injectable ESA utilization and thus limit the
market potential for vadadustat if they are approved and launched commercially. Other new therapies are in development for the
treatment of conditions inclusive of renal anemia that may impact the market for anemia-targeted treatment.
A biosimilar is a biologic product that is approved based on demonstrating that it is highly similar to an existing, FDA-approved
branded biologic product. The patents for the existing, branded biologic product must expire in a given market before biosimilars may
enter that market without risk of being sued for patent infringement. In addition, an application for a biosimilar product cannot be
approved by the FDA until 12 years after the existing, branded product was approved under a Biologics License Application, or BLA.
The patents for epoetin alfa, an injectable ESA, expired in 2004 in the European Union, and the remaining patents expired between
2012 and 2016 in the United States. Because injectable ESAs are biologic products, the introduction of biosimilars into the injectable
ESA market in the United States will constitute additional competition for vadadustat if we are able to obtain approval for and
commercially launch our product. Several biosimilar versions of injectable ESAs are available for sale in the European Union. In the
United States, Pfizer’s biosimilar version of injectable ESAs, Retacrit® (epoetin alfa-epbx), was approved by the FDA in May 2018
and launched in November 2018 by Vifor Pharma.
Auryxia
Hyperphosphatemia Competition
Auryxia competes in the Hyperphosphatemia Indication in the United States with other FDA-approved phosphate binders such as
Renagel® (sevelamer hydrochloride) and Renvela® (sevelamer carbonate), both marketed by Genzyme Corporation (a wholly-owned
subsidiary of Sanofi), PhosLo® and Phoslyra® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol®
(lanthanum carbonate), marketed by Shire Pharmaceuticals 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
options such as aluminum, lanthanum and magnesium. Many of the phosphate binders listed above are now also available in generic
forms. In addition, other phosphate binders are in various phases of development, including OPKO Health Inc.’s Alpharen™ Tablets
(fermagate tablets) and Ardelyx, Inc’s tenapanor, that may impact the market for Auryxia.
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Iron Deficiency Anemia Competition
Auryxia competes in the IDA Indication in the United States with over-the-counter oral iron, other prescription oral iron formulations,
including ferrous sulfate, ferrous gluconate, ferrous fumerate, and polysaccharide iron complex, and IV iron formulations, including
Feraheme® (ferumoxytol injection), Venofer® (iron sucrose injection), Ferrlicit® (sodium ferric gluconate complex in sucrose
injection), Injectafer® (ferric carboxymaltose injection), and Triferic® (ferric pyrophosphate citrate).
In addition, other new therapies are available for the treatment of IDA that may impact the market for Auryxia, such as Shield
Therapeutics’ ferric maltol, which is currently approved in Europe as Ferracru® for IDA and more recently in the United States as
Accrufer®.
Government Regulation and Product Approvals
Government authorities in the United States, at the federal, state and local level, and in other countries and jurisdictions, including the
European Union, extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval,
packaging, storage, recordkeeping, labeling, advertising, promotion, distribution, marketing, sales, pricing, reimbursement, post-
approval monitoring and reporting, and import and export of pharmaceutical products. The processes for obtaining regulatory
approvals in the United States and in foreign countries and jurisdictions, along with subsequent compliance with applicable statutes
and regulations and other regulatory requirements, require the expenditure of substantial time and financial resources.
Review and Approval of Drug Products in the United States
In the United States, the FDA approves and regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and
implementing regulations. The failure to comply with applicable requirements under the FDCA and other applicable laws at any time
during the product development process, approval process or after approval may subject an applicant and/or sponsor to a variety of
administrative or judicial sanctions, including refusal by the FDA to approve pending applications, withdrawal of an approval,
imposition of a clinical hold, issuance of warning letters and other types of letters, product recalls, product seizures, total or partial
suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement of profits, or
civil or criminal investigations and penalties brought by the FDA and the Department of Justice or other governmental entities.
An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the
following:
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completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good
laboratory practice, or GLP, regulations and consistent with International Council for Harmonisation of Technical
Requirements for Pharmaceuticals for Human Use, or ICH, requirements;
submission to the FDA of an IND, which must be reviewed and active by the FDA before human clinical trials may begin;
approval by an independent local or central institutional review board, or IRB, representing each clinical site before each
clinical trial may be initiated;
performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, to
establish the safety and efficacy of the proposed product candidate for each indication;
preparation and submission to the FDA of an NDA requesting marketing for one or more proposed indications;
review of the product candidate by an FDA advisory committee, where appropriate or if applicable;
satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product
candidate, or components thereof, are produced to assess compliance with current Good Manufacturing Practices, or
cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product
candidate’s identity, strength, quality and purity;
satisfactory completion of FDA audits of clinical trial sites and records to assure compliance with GCPs and good
practices, 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, collection and reporting of
serious adverse events and other activities;
payment of user fees and securing FDA approval of an NDA; and
compliance with any post-approval requirements and/or commitments, including the potential requirement to implement a
risk evaluation and mitigation strategy, or REMS, and potentially post-market requirement, or PMR, and commitment, or
PMC, studies.
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Preclinical Studies
Before an applicant begins testing a compound with potential therapeutic value in humans, the product candidate enters the preclinical
testing stage. Preclinical studies include laboratory evaluation of the purity and stability of the manufactured drug substance or active
pharmaceutical ingredient and the formulated drug or drug product, as well as in vitro and animal studies to assess the safety and
activity of the product candidate for initial testing in humans and to establish a rationale for therapeutic use. The conduct of preclinical
studies is subject to federal regulations and requirements, including GLP regulations. The results of the preclinical tests, together with
manufacturing information, analytical data, any available clinical data or literature and plans for clinical studies, among other things,
are submitted to the FDA as part of an IND. Some long-term preclinical testing, such as animal tests of reproductive adverse events
and carcinogenicity, and long-term toxicity studies, will likely continue after the IND is submitted through the time of the NDA
submission.
The IND and IRB Processes
Clinical trials involve the administration of the investigational product to human patients under the supervision of qualified
investigators in accordance with GCP requirements, which include, among other things, the requirement that all research patients
provide their voluntary informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under
written study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives of the study, the parameters
to be used in monitoring safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent
protocol amendments must be submitted to the FDA as part of the IND.
An IND is an exemption from the FDCA that allows an unapproved drug to be shipped through interstate commerce for use in an
investigational clinical trial and a request for FDA authorization to administer an investigational drug to humans. Such authorization
must be obtained prior to interstate shipment and administration of any new drug that is not the subject of an approved NDA. As a
required component of the IND application, applicants must submit a protocol for each clinical trial and any subsequent protocol
amendments. In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available
clinical data or literature and plans for clinical trials, among other things, are submitted to the FDA as part of an IND. The FDA
requires a 30-day waiting period after the submission of each IND before clinical trials may begin. This waiting period is designed to
allow the FDA to review the IND to determine whether human research patients will be exposed to unreasonable health risks. At any
time during this 30-day period, or thereafter, the FDA may raise concerns or questions about the conduct of the trials as outlined in the
IND and impose a clinical hold or partial clinical hold or require that the sponsor amend the clinical protocol to include additional
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 time a clinical hold was imposed).
Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial clinical hold on that trial.
A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing
investigation. A partial clinical hold is a delay or suspension of only part of the clinical work requested under the IND. For example, a
specific protocol or part of a protocol is not allowed to proceed, while other protocols may do so. No more than 30 days after
imposition of a clinical hold or partial clinical hold, the FDA will provide the sponsor a written explanation of the basis for the hold.
Following issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor
that the investigation may proceed. The FDA will base that determination on information provided by the sponsor correcting the
deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed. Clinical holds are imposed by the
FDA whenever there is concern for patient safety and may be a result of new data, findings, or developments in clinical, nonclinical,
and/or chemistry, manufacturing, and controls, or CMC.
A sponsor may choose, but is not required, to conduct a foreign clinical trial under an IND. When a foreign clinical trial is conducted
under an IND, all FDA IND requirements must be met unless waived. When the foreign clinical trial is not conducted under an IND,
the sponsor must ensure that the trial complies with certain FDA regulatory requirements in order to use the trial as support for an IND
or application for marketing approval. These requirements to protect the rights, welfare, and safety of patients are also stipulated in
applicable ICH guidance.
In addition to the foregoing IND requirements, an IRB representing each institution participating in the clinical trial must review and
approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct a continuing review and
reapprove the trial at least annually. The IRB must review and approve, among other things, the trial protocol and informed consent
information to be provided to study patients. An IRB must operate in compliance with FDA regulations. An IRB can suspend or
terminate approval of a clinical trial at its institution, or an institution 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 patients.
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Additionally, some clinical trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a
data monitoring committee, or DMC. DMCs may be charged with monitoring efficacy, safety, and/or study conduct. A DMC provides
a recommendation for whether or not a clinical trial should move forward at designated check points based on available data from the
trial. A recommendation by a DMC to suspend or terminate development during any phase of clinical trials can occur if it is
determined that the participants or patients are being exposed to an unacceptable health risk.
Information about certain clinical trials must be submitted within specific timeframes to the National Institutes of Health, or NIH, for
public dissemination on its website.
Expanded Access to an Investigational Drug for Treatment Use
Expanded access, sometimes called “compassionate use,” is the use of investigational new drug products outside of clinical trials to
treat patients with serious or immediately life-threatening diseases or conditions when there are no comparable or satisfactory
alternative treatment options. The rules and regulations related to expanded access are intended to improve access to investigational
drugs for patients who may benefit from investigational therapies. FDA regulations allow access to investigational drugs under an
IND by the company or the treating physician for treatment purposes on a case-by-case basis for: individual patients (single-patient
IND applications for treatment in emergency settings and non-emergency settings); intermediate-size patient populations; and larger
populations for use of the drug under a treatment protocol or Treatment IND Application.
When considering an IND application for expanded access to an investigational product with the purpose of treating a patient or a
group of patients, the sponsor and treating physicians or investigators will determine suitability when all of the following criteria
apply: patient(s) have a serious or immediately life-threatening disease or condition and there is no comparable or satisfactory
alternative therapy to diagnose, monitor, or treat the disease or condition; the potential patient benefit justifies the potential risks of the
treatment and the potential risks are not unreasonable in the context or condition to be treated; and the expanded use of the
investigational drug for the requested treatment will not interfere with initiation, conduct, or completion of clinical investigations that
could support marketing approval of the product candidate or otherwise compromise the potential development of the product
candidate.
On December 13, 2016, the 21st Century Cures Act, or Cures Act, established (and the 2017 Food and Drug Administration
Reauthorization Act later amended) a requirement that sponsors of one or more investigational drugs for the treatment of a serious
disease(s) or condition(s) make publicly available their policy for evaluating and responding to requests for expanded access for
individual patients. Although these requirements were rolled out over time, they have now come into full effect. This provision
requires drug and biologic companies to make publicly available their policies for expanded access for individual patient access to
products intended for serious diseases. Sponsors are required to make such policies publicly available upon the earlier of initiation of a
Phase 2 or Phase 3 study; or 15 days after the drug or biologic receives designation as a breakthrough therapy, fast track product, or
regenerative medicine advanced therapy.
In addition, on May 30, 2018, the Right to Try Act was signed into law. The law, among other things, provides a federal framework
for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are
undergoing investigation for FDA approval. Under certain circumstances, eligible patients can seek treatment without enrolling in
clinical trials and without obtaining FDA permission under the FDA expanded access program. There is no obligation for a drug
manufacturer to make its product candidates available to eligible patients as a result of the Right to Try Act, but the manufacturer must
develop an internal policy and respond to patient requests according to that policy.
Human Clinical Trials in Support of an NDA
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified
investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects
provide their informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under written
study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives of the study, the parameters to be
used in monitoring safety and the effectiveness criteria to be evaluated.
Human clinical trials are typically conducted in four sequential phases, which may overlap or be combined:
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Phase 1. The product candidate is initially introduced into a small number of healthy human subjects or, in certain
indications such as cancer, patients with the target disease or condition (e.g., cancer) and tested for safety, dosage
tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness
and to determine optimal dosage.
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Phase 2. The product candidate is administered to a limited patient population to identify 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 optimal 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 patient population, generally at geographically dispersed clinical trial
sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the
product candidate for approval, identify adverse effects, establish the overall risk-benefit profile of the product candidate
and to provide adequate information for the labeling of the product candidate.
Phase 4. Post-approval studies may be conducted after initial marketing approval. These studies are used to gain
additional experience from the treatment of patients in the intended therapeutic indication.
Progress reports detailing the results of the clinical trials conducted under the IND must be submitted at least annually to the FDA and,
more frequently, if serious adverse events occur. In addition, IND safety reports must be submitted to the FDA for any of the
following: serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing that suggest a
significant risk in humans exposed to the drug; and any clinically important increase in the case of a serious suspected adverse
reaction over that listed in the protocol or investigator brochure. The FDA or the sponsor or the data monitoring committee may
suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to
an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution, or an institution it
represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with
unexpected serious harm to patients. The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the
integrity of the clinical data submitted.
Under the Pediatric Research Equity Act of 2003, or PREA, an NDA or supplement thereto must contain data that are adequate to
assess the safety and effectiveness of the drug product for the claimed indications in all relevant pediatric subpopulations, and to
support dosing and administration for each pediatric subpopulation for which the product is safe and effective. With enactment of the
Food and Drug Administration Safety and Innovation Act or FDASIA, in 2012, sponsors must also submit pediatric study plans prior
to the assessment data. Those plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct,
including study objectives and design, any deferral or waiver requests, and other information required by regulation. The legislation
requires the FDA to meet with drug sponsors by no later than the end-of-Phase 1 meeting for serious or life-threatening diseases and
by no later than ninety days after the FDA’s receipt of the study plan. The FDA may, on its own initiative or at the request of the
applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or
partial waivers from the pediatric data requirements.
Submission of an NDA to the FDA
Assuming successful completion of required clinical testing and other requirements, the results of the preclinical studies and clinical
trials, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among
other things are submitted to the FDA as part of an NDA requesting approval to market the product candidate for one or more
indications. Under federal law, the submission of most NDAs is subject to an application user fee, which for federal fiscal year 2020
is $2,942,965 for an application requiring clinical data. The sponsor of an approved NDA is also subject to an annual program fee,
which for fiscal year 2020 is $325,424. Certain exceptions and waivers are available for some of these fees, such as an exception from
the application fee for product candidates with orphan designation and a waiver for certain small businesses.
The FDA conducts a preliminary review of an NDA within 60 days of its receipt and strives to inform the sponsor by the 74th day
after the FDA’s receipt of the submission to determine whether the application is sufficiently complete to permit substantive review.
This is known as the filing decision. The FDA may request additional information rather than accept an NDA for filing. In this event,
the application must be resubmitted with the additional information. The resubmitted application 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 substantive review. The FDA has
agreed to certain performance goals in the review process of NDAs. Most such applications are meant to be reviewed within ten
months from the date of filing, and most applications 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 time of submission of the NDA. The review process may be extended by the FDA for three additional months to
consider new information or clarification provided by the applicant to address an outstanding deficiency identified by the FDA
following the original submission.
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Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is or will be manufactured. These
pre-approval inspections may cover all facilities associated with an NDA submission, including drug component manufacturing such
as active pharmaceutical ingredients, finished drug product manufacturing, control testing laboratories, as well as packaging and
labeling facilities. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in
compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
The applicant of the NDA may also have their records, processes, procedures, training, and other aspects reviewed during an
inspection. The FDA must implement a protocol to expedite review of responses to inspection reports pertaining to certain drug
applications, including applications for drugs in a shortage or drugs for which approval is dependent on remediation of conditions
identified in the inspection report.
In addition, as a condition of approval, the FDA may require an applicant to develop a REMS. REMS use risk minimization strategies
beyond the professional labeling to ensure that the benefits of the product outweigh the potential risks.
Finally, the FDA may refer an application for a novel drug to an advisory committee or explain why such referral was not made.
Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews,
evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is
not bound by the recommendations of an advisory committee, but it considers such recommendations 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 condition. These programs are referred to as fast track designation, breakthrough
therapy designation, priority review designation.
Specifically, the FDA may designate a product for fast track review if it is intended, whether alone or in combination with one or more
other drugs, for the treatment of a serious or life-threatening disease or condition, and it demonstrates the potential to address unmet
medical needs for such a disease or condition. For fast track products, sponsors may have greater interactions with the FDA and the
FDA may initiate review of sections of a fast track product’s NDA before the application is complete. This rolling review may be
available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may
be effective. The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information
and the sponsor must pay applicable user fees. However, the FDA’s time period goal for reviewing a fast track application does not
begin until the last section of the NDA is submitted. In addition, the fast track designation may be withdrawn by the FDA if the FDA
believes that the designation is no longer supported by data emerging in the clinical trial process.
Second, in 2012, Congress enacted the Food and Drug Administration 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 combination with one or more other drugs, to treat a serious or life-
threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement
over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical
development. The FDA may take certain actions with respect to breakthrough therapies, including holding meetings with the sponsor
throughout the development process; providing timely 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 condition and, if approved, would
provide a significant improvement in safety or effectiveness. The FDA determines, on a case-by-case basis, whether the proposed drug
represents a significant improvement when compared with other available therapies. Significant improvement may be illustrated by
evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting drug
reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety
and effectiveness in a new subpopulation. A priority designation is intended to direct overall attention and resources to the evaluation
of such applications, and to shorten the FDA’s review clock goal for taking action on a marketing application from ten months to six
months. For new chemical entities, or NCEs, the review clock starts after the NDA is filed with a total clock of twelve and eight
months, respectively.
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Priority Review Vouchers
A PRV is a voucher that the FDA issues to a sponsor of a rare pediatric disease or tropical disease product application at the time of
the marketing application approval. Vouchers are transferrable to other sponsors that may apply it to their NDAs or BLAs. A PRV
entitles the holder to designate a single human drug application submitted under Section 505(b)(1) of the U.S. Federal Food, Drug, and
Cosmetic Act or Section 351 of the Public Health Service Act as qualifying for a priority review. An FDA priority review may
expedite the review process of a marketing application reducing the review time from ten months after formal acceptance of the file to
six months after formal acceptance of the file. Applying the PRV to a marketing application does not ensure the FDA’s approval of
the marketing application and all requirements supporting the safety and efficacy of the product must be met.
The FDA’s Decision on an NDA
On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the
manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial
marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines
the deficiencies in the submission and may require substantial additional testing, analyses, or information in order for the FDA to
reconsider the application. This may include the requirement to conduct another clinical study or studies. If and when those
deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The
FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included. Even with
submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria
for approval.
If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings
or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to
further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after
commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including
REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further
marketing of a product based on the results of post-market studies or surveillance programs. After approval, many types of changes to
the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further
testing requirements and FDA review and approval.
Post-Approval Requirements and Commitments
If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications
for use may otherwise be limited, which could restrict the commercial value of the product. Further, the FDA may require that certain
contraindications, warnings or precautions be included in the product labeling. In addition, conditions of NDA approval may include
sponsor agreement to PMR or PMC studies, which are designed to further assess drug safety and effectiveness and may require testing
and surveillance programs to monitor the safety of approved products that have been commercialized. These may include additional
studies, registries, data collection, analyses, and/or information.
Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA,
including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution,
advertising and promotion and reporting of adverse experiences with the product. After approval, most changes to the approved
product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are
continuing, annual user fee requirements for any marketed products and the establishments at which such products are manufactured,
as well as new application fees for supplemental applications with clinical data.
In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to
register their establishments with the FDA and state agencies and are subject to periodic unannounced inspections by the FDA and
these state agencies for compliance with cGMP requirements. Changes to the manufacturing process are strictly regulated and often
require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations
from cGMP and impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the
sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and
quality control to maintain cGMP compliance.
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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 after the product reaches the market. Later discovery of previously unknown problems with a product,
including adverse events of unanticipated 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 information; imposition of post-market studies or
clinical trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential
consequences include, among other things:
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restrictions on the marketing or manufacturing of the product, suspension of the approval, or complete withdrawal of the
product from the market or product recalls;
fines, warning letters or holds on post-approval clinical trials;
refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product
license approvals;
product seizure or detention, or refusal to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products placed on the market.
This regulation includes, among other things, standards and regulations for direct-to-consumer advertising, communications regarding
unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the Internet and social
media. Promotional claims about a product candidate’s safety or effectiveness are prohibited before the product candidate is approved.
After 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 information. In the United States, healthcare professionals are generally permitted 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
practice of medicine. However, FDA regulations impose rigorous restrictions on manufacturers’ communications, prohibiting the
promotion of off-label uses. It may be permissible, under very specific conditions, for a manufacturer to engage in nonpromotional,
truthful and non-misleading communication regarding off-label information, such as distributing scientific or medical journal
information. In addition, companies may also promote information that it consistent with the prescribing information and have the
ability to proactively speak to formulary committee members of payors regarding data for an unapproved drug or unapproved uses of
an approved drug under some relatively recent guidance from the FDA. However, if a company is found to have promoted off-label
uses, it may become subject to adverse public relations and administrative and judicial enforcement by the FDA, the Department of
Justice, or the Office of the Inspector General of the Department of Health and Human Services, as well as state authorities. This
could subject a company to a range of penalties 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 promotion and has also requested that companies enter
into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
In addition, the distribution of prescription pharmaceutical products and drug samples are subject to the Prescription Drug Marketing
Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, which regulate the
distribution and tracing of prescription drugs and prescription drug samples at the federal level and set minimum standards for the
regulation of drug distributors by the states. The PDMA, its implementing regulations and state laws limit the distribution of
prescription pharmaceutical product samples, and the DSCA imposes requirements to ensure accountability in distribution and to
identify and remove counterfeit and other illegitimate products from the market.
Abbreviated New Drug Applications for Generic Drugs
In 1984, with 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 active ingredients as, and to be bioequivalent to,
drugs previously approved by the FDA pursuant to NDAs. To obtain approval of a generic drug, an applicant must submit an
abbreviated new drug application, or ANDA, to the agency. An ANDA is a comprehensive submission that contains, among other
things, data and information pertaining to the active pharmaceutical ingredient, bioequivalence, drug product formulation,
specifications and stability of the generic drug, as well as analytical methods, manufacturing process validation data and quality
control procedures. ANDAs are “abbreviated” because they generally do not include preclinical and clinical data to demonstrate safety
and effectiveness. Instead, in support of such applications, a generic manufacturer may rely on the preclinical and clinical testing
previously conducted for a drug product previously approved under an NDA, known as the reference-listed drug, or RLD.
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Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to
the active ingredients, the route of administration, the dosage form, the strength of the drug and the conditions of use of the drug. At
the same time, the FDA must also determine that the generic drug is “bioequivalent” to the innovator drug. Under the statute, a generic
drug is bioequivalent to an RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and
extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates whether the generic product is
“therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also
referred to as the “Orange Book.” Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable
for the RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of
therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the prescribing
physician or patient.
Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until 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 entity. For the purposes of this provision, a new chemical entity, or NCE, is a drug that contains no active moiety that has
previously been approved by the FDA in any other NDA. An active moiety is the molecule or ion responsible for the physiological or
pharmacological action of the drug substance. In cases where such NCE exclusivity has been granted, an ANDA may not be filed with
the FDA until the expiration of five years unless the submission is accompanied by a Paragraph IV certification, in which case the
applicant may submit its application four years following the original product approval. The FDCA also provides for a period of three
years of exclusivity if the NDA includes reports of one or more new clinical investigations, other than bioavailability or
bioequivalence studies, that were conducted by or for the applicant and are essential to the approval of the application.
The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical
investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the
approval of the application. This three-year exclusivity period often protects changes to a previously approved drug product, such as a
new dosage form, route of administration, combination or indication. Three-year exclusivity would be available for a drug product that
contains a previously approved active moiety, provided the statutory requirement for a new clinical investigation is satisfied. Unlike
five-year NCE exclusivity, an award of three-year exclusivity does not block the FDA from accepting ANDAs 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 application 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 exclusivities, or is on the FDA’s drug shortage list. The new legislation also authorizes FDA to expedite review of
‘‘competitor generic therapies’’ or drugs with inadequate generic competition, including holding meetings with or providing advice to
the drug sponsor prior to submission of the application.
Hatch-Waxman Patent Certification and the 30-Month Stay
Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent with claims that cover
the applicant’s product or an approved method of using the product. Each of the patents listed by the NDA sponsor is published in the
Orange Book. When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning
any patents listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA
applicant is not seeking approval. To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already
approved product, the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange
Book to the same extent that an ANDA applicant would.
Specifically, the applicant must certify with respect to each patent that:
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the required patent information has not been filed;
the listed patent has expired;
the listed patent has not expired, but will expire on a particular date and approval is sought after patent expiration; or
the listed patent is invalid, unenforceable or will not be infringed by the new product.
A certification that the new product will not infringe the already approved product’s listed patents or that such patents are invalid or
unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicates that it is not
seeking approval of a patented method of use, the application will not be approved until all the listed patents claiming the referenced
product have expired (other than method of use patents involving indications for which the applicant is not seeking approval).
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If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV
certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders
may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent
infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving
the ANDA until the earlier of 30 months after the receipt of the Paragraph IV notice, expiration of the patent, or a decision in the
infringement case that is favorable to the ANDA applicant.
Pediatric Studies and Exclusivity
Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the
attachment of an additional six months of marketing protection to the term of any existing 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 written request from the FDA for such data. The data do not need to show the product is effective in the pediatric population
studied, rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of
requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory
periods of exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but it
effectively extends the regulatory period during which the FDA cannot approve another application. With regard to patents, the six-
month pediatric exclusivity period will not attach to any patents for which an ANDA or 505(b)(2) applicant submitted a paragraph IV
patent certification, unless the NDA sponsor or patent owner first obtains a court determination that the patent is valid and infringed
by the proposed product.
Patent Term Restoration 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 restoration of up to five years for patent term lost during product development and the FDA regulatory review. The
restoration period granted is typically one-half the time between the effective date of an IND and the submission date of an NDA, plus
the time between the submission date of an NDA and the ultimate approval date. Patent term restoration cannot be used to extend the
remaining term of a patent past a total of 14 years from the product’s approval date. Only one patent applicable to an approved drug
product is eligible for the extension, and the application for the extension must be submitted prior to the expiration of the patent in
question. A patent that covers multiple drugs for which approval is sought can only be extended in connection with one of the
approvals. The U.S. Patent and Trademark Office reviews and approves the application for any patent term extension or restoration in
consultation with the FDA.
Review and Approval of Drug Products Outside the United States
In order to market any product outside of the United States, a company must also comply with numerous and varying regulatory
requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical
trials, marketing authorization, commercial sales and distribution 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 authorities before it can
commence clinical trials or marketing of the product in those countries or jurisdictions. The approval process ultimately varies
between countries and jurisdictions and can involve additional product testing and additional administrative review periods. The time
required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA
approval. Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in
obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.
Clinical Trial Approval in the European Union
Requirements for the conduct of clinical trials in the European Union including GCP are set forth in the Clinical Trials Directive
2001/20/EC, or the Clinical Trials Directive, and the GCP Directive 2005/28/EC, or the GCP Directive. Pursuant to the Clinical Trials
Directive and the GCP Directive 2005/28/EC, as amended, a system for the approval of clinical trials in the European Union has been
implemented through national legislation of the EU member states. Under this system, approval must be obtained from the competent
national authority of each EU member state in which a study is planned to be conducted. To this end, a clinical trial application, or
CTA, is submitted to the local competent authority in each country (or member state) where the clinical trial is being conducted,
which must be supported by an investigational medicinal product dossier, or IMPD, and further supporting information prescribed by
Clinical Trials Directive and the GCP Directive and other applicable guidance documents. These documents may be amended and/or
updated by the EC at any time. Furthermore, a clinical trial may only be started after a competent ethics committee has issued a
favorable opinion on the clinical trial application in that country.
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In April 2014, the European Union passed the new Clinical Trials Regulation (EU) No 536/2014, or the new Clinical Trials
Regulation, which is set to replace the current Clinical Trials Directive. To ensure that the rules for clinical trials are identical
throughout the European Union, the new EU clinical trials legislation was passed as a regulation that is directly applicable in all EU
member states. All clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials
Directive until the new Clinical Trials Regulation becomes applicable. According to the current plans of the European Medicines
Agency, or EMA, the new Clinical Trials Regulation is expected to become applicable in 2020. The Clinical Trials Directive will,
however, still apply three years from the date of entry into application of the new Clinical Trials Regulation to (i) clinical trials
applications submitted before the entry into application and (ii) clinical trials applications submitted within one year after the entry
into application if the sponsor opts for old system.
The new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trial in the European Union. The main
characteristics of the regulation include: a streamlined application procedure via a single entry point, the EU portal; a single set of
documents to be prepared and submitted for the application as well as simplified reporting procedures that will spare sponsors from
submitting broadly identical information separately to various bodies and different member states; a harmonized procedure for the
assessment of applications for clinical trials, which is divided in two parts (Part I is assessed jointly by all member states concerned,
and Part II is assessed separately by each member state concerned); strictly defined deadlines for the assessment of clinical trial
applications; and the involvement of the ethics committees in the assessment procedure in accordance with the national law of the
member state concerned but within the overall timelines defined by the Clinical Trials Regulation.
As in the United States, there are similar requirements in the European Union for posting clinical trial information online, and in other
countries as well.
PRIME Designation in the European Union
In March 2016, the EMA launched an initiative, the PRIority MEdicines, or PRIME, scheme, to facilitate development of product
candidates in indications, often rare, for which few or no therapies currently exist. The PRIME scheme is intended to encourage drug
development in areas of unmet medical need and provides accelerated assessment of products representing substantial innovation
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 designation,
including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and
other development program elements, and accelerated marketing authorization application assessment once a dossier has been
submitted. Importantly, a dedicated agency contact and rapporteur from the Committee for Human Medicinal Products, or CHMP, or
Committee for Advanced Therapies, or CAT, are appointed early in the PRIME scheme, facilitating increased understanding of the
product at the EMA’s committee level. A kick-off meeting initiates these relationships and includes a team of multidisciplinary
experts at the EMA to provide guidance on the overall development and regulatory strategies.
Marketing Authorization
To obtain marketing approval of a product under EU regulatory systems, an applicant must submit a marketing authorization
application, or MAA, either under a centralized or decentralized procedure. The centralized procedure provides for the grant of a
single marketing authorization 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 active substance indicated for the treatment of certain
diseases. For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative
or for which a centralized process is in the interest of patients, the centralized procedure may be optional.
Under the centralized procedure, the Committee for Medicinal Products for Human Use, or the CHMP, established at the EMA is
responsible for conducting the initial assessment of a product. The CHMP is also responsible for several post-authorization and
maintenance activities, such as the assessment of modifications or extensions to an existing marketing authorization. Under the
centralized procedure in the European Union, the maximum timeframe for the evaluation of an MAA is 210 days, excluding clock
stops, when additional information or written or oral explanation is to be provided by the applicant in response to questions of the
CHMP. Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product is of major interest
from the point of view of public health and in particular from the viewpoint of therapeutic innovation. In this circumstance, the EMA
ensures that the opinion of the CHMP is given within 150 days.
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The decentralized procedure is available to applicants who wish to market a product in various EU member states where such product
has not received marketing 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 application performed by one member state designated by the
applicant, known as the reference member state. Under this procedure, an applicant submits an application based on identical dossiers
and related materials, including a draft summary of product characteristics, and draft labeling and package leaflet, to the reference
member state and concerned member states. The reference member state prepares a draft assessment report and drafts of the related
materials within 210 days after receipt of a valid application. 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 potential serious risk to public health,
the disputed points are subject to a dispute resolution mechanism and may eventually be referred to the European Commission, whose
decision is binding on all member states.
Within this framework, manufacturers may seek approval of hybrid medicinal products under Article 10(3) of Directive 2001/83/EC.
Hybrid applications rely, in part, on information and data from a reference product and new data from appropriate pre-clinical tests
and clinical trials. Such applications are necessary when the proposed product does not meet the strict definition of a generic
medicinal product, or bioavailability studies cannot be used to demonstrate bioequivalence, or there are changes in the active
substance(s), therapeutic indications, strength, pharmaceutical form or route of administration of the generic product compared to the
reference medicinal product. In such cases the results of tests and trials must be consistent with the data content standards required in
the Annex to the Directive 2001/83/EC, as amended by Directive 2003/63/EC.
Hybrid medicinal product applications have automatic access to the centralized procedure when the reference product was authorized
for marketing via that procedure. Where the reference product was authorized via the decentralized procedure, a hybrid application
may be accepted for consideration under the centralized procedure if the applicant shows that the medicinal product constitutes a
significant therapeutic, scientific or technical innovation, or the granting of a community authorization for the medicinal product is in
the interest of patients at the community level.
A marketing authorization may be granted only to an applicant established in the European Union. Regulation (EC) No. 1901/2006, or
Pediatric Regulation, provides that prior to obtaining a marketing authorization in the European Union, an applicant must demonstrate
compliance with all measures included in a Pediatric Investigation Plan, or PIP, approved by the Pediatric Committee of the EMA, or
PDCO, covering all subsets of the pediatric population, unless the EMA has granted a product-specific waiver, class waiver, or a
deferral for one or more of the measures included in the PIP. The PIP sets out the timing and measures proposed to generate data to
support a pediatric indication of the drug for which marketing authorization is being sought. The PDCO can grant a deferral of the
obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of
the product in adults. Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data is not
needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the
product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over
existing treatments for pediatric patients. Once the marketing authorization is obtained in all member states of the European Union and
study results are included in the product information, even when negative, the product is eligible for six months’ supplementary
protection certificate extension. For orphan-designated medicinal products, the 10-year period of market exclusivity is extended to
12 years.
Periods of Authorization and Renewals in the European Union
A marketing authorization is valid for five years, in principle, and it may be renewed after five years on the basis of a reevaluation of
the risk-benefit balance by the EMA or by the competent authority of the relevant EU member state. To that end, the marketing
authorization 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 variations introduced since the marketing authorization was granted, at
least six months before the marketing authorization ceases to be valid. Once renewed, the marketing authorization is valid for an
unlimited period, unless the European Commission or the relevant competent authority of the EU member state decides, on justified
grounds relating to pharmacovigilance, to proceed with one additional five-year renewal period. Any marketing authorization that is
not followed by the marketing 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 marketing authorization within three years after authorization ceases to be valid.
Regulatory Data Exclusivity in the European Union
In the European Union, innovative medicinal products authorized in the European Union on the basis of a full marketing authorization
application (as opposed to an application for marketing authorization that relies on data available in the marketing authorization
dossier for another, previously approved, medicinal product) are entitled to eight years of data exclusivity. During this period,
applicants for authorization of generics of these innovative products cannot rely on data contained in the marketing authorization
dossier submitted for the innovative medicinal product. Innovative medicinal products are also entitled to ten years’ market
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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 marketing authorization
holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to
authorization, is held to bring a significant clinical benefit in comparison with existing therapies. Even if a compound is considered to
be a new chemical entity so that the innovator gains the prescribed period of data exclusivity, another company may market another
version of the product if such company obtained marketing authorization based on an MAA with a complete independent data package
of pharmaceutical tests, preclinical tests and clinical trials.
Pediatric Studies and Exclusivity
Prior to submitting a marketing authorization application in the European Union, applicants must demonstrate compliance with all
measures included in an EMA approved PIP covering all subsets of the pediatric population, 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 respective requirements
for all marketing authorization procedures are set forth in the Pediatric Regulation. This requirement also applies when a company
wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already authorized. The Pediatric
Committee of the EMA, or PDCO, may grant deferrals for some medicines, allowing a company to delay development of the
medicine for children until there is enough information to demonstrate its effectiveness and safety in adults. The PDCO may also grant
waivers when development of a medicine for children is not needed or is not appropriate, such as for diseases that only affect the
elderly population. Before an MAA can be filed, or an existing marketing authorization can be amended, the EMA determines that
companies actually comply with the agreed studies and measures listed in each relevant PIP. If an applicant obtains a marketing
authorization in all EU member states, or a marketing authorization granted in the Centralized Procedure by the European
Commission, and the study results for the pediatric population are included in the product information, even when negative, the
medicine is then eligible for an additional six month period of qualifying patent protection through extension of the term of the
Supplementary Protection Certificate.
Brexit and the Regulatory Framework in the United Kingdom
On June 23, 2016, the electorate in the United Kingdom voted in favor of leaving the European Union, commonly referred to as
Brexit. Following protracted negotiations, the United Kingdom left the European Union on January 31, 2020. Under the withdrawal
agreement, there is a transitional period until December 31, 2020 (extendable up to two years). Discussions between the United
Kingdom and the EU have so far mainly focused on finalizing withdrawal issues and transition agreements but have been extremely
difficult to date. To date, only an outline of a trade agreement has been reached. Much remains open, but the Prime Minister has
indicated that the United Kingdom will not seek to extend the transitional period beyond the end of 2020. If no trade agreement has
been reached before the end of the transitional period, there may be significant market and economic disruption. The Prime Minister
has also indicated that the United Kingdom will not accept high regulatory alignment with the European Union.
Since the regulatory framework for pharmaceutical products in the United Kingdom covering quality, safety, and efficacy of
pharmaceutical products, clinical trials, marketing authorization, commercial sales, and distribution of pharmaceutical products is
derived from EU directives and regulations, Brexit could materially impact the future regulatory regime that applies to products and
the approval of product candidates in the United Kingdom. Any delay in obtaining, or an inability to obtain, any marketing approvals,
as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or
the European Union for our product candidates, which could significantly and materially harm our business.
General Data Protection Regulation
The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Union, including
personal health data, is subject to the EU General Data Protection Regulation, or GDPR, which became effective on May 25, 2018.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including
requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data
relates when required, providing information to individuals regarding data processing activities, implementing safeguards to protect
the security and confidentiality of personal data, providing notification 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 European Union,
including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including
potential fines of up to €20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of
action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain
compensation for damages resulting from violations of the GDPR. Compliance with the GDPR will be a rigorous and time-intensive
process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.
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Pharmaceutical Coverage, Pricing and Reimbursement
In the United States and markets in other countries, patients who are prescribed treatments for their conditions 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
authorities. 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 United States such as Medicare and Medicaid, commercial health insurers and
managed care organizations, provide coverage, and establish adequate reimbursement levels for, the product. The process for
determining whether a payor will provide coverage for a product may be separate from the process for setting 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-effectiveness 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 particular indication.
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-effectiveness of the product, in addition
to the costs required to obtain FDA or other comparable marketing approvals. Nonetheless, product candidates may not be considered
medically necessary or cost effective. A decision by a third-party payor not to cover a product candidate could reduce physician
utilization once the product is approved and have a material adverse effect on sales, results of operations and financial condition.
Additionally, 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 determination 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.
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 implementing cost-containment programs, including price
controls, restrictions on reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-
containment measures, and adoption of more restrictive policies in jurisdictions with existing 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 time. Even if favorable coverage and reimbursement status is attained for one or more products for which a
company or its collaborators receive marketing approval, less favorable coverage policies and reimbursement rates may be
implemented in the future.
For example, there have been several recent U.S. congressional inquiries and proposed federal and proposed and enacted state
legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and
manufacturer patient 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 administration, or Administration, have each indicated
that it will continue to seek new legislative and/or administrative measures to control drug costs. For example, on May 11, 2018, the
Administration issued a plan to lower drug prices. Under this blueprint for action, the Administration indicated that the Department of
Health and Human Services, or HHS, will: take steps to end the gaming of regulatory and patent processes by drug makers to unfairly
protect monopolies; advance biosimilars and generics to boost price competition; evaluate the inclusion of prices in drug makers’
advertisements to enhance price competition; speed access to and lower the cost of new drugs by clarifying policies for sharing
information between insurers and drug makers; avoid excessive pricing by relying more on value-based pricing by expanding
outcome-based payments in Medicare and Medicaid; work to give Part D plan sponsors more negotiation power with drug makers;
examine which Medicare Part B drugs could be negotiated for a lower price by Part D plans, and improving the design of the Part B
Competitive Acquisition Program; update Medicare’s drug-pricing dashboard to increase transparency; prohibit Part D contracts that
include “gag rules” that prevent pharmacists from informing patients when they could pay less out-of-pocket by not using insurance;
and require that Part D plan members be provided with an annual statement of plan payments, out-of-pocket spending, and drug price
increases. In addition, on December 23, 2019, the Administration published a proposed rulemaking that, if finalized, would allow
states or certain other non-federal government entities to submit importation program proposals to FDA for review and approval.
Applicants would be required to demonstrate their importation plans pose no additional risk to public health and safety and will result
in significant cost savings for consumers. At the same time, FDA issued draft guidance that would allow manufacturers to import
their own FDA-approved drugs that are authorized for sale in other countries (multi-market approved products).
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control
pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain
product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
other countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using
bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and
other health care programs. These measures could reduce the ultimate demand for our products, once approved, or put pressure on our
product pricing. It is expected that additional 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 additional pricing pressures.
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Outside the United States, ensuring adequate coverage and payment for a product also involves challenges. Pricing of prescription
pharmaceuticals is subject to governmental control in many countries. Pricing negotiations with governmental authorities can extend
well beyond the receipt of regulatory marketing approval for a product and may require a clinical trial that compares the cost
effectiveness of a product to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in
commercialization.
In the European Union, pricing and reimbursement schemes vary widely from country to country. Some countries provide that
products may be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional
studies that compare the cost-effectiveness of a particular drug candidate to currently available therapies or so-called health
technology assessments, in order to obtain reimbursement or pricing approval. For example, the European Union provides options for
its member states to restrict the range of products for which their national 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 member
states allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to
physicians to limit prescriptions. Recently, many countries in the European Union have increased the amount of discounts required on
pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the
severe fiscal and debt crises experienced by many countries in the European Union. The downward pressure on health care costs in
general, particularly prescription drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of
new products. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations
may continue after reimbursement has been obtained. Reference pricing used by various EU member states, and parallel trade, i.e.,
arbitrage between low-priced and high-priced member states, can further reduce prices. There can be no assurance that any country
that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing
arrangements for any products, if approved in those countries.
Healthcare Law and Regulation
Healthcare providers and third-party payors play a primary role in the recommendation and prescription of drug products that are
granted marketing approval. Arrangements with providers, consultants, third-party payors and customers are subject to broadly
applicable fraud and abuse, anti-kickback, false claims laws, reporting of payments to physicians, teaching hospitals and other
healthcare providers, patient privacy laws and regulations, and other healthcare laws and regulations that may constrain business
and/or financial arrangements. Restrictions under applicable federal and state healthcare laws and regulations include the following:
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the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully
soliciting, offering, paying, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or
reward either the referral of an individual for, or the purchase, order or recommendation 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 penalties laws,
which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the
federal government, claims for payment that are false, fictitious or fraudulent or knowingly making, using or causing to be
made or used a false record or statement to avoid, decrease or conceal an obligation to pay money to the federal
government.
the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal
criminal laws that prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to
defraud any healthcare benefit program or making false statements relating to healthcare matters;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective
implementing regulations, including the Final Omnibus Rule published in January 2013, which impose obligations,
including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually
identifiable health information;
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 connection with the delivery of or payment for healthcare
benefits, items or services;
the U.S. Foreign Corrupt Practices 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;
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the federal transparency requirements, known as the federal Physician Payments Sunshine Act (renamed the Open
Payments Act), under the Patient Protection and Affordable Care Act, as amended by the Health Care Education
Reconciliation Act, or ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to
report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United States Department of Health
and Human Services, information related to payments and other transfers of value made by that entity to physicians and
teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;
the PDMA and its implementation regulations, as well as the DSCA, which regulate the distribution and tracing of
prescription drugs and prescription drug samples at the federal level, and set minimum standards for the regulation of drug
distributors by the states; and
analogous state and foreign laws and regulations, such as state anti-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 gift 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.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines,
such as the Pharmaceutical Research and Manufacturers of America Code on Interactions with Health Care Professionals, known as
the PhRMA Code. State and foreign laws also govern the privacy and security of health information in some circumstances, many of
which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Healthcare Reform
A primary trend in the United States 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 pharmaceutical and biopharmaceutical products, limiting coverage
and reimbursement for drugs and other medical products, government control and other changes to the healthcare system in the United
States.
By way of example, the United States and state governments continue to propose and pass legislation designed to reduce the cost of
healthcare.
In March 2010, the United States Congress enacted the ACA, which, among other things, includes changes to the coverage and
payment for products under government health care programs. Among the provisions of the ACA of importance to our potential drug
candidates are:
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an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic
agents, apportioned among these entities according to their market share in certain government healthcare programs,
although this fee would not apply to sales of certain products approved exclusively for orphan indications;
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage
to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a
manufacturer’s Medicaid rebate liability;
expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for
both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and
reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate liability to prescriptions for
individuals enrolled in Medicare Advantage plans;
addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are
calculated for drugs that are inhaled, infused, instilled, implanted or injected;
expanded the types of entities eligible for the 340B drug discount program;
established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% point-of-
sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period
as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical
effectiveness research, along with funding for such research;
the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the Medicare
program to reduce expenditures by the program that could result in reduced payments for prescription drugs. However, the
IPAB implementation has been not been clearly defined. The Affordable Care Act provided that under certain
circumstances, IPAB recommendations will become law unless Congress enacts legislation that will achieve the same or
greater Medicare cost savings; and
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established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery
models to lower Medicare and Medicaid spending, potentially including prescription drug spending. Funding has been
allocated to support the mission of the Center for Medicare and Medicaid Innovation from 2011 to 2019.
Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted. These changes include the
Budget Control Act of 2011, which, among other things, led to aggregate reductions to Medicare payments to providers of 2% per
fiscal year that started in 2013 and will stay in effect through 2029 unless additional Congressional action is taken, and the American
Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the
statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may
result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our
product candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed
or used. Further, there have been several recent U.S. congressional inquiries and proposed state and federal legislation designed to,
among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient
programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.
Since enactment of the ACA, there have been numerous legal challenges and Congressional actions to repeal and replace provisions of
the law. For example, with enactment of the Tax Cuts and Jobs Act of 2017, which was signed by the President 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, is no longer effective in 2019. According to the Congressional Budget Office, the repeal of the individual mandate
will cause 13 million fewer Americans to be insured by 2027 and premiums in insurance markets may rise. Additionally, on January
22, 2018, the President signed a continuing resolution on appropriations for fiscal year 2018 that delayed the implementation of
certain ACA-mandated fees, including the so-called “Cadillac” tax on certain high cost employer-sponsored insurance plans, the
annual fee imposed on certain health insurance providers based on market share, and the medical device excise tax on non-exempt
medical devices. Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to
increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in
Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole”. Congress will
likely consider other legislation to replace elements of the ACA during the next Congressional session.
In addition, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the individual mandate
portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the mandate was repealed as part of the
Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well. The current administration and CMS have both stated
that the ruling will have no immediate effect, and on December 30, 2018 the same judge issued an order staying the judgment pending
appeal. The current administration recently represented to the Court of Appeals considering this judgment that it does not oppose the
lower court’s ruling. On July 10, 2019, the Court of Appeals for the Fifth Circuit heard oral argument in this case. On December 18,
2019, that court affirmed the lower court’s ruling that the individual mandate portion of the ACA is unconstitutional and it remanded
the case to the district court for reconsideration of the severability question and additional analysis of the provisions of the ACA.
Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.
The Administration has also taken executive actions to undermine or delay implementation of the ACA. Since January 2017, the
President has signed two Executive Orders designed to delay the implementation of certain provisions of the ACA or otherwise
circumvent some of the requirements for health insurance mandated by the ACA. One Executive Order directs federal agencies with
authorities and responsibilities under the ACA to waive, defer, grant exemptions from, or delay the implementation of any provision
of the ACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or
manufacturers of pharmaceuticals or medical devices. The second Executive Order terminates the cost-sharing subsidies that
reimburse insurers under the ACA. Several state Attorneys General filed suit to stop the administration from terminating the subsidies,
but their request for a restraining order was denied by a federal judge in California on October 25, 2017. In addition, CMS has recently
proposed regulations that would give states greater flexibility in setting benchmarks for insurers in the individual and small group
marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such
marketplaces. Further, on June 14, 2018, U.S. Court of Appeals for the Federal Circuit ruled that the federal government was not
required to pay more than $12 billion in ACA risk corridor payments to third-party payors who argued were owed to them. The effects
of this gap in reimbursement on third-party payors, the viability of the ACA marketplace, providers, and potentially our business, are
not yet known.
Laws Relating to Foreign Trade
We are subject to various federal and foreign laws that govern our international business practices. These laws include the FCPA
which prohibits U.S. companies and their representatives from paying, offering to pay, promising, or authorizing the payment of
anything of value to any foreign government official, government staff member, political party, or political 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 definition of a foreign government
official. Additionally, interactions with or on the part of our partners, collaborators, contract research organizations, vendors or other
agents may also implicate the FCPA. The FCPA also requires public companies to make and keep books and records that accurately
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and fairly reflect their transactions and to devise and maintain an adequate system of internal accounting controls. Compliance with
the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition, the FCPA
presents unique challenges in the pharmaceutical 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 pharmaceutical companies to
hospitals in connection with clinical trials and other work have been deemed to be improper payments to government officials and
have led to FCPA enforcement actions.
Our international operations could also be subject to compliance with national laws of other countries, such as the United Kingdom
Bribery Act. of 2010, or U.K. Bribery Act. The U.K. Bribery Act applies to any company “carrying on business” in the United
Kingdom, irrespective of where the offending conduct occurs. The U.K. Bribery Act applies to bribery activities 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
function. The failure by a company to prevent third parties from providing a bribe on its behalf could also constitute an offense.
Penalties under the U.K. Bribery Act include potentially unlimited fines for companies and criminal sanctions for corporate officers
under certain circumstances.
There are local antibribery and anticorruption laws in countries where we are conducting clinical trials, such as Brazil and Russia, and
many of these also carry the risk of significant financial or criminal penalties. Our clinical trial operations could also result in
enforcement actions by U.S., U.K., or other governmental authorities. There are also trade laws within the United States and in other
regions that regulate the sale, purchase, import, export, reexport, transfer and shipment of goods, currency, products, materials,
services and technology. Violations of these laws can lead to serious consequences, including substantial fines.
Other Regulations
We are also subject to numerous federal, state and local laws relating to such matters as safe working conditions, manufacturing
practices, environmental protection, fire hazard control, and disposal of hazardous or potentially hazardous substances. We may incur
significant costs to comply with such laws and regulations now or in the future.
Employees
As of December 31, 2019, we had 360 employees, 358 of whom were full-time. None of our employees is represented by any
collective bargaining unit. We believe that we maintain good relations with our employees.
Available Information
Our principal executive offices are located at 245 First Street, Cambridge, Massachusetts 02142. Our telephone number is (617) 871-
2098. Our website address is www.akebia.com. The information 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 Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, as soon as reasonably practicable
after they are electronically filed with or furnished to the U.S. Securities and Exchange Commission.
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Item 1A.
Risk Factors
We face a variety of risks and uncertainties in our business. Additional risks and uncertainties not presently known to us or that we
currently believe to be immaterial may also become important factors that affect our business. If any of the following risks occurs, our
business, financial statements and future growth prospects could be materially and adversely affected.
Risks Related to our Financial Position and Need for Additional Capital
We have incurred significant losses since our inception, and anticipate that we will continue to incur significant losses and cannot
guarantee when, if ever, we will become profitable or attain positive cash flows.
Investment in pharmaceutical product development and commercialization is highly speculative because it entails upfront capital
expenditures and significant risk that a product candidate will fail to gain marketing approval or that an approved product will not be
commercially viable. Since our inception, we have devoted most of our resources to research and development, including our
preclinical and clinical development activities and, following the merger, or the Merger, whereby Keryx Biopharmaceuticals, Inc., or
Keryx, became a wholly owned subsidiary of ours, commercialization. We have financed our operations primarily through sales of
equity securities, our strategic collaborations and, following the Merger, product revenues and debt. Prior to the Merger, 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 have incurred net losses each year since our inception, including net losses of $279.7 million for the year ended December 31,
2019. As of December 31, 2019, we had an accumulated deficit of $794.1 million. We cannot guarantee when, if ever, we will become
profitable. Our ability to generate product revenue and achieve profitability depends significantly on our success in many areas,
including the following:
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developing, commercializing and marketing Auryxia, vadadustat, if approved, or any other product or product candidate,
including those that may be in-licensed or acquired;
completing preclinical and clinical development of our product candidates;
seeking and obtaining marketing approvals for our product candidates after completion of clinical studies and the timing
of such approvals, and maintaining marketing approvals for Auryxia or any other product;
developing sustainable and scalable manufacturing processes for Auryxia, vadadustat and any other product or product
candidate, including those that may be in-licensed or acquired;
establishing and maintaining supply and manufacturing relationships with third parties that can provide adequate products
that are compliant with good manufacturing practices, or GMPs, and services to support the clinical development and the
market demand for our products and product candidates, including those that may be in-licensed or acquired;
launching and commercializing our product candidates, if approved, either directly or with a collaborator or distributor;
obtaining sufficient pricing and reimbursement for Auryxia, vadadustat and any other product or product candidate,
including those that may be in-licensed or acquired, from private and governmental payors;
obtaining market acceptance of Auryxia, vadadustat 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;
addressing any competing products;
identifying, assessing, acquiring, in-licensing and/or developing new product candidates;
negotiating favorable terms in any transaction into which we may enter, including collaboration, merger, acquisition and
licensing arrangements;
maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and
know-how;
integrating following the Merger; and
attracting, hiring and retaining qualified personnel.
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We expect to continue to incur significant expenses and operating losses for the foreseeable future. The amount of our future net
losses will depend, in part, on the rate of our future expenditures, and our financial position will depend, in part, on our product
revenue from Auryxia and, if approved, vadadustat, and our ability to obtain additional funding. We expect to continue to incur
significant expenses if and as we:
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conduct our development program of vadadustat for the treatment of anemia due to chronic kidney disease, or CKD,
including PRO2TECT and INNO2VATE and other ongoing or planned studies with respect to vadadustat, and develop
plans for and conduct the preclinical and clinical development of any other potential product candidates;
continue our commercialization activities for Auryxia and plan for the commercialization of vadadustat, if approved, and
any other product or product candidate, including those that may be in-licensed or acquired;
continue our Merger-related integration activities;
seek marketing approvals for our product candidates that successfully complete clinical studies, and maintain marketing
approvals for Auryxia and any product candidate for which we obtain marketing approval, including complying with any
post-marketing regulatory requirements;
have our product candidates manufactured for clinical trials and for commercial sale;
initiate any post-marketing approval studies, Phase 4 studies or any other clinical trials for Auryxia or any other product,
including those that may be in-licensed or acquired;
seek to discover additional product candidates;
engage in transactions, including strategic, merger, collaboration, acquisition and licensing transactions, pursuant to which
we would market and develop commercial products, or develop and commercialize other product candidates and
technologies;
make royalty, milestone or other payments under our license agreements and any future license agreements;
maintain, protect and expand our intellectual property portfolio;
attract and retain skilled personnel;
continue to create additional infrastructure and expend additional resources to support our operations as a public company,
including any additional infrastructure and resources necessary to support the transition from our prior status as an
emerging growth company; and
experience any delays or encounter issues with any of the above.
We also could be forced to expend significant resources in our legal proceedings, as described under Part I, Item 3. Legal Proceedings,
or any other such legal proceedings brought by or against us in the future.
Because of the numerous risks and uncertainties associated with pharmaceutical product development and commercialization, we are
unable to accurately predict the timing or amount of increased expenses. 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 operations may not be a good indication
of our future performance. In any particular quarter, the progress of our clinical development and our operating results could be below
the expectations of securities analysts or investors, which could cause our stock price to decline.
Even if we succeed in receiving marketing approval for and are able to commercialize vadadustat, we will continue to incur
substantial research and development and other expenditures to develop and market, if approved, any other product candidates as well
as any costs relating to continued commercialization and post-marketing requirements for Auryxia, vadadustat and any other products
or product candidates that may receive marketing approval, including those that may be in-licensed or acquired. Our prior losses and
expected future losses have had and will continue to have an adverse effect on our stockholders’ equity and working capital.
Our expenses could increase beyond expectations if we are required by the U.S. Food and Drug Administration, or FDA, the European
Medicines Agency, or EMA, or other regulatory authorities, or if we otherwise believe it is necessary, to change our manufacturing
processes or assays, to amend or replace our study protocols, to repeat any of our clinical trials, to perform studies in addition to,
different from or larger than those currently expected, or if there are any delays in completing our clinical trials or the development of
any of our product candidates. Even if our product candidates are approved for commercial sale, we anticipate incurring significant
costs associated with commercialization. In addition, our ability to generate revenue would be negatively affected if the size of our
addressable patient population is not as significant as we estimate, an indication approved by regulatory authorities is narrower than
we expect, or the patient population for treatment is narrowed by competition, physician choice, coverage or reimbursement, or payor
or treatment guidelines. Even though we generate product revenue from Auryxia and may generate revenues from the sale of products
and any product candidates that may be approved in the future, including those that may be in-licensed or acquired, we may never
generate revenue that is significant enough to become and remain profitable, and we may need to obtain additional funding to continue
operations.
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We will require substantial additional financing to achieve our goals. A failure to obtain this necessary capital when needed could
force us to delay, limit, reduce or terminate our product development or commercialization efforts.
As of December 31, 2019, our cash and cash equivalents and available for sale securities were $147.7 million. We expect to continue
to expend substantial amounts for the foreseeable future continuing the commercialization of Auryxia and developing and
commercializing vadadustat, if approved, and any other products or product candidates, including those that may be in-licensed or
acquired. These expenditures will include costs associated with research and development, potentially obtaining marketing approvals
and having our products manufactured, as well as marketing and selling products approved for sale, if any. In addition, other
unanticipated costs may arise, including as a result of our decision to include certain elements in our development programs. Because
the outcome of our current and anticipated clinical trials is highly uncertain, we cannot reasonably estimate the actual amount of
funding necessary to successfully complete the development and commercialization of our product candidates. Our future capital
requirements depend on many factors, including:
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significant costs associated with our global Phase 3 development program for vadadustat for the treatment of anemia due
to CKD. As of December 31, 2019, we expect the remaining external aggregate contract research organization, or CRO,
costs of PRO2TECT and INNO2VATE, which have enrolled 7,436 patients, to be in the range of $80.0 million to $100.0
million; the estimated costs for PRO2TECT and INNO2VATE could increase significantly due to a number of factors,
including detection of unexpected safety signals, modification of clinical trial protocols, performing other studies in
support of the Phase 3 program, choosing to add third party vendors to support the program, and any other factor that
could delay completion of PRO2TECT and INNO2VATE;
the cost and timing of commercialization activities for Auryxia, vadadustat and any other products or product candidates,
including those that may be in-licensed or acquired, if approved for marketing, including product manufacturing,
marketing, sales and distribution costs;
the results of our meetings with the FDA, the EMA and other regulatory authorities and any consequential effects,
including on study design, study size and resulting operating costs;
difficulties or delays in enrolling patients in our clinical trials;
the timing of, and the costs involved in obtaining, and, if approved, maintaining marketing approvals for vadadustat and
any other product candidates that we may develop or acquire, including to fund the preparation and filing of regulatory
submissions with the FDA, the EMA and other regulatory authorities, if clinical studies are successful, and the costs of
maintaining marketing approvals for Auryxia or any other product, including those that may be in-licensed or acquired;
the cost of conducting clinical studies or any post-marketing approval studies, Phase 4 studies or any other clinical trials
for Auryxia;
the outcome of our efforts to obtain marketing approval for vadadustat in the United States, Europe and in other
jurisdictions and any other product candidates, including those that may be in-licensed or acquired;
the scope, progress, results and costs of additional preclinical, clinical, or other studies for vadadustat and Auryxia, as well
as any studies of any other products or product candidates, including those that may be in-licensed or acquired;
the cost of securing and validating commercial manufacturing of vadadustat and any other product candidates, including
those that may be in-licensed or acquired, and maintaining our manufacturing arrangements for Auryxia or any other
products, including those that may be in-licensed or acquired, or securing and validating additional arrangements;
the costs involved in preparing, filing and prosecuting patent applications and maintaining, defending and enforcing our
intellectual property rights, including litigation costs, and the outcome of such litigation;
the costs involved in any legal proceedings to which we are a party;
Merger-related integration costs;
our ability to attract, hire and retain qualified personnel; and
the extent to which we engage in transactions, including collaboration, merger, acquisition and licensing transactions,
pursuant to which we would develop and market commercial products, or develop other product candidates and
technologies.
42
Furthermore, we expect to continue to incur additional costs associated with operating as a larger company following the Merger and
as a public company, including any additional infrastructure and resources necessary to support the transition from our prior status as
an emerging growth company. Accordingly, we will need to obtain substantial additional funding in connection with our continuing
operations. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our
research and development programs or any future commercialization efforts.
We expect our cash resources and the receipt of a $15.0 million regulatory milestone from MTPC, assuming approval of vadadustat in
Japan, to fund our current operating plan well into 2021. We have based these estimates on assumptions that may prove to be wrong,
and we could use our available capital resources sooner than we currently expect. Furthermore, our development milestones may not
be achieved, we may not receive the anticipated funding from our collaboration partners, and we may not secure other sources of
financing. If and until we can generate a sufficient amount of product revenues, we expect to finance future cash needs through public
or private equity or debt transactions, payments from our collaborators, royalty transactions, strategic transactions, or a combination of
these approaches. Even if we believe we have sufficient funds for our current or future operating plans, we may seek additional capital
if market conditions are favorable or if we have specific strategic objectives.
Any additional fundraising efforts may divert our management’s attention away from their day-to-day activities, which may adversely
affect our ability to develop and commercialize Auryxia, vadadustat and any other products or product candidates. Also, additional
funds may not be available to us in sufficient amounts or on acceptable terms or at all. If we are unable to raise additional capital in
sufficient amounts when needed or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the
development or commercialization of Auryxia, vadadustat and any other products or product candidates. Any of these events could
significantly harm our business, financial condition and prospects.
Our obligations in connection with the Loan Agreement with Pharmakon could adversely affect our financial condition and
restrict our operations.
We entered into a loan agreement, or the Loan Agreement, with Pharmakon, pursuant to which term loans in an aggregate principal
amount of $100.0 million, or the Term Loans, were made available to us in two tranches. The first tranche of $80 million closed on
November 25, 2019, and we have the option to draw down the second tranche of $20.0 million on or before December 31, 2020,
subject to the satisfaction of customary conditions. See Note 11 to our consolidated financial statements in Part II, Item 8 – Financial
Statements and Supplementary Data for additional information regarding our obligations under the Loan Agreement. Our Loan
Agreement with Pharmakon contains affirmative and negative covenants applicable to us and our subsidiaries, including maintaining,
on an annual basis, a minimum liquidity threshold starting in 2021, and on a quarterly basis, a minimum net sales threshold for
Auryxia starting in the fourth quarter of 2020. Failure to maintain compliance with these covenants could result in an event of default
under the Loan Agreement.
In the event there is an acceleration of our and certain of our subsidiaries’ liabilities under the Loan Agreement as a result of an event
of default, we may not have sufficient funds or may be unable to arrange for additional financing to repay the liabilities or to make any
accelerated payments, and Pharmakon could seek to enforce security interests in the collateral securing the Loan Agreement and
Keryx’s guarantee of the Term Loans, which could have a material adverse effect on our business, financial condition and results of
operations.
The Loan Agreement permits voluntary prepayment at any time in whole or in part, subject to prepayment premiums and make-whole
premiums prior to certain dates. Upon a change of control, mandatory prepayment provisions require us to prepay the principal
amount outstanding, the applicable prepayment premium and make-whole premium and accrued and unpaid interest. In addition, our
obligations in connection with the Loan Agreement could have additional significant adverse consequences, including, among other
things:
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restricting our activities, including limitations on transferring certain of our assets, engaging in certain transactions,
incurring certain additional indebtedness, creating certain liens, paying dividends or making certain other distributions and
making certain investments;
limiting our flexibility in planning for, or reacting to, changes in our business and our industry;
placing us at a competitive disadvantage compared to our competitors who have a smaller amount of debt or competitors
with comparable debt at more favorable interest rates; and
limiting our ability to borrow additional amounts for working capital, capital expenditures, research and development
efforts, acquisitions, debt service requirements, execution of our business strategy and other purposes.
Any of these factors could materially and adversely affect our business, financial condition and results of operations.
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Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights
to our product and product candidates on unfavorable terms to us.
We expect to finance our cash needs through product revenues, public or private equity or debt transactions, payments from our
collaborators, royalty transactions, strategic transactions, or a combination of these approaches. To the extent that we raise additional
capital through the sale of equity or convertible debt securities, the ownership interests of our common stockholders will be diluted,
our fixed payment obligations may increase, any such securities may have rights senior to those of our common stock, and the terms
may include liquidation or other preferences and anti-dilution protections that adversely affect the rights of our common stockholders.
Debt financing, if available, may involve agreements that would restrict our operations and potentially impair our competitiveness,
such as limitations on our ability to incur additional debt, make capital expenditures, declare dividends, acquire, sell or license
intellectual property rights, and other operating restrictions that could adversely impact our ability to conduct our business. If we raise
additional funds through royalty transactions, we may have to relinquish valuable rights to our portfolio and future revenue streams,
and enter into agreements that would restrict our operations and strategic flexibility. If we raise additional funds through strategic
transactions with third parties, we may have to do so at an earlier stage than otherwise would be desirable. In connection with any
such strategic transactions, 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 additional funds when
needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts for Auryxia,
vadadustat, or any other products or product candidates that we develop or acquire, or grant rights to develop and market product
candidates that we would otherwise prefer to develop and market ourselves.
We may engage in strategic transactions to acquire assets, businesses, or rights to products, product candidates or technologies or
form collaborations or make investments in other companies or technologies that could harm our operating 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 additional strategic transactions to expand and diversify our portfolio, including
through the acquisition of assets, businesses, or rights to products, product candidates or technologies or through strategic alliances or
collaborations, similar to the Merger and our collaboration and license arrangements. We may not identify suitable strategic
transactions, or complete such transactions in a timely manner, on a cost-effective basis, or at all. Moreover, we may devote resources
to potential opportunities that are never completed or we may incorrectly judge the value or worth of such opportunities. Even if we
successfully execute a strategic transaction, we may not be able to realize the anticipated benefits of such transaction, may incur
additional debt or assume unknown or contingent liabilities in connection therewith, and may experience losses related to our
investments in such transactions. Integration of an acquired company or assets into our existing business may not be successful and
may disrupt ongoing operations, require the hiring of additional personnel and the implementation of additional internal systems and
infrastructure, and require management resources that would otherwise focus on developing our existing business. Even if we are able
to achieve the long-term benefits of a strategic transaction, 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 operations and financial condition.
In addition, future transactions may entail numerous operational, financial and legal risks, including:
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incurrence of substantial debt, dilutive issuances of securities or depletion of cash to pay for acquisitions;
exposure to known and unknown liabilities, including possible intellectual property infringement claims, violations of
laws, tax liabilities and commercial disputes;
higher than expected acquisition and integration costs;
difficulty in integrating operations and personnel of any acquired business;
increased amortization expenses or, in the event that we write-down the value of acquired assets, impairment losses;
impairment of relationships with key suppliers or customers of any acquired business due to changes in management and
ownership;
inability to retain personnel, customers, distributors, vendors and other business partners integral to an in-licensed or
acquired product, product candidate or technology;
potential failure of the due diligence processes to identify significant problems, liabilities or other shortcomings or
challenges;
entry into indications or markets in which we have no or limited direct prior development or commercial experience and
where competitors in such markets have stronger market positions; and
other challenges associated with managing an increasingly diversified business.
If we are unable to successfully manage any transaction in which we may engage, our ability to develop new products and continue to
expand and diversify our portfolio may be limited.
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Risks Related to our Merger with Keryx
We may fail to realize the anticipated benefits of our merger with Keryx, those benefits may take longer to realize than expected,
and we may encounter significant integration difficulties and liabilities, which may have a material adverse effect on our business
and financial position.
On December 12, 2018, we completed the Merger. There can be no assurance that we will realize the full benefit of the anticipated
synergies and cost savings relating to the Merger or that these benefits will be realized within the expected time frames or at all. Our
ability to realize the anticipated benefits of the Merger will depend, to a large extent, on our ability to continue to integrate our
business and Keryx’s business and realize anticipated growth opportunities and synergies. If we are unable to successfully integrate
the businesses, or integrate them in a timely fashion, we may face material adverse effects including, but not limited to (i) diversion of
the attention of management and key personnel and potential disruption of our ongoing business, (ii) the loss of employees, (iii)
challenges of managing a larger company, including challenges of conforming standards, controls, procedures and accounting and
other policies and compensation structures, (iv) difficulties in achieving anticipated cost savings, (v) declines in our results of
operations, financial condition or cash flows, (vi) a decline in the market price of our common stock, and (vii) potential liabilities,
adverse consequences, increased expenses or other problems associated with our company following completion of the Merger. Many
of these factors are outside of our control, and any one of them could result in increased costs, decreased expected revenues and
further diversion of management time and energy, which could materially impact our business, financial statements and prospects.
In addition, following the Merger, we have become responsible for Keryx’s liabilities and obligations, including with respect to legal,
financial, regulatory and compliance matters, including certain post-approval regulatory requirements with respect to Auryxia and
obligations under collaboration, license, supply and manufacturing agreements. These obligations will result in additional cost and
investment by us and, if we have underestimated the amount of these costs and investments or if we fail to satisfy any such
obligations, we may not realize the anticipated benefits of the transaction. Also, due to the Merger and ongoing integration, we may
forego or delay pursuit of other opportunities that may have proven to have greater commercial potential.
Further, it is possible that there may be unknown, contingent or other liabilities or problems that may arise in the future, the existence
and/or magnitude of which we were previously unaware. Any such liabilities or problems could have an adverse effect on our
business, financial condition or results of operations.
Lawsuits have been filed challenging the Merger and additional lawsuits may be filed in the future. Any monetary damages, or
other adverse judgment could have a material adverse effect on us.
There is an ongoing putative class action lawsuit filed by purported Keryx shareholders challenging the disclosures made in
connection with the Merger. In addition, a stockholder of Keryx filed a complaint against Keryx pursuant to Section 220 of the
Delaware General Corporation Law, which sought inspection of various Keryx books and records, purportedly to investigate “possible
wrongdoing,” in connection with Keryx’s negotiation and approval of the Merger, as well as the independence of former members of
Keryx’s Board of Directors (some of whom are current members of our Board of Directors). See Part I, Item 3. Legal Proceedings for
further information relating to the lawsuits. Additional lawsuits arising out of the Merger may be filed in the future. We could be
forced to expend significant resources in the defense of these lawsuits, including but not limited to, costs associated with the
indemnification of Keryx and Akebia directors and officers, and the lawsuits, regardless of outcome, could have a negative effect on
our reputation, stock price and results of operations. In addition, monetary damages or other adverse judgment would have a material
adverse effect on our business and financial position.
Our financial statements include goodwill and other intangible assets as a result of the Merger. These assets could become
impaired in the future under certain conditions.
The Merger added approximately $384.7 million of goodwill and definite lived intangible assets to our financial statements as of
December 12, 2018. Our definite lived intangible assets are amortized over their estimated useful lives. In accordance with generally
accepted accounting principles, or GAAP, we are required annually, or more frequently upon certain indicators of impairment, to
review our estimates and assumptions underlying the fair value of our goodwill and our definite lived intangible assets when
indicators of impairment are present. Conditions 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 initiatives, and the deterioration of our market
capitalization such that it is significantly below our net book value. To the extent we conclude that goodwill and/or definite lived
intangible assets have become impaired, we may be required to incur material write-offs relating to such impairment and any such
write-offs could have a material impact on our future operating results and financial position.
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Risks Related to Commercialization
Our ability to successfully commercialize our product, Auryxia, our late-stage product candidate, vadadustat, if approved, and any
other product or product candidate, including our ability to achieve their widespread market acceptance, is critical to the success of
our business.
Our ability to generate significant product revenue will depend almost entirely on our ability to execute on our commercialization
plans, the level of market adoption for, and the availability of and continued use of our product, Auryxia, and, if approved, our late-
stage product candidate, vadadustat, by physicians, hospitals, dialysis clinics, wholesalers, patients, and/or healthcare payors,
including government payors, consumers, managed care organizations, pharmacy benefit managers, and pharmacies. If we are not
successful in commercializing Auryxia and vadadustat, if approved, including achieving and maintaining an adequate level of market
adoption, our profitability and our future business prospects will be adversely impacted. Market acceptance of Auryxia and any other
product or product candidate that may be approved, including vadadustat, depends on a number of other factors, including:
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the availability of adequate coverage and reimbursement by third party payors and governmental authorities;
the safety and efficacy of the product, as demonstrated in clinical trials and in the post-marketing setting;
the prevalence and complications of the disease treated by our product;
the clinical indications for which the product is approved and the product label approved by regulatory authorities,
including any warnings or limitations that may be required on the label as a consequence of potential safety risks
associated with the product;
the countries in which marketing approvals are obtained;
the claims we and our collaborators are able to make regarding the safety and efficacy of the product;
the success of our physician and patient communications and education programs;
acceptance by physicians and patients of the product as a safe and effective treatment and the willingness of the target
patient population to try new therapies and of physicians to prescribe new therapies;
the cost, safety and efficacy of the product in relation to alternative treatments;
the timing of receipt of marketing approvals and product launch relative to competing products and potential generic
entrants;
relative convenience and ease of administration;
the prevalence and severity of adverse side effects;
adverse publicity about our products or favorable or adverse publicity about competing products;
the availability of discounts, rebates, and price concessions;
the effectiveness of our and our collaborators’ sales, marketing and distribution efforts; and
the restrictions on the use of the product together with other medications, if any.
Market acceptance is critical to our ability to generate significant product revenue. In addition, any product or product candidate, if
approved and commercialized, may achieve only limited market acceptance or none at all. If any of our approved products is not
accepted by the market to the extent that we expect, we may not be able to generate product revenue and our business would suffer.
Generic competitors are seeking approval of generic versions of Auryxia and the market entry of one or more generic competitors
would limit Auryxia sales and have an adverse impact on our business and results of operation.
Although composition and use of Auryxia are currently claimed by 15 issued patents that are listed in the FDA’s Orange Book, we
cannot assure that we will be successful in defending against third parties attempting to invalidate or design around our patents or
assert that our patents are invalid or otherwise unenforceable or not infringed, or in competing against third parties introducing generic
equivalents of Auryxia or any of our future products.
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The Hatch-Waxman Act allows applicants seeking to market a generic equivalent of a drug that relies, in whole or in part, on the
FDA’s prior approval of a patented brand name drug, to provide notice to the holder of the New Drug Application, or NDA, for the
brand name drug of its application, called a Paragraph IV certification notice, if the applicant is seeking to market its product prior to
the expiration of the patents with claims directed to the brand name drug. After the introduction of a generic competitor, a significant
percentage of the prescriptions written for a product may be filled with the generic version, resulting in a loss in sales of the branded
product. We have received Paragraph IV certification notice letters regarding Abbreviated New Drug Applications, or ANDAs,
submitted to the FDA requesting approval for generic versions of Auryxia tablets (210 mg iron per tablet), have filed certain
complaints for patent infringement relating to such ANDAs, and have entered into a settlement and license agreement with one such
ANDA filer. See Part I, Item 3. Legal Proceedings for further information relating to the ANDAs, lawsuits and settlements. Generic
competition for Auryxia or any of our future products could have a material adverse effect on our sales, results of operations and
financial condition.
In addition, litigation to enforce or defend intellectual property rights is complex, costly and involves significant management time. If
our Orange Book listed patents are successfully challenged by a third party and a generic version of Auryxia is approved and
launched, revenue from Auryxia could decline significantly, which would have a material adverse effect on our sales, results of
operations and financial condition.
If we are unable to maintain sales, marketing and distribution capabilities or to enter into additional agreements with third parties,
we may not be successful in commercializing Auryxia, vadadustat or any other products or product candidates, if approved.
In order to market Auryxia, we intend to continue to invest in sales and marketing, which will require substantial effort and significant
management and financial resources. We will need to devote significant effort, in particular, to recruiting individuals with experience
in the sales and marketing of pharmaceutical products. Competition for personnel with these skills is significant.
There are risks involved with maintaining our own sales, marketing and distribution capabilities, including the following:
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potential inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;
potential inability of sales personnel to obtain access to physicians;
potential lack of complementary products to be offered by sales personnel, which may put us at a competitive
disadvantage relative to companies with more extensive product lines; and
costs and expenses associated with maintaining our own sales and marketing organization.
If we are unable to maintain our own sales, marketing and distribution capabilities and our arrangements with third parties with
respect to sales, marketing and distribution, or we are unsuccessful in entering into additional arrangements with third parties to sell,
market and distribute or are unable to do so on terms that are favorable to us, we will not be successful in commercializing Auryxia,
vadadustat, or any other product or product candidates.
Coverage and reimbursement may be limited or unavailable in certain market segments for Auryxia, vadadustat or any other
products or product candidates, if approved, which could make it difficult for us to sell any approved products profitably.
Market acceptance and sales of any approved products depends significantly on the availability of adequate coverage and
reimbursement from third party payors and may be affected by existing and future healthcare reform measures. Government
authorities, third party payors, and pharmacy benefit managers, or PBMs, decide which drugs they will cover, as well as establish
formularies or implement other mechanisms to manage utilization of products and determine reimbursement levels. Coverage and
reimbursement by a third-party payor or PBM may depend upon a number of factors, including the determination that use of a product
is:
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a covered benefit under the health plan;
safe, effective and medically necessary;
appropriate for the specific patient; and
cost effective.
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Obtaining coverage and reimbursement approval for a product from a government or other third-party payor is a time consuming and
costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to
the payor. In the United States, there are multiple government and private third-party payors with varying coverage and
reimbursement levels for pharmaceutical products, and the timing of commencement of reimbursement by a government payor is
dependent on the assignment of codes via the Healthcare Common Procedure Coding System, which codes are assigned on a quarterly
basis. Within Medicare, for oral drugs dispensed by pharmacies and also administered in facilities, coverage and reimbursement may
vary depending on the setting. The Centers for Medicare & Medicaid Services, or CMS, local Medicare administrative contractors,
Medicare Part D plans and/or PBMs operating on behalf of Medicare Part D plans, may have some responsibility for determining the
medical necessity of such drugs, and therefore coverage, for different patients. Different reimbursement methodologies may apply,
and CMS may have some discretion in interpreting their application in certain settings.
As an oral drug, Auryxia is covered by Medicare only under Part D. In September 2018, CMS communicated to Medicare Part D
sponsors that CMS does not consider Auryxia to be covered under Part D when it is used solely for the treatment of iron deficiency
anemia in patients with CKD not on dialysis, or the IDA Indication. CMS does, however, consider Auryxia to be a covered Part D
drug when it is used for its other FDA-approved indication, the control of serum phosphorus levels in CKD patients on dialysis, or the
Hyperphosphatemia Indication. As a result, Part D sponsors require a prior authorization for all Auryxia prescriptions for Medicare
beneficiaries to ensure that Auryxia is being used for the Part D covered indication. On October 15, 2019, we filed a complaint in the
United States District Court for the District of Massachusetts against CMS and the U.S. Department of Health and Human Services, or
HHS, challenging CMS’s decision that Auryxia would no longer be covered by Medicare for the IDA Indication and CMS’s related
decision that imposed the prior authorization requirement for Auryxia in the Hyperphosphatemia Indication. On February 4, 2020, the
court denied our request for a preliminary injunction. We filed an expedited appeal with the Court of Appeals for the First Circuit
challenging the district court’s denial of our motion for a preliminary injunction. The appeal is currently pending. If we are
unsuccessful in our efforts to obtain Part D coverage for the IDA Indication, our ability to commercialize Auryxia for this indication
will continue to be adversely impacted. While we believe that the vast majority of the Part D prescriptions written for Auryxia today
are for the Hyperphosphatemia Indication and therefore will continue to be covered by Part D plans with prior authorization, the prior
authorization requirement and the CMS decision have had and may continue to have an adverse impact on market acceptance of
Auryxia, sales of Auryxia for the Hyperphosphatemia Indication and the IDA Indication, respectively, and ultimately on the timing
and number of prescriptions and Auryxia product revenue, and may influence physicians’ prescribing decisions. Sales of Auryxia for
the Hyperphosphatemia Indication and the IDA Indication have been negatively impacted, and may continue to be negatively affected,
as a result of the CMS decision. Even if we are successful in overturning the CMS decision, the negative impact that the original
decision had on the growth of sales of Auryxia for the Hyperphosphatemia Indication and the IDA Indication will continue, although
less significantly than if the CMS decision is not overturned. We cannot predict the future impact of the CMS determination or prior
authorization changes on our operations and they could have a material adverse effect on our revenue and results of operations going
forward.
Medicaid reimbursement of drugs will also vary by state. Private third-party payor reimbursement policies may also vary and may or
may not be consistent with Medicare reimbursement methodologies. Manufacturers of outpatient prescription 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.
Additionally, 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. 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 competitive disadvantage relative to companies with more extensive product lines. In addition, third party payors,
PBMs and other entities that purchase our products may impose restrictions on our ability to raise prices for our products over time
without incurring additional costs. We cannot be sure that coverage or adequate reimbursement will be available for our product or
any of our potential future products. Even if we obtain coverage for any 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 commercialize certain of our products.
If we are unable to obtain or maintain contracts with key distribution partners, our business could be materially harmed.
As disclosed in this Annual Report on Form 10-K for the year ended December 31, 2019, we had four distributors, Fresenius Medical
Care Rx, McKesson Corporation, Cardinal Health, Inc. and Amerisource Bergen Drug Corporation, that, in the aggregate, accounted
for a significant percentage of our gross accounts receivable as of December 31, 2019. If we are not able to maintain our contracts
with these key distributors on favorable terms, on a timely basis or at all, or if there is any adverse change in one or more of these
distributors’ business practices or financial condition, or such distributors’ end users’ prescribing practices or clinical protocols, it
would adversely impact the market opportunity for Auryxia, our product revenues and operating results.
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Further, if vadadustat is approved and included in the fixed reimbursement model for a bundle of dialysis services, or the bundle, we
would be required 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, Inc., or DaVita, and Fresenius
Medical Care, or Fresenius, which account for a vast majority of the dialysis population in the United States. In May 2017, we entered
into a license agreement, which was amended and restated in April 2019, pursuant to which we granted Vifor (International) Ltd., or
Vifor Pharma, an exclusive license to sell vadadustat to Fresenius Kidney Care Group LLC, or FKC, and certain third party dialysis
organizations, or the Third Party Dialysis Organizations, approved by us, in the United States. The license would be effective upon the
following: FDA approval of vadadustat for anemia due to CKD in adult patients with the dialysis-dependent CKD, the earlier of
CMS’s determination that vadadustat will be reimbursed using the Transitional Drug Add-On Payment Adjustment, or the TDAPA,
and inclusion in a bundled reimbursement model, and a milestone payment by Vifor Pharma. Under this amended license agreement
with Vifor Pharma, or the Vifor Agreement, FKC and the Third Party Dialysis Organizations are not obligated to utilize vadadustat in
its clinics. In addition, even if FKC and the Third Party Dialysis Organizations choose to utilize vadadustat in their clinics in the
United States, they are not restricted from utilizing other therapies for anemia due to CKD. The Vifor Agreement restricts us from
directly supplying vadadustat to FKC or any other affiliate of Fresenius Medical Care North America and the Third Party Dialysis
Organizations. The Vifor Agreement does not restrict us from entering into supply agreements with other dialysis clinics, such as
DaVita; however, these dialysis clinics may choose not to contract with us for vadadustat or they may choose to contract with us for a
limited supply of vadadustat. If vadadustat is approved and we are not able to maintain the Vifor Agreement or enter into a supply
agreement with DaVita, our business may be materially harmed.
Although we currently believe it is likely that vadadustat, if approved, will be reimbursed using the TDAPA followed by
reimbursement via the bundled reimbursement model, if vadadustat is neither reimbursed under the TDAPA nor the bundled
reimbursement model, then the Vifor Agreement will not become effective, and patients would access vadadustat through contracts
we negotiate with third party payors for reimbursement of vadadustat, which would be subject to the risks and uncertainties described
above. Additionally, if there are updates to the TDAPA rule that decrease the basis for reimbursement or eligibility criteria during the
transition period or if the TDAPA is eliminated, then our profitability may be adversely affected.
In addition, we may be unable to sell 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 alternative therapies or look to negotiate their contracts with us.
Our profitability may also be affected if our costs of production increase faster than increases in reimbursement levels. Adequate coverage
and reimbursement of our products by government and private insurance plans are central to patient and provider acceptance of any
products for which we receive marketing approval.
The successful commercialization of Auryxia, vadadustat or any other products or product candidates, if approved, will depend in
part on the extent to which third party payors and government authorities establish adequate reimbursement levels and pricing
policies.
Third party payors are increasingly attempting to contain healthcare costs by limiting both coverage and reimbursement levels for new
drugs. As a result, significant uncertainty exists as to whether and how much reimbursement third party payors will provide for newly
approved drugs which, in turn, will put downward pressure on the pricing of drugs. Cost control initiatives may decrease coverage and
payment levels for any drug and, in turn, the price that we will be able to charge and/or the volume of our sales. Certain third party
payors require prior authorization for, or even refuse to provide, reimbursement for Auryxia, and others may do so in the future with
respect to Auryxia, vadadustat and any of our other products or product candidates. In addition, certain third party payors require some
form of prior authorization for the administration of ESAs for the treatment of anemia due to CKD within the non-dialysis patient
population, and a similar prior authorization may be applicable to the HIF-PHI class for the treatment of anemia due to CKD within
the non-dialysis patient population. Our business would be materially adversely affected if we are not able to receive approval for
reimbursement from third party payors on a broad, timely or satisfactory basis; if reimbursement is subject to overly broad or
restrictive prior authorization requirements; or if reimbursement is not maintained at satisfactory levels or becomes subject to prior
authorization. We are unable to predict all changes to the coverage or reimbursement methodologies that will be applied by private or
government payors.
In addition, in some countries, including member states of the European Union, or EU, the pricing of prescription pharmaceuticals is
subject to governmental control. In these countries, pricing negotiations with governmental authorities can take a significant amount of
time after receipt of marketing approval for a product. In addition, there can be considerable pressure by governments and other
stakeholders on prices and reimbursement levels, including as part of cost containment measures. Political, economic and regulatory
developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.
Reference pricing used by various EU member states and parallel distribution, or arbitrage between low-priced and high-priced member
states, can further reduce prices, and in certain instances render commercialization in certain markets infeasible or disadvantageous from a
financial perspective. In some countries, we or our collaborators may be required to conduct a clinical trial or other studies that compare
the cost-effectiveness of our product and/or our product candidates to other available products in order to obtain or maintain
reimbursement or pricing approval. Publication of discounts by third party payors or government authorities 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
unsatisfactory levels, the commercial launch of our product and/or product candidates could be delayed, possibly for lengthy periods of
time, we or our collaborators may not launch at all in a particular 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.
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Recently, there has been considerable public and government scrutiny in the United States of pharmaceutical pricing and proposals to
address the perceived high cost of pharmaceuticals. There have also been several recent state legislative efforts to address drug costs,
which generally have focused on increasing transparency around drug costs or limiting drug prices or price increases. Adoption of new
legislation at the federal or state level could affect demand for, or pricing of, our product candidates, if approved, and could diminish
our ability to establish what we believe is a fair price for our products, ultimately diminishing our revenue for our products if they are
approved.
We face substantial competition, which may result in others discovering, developing or commercializing products before, or more
successfully than, we do.
The development and commercialization of new drugs is highly competitive and subject to rapid and significant technological change.
Our future success depends on our ability to demonstrate and maintain a competitive advantage with respect to the development and
commercialization of our product and product candidates. Our objective is to continue to commercialize Auryxia and develop and
commercialize new products with superior efficacy, convenience, tolerability and/or safety. In many cases, any approved products that
we commercialize will compete with existing, market-leading products.
Auryxia is competing in the hyperphosphatemia market in the United States with other FDA-approved phosphate binders such as
Renagel® (sevelamer hydrochloride) and Renvela® (sevelamer carbonate), both marketed by Genzyme Corporation (a wholly-owned
subsidiary of Sanofi), PhosLo® and Phoslyra® (calcium acetate), marketed by Fresenius Medical Care North America, Fosrenol®
(lanthanum carbonate), marketed by Shire Pharmaceuticals 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
options such as aluminum, lanthanum and magnesium. Most of the phosphate binders listed above are now also available in generic
forms. In addition, other agents are in development, including OPKO Health Inc.’s Alpharen™ Tablets (fermagate tablets) and Ardelyx,
Inc.’s tenapanor, that may impact the market for Auryxia.
Auryxia is competing in the IDA market in the United States with over-the-counter oral iron, ferrous sulfate, other prescription oral
iron formulations, including ferrous gluconate, ferrous fumerate, and polysaccharide iron complex, and IV iron formulations,
including Feraheme® (ferumoxytol injection), Venofer® (iron sucrose injection), Ferrlicit® (sodium ferric gluconate complex in
sucrose injection), Injectafer® (ferric carboxymaltose injection), and Triferic® (ferric pyrophosphate citrate).
In addition, other new therapies for the treatment of IDA may impact the market for Auryxia, such as Shield Therapeutics’ Feraccru®
(ferric maltol), which is available in Europe for IDA and Accrufer® (ferric maltol), which is approved in the United States for IDA.
Furthermore, Auryxia’s commercial opportunities may be reduced or eliminated if our competitors develop and market products that
are less expensive, more effective or safer than Auryxia. Other companies have product candidates in various stages of pre-clinical or
clinical development to treat diseases and complications of the diseases for which we are marketing Auryxia.
If vadadustat is approved and launched commercially, competing drugs may include EPOGEN® (epoetin alfa) and Aranesp®
(darbepoetin alfa), both commercialized by Amgen, Procrit® (epoetin alfa) and Eprex® (epoetin alfa), commercialized by Johnson &
Johnson in the United States and Europe, respectively, and Mircera® (methoxy PEG-epoetin beta), commercialized by Vifor Pharma
in the United States and Roche Holding Ltd. outside the United States. We may also face competition from potential new anemia
therapies. There are several other HIF-PHI product candidates in various stages of development for anemia indications that may be in
direct competition with vadadustat, if and when they are approved and launched commercially. These candidates are being developed
by such companies as FibroGen, Japan Tobacco International, GlaxoSmithKline plc and Bayer HealthCare AG. FibroGen, together
with its collaboration partners, Astellas Pharma Inc. and AstraZeneca PLC, is currently in global Phase 3 clinical development of its
product candidate, roxadustat. The product has launched for the treatment of anemia of CKD in patients on dialysis, or DD-CKD, in
Japan and both DD-CKD and for the treatment of anemia of CKD in patients not on dialysis, or NDD-CKD, in China. FibroGen
announced that the FDA has completed its filing review of its NDA for roxadustat for both DD-CKD and NDD-CKD and set a
Prescription Drug User Fee Act date of December 20, 2020. They have stated they expect Astellas to file a marketing authorization
application in the European Union, or MAA, for both indications in the second quarter of 2020. GlaxoSmithKline plc is currently in
global Phase 3 clinical development of its product candidate, daprodustat. Japan Tobacco International and Bayer HealthCare AG are
currently in Phase 3 clinical development of their product candidates in Japan. GlaxoSmithKline plc and Japan Tobacco International
have submitted NDAs for their product candidates for the treatment of renal anemia in Japan. In addition, certain companies are
developing potential new therapies for renal-related diseases that could potentially reduce injectable ESA utilization and thus limit the
market potential for vadadustat if they are approved and launched commercially. Other new therapies are in development for the
treatment of conditions inclusive of renal anemia that may impact the market for anemia-targeted treatment.
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A biosimilar is a biologic product that is approved based on demonstrating that it is highly similar to an existing, FDA-approved
branded biologic product. The patents for the existing, branded biologic product must expire in a given market before biosimilars may
enter that market without risk of being sued for patent infringement. In addition, an application for a biosimilar product cannot be
approved by the FDA until 12 years after the existing, branded product was approved under a Biologics License Application, or BLA.
The patents for epoetin alfa, an injectable ESA, expired in 2004 in the EU, and the remaining patents expired between 2012 and 2016
in the United States. Because injectable ESAs are biologic products, the introduction of biosimilars into the injectable ESA market in
the United States will constitute additional competition for vadadustat if we are able to obtain approval for and commercially launch
our product. Several biosimilar versions of injectable ESAs are available for sale in the EU. In the United States, Pfizer’s biosimilar
version of injectable ESAs, Retacrit® (epoetin alfa-epbx), was approved by the FDA in May 2018 and launched in November 2018.
Many of our potential competitors have significantly greater financial, manufacturing, marketing, drug development, technical and
human resources than we do. Large pharmaceutical companies, in particular, have extensive experience in clinical testing, obtaining
marketing approvals, recruiting patients and manufacturing pharmaceutical products. Large and established companies such as Amgen
and Roche, among others, compete in the market for drug products to treat kidney disease. In particular, these companies have greater
experience and expertise in conducting preclinical testing and clinical trials, obtaining marketing approvals, manufacturing such
products on a broad scale and marketing approved products. These companies also have significantly greater research and marketing
capabilities than we do and may also have products that have been approved or are in late stages of development, and have
collaborative arrangements in our target markets with leading companies and research institutions. Established pharmaceutical
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 competitors. As a result of all of these factors, our competitors may succeed in obtaining patent protection and/or
marketing approval, or discovering, developing and commercializing competitive products, before, or more effectively than, we do. If
we are not able to compete effectively against potential competitors, our business will not grow and our financial condition and
operations will suffer.
The commercialization of Riona in Japan and our current and potential future efforts with respect to the development and
commercialization of our products and product candidates outside of the United States subject us to a variety of risks associated
with international operations, which could materially adversely affect our business.
Our Japanese sublicensee, Japan Tobacco, Inc., or JT, and its subsidiary, Torii Pharmaceutical 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 patients
with CKD, including DD-CKD and NDD-CKD in Japan. We also granted Otsuka Pharmaceutical Co. Ltd., or Otsuka, exclusive rights
to commercialize vadadustat in Europe, China and certain other markets, subject to marketing approvals. In Japan and certain other
countries in Asia, we granted Mitsubishi Tanabe Pharma Corporation, or MTPC, exclusive rights to commercialize vadadustat, subject
to marketing approvals. We are also conducting our global Phase 3 development with respect to vadadustat for the treatment of
anemia due to CKD, and MTPC is carrying out development efforts for vadadustat in Japan. In July 2019, MTPC submitted a
Japanese New Drug Application, or JNDA, to the Ministry of Health, Labor and Welfare in Japan for manufacturing and marketing
approval of vadadustat, as a treatment for anemia due to CKD. As a result of these and other activities, we are or may become subject
to additional risks in developing and commercializing our product and product candidates outside the United States, including:
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political, regulatory, compliance and economic developments that could restrict our ability to manufacture, market and
sell our products;
changes in international medical reimbursement policies and programs;
changes in healthcare policies of foreign jurisdictions;
trade protection measures, including import or export licensing requirements and tariffs;
our ability to develop relationships with qualified local distributors and trading companies;
political and economic instability in particular foreign economies and markets;
diminished protection of intellectual property in some countries outside of the United States;
differing labor regulations and business practices;
regulatory and compliance risks that relate to maintaining accurate information and control over sales and distributors’
and service providers’ activities that may fall within the purview of the U.S. Foreign Corrupt Practices Act, or FCPA, the
UK Bribery Act or similar local regulation;
compliance with the EU General Data Protection Regulation, or GDPR;
economic weakness, including inflation, or political instability in particular foreign economies and markets;
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compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;
potentially negative consequences from changes in or interpretations of tax laws;
foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other
obligations incident to doing business in another country;
workforce uncertainty in countries where labor unrest is more common than in the United States;
production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and
business interruptions resulting from geopolitical actions, including war and terrorism or natural disasters including
earthquakes, typhoons, floods and fires.
Any of these factors may, individually or as a group, have a material adverse effect on our business and results of operations. As and if
we continue to expand our commercialization efforts, we may encounter new risks.
Risks Related to the Clinical Development of Vadadustat and our Other Product Candidates
In addition to Auryxia, we will continue to depend heavily on the success of our product candidate, vadadustat, which is currently
in Phase 3 development. Clinical drug development involves a lengthy and expensive process with an uncertain outcome. We will
incur additional costs in connection with, and may experience delays in completing, or ultimately be unable to complete, the
development and commercialization of vadadustat and any other product candidates.
The risk of failure in drug development is high. We currently have only one commercial product, Auryxia, and one product candidate,
vadadustat, in clinical development, and we depend heavily on the successful commercialization of Auryxia and the successful clinical
development, marketing approval and commercialization of vadadustat, which may never occur. Before obtaining marketing approval
from regulatory authorities 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. 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 time
during the clinical trial process. Further, the results of preclinical studies and early clinical trials of our product candidates may not be
predictive of the results of later-stage clinical trials, and interim results of a clinical trial do not necessarily predict final results.
Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have
believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain
marketing approval of their product candidates. It is impossible to predict when or if any of our product candidates will prove effective
or safe in humans or will receive marketing approval.
We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to
receive or maintain marketing approval or commercialize our product candidates. Our clinical trials may take longer to complete than
currently anticipated, or may be delayed, suspended, required to be repeated, prematurely terminated or may not successfully
demonstrate safety and/or efficacy for a variety of other reasons, such as:
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the costs are greater than we anticipate;
the number of patients required for clinical trials of our product candidates may be larger than we anticipate;
enrollment in our clinical trials and accrual of major adverse cardiovascular events, or MACE, events may be slower than
we anticipate, or participants may drop out of these clinical trials at a higher rate than we anticipate;
our third party contractors, such as our CROs, may fail to comply with regulatory requirements, perform effectively, or
meet their contractual obligations to us in a timely manner, or at all, or we may fail to communicate effectively or provide
the appropriate level of oversight of such third party contractors;
the supply or quality of our starting materials, drug substance and drug product necessary to conduct clinical trials of our
product candidates may be insufficient or inadequate;
regulators, independent data monitoring committees, or IDMCs, institutional review boards, or IRBs, safety committees,
or ethics committees, 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 demonstrate a
benefit from using our product candidate, or a finding that the participants are being exposed to unacceptable health risks;
clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators
may require us, to conduct additional clinical trials, repeat a clinical trial or abandon product development programs;
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lack of adequate funding to continue a clinical trial, including unforeseen costs due to enrollment delays, requirements to
conduct additional clinical trials or repeat a clinical trial and increased expenses associated with the services of our CROs
and other third parties;
failure to initiate, delay of or failure to complete a clinical trial as a result of an Investigational New Drug application, or
IND, being placed on clinical hold by the FDA, the EMA, the Japanese Pharmaceuticals and Medical Devices Agency, or
PMDA, or other regulatory authorities, or for other reasons;
we may determine to change or expand a clinical trial, including after it has begun;
clinical trial sites and investigators deviating 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 effectively or provide the
appropriate level of oversight of such clinical sites and investigators;
delay or failure in having patients complete a clinical trial or return for post-treatment follow-up;
delay or failure in recruiting and enrolling suitable patients to participate in a clinical trial;
inability, delay, or failure in identifying and maintaining a sufficient number of clinical trial sites, many of which may
already be engaged in other clinical programs;
delay or failure in reaching agreement with the FDA, the EMA, the PMDA or other regulatory authorities on a clinical
trial design upon which we are able to execute;
delay or failure in obtaining authorization to commence a clinical trial or inability to comply with conditions imposed by a
regulatory authority regarding the scope or design of a clinical trial;
delays in reaching, or failure to reach, agreement on acceptable terms with prospective clinical trial sites and prospective
CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and
clinical trial sites;
the FDA, the EMA, the PMDA or other regulatory authorities may require us to submit additional data or impose further
requirements before permitting us to initiate a clinical trial or during an ongoing clinical trial;
the FDA, the EMA, the PMDA or other regulatory authorities may disagree with our clinical trial design and our
interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and
commented on the design for our clinical trials;
the design of our clinical trials;
failure to comply with good practice quality guidelines and regulations, or GXP, including good laboratory practice, good
clinical practice, or GCP, and current good manufacturing practice, or cGMP; or
changes in governmental regulations or administrative actions.
If we are unable to successfully complete clinical trials of our product candidates or other studies, if the results of those trials and
studies are not positive or are only modestly positive, or if there are concerns with the profile due to efficacy or safety, or if any of the
factors listed above occur, the following may occur:
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regulators may require that we conduct additional clinical trials, repeat clinical trials or conduct other studies of our
product candidates beyond those that we currently contemplate;
we may be delayed in obtaining marketing approval for our product candidates;
we may not obtain marketing approval for our product candidates at all;
we may obtain approval for indications or patient populations that are not as broad as intended or desired;
we may obtain approval with labeling that includes significant use or distribution restrictions or safety warnings that
would reduce the potential market for our products or inhibit our ability to successfully commercialize our products;
we may be subject to additional post-marketing restrictions and/or requirements; or
the product may be removed from the market after obtaining marketing approval.
Our product development costs will also increase if we experience delays in preclinical and clinical development or receiving the
requisite marketing 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 our product candidates or allow our competitors 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 operations.
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We may find it difficult to enroll patients in our clinical studies, which could delay or prevent clinical studies of our product
candidates.
Identifying and qualifying patients to participate in clinical studies of our product candidates is critical to our success. The timing of
our clinical studies depends, in part, on the speed at which we can recruit patients to participate in testing our product candidates.
Patients may be unwilling to participate in our clinical studies because of concerns about adverse events observed with the current
standard of care, competitor products and/or other investigational agents, in each case for the same indications and/or similar patient
populations. In addition, patients currently receiving treatment with the current standard of care or a competitor product may be
reluctant to participate in a clinical trial with an investigational drug. Finally, competition for clinical trial sites may limit our access to
patients appropriate for studies of vadadustat and any other product candidates. As a result, the timeline for recruiting patients and
conducting studies may be delayed. These delays could result in increased costs, delays in advancing our development of our product
candidates, or termination of the clinical studies altogether.
We may not be able to identify, recruit and enroll a sufficient number of patients, or those with required or desired characteristics, to
complete our clinical studies in a timely manner. Patient enrollment is affected by many factors, including:
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severity of the disease under investigation;
design of the study protocol;
size and nature of the patient population;
eligibility criteria for, and design of, the study in question;
perceived risks and benefits of the product candidate under study, including as a result of adverse effects observed in
similar or competing therapies;
proximity and availability of clinical study sites for prospective patients;
availability of competing therapies and clinical studies and clinicians’ and patients’ perceptions as to the potential
advantages of the product candidate being studied in relation to available therapies or other product candidates in
development;
efforts to facilitate timely enrollment in clinical studies;
clinical trial sites and investigators failing to perform effectively;
patient referral practices of physicians; and
ability to monitor patients adequately during and after treatment.
We may not be able to initiate or continue clinical studies if we cannot enroll a sufficient number of eligible patients to participate in
the clinical studies required by regulatory agencies. If we have difficulty enrolling a sufficient number of patients to conduct our
clinical studies as planned, we may need to delay, limit or terminate ongoing or planned clinical studies, any of which could have a
material adverse effect on our business.
We may not be able to conduct clinical trials in some jurisdictions outside of the United States.
We and our collaboration partners currently expect to seek marketing approval of vadadustat for the treatment of anemia due to CKD
in markets outside the United States, including the EU, and our collaboration partner, MTPC, submitted a JNDA for vadadustat for the
treatment of anemia due to CKD in July 2019 in Japan. Our ability to successfully initiate, enroll and complete a clinical study in any
country outside of the United States is subject to numerous additional risks unique to conducting business in jurisdictions outside the
United States, including:
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difficulty in establishing or managing relationships with qualified CROs, physicians and clinical trial sites;
different local standards for the conduct of clinical studies;
difficulty in complying with various and complex import laws and regulations when shipping drug to certain countries;
and
the potential burden of complying with a variety of laws, medical standards and regulatory requirements, including the
regulation of pharmaceutical and biotechnology products and treatments.
Data obtained from studies conducted in the United States may not be accepted by the EMA, the PMDA and other regulatory
authorities outside of the United States. Also, certain jurisdictions require data from studies conducted in their country in order to
obtain approval in that country. For example, in Japan, MTPC conducted a Phase 3 program of vadadustat, which is separate from our
global Phase 3 program of vadadustat.
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If we or our collaboration partners have difficulty conducting our clinical studies in jurisdictions outside the United States as planned,
we may need to delay, limit or terminate ongoing or planned clinical studies, any of which could have a material adverse effect on our
business.
Positive results from preclinical and clinical studies are not necessarily predictive of the results of any future clinical studies.
Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure can occur at any
time during the clinical trial process. Success in preclinical studies may not be predictive of similar results in humans during clinical
trials, successful results from early or small clinical trials may not be replicated in later and larger clinical trials, and successful interim
results from ongoing clinical studies may not be indicative of results obtained when those studies are completed. For example, our
encouraging preclinical and clinical results for vadadustat thus far do not ensure that the results of any future clinical trials will
demonstrate similar results. Our global Phase 3 development program for vadadustat has enrolled a larger number of patients and will
treat patients for longer periods than our prior trials, which will result in a greater likelihood that adverse events may be observed. Due
to these and other differences between our global Phase 3 development program for vadadustat and our prior trials, our positive results
from preclinical and clinical studies may not be replicated in our global Phase 3 development program for vadadustat. Many
companies in the biopharmaceutical industry have suffered significant setbacks in late-stage clinical trials after achieving positive
results in early stage development, and we may face similar setbacks. If the results of our ongoing or future clinical trials for
vadadustat or any other product candidates are inconclusive with respect to efficacy, if we do not meet our clinical endpoints with
statistical significance, or if there are safety concerns or adverse events, we may be prevented from or delayed in obtaining marketing
approval for vadadustat or any other product candidates.
We may not be successful in our efforts to identify, acquire, discover, develop and commercialize additional products or product
candidates, which could impair our ability to grow.
Although we continue to focus a substantial amount of our efforts on the commercialization of Auryxia and the development and
potential commercialization of vadadustat, a key element of our long-term growth strategy is to acquire, develop and/or market
additional products and product candidates. Research programs to identify product candidates require substantial technical, financial
and human resources, regardless of whether product candidates are ultimately identified. Our research and development programs may
initially show promise, yet fail to yield product candidates for clinical development or commercialization for many reasons, including
the following:
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the research methodology used may not be successful in identifying potential indications and/or product candidates;
we may not be able or willing to assemble sufficient resources to acquire or discover additional product candidates;
a product candidate may be shown to have harmful side effects, a lack of efficacy or otherwise does not meet applicable
regulatory criteria;
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 continued development of that product
candidate is no longer reasonable;
a product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; or
a product candidate may not be accepted as safe and effective by patients, the medical community, or third party payors, if
applicable.
If any of these events occurs, we may be forced to abandon our research and development efforts for one or more of our programs, or
we may not be able to identify, discover, develop or commercialize additional product candidates, which would have a material
adverse effect on our business.
Because we have limited financial and managerial resources, we focus on research programs and product candidates for specific
indications. As a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that
later prove to have greater commercial potential or a greater likelihood of success. Our resource allocation decisions may cause us to
fail to capitalize on viable commercial products or profitable market opportunities.
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Because our internal research capabilities are limited, we may be dependent upon other pharmaceutical and biotechnology companies,
academic scientists, and other researchers to sell or license products or technology to us. The success of this strategy depends partly
upon our ability to identify, select, and acquire promising product candidates and products. The process of proposing, negotiating and
implementing a license or acquisition of a product candidate or an approved product is lengthy and complex. Other companies,
including some with substantially greater financial, marketing and sales resources, may compete with us for the license or acquisition
of a product candidate or an approved product. We have limited resources to identify and execute the acquisition or in-licensing of
third party products, businesses, and technologies and integrate them into our current infrastructure.
Moreover, we may devote resources to potential acquisitions or in-licensing opportunities that are never completed, or we may fail to
realize the anticipated benefits of such efforts, including, for example, with respect to the Merger. Any product candidate that we
acquire may require additional development efforts prior to commercial sale, including extensive clinical testing and approval by the
FDA, the EMA, the PMDA or other regulatory authorities, or post-approval testing or other requirements if approved. All product
candidates are prone to risks of failure typical of pharmaceutical product development, including the possibility that a product
candidate will not be shown to be sufficiently safe and effective for approval by regulatory authorities. In addition, we cannot provide
assurance that any products that we develop or approved products that we acquire will be manufactured profitably, achieve market
acceptance or not require substantial post-marketing clinical trials.
Accordingly, there can be no assurance that we will ever be able to identify additional therapeutic opportunities for our product
candidates or to acquire or develop suitable potential product candidates or approved products, which could materially adversely affect
our future growth and prospects. We may focus our efforts and resources on potential product candidates or other programs that
ultimately prove to be unsuccessful.
Auryxia, vadadustat or any other products and product candidates may cause undesirable side effects or have other properties that
delay or limit their commercial potential, or in the case of our product candidates, prevent their marketing approval.
Undesirable side effects caused by our product or product candidates or competing commercial products or product candidates in
development that utilize a common mechanism of action could cause us or regulatory authorities to interrupt, delay or halt clinical
trials, could result in a more restrictive label or the delay, denial or withdrawal of marketing approval by the FDA or other regulatory
authorities, and could lead to potential product liability claims. Results of our clinical trials could reveal a high and unacceptable
severity and prevalence of side effects or unexpected characteristics.
If we or others identify undesirable side effects caused by Auryxia, vadadustat, or any other products or product candidates, either
before or after receipt of marketing approval, a number of potentially significant negative consequences could result, including:
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our clinical trials may be put on hold;
patient recruitment could be slowed, and enrolled patients may not want to complete the clinical trial;
we may be unable to obtain marketing approval for our product candidates or regulatory authorities may withdraw
approvals of products;
regulatory authorities may require warnings on the label such as the warning on Auryxia’s label regarding iron overload;
Risk Evaluation and Mitigation Strategies, or REMS, or FDA-imposed risk management plans that use risk minimization
strategies to ensure that the benefits of certain prescription drugs outweigh their risks, may be required;
we could be sued and held liable for harm caused to patients; and
our reputation may suffer.
Any of these events could prevent us from achieving or maintaining marketing approval and, ultimately, market acceptance of
Auryxia, vadadustat or any other products or product candidates, could substantially increase our costs, and could significantly impact
our ability to successfully commercialize Auryxia, vadadustat or any other products and product candidates and generate revenues.
The patient populations treated with Auryxia and the patients in our clinical studies for vadadustat have CKD, a serious disease that
increases the risk of cardiovascular disease including heart attacks and stroke and, ultimately, may cause kidney failure. Many patients
with CKD are elderly with comorbidities making them susceptible to significant health risks. Therefore, the likelihood of these
patients having adverse events, including serious adverse events, while participating in our studies is high.
In our Phase 1 and Phase 2 studies of vadadustat, adverse events were reported. For example, in our Phase 2b study of vadadustat in
non-dialysis patients with anemia due to CKD, one subject with multiple co-morbidities and concomitant medications, including
chlorthalidone, had a serious adverse event of liver function test abnormal, considered a case of drug induced liver injury meeting the
biochemical criteria of Hy’s Law, which was assessed as probably related to vadadustat. Serious adverse events considered related to
vadadustat and any other product candidates could have a material adverse effect on the development of such 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 information, and additional unexpected adverse events may be observed in future clinical trials.
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The most commonly reported adverse reactions in the clinical trials that supported the approval of Auryxia for the Hyperphosphatemia
Indication in the United States included diarrhea (21%), discolored feces (19%), nausea (11%), constipation (8%), vomiting (7%), and
cough (6%). Gastrointestinal adverse reactions were the most common reason for discontinuing Auryxia (14%) in clinical trials for the
Hyperphosphatemia Indication. The most commonly reported adverse reactions in the clinical trials that supported the approval of
Auryxia in the United States for the IDA Indication included discolored feces (22%), diarrhea (21%), constipation (18%), nausea
(10%), abdominal pain (5%) and hyperkalemia (5%). Diarrhea was the most common reason for discontinuing Auryxia (2.6%) in
clinical trials for the IDA Indication.
Furthermore, any post-marketing clinical trials conducted, if successful, may expand the patient populations treated with Auryxia, or
any other products we acquire or for which we receive marketing approval, within or outside of their current indications or patient
populations, which could result in the identification of previously unknown side effects, increased frequency or severity of known side
effects, or detection of unexpected safety signals. In addition, as Auryxia and any other products are commercialized, they will be
used in larger patient populations and in less rigorously controlled environments than in clinical studies. As a result, regulatory
authorities, healthcare practitioners, third party payors or patients may perceive or conclude that the use of Auryxia or any other
products are associated with serious adverse effects, undermining our commercialization efforts.
Further, if we or others identify previously unknown side effects, if known side effects are more frequent or severe than in the past, if
we or others detect unexpected safety signals for our products or product candidates, including Auryxia, vadadustat, or any product or
product candidate perceived to be similar to Auryxia, vadadustat, or any other products or product candidates, or if any of the
foregoing are perceived to have occurred, either before or after receipt of marketing approval, a number of potentially significant
negative consequences could result, including:
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sales may be impaired;
regulatory approvals may be restricted or withdrawn;
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 authorities 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;
reformulation of the product, additional nonclinical or clinical studies, changes in labeling or changes to or re-approvals of
manufacturing facilities may be required;
we may be precluded from pursuing additional development opportunities to enhance the clinical profile of a product
within its indicated populations, or studying the product or product candidate in additional indications and populations or
in new formulations; and
government investigations or lawsuits, including class action suits, may be brought against us.
Any of the above occurrences could delay or prevent us from achieving or maintaining marketing approval, harm or prevent sales of
Auryxia or, if approved, vadadustat or other product candidates, increase our expenses and impair or prevent our ability to
successfully commercialize Auryxia, vadadustat or any other products or product candidates
Risks Related to Regulatory Approval of Our Product Candidates
We may be delayed in obtaining, or be unable to obtain, marketing approval or reimbursement for vadadustat or any other product
candidate in certain countries outside of the United States.
Regulatory authorities outside of the United States will require compliance with numerous and varying requirements. The approval
procedures vary among jurisdictions and may involve requirements for additional testing, and the time required to obtain approval
may differ from that required to obtain FDA approval. In addition, in many countries outside the United States, a drug product 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 FDA does not ensure approval by regulatory or reimbursement authorities
outside the United States, and approval by one regulatory or reimbursement authority outside the United States does not ensure
approval by the FDA or any other regulatory or reimbursement authorities. However, the failure to obtain approval or reimbursement
in one jurisdiction may negatively impact our ability to obtain approval or reimbursement in another jurisdiction. The marketing
approval process in countries outside of the United States may include all of the risks associated with obtaining FDA approval and, in
some cases, additional risks. We may not obtain such regulatory or reimbursement approvals on a timely basis, if at all. We may not
be able to file for marketing approvals and may not receive the necessary approvals to commercialize our product candidates in any
market. Also, favorable pricing in certain countries depends on a number of factors, some of which are outside of our control.
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Additionally, on June 23, 2016, the electorate in the United Kingdom voted in favor of leaving the European Union, commonly
referred to as Brexit. Following protracted negotiations, the United Kingdom left the European Union on January 31, 2020. Under the
withdrawal agreement, there is a transitional period until December 31, 2020 (extendable up to two years). Discussions between the
United Kingdom and the European Union have so far mainly focused on finalizing withdrawal issues and transition agreements but
have been extremely difficult to date. To date, only an outline of a trade agreement has been reached. Much remains open, but the
Prime Minister has indicated that the United Kingdom will not seek to extend the transitional period beyond the end of 2020. If no
trade agreement has been reached before the end of the transitional period, there may be significant market and economic disruption.
The Prime Minister has also indicated that the United Kingdom will not accept high regulatory alignment with the European Union.
Since the regulatory framework for pharmaceutical products in the United Kingdom covering quality, safety, and efficacy of
pharmaceutical products, clinical trials, marketing authorization, commercial sales, and distribution of pharmaceutical products is
derived from EU directives and regulations, Brexit could materially impact the future regulatory regime that applies to products and
the approval of product candidates in the United Kingdom. Any delay in obtaining, or an inability to obtain, any marketing approvals,
as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or
the EU for our product candidates, which could significantly and materially harm our business.
Products approved for marketing are subject to extensive post-marketing regulatory requirements and could be subject to post-
marketing restrictions or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory
requirements or if we experience unanticipated problems with our products, or product candidates, when and if any of them is
approved.
Marketing approvals may be subject to limitations on the approved indicated uses for which the product may be marketed or other
conditions of approval, or contain requirements for potentially costly post-marketing studies and surveillance to monitor the safety and
efficacy of the product, including REMS, or registries or observational studies. For example, in connection with the FDA approvals of
Auryxia, we initially committed to the FDA to conduct certain post-approval pediatric studies of Auryxia under the Pediatric Research
Equity Act of 2003, or PREA. With regard to our Hyperphosphatemia Indication, we committed to completing the post-approval
pediatric study and submitting a final report to the FDA by December 31, 2019. With regard to our IDA Indication, we committed to
completing the post-approval pediatric study and submitting a final report to the FDA by January 2023. We cannot guarantee that we
will be able to complete these studies and submit the final reports in a timely manner. For example, with regard to the
Hyperphosphatemia Indication, we did not complete and submit the post-marketing requirement pediatric clinical study report by
December 31, 2019, and we received a notification of noncompliance with PREA. We are requesting an extension of this deadline. If
we are unable to complete these studies successfully, we will need to inform the FDA, have further discussions, and if the FDA finds
that we failed to comply with pediatric study requirements, it could initiate proceedings to seize or enjoin the sale of Auryxia, which
would have a material adverse impact on our ability to commercialize Auryxia and our ability to generate revenues from Auryxia. In
addition, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and
recordkeeping for Auryxia, and any other product for which we receive regulatory approval, will be subject to extensive and ongoing
regulatory requirements. These requirements include submissions of safety and other post-marketing information and reports, as well
as continued compliance with cGMPs and GCPs for any clinical trials that we conduct post-approval.
Moreover, the FDA and other regulatory authorities closely regulate the post-approval marketing and promotion of drugs to ensure
drugs are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and
other regulatory authorities impose stringent restrictions on companies’ communications regarding use of their products, and if we
promote our products beyond their approved indications or inconsistent with the approved label, we may be subject to enforcement
actions or prosecution arising from such activities. Violations of the U.S. Federal Food, Drug, and Cosmetic Act, or the FD&C Act,
relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state healthcare fraud and
abuse and other laws, as well as state consumer protection laws, insurance fraud laws, third party payor actions, shareholder actions
and other lawsuits.
Post-approval discovery of previously unknown problems with an approved product, including adverse events of unanticipated
severity or frequency or relating to manufacturing operations or processes, or failure to comply with regulatory requirements, may
result in, among other things:
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restrictions on the marketing, distribution, use or manufacturing of the product;
withdrawal of the product from the market, or product recalls;
restrictions on the labeling or marketing of a product;
fines, restitution or disgorgement of profits or revenues;
warning or untitled letters or clinical holds;
refusal by the FDA or other regulatory authorities to approve pending applications or supplements to approved
applications filed by us, or suspension or revocation of product approvals;
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product seizure or detention, or refusal to permit the import or export of products;
REMS; and
injunctions or the imposition of civil or criminal penalties.
Non-compliance with FDA, the EMA, the PMDA and other regulatory authorities’ requirements regarding safety monitoring or
pharmacovigilance can also result in significant financial penalties.
The FDA’s policies and those of other regulatory authorities may change, and additional government regulations may be enacted. We
cannot predict the likelihood, nature or extent of government regulations that may arise from future legislation or administrative
action, either in the United States or in other jurisdictions. If we are slow or unable to adapt to changes in existing requirements or the
adoption of new requirements or policies, or are not able to maintain regulatory compliance, we may lose any marketing approval that
we may have obtained and we may not achieve or sustain profitability, which would materially adversely affect our business.
Even if we obtain favorable clinical results in our Phase 3 studies, we may not be able to obtain marketing approval for, or
successfully commercialize, vadadustat, or we may experience significant delays in doing so, any of which would materially harm
our business.
The clinical trials of our product candidates are, and the manufacturing and marketing of our product candidates will be, subject to
extensive and rigorous review and regulation by numerous governmental authorities in the United States, and in other countries where
we and our collaborators intend to test and, if approved, market any product candidates. Before obtaining marketing approval for the
commercial sale of any product candidate, we must demonstrate through extensive preclinical testing and clinical trials that the
product candidate is safe and effective for use in each target indication. This process can take many years and marketing approval may
never be achieved. Of the large number of drugs in development in the United States and in other jurisdictions, only a small
percentage successfully complete the FDA’s and other jurisdictions’ marketing approval processes and are commercialized.
Accordingly, even if we are able to obtain the requisite capital to continue to fund our development programs, we may be unable to
successfully develop or commercialize vadadustat or any other product candidates.
We and Otsuka, our collaboration partner, are not permitted to market vadadustat in the United States until we receive approval from
the FDA, in the EU until we receive approval from the EMA, or in any other jurisdiction until the requisite approval from regulatory
authorities in such jurisdiction is received. MTPC, our collaboration partner in Asia, will not be permitted to market vadadustat in
Japan without approval from the PMDA or in any other jurisdiction until the requisite approval from regulatory authorities in such
jurisdiction is received. As a condition to receiving marketing approval for vadadustat, we must complete Phase 3 studies and any
additional preclinical or clinical studies required by the FDA, the EMA, the PMDA or other regulatory authorities. Vadadustat may
not be successful in clinical trials or receive marketing approval. Further, vadadustat may not receive marketing approval even if it is
successful in clinical trials.
Obtaining marketing approval in the United States and other jurisdictions is a complex, lengthy, expensive and uncertain process that
typically takes many years and depends upon numerous factors, including the substantial discretion of the regulatory authorities. Even
if our product candidates demonstrate safety and efficacy in clinical studies, the regulatory agencies may not complete their review
processes in a timely manner, or we may not be able to obtain marketing approval. Furthermore, approval of a drug does not ensure
successful commercialization. For example, on September 23, 2015, the European Commission, or EC, approved Fexeric for the
control of hyperphosphatemia, in adult patients with CKD. Pursuant to the sunset clause under EU law, the EC’s approval of Fexeric
in the EU was contingent on, among other things, our commencing marketing of Fexeric within three years; although we successfully
negotiated an extension to December 23, 2019, we did not commence marketing Fexeric by such date and therefore the Fexeric
approval in the EU has ceased to be valid.
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If the results of our global Phase 3 studies for vadadustat are positive, we plan to file for regulatory approval in the United States and
other regions. In February 2020, we entered into a letter agreement, or the Letter Agreement, with Vifor Pharma relating to Vifor
Pharma’s agreement with a third party to purchase a Priority Review Voucher issued by the FDA, or the PRV, subject to satisfaction
of customary closing conditions, or the PRV Purchase. Although a PRV entitles the holder to priority review of an NDA or a
Biologics License Application for a new drug, which reduces the target FDA review time to six months after official acceptance of the
submission, the utilization of a PRV does not ensure a faster review or faster approval compared to products considered for approval
under conventional FDA procedures, and in any event does not assure ultimate approval by FDA. Furthermore, even if utilization of
the PRV enables a faster approval of vadadustat, it may not result in faster commercialization of vadadustat. For more information on
risks related to commercialization of vadadustat, see “Risks Related to Commercialization”. In addition, pursuant to the Letter
Agreement, we will pay Vifor Pharma $10.0 million within fifteen business days after the closing of the PRV Purchase. Vifor Pharma
is obligated to retain all rights to, and maintain the validity of, the PRV until we and Vifor Pharma (a) enter into a definitive agreement
setting forth the financial and other terms by which Vifor Pharma will assign the PRV to us for use with our planned NDA for
vadadustat for the treatment of anemia due to CKD in both dialysis-dependent and non-dialysis dependent patients, or (b) make a
mutual decision to sell the PRV and share the proceeds based on certain terms. We may not come to terms with Vifor Pharma on
assigning the PRV to us, and even if we do, we and Vifor Pharma may decide not to use the PRV for vadadustat and, instead, resell it.
In the event of resale of the PRV at a price lower than the purchase price, our share of the proceeds from the resale would be lower
than our $10.0 million contribution.
In addition, the safety concerns associated with the current standard of care for the indications for which we are seeking marketing
approval for our product candidates may affect the FDA’s, the EMA’s, the PMDA’s or other regulatory authorities’ review of the
safety results of our compounds in development. Further, the policies or regulations, 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 jurisdictions. It is
possible that vadadustat and any other product candidates will never obtain marketing approval. The FDA may delay, limit or deny
approval of vadadustat or any other product candidates for many reasons including, among others:
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we may not be able to demonstrate that vadadustat is safe and effective in treating anemia due to CKD or that any other
product candidate is safe and effective for its proposed indication(s) to the satisfaction of the FDA;
the results of our clinical trials may only be modestly positive, 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 statistical or clinical significance required by the FDA for
marketing approval;
the FDA may disagree with the number, design, size, conduct or implementation of our clinical trials;
the FDA may not approve the formulation, labeling or specifications we request for vadadustat or any other product
candidate;
the FDA may approve vadadustat or any other product candidate for use only in a small patient population or for fewer or
more limited indications than we request;
the FDA may require that we conduct additional clinical trials or repeat one or more clinical trials;
the FDA may grant approval contingent on the performance of costly post-marketing clinical trials;
we, or our CROs or vendors, may fail to comply with GXP;
the CROs that we retain to conduct our clinical trials may not perform effectively or take actions that adversely impact our
clinical trials, or we may fail to communicate effectively or provide the appropriate level of oversight of our CROs;
we or our third party manufacturers may fail to perform in accordance with the FDA’s cGMP requirements;
the FDA may disagree with inclusion of data obtained from certain regions outside the United States to support the NDA
for potential reasons such as differences in clinical practice from United States standards;
the FDA may disagree with our interpretation of data from our preclinical studies and clinical trials;
the FDA could deem that our financial relationships with certain principal investigators constitute a conflict of interest,
such that the data from those principal investigators may not be used to support our applications;
an FDA Advisory Committee or other regulatory advisory group or authority could recommend non-approval or
restrictions on approval;
the FDA’s decision-making regarding vadadustat and any other product candidates may be impacted by the results of
competitors’ clinical trials and safety concerns of marketed products used to treat the same indications as the indications
for which vadadustat and any other product candidates are being developed;
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the FDA may not approve the manufacturing processes or facilities of third party manufacturers with whom we contract;
or
the policies or regulations of the FDA may significantly change in a manner that renders our clinical data insufficient for
approval, or requires us to amend or submit new clinical protocols.
In addition, similar reasons may cause the EMA or the PMDA or other regulatory authorities to delay, limit or deny approval of
vadadustat or any other product candidate outside the United States.
If we experience delays in obtaining approval, or if we fail to obtain approval of our product candidates, the commercial prospects for
our product candidates may be harmed and our ability to generate revenues will be materially impaired, which could have a material
adverse effect on our business.
Risks Related to Government Regulation and Compliance
We are subject to a complex regulatory scheme that requires significant resources to ensure compliance. Failure to comply with
applicable laws could subject us to government scrutiny or government enforcement, potentially resulting in costly investigations
and/or fines or sanctions, or impacting our relationships with key regulatory agencies such as the FDA, SEC or the EMA.
A variety of laws apply to us or may otherwise restrict our activities, including the following:
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laws and regulations governing the conduct of preclinical and clinical studies in the United States and other countries in
which we are conducting such studies;
laws and regulations in the United States and in countries in which we are interacting with healthcare providers, patients,
patient organizations and other constituencies that prohibit promoting a drug prior to approval and/or reimbursement;
laws and regulations of countries outside the United States that prohibit pharmaceutical companies from promoting
prescription drugs to the general public;
laws, regulations and industry codes that vary from country to country and govern our relationships with healthcare
providers, patients, patient organizations, and other constituencies, prohibit certain types of gifts and entertainment,
establish codes of conduct and, in some instances, require disclosure to, or approval by, regulatory authorities for us to
engage in arrangements with such constituencies;
anti-corruption and anti-bribery laws, including the FCPA, the UK Bribery Act and various other anti-corruption laws in
countries outside of the United States;
data privacy laws existing in the United States, the EU 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 Information Technology for
Economic and Clinical Health Act, or HITECH, the GDPR, and state privacy and data protection laws, such as the
California Consumer Privacy Act, or CCPA, as well as state consumer protection laws;
federal and state laws requiring the submission of accurate product prices and notifications of price increases;
federal and state securities laws; and
international trade laws, which are laws that regulate the sale, purchase, import, export, re-export, transfer and shipment of
goods, products, materials, services and technology.
Compliance with these and other applicable laws and regulations requires us to expend significant resources. Failure to comply with
these laws and regulations may subject us to government investigations, enforcement actions by regulatory authorities, penalties,
damages, fines, the restructuring of our operations, or the imposition of a clinical hold, any of which could materially adversely affect
our business and would result in increased costs and diversion of management attention and could delay or prevent the development,
regulatory approval and commercialization of our product candidates, any of which could have a material adverse effect on our
business.
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We will incur significant liability if it is determined that we are promoting any “off-label” use of Auryxia or any other product we
may develop, acquire or in-license or if it is determined that any of our activities violates the federal Anti-Kickback Statute.
Physicians are permitted 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 communications regarding unapproved uses of an approved drug. Companies are not
permitted to promote drugs for unapproved uses or in a manner that is inconsistent with the FDA-approved labeling. There are also
restrictions about making comparative or superiority claims based on safety or efficacy that are not supported by substantial evidence.
Accordingly, we may not promote Auryxia in the United States for use in any indications other than the Hyperphosphatemia
Indication and the IDA Indication, and all promotional claims must be consistent with the FDA-approved labeling for Auryxia.
Promoting a drug off-label is a violation of the FD&C Act and can give rise to liability under the federal False Claims Act, as well as
under additional federal and state laws and insurance statutes. The FDA, the Department of Justice and other regulatory and
enforcement authorities enforce laws and regulations prohibiting promotion of off-label uses and the promotion of products for which
marketing approval has not been obtained, as well as the false advertising or misleading promotion of drugs. In addition, laws and
regulations govern the distribution and tracing of prescription drugs and prescription drug samples, including the Prescription Drug
Marketing Act of 1976 and the Drug Supply Chain Security Act, which regulate the distribution and tracing of prescription drugs and
prescription drug samples at the U.S. federal level and set minimum standards for the regulation 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 promotion or
improper distribution of drugs will be subject to significant liability, potentially including civil and administrative remedies as well as
criminal sanctions.
Notwithstanding the regulatory restrictions on off-label promotion, the FDA and other regulatory authorities allow companies to
engage in truthful, non-misleading, and non-promotional scientific communications concerning their products in certain
circumstances. In addition, under some relatively recent guidance from the FDA, companies may also promote information that is
consistent with the prescribing information and proactively speak to formulary committee 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 constituencies in compliance with all applicable laws, regulatory guidance and industry best practices.
Although we believe we have put in place a robust compliance program and processes designed to ensure that all such activities are
performed in a legal and compliant manner, Auryxia is our first commercial product so our implementation of our compliance
program in connection with commercialization activities is still relatively new.
In addition, if a company’s activities are determined to have violated the federal Anti-Kickback Statute, this can also give rise to
liability under the federal False Claims Act and such violations can result in significant fines, criminal and civil remedies, and
exclusion from Medicare and Medicaid. There is increased government focus on relationships between the pharmaceutical industry
and physicians, pharmacies (especially specialty pharmacies), and other sources of referrals. Common industry activities, such as
speaker programs, insurance assistance and support, relationships with foundations providing copayment assistance, and relationships
with patient organizations and patients are receiving increased governmental attention. If any of our relationships or activities is
determined to violate applicable federal and state anti-kickback laws, false claims laws, or other laws or regulations, the company
and/or company executives, employees, and other representatives could be subject to significant fines and criminal sanctions,
imprisonment, and potential exclusion from Medicare and Medicaid.
Recent efforts to pursue regulatory reform may limit the FDA’s ability to engage in oversight and implementation activities in the
normal course, and that could negatively impact our business.
Recently, there have been several executive actions taken, including the issuance of a number of executive orders, that could impose
significant burdens on, or otherwise materially delay, the FDA’s ability to engage in routine regulatory and oversight activities such as
implementing statutes through rulemaking, issuance of guidance, and review and approval of marketing applications. On January 30,
2017, an executive order, applicable to all executive agencies including the FDA, was issued that requires that for each notice of
proposed rulemaking or final regulation to be issued in fiscal year 2017, the agency shall identify at least two existing regulations to
be repealed, unless prohibited by law. These requirements are referred to as the “two-for-one” provisions. This executive order
includes a budget neutrality provision that requires the total incremental cost of all new regulations in the 2017 fiscal year, including
repealed regulations, to be no greater than zero, except in limited circumstances. For fiscal years 2018 and beyond, the executive order
requires agencies to identify regulations to offset any incremental cost of a new regulation. Interim guidance issued by the Office of
Information and Regulatory Affairs within the Office of Management and Budget on February 2, 2017, indicates that the “two-for-
one” provisions may apply not only to agency regulations, but also to significant agency guidance documents. It is difficult to predict
how these requirements will be implemented, and the extent to which they will impact the FDA’s ability to exercise its regulatory
authority. If these executive actions impose constraints on FDA’s ability to engage in oversight and implementation activities in the
normal course, our business may be negatively impacted.
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Compliance with privacy and data security requirements could result in additional costs and liabilities 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
penalties, which may have a material adverse effect on our business, financial condition or results of operations.
The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information worldwide is
rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every jurisdiction in which we operate
has established its own data security and privacy frameworks with which we must comply. For example, the collection, 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 European Economic Area, or EEA, in May 2018. The GDPR is wide-
ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to
processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates when required,
providing information to individuals regarding data processing activities, implementing safeguards to protect the security and
confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third party
processors. The GDPR increases our obligations with respect to sponsors with clinical trial sites in the EEA by expanding the
definition of personal data to include coded data and requiring changes to informed consent practices and more detailed notices for
clinical trial patients and investigators. In addition, the GDPR also imposes strict rules on the transfer of personal data to countries
outside the EU, including the United States and, as a result, increases the scrutiny that clinical trial sites located in the EEA should
apply to transfers of personal data from such sites to countries that are considered to lack an adequate level of data protection, such as
the United States. The GDPR also permits data protection authorities to require destruction of improperly gathered or used personal
information and/or impose substantial fines for violations of the GDPR, which can be up to four percent of global revenues or 20
million Euros, whichever is greater, and it also confers a private right of action on data patients and consumer associations to lodge
complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the
GDPR. In addition, the GDPR provides that EU member states may make their own further laws and regulations limiting the
processing of personal data, including genetic, biometric or health data.
Given the breadth and depth of changes in data protection obligations, complying with the GDPR’s requirements is rigorous and time
intensive and requires significant resources and a review of our technologies, systems and practices, 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 regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data
or other personal information from our clinical trials, could require us to change our business practices and put in place additional
compliance mechanisms, may interrupt or delay our development, regulatory and commercialization activities and increase our cost of
doing business, and could lead to government enforcement actions, private litigation and significant fines and penalties against us and
could have a material adverse effect on our business, financial condition or results of operations.
In addition, numerous other federal and state laws, including state security breach notification laws, state health information privacy
laws and federal and state consumer protection laws, govern the collection, use, and storage of personal information. For example, the
CCPA went into effect on January 1, 2020, which creates new individual privacy rights for consumers (as that word is broadly defined
in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households.
Failure to comply with these laws, as well as local laws outside of the U.S. in countries where we are conducting clinical trials,
regarding privacy and security of personal information could expose us to fines and penalties under such laws. Even if we are not
determined to have violated these laws, government investigations into these issues typically require the expenditure of significant
resources and generate negative publicity, which could harm our reputation and our business.
Our relationships with healthcare providers, physicians and third party payors are subject to applicable anti-kickback, fraud and
abuse, false claims, transparency, health information privacy and security, and other healthcare laws and regulations, which, in
the event of a violation, could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm,
administrative burdens and diminished profits and future earnings.
Healthcare providers, physicians and third party payors play a primary role in the recommendation and prescription of Auryxia and
any other product candidates for which we obtain marketing approval. Our arrangements with healthcare providers, physicians and
third party payors expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the
business or financial arrangements and relationships through which we market, sell and distribute Auryxia and any other products or
product candidates for which we obtain marketing approval. In addition, we may be subject to transparency laws and patient privacy
regulation by federal and state governments and by governments in foreign jurisdictions in which we conduct our business.
Restrictions under applicable federal and state healthcare laws and regulations include the following:
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the FD&C Act which among other things, strictly regulates drug product marketing and promotion and prohibits
manufacturers from marketing such products for off-label use;
federal laws that require pharmaceutical manufacturers to report certain calculated product prices to the government or
provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement
under government healthcare programs, and laws requiring notification of price increases;
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the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering,
receiving or providing remuneration, 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 recommendation 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 imposes criminal and civil penalties, including through civil whistleblower or qui tam actions,
against individuals or entities for, among other things, knowingly presenting, 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 obligation to pay money to the federal government, with
potential liability including mandatory treble damages and significant per-claim penalties, currently set at $5,500 to
$11,000 per false claim, and violations of the FD&C Act, the federal government pricing laws, and the federal Anti-
Kickback Statute trigger liability under the federal False Claims Act;
HIPAA imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making
false statements relating to healthcare matters;
HIPAA, as amended by the HITECH, and their respective implementing regulations, also imposes obligations, including
mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually
identifiable health information;
the federal Physician Payments Sunshine Act (renamed the Open Payments Act) requires applicable manufacturers of
covered drugs to report payments and other transfers of value to physicians and teaching hospitals;
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and gift ban and
transparency statutes, may apply to sales or marketing 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 often differ from state to state, thus complicating compliance efforts; and
U.S. state laws restricting interactions with healthcare providers and other members of the healthcare community or
requiring pharmaceutical 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 exceptions and safe
harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws. In
addition, recent healthcare reforms have strengthened these laws. For example, the Health Care Reform Act, among other things,
amended the intent requirement of the federal Anti-Kickback Statute. A person or entity 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 violations
of the Anti-Kickback Statute are now deemed violations of the False Claims Act.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines,
such as the Pharmaceutical Research and Manufacturers of America Code on Interactions with Health Care Professionals, known as
the PhRMA Code. Additionally, some state and local laws require the registration of pharmaceutical sales representatives in the
jurisdiction. State and foreign laws also govern the privacy and security of health information in some circumstances, many of which
differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Efforts to ensure that our business arrangements with third parties comply with applicable healthcare laws and regulations involve
substantial costs. One of the potential areas for governmental scrutiny involves federal and state requirements for pharmaceutical
manufacturers to submit accurate price reports to the government. Because our processes for calculating applicable government prices
and the judgments involved in making these calculations involve subjective decisions and complex methodologies, these calculations
are subject to risk of errors and differing interpretations. In addition, they are subject to review and challenge by the applicable
governmental agencies, or potential qui tam complaints, and it is possible that such reviews could result in changes, recalculations, or
defense costs that may have adverse legal or financial consequences. It is possible that governmental authorities will conclude that our
business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or
other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other governmental
regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines,
imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the
curtailment or restructuring of our operations. If any of the physicians or other healthcare providers or entities 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 administrative sanctions,
including exclusions from participation in government funded healthcare programs.
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Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of and
commercialize our product candidates and affect the prices we may obtain for any products that are approved in the United States
or foreign jurisdictions.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed
changes regarding the healthcare system that could prevent or delay marketing approval of our product candidates, restrict or regulate
post-approval activities and affect our ability to profitably sell Auryxia and any other products or product candidates for which we
obtain marketing approval. The pharmaceutical industry has been a particular focus of these efforts and has been significantly affected
by legislative initiatives. Current laws, as well as other healthcare reform measures that may be adopted in the future, may result in
more rigorous coverage criteria and in additional downward pressure on the price that we receive for any FDA approved product, such
as Auryxia.
In the United States, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, or the MMA, changed the way
Medicare covers and pays for pharmaceutical products. The legislation 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 addition, this
legislation provided authority for limiting the number of drugs that will be covered in any therapeutic class. Cost reduction initiatives
and other provisions of this legislation 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 often follow Medicare coverage
policy and payment limitations in setting their own reimbursement rates. Therefore, any reduction in reimbursement that results from
the MMA may result in a similar reduction in payments from private payors.
In March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and
Education Reconciliation Act of 2010, or, collectively, the ACA. Among the provisions of the ACA of potential importance to our
business including, without limitation, our ability to commercialize and the prices we obtain for Auryxia and may obtain for any of
our product candidates that are approved for sale, are the following:
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an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription drugs and
biologic agents;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;
expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal anti-kickback statute,
new government investigative powers and enhanced penalties for noncompliance;
a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% point-of-sale
discounts off negotiated prices;
extension of manufacturers’ Medicaid rebate liability;
expansion of eligibility criteria for Medicaid programs;
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;
new requirements to report certain financial arrangements with physicians and teaching hospitals;
a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical
effectiveness research, along with funding for such research.
In addition, other legislative changes and regulatory 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 reductions to Medicare payments to providers of
2% per fiscal year which will remain in effect through 2029 unless additional congressional action is taken, and the American
Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the
statute of limitations period for the government to recover overpayments to providers from three to five years. In addition, other
legislative and regulatory changes have been proposed, but not yet adopted. For example, in July 2019, HHS proposed regulatory
changes in kidney health policy and reimbursement. Any new legislative or regulatory changes may result in additional reductions in
Medicare and other healthcare funding and otherwise affect the prices we may obtain for Auryxia or any product candidates for which
we may obtain regulatory approval or the frequency with which Auryxia and any such product candidate is prescribed or used. Further,
there have been several recent U.S. congressional inquiries and proposed state and federal legislation designed to, among other things,
bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs
of drugs under Medicare and reform government program reimbursement methodologies for drug products.
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We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in
additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and
additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians
receive for administering any approved product. Reductions in reimbursement levels may negatively impact the prices we receive or
the frequency with which our products are prescribed or administered. Any reduction in reimbursement from Medicare or other
government programs may result in a similar reduction in payments from private payors.
With the enactment of the Tax Cuts and Jobs Act of 2017, Congress repealed the “individual mandate.” The repeal of this provision,
which requires most Americans to carry a minimal level of health insurance, will become effective in 2019. According to the
Congressional Budget Office, the repeal of the individual mandate will cause an estimated 13 million fewer Americans to be insured
in 2027 and premiums in insurance markets may rise. Additionally, on January 22, 2018, the President signed a continuing resolution
on appropriations for fiscal year 2018 that delayed the implementation of certain ACA-mandated fees, including the so-called
“Cadillac” tax on certain high cost employer-sponsored insurance plans, the annual fee imposed on certain health insurance providers
based on market share, and the medical device excise tax on non-exempt medical devices. Further, the Bipartisan Budget Act of 2018,
among other things, amended the ACA, effective January 1, 2019, to increase from 50% to 70% the point-of-sale discount that is
owed by pharmaceutical manufacturers who participate in Medicare Part D and close the coverage gap in most Medicare drug plans,
commonly referred to as the “donut hole”. Further, each chamber of the U.S. Congress has put forth multiple bills designed to repeal
or repeal and replace portions of the ACA. Although none of these measures has been enacted by Congress to date, Congress may
consider other legislation to repeal and replace elements of the ACA.
The current administration has also taken executive actions to undermine or delay implementation of the ACA. Since January 2017,
the President has signed two Executive Orders designed to delay the implementation of certain provisions of the ACA or otherwise
circumvent some of the requirements for health insurance mandated by the ACA. One Executive Order directs federal agencies with
authorities and responsibilities under the ACA to waive, defer, grant exemptions from, or delay the implementation of any provision
of the ACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or
manufacturers of pharmaceuticals or medical devices. The second Executive Order terminates the cost-sharing subsidies that
reimburse insurers under the ACA. Several state Attorneys General filed suit to stop the administration from terminating the subsidies,
but their request for a restraining order was denied by a federal judge in California on October 25, 2017. In addition, CMS has recently
proposed regulations that would give states greater flexibility in setting benchmarks for insurers in the individual and small group
marketplaces, which may have the effect of relaxing the essential health benefits required under the ACA for plans sold through such
marketplaces. Further, on June 14, 2018, the U.S. Court of Appeals for the Federal Circuit ruled that the federal government was not
required to pay more than $12 billion in ACA risk corridor payments to third party payors who argued that such payments were owed
to them. The effects of this gap in reimbursement on third party payors, providers, and potentially our business, are not yet known.
Further, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the individual mandate portion
of the ACA is an essential and inseverable feature of the ACA and, therefore, because the mandate was repealed as part of the Tax
Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well. The current administration and CMS have both stated that
the ruling will have no immediate effect, and on December 30, 2018 the same judge issued an order staying the judgment pending
appeal. The current administration has recently represented to the court of appeals considering this judgment that it does not oppose
the lower court’s ruling. On July 10, 2019, the Court of Appeals for the Fifth Circuit heard oral argument in this case. In those
arguments, the current administration argued in support of upholding the lower court decision. However, in a subsequent filing, the
U.S. Department of Justice contended that the ACA should be invalidated only in the states that are suing, rather than all states. On
December 18, 2019, that court affirmed the lower court’s ruling that the individual mandate portion of the ACA is unconstitutional
and it remanded the case to the district court for reconsideration of the severability question and additional analysis of the provisions
of the ACA. Litigation and legislation over the ACA are likely to continue, with unpredictable and uncertain results.
The costs of prescription pharmaceuticals have also been the subject of considerable discussion in the United States, and members of
U.S. Congress and the current administration have stated that they will address such costs through new legislative and administrative
measures. To date, there have been several recent U.S. congressional inquiries and proposed and enacted state and federal legislation
designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer
patient 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 administration have each indicated that it will continue to seek new legislative
and/or administrative measures to control drug costs. Including measures to permit Medicare Part D plans to negotiate the price of
certain drugs under Medicare Part B, to allow some states to negotiate drug prices under Medicaid, and to eliminate cost sharing for
generic drugs for low-income patients.
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Specifically, there have been several recent U.S. congressional inquiries and proposed federal and proposed and enacted state
legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and
manufacturer patient 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 administration have each indicated that it will continue
to seek new legislative and/or administrative measures to control drug costs. For example, on May 11, 2018, the current administration
issued a plan to lower drug prices. Under this blueprint for action, the current administration indicated that HHS will take steps to end
the gaming of regulatory and patent processes by drug makers to unfairly protect monopolies, advance biosimilars and generics to
boost price competition, evaluate the inclusion of prices in drug makers’ ads to enhance price competition, speed access to and lower
the cost of new drugs by clarifying policies for sharing information between insurers and drug makers, avoid excessive pricing by
relying more on value-based pricing by expanding outcome-based payments in Medicare and Medicaid, work to give Medicare Part D
plan sponsors more negotiation power with drug makers, examine which Medicare Part B drug prices could be negotiated by Medicare
Part D plans, improve the design of the Medicare Part B Competitive Acquisition Program, update Medicare’s drug-pricing dashboard
to increase transparency, prohibit Medicare Part D contracts that include “gag rules” that prevent pharmacists from informing patients
when they could pay less out-of-pocket by not using insurance, and require that Medicare Part D plan members be provided with an
annual statement of plan payments, out-of-pocket spending, and drug price increases. In addition, on December 23, 2019, the current
administration published a proposed rulemaking that, if finalized, would allow states or certain other non-federal government entities
to submit importation program proposals to FDA for review and approval. Applicants would be required to demonstrate their
importation plans pose no additional risk to public health and safety and will result in significant cost savings for consumers. At the
same time, FDA issued draft guidance that would allow manufacturers to import their own FDA-approved drugs that are authorized
for sale in other countries (multi-market approved products).
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control
pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain
product access, marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
other countries and bulk purchasing. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding
procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other
healthcare programs. These measures could reduce the ultimate demand for our products or put pressure on our product pricing.
It is likely that federal and state legislatures within the United States and foreign governments will continue to consider changes to
existing healthcare legislation. We expect that additional 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 marketing approval or additional pricing
pressures. We cannot predict the reform initiatives that may be adopted in the future or whether initiatives that have been adopted will
be repealed or modified. The continuing efforts of the government, insurance companies, managed care organizations and other payors
of healthcare services to contain or reduce costs of healthcare may adversely affect:
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the demand for Auryxia and any products candidates for which we receive marketing 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.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or
incur costs that could harm our business.
We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures
and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve the use of hazardous
and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We
generally contract with third parties for the use and disposal of these materials and wastes. We cannot eliminate the risk of
contamination or injury from these materials. In the event of contamination or injury resulting from the use of hazardous materials by
our employees, contractors or consultants, we could be held liable for any resulting damages, and any liability could exceed our
resources. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such
laws and regulations.
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Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our
employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential
liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us in connection
with our storage or disposal of biological, hazardous or radioactive materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and
regulations. These current or future laws and regulations may impair our research, development or production efforts. Our failure to
comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.
Risks Related to our Reliance on Third Parties
If the licensor of certain intellectual property relating to Auryxia terminates, modifies or threatens to terminate existing contracts
or relationships with us, our business may be materially harmed.
We do not own the rights to our product, Auryxia. We have licensed and sublicensed the rights, patent or 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
commercialization due diligence requirements on us. In addition, under the license agreement, we must pay royalties based on a mid-
single digit percentage of net sales of product resulting from the licensed technologies, including Auryxia, and pay the patent filing,
prosecution and maintenance costs related to the license. If we do not meet our obligations in a timely manner, or if we otherwise
breach the terms of our license agreement, Panion could terminate the agreement, and we would lose the rights to Auryxia. For
example, following announcement of the Merger, Panion notified Keryx in writing that Panion would terminate the license agreement
on November 21, 2018 if Keryx did not cure the breach alleged by Panion, specifically, that Keryx failed to use commercially
reasonable best efforts to commercialize Auryxia outside the United States. Keryx disagreed with Panion’s claims, and the parties
entered discussions to resolve this dispute. On October 24, 2018, prior to the consummation of the Merger, we, Keryx and Panion
entered into a letter agreement, or the Panion Letter Agreement, pursuant to which Panion agreed to rescind any and all prior
termination threats or notices relating to the license agreement and waived its rights to terminate the license agreement based on any
breach by us of our obligation to use commercially reasonable efforts to commercialize Auryxia outside the United States until the
parties execute an amendment to the license agreement, in accordance with the terms of the Panion Letter Agreement, following
consummation 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 Letter
Agreement. See Note 4 to the Consolidated Financial Statements contained in this Annual Report on Form 10-K for additional
information 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
attempt to terminate the Panion Amended License Agreement in the future.
In addition, 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.
From time to time, 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
commercialization of Auryxia, could require or result in litigation or arbitration, which would be time-consuming and expensive,
could lead to the termination of the Panion Amended License Agreement, or force us to negotiate a revised or new license agreement
on terms less favorable than the original. In addition, in the event that the owners and/or licensors of the rights we license were to
enter into bankruptcy or similar proceedings, we could potentially lose our rights to Auryxia or our rights could otherwise be
adversely affected, which could prevent us from continuing to commercialize Auryxia.
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We rely on third parties to conduct preclinical and clinical studies for our product and product candidates. If they do not
successfully carry out their contractual duties, comply with regulatory requirements or meet expected deadlines, we may not be
able to optimize the commercialization of Auryxia or obtain marketing approval for or commercialize vadadustat or any other
product candidates, and our business could be substantially harmed.
We do not have the ability to independently conduct preclinical and clinical trials. We are currently relying, and expect to continue to
rely, on third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to conduct
our current and future preclinical studies and our clinical trials, including our global Phase 3 development program for vadadustat. The
third parties on whom we rely may fail to perform effectively, or terminate their engagement with us, for a number of reasons,
including the following:
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if the quantity or accuracy of the data obtained by the third parties is compromised due to their failure to adhere to clinical
trial protocols or to regulatory requirements, or if the third parties otherwise fail to comply with clinical trial protocols,
perform effectively or meet expected deadlines;
if third parties experience staffing difficulties;
if we fail to communicate effectively or provide the appropriate level of oversight;
if third parties undergo changes in priorities or corporate structure or become financially distressed; or
if they form relationships with other entities, some of which may be our competitors.
Any of these events could cause our preclinical and clinical trials, including post-approval clinical trials, to be extended, delayed,
suspended, required to be repeated or terminated, or we may receive untitled warning letters or be the subject of an enforcement action
which could result in our failing to obtain marketing approval of vadadustat or any other product candidates on a timely basis, or at all,
or fail to maintain marketing approval of Auryxia or any other approved products, any of which would adversely affect our business
operations. In addition, if the third parties on whom we rely fail to perform effectively or terminate their engagement with us, we may
need to enter into alternative arrangements, which could delay, perhaps significantly, the continued optimization of the
commercialization of Auryxia and the development and commercialization of vadadustat and any other product candidates.
Even though we do not directly control the third parties on whom we rely to conduct our preclinical and clinical trials and therefore
cannot guarantee the satisfactory and timely performance of their obligations to us, we are nevertheless responsible for ensuring that
each of our clinical trials is conducted in accordance with the applicable protocol, legal and regulatory requirements, including GXP
requirements, and scientific standards, and our reliance on these third parties, including CROs, will not relieve us of our regulatory
responsibilities. If we or any of our CROs, their subcontractors, or clinical trial sites fail to comply with applicable GXP requirements,
the clinical data generated in our clinical trials may be deemed unreliable or insufficient, our clinical trials could be put on hold, and/or
the FDA, the EMA or other regulatory authorities may require us to perform additional clinical trials before approving our marketing
applications. In addition, our clinical trials must be conducted with drug product that meets certain specifications and is manufactured
under applicable cGMP regulations. These requirements include, among other things, quality control, quality assurance, and the
satisfactory maintenance of records and documentation.
We also rely on third parties to store and distribute drug supplies for our clinical trials. Any performance failure on the part of our
distributors could delay clinical development or marketing approval of our product candidates or commercialization of our products,
resulting in additional costs and depriving us of potential product revenue. In addition, we are using an active comparator in our
PRO2TECT and INNO2VATE clinical programs for vadadustat. If our distributors are unable to obtain sufficient supply of the active
comparator for any reason, or supply active comparator to clinical trial sites in a timely manner, our clinical trials may be extended,
delayed, suspended or terminated.
We rely on third parties to conduct all aspects of our product manufacturing. The loss of these manufacturers, their failure to
supply us on a timely basis, or their failure to successfully carry out their contractual duties or comply with regulatory
requirements could cause delays in our current and future capacity and substantially harm our business.
We do not have any manufacturing facilities and do not expect to independently manufacture any product or product candidates. We
currently rely on third party manufacturers to produce all of our commercial, clinical and preclinical material supply. We expect to
continue to rely on existing or alternative third-party manufacturers to supply our ongoing and planned preclinical and clinical trials
and for commercial production. Our reliance on third party manufacturers increases the risk that we will not have sufficient quantities
of our product and product candidates or the ability to obtain such quantities at an acceptable cost or quality, which could delay,
prevent or impair our development or commercialization efforts.
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We currently have two suppliers of Auryxia’s drug substance, one of them with two approved sites, and one supplier with three
approved sites for the supply of Auryxia drug product. If any of our suppliers were to limit or terminate production, or otherwise fail
to meet the quality or delivery requirements needed to supply Auryxia at adequate levels, we could experience losses of revenue that
could materially and adversely impact our results of operations. We have entered into supply agreements with Esteve Química, S.A.
and Patheon Inc. for the manufacture of vadadustat drug substance and drug product, respectively, for commercial use. While we
intend to put additional supply arrangements in place for commercial manufacturing of vadadustat, we may be unsuccessful in doing
so or achieving sufficient redundancy due to a number of factors, including that we may not be able to negotiate binding agreements at
commercially reasonable terms. For example, a contract manufacturer may require a substantial financial commitment, including a
commitment to fund the purchase of a new facility or equipment. If we are unsuccessful in implementing redundant supply
arrangements for commercial quantities of vadadustat, if our commercial supply arrangements for Auryxia or vadadustat are
terminated, or if any of our third party manufacturers is unable to fulfill the terms of their agreements with us, are subject to regulatory
review, or cease their operations for any reason, it could result in delays to our marketing approval for vadadustat and risk that we
would not have sufficient quantities of our product candidates and products for clinical trials and commercialization. Even if we are
ultimately successful in entering into redundant supply arrangements for commercial manufacturing of vadadustat, the timing of such
additional arrangements is uncertain.
If any of our third party manufacturers cannot perform as agreed, including a misappropriation of our proprietary information, or if
they terminate their engagements with us, we may be forced to manufacture the materials ourselves, for which we currently do not
have the capabilities or resources, or enter into agreements with other third party manufacturers, which we may not be able to do on
favorable or reasonable terms, if at all. 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 alternative may not
exist. These factors would increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order
to have another third party manufacture Auryxia or our product candidates. If we are required to change manufacturers for any reason,
we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and
with all applicable regulations and guidelines. The delays associated with the verification of a new manufacturer could negatively
affect our ability to continue to commercialize or satisfy patient demand for Auryxia or any other product candidate for which we
receive marketing approval, or develop and receive marketing approval for our product candidates in a timely manner or within budget.
The facilities and processes used by our third party manufacturers to manufacture Auryxia may be inspected by the FDA and other
regulatory authorities at any time, and the facilities and processes used by our third party manufacturers to manufacture our product
candidates will be inspected by the FDA, the EMA, PMDA and other regulatory authorities prior to or after we submit our marketing
application. We do not control the manufacturing processes of, and are completely dependent on, our third party manufacturers for
compliance with cGMP requirements for manufacture of certain starting materials, drug substance and finished drug product. If our
third party manufacturers cannot successfully manufacture material that conforms to our specifications and regulatory requirements,
we will not be able to maintain marketing approval for Auryxia or secure and/or maintain marketing approval for our product
candidates. In addition, we have no control over the ability of our third party manufacturers to maintain adequate quality control,
quality assurance and qualified personnel. If the FDA, the EMA or other regulatory authorities do not approve the facilities being used
to manufacture our product candidates, or if they withdraw any approval of the facilities being used to manufacture Auryxia or any
other product candidates for which we receive marketing approval, we may need to find alternative manufacturing facilities, which
would significantly impact our ability to continue commercializing Auryxia or develop, obtain marketing approval for or market our
product candidates, if approved. Moreover, the failure of our third party manufacturers to comply with applicable regulations could
result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of
approvals, license revocation, seizures or recalls of Auryxia or our product candidates operating restrictions or criminal prosecutions,
any of which could significantly and adversely affect the supply of Auryxia or our product candidates. Also, if our starting materials,
drug substance or drug product are damaged or lost while in our third party manufacturers’ control, it may impact our ability to supply
our products or product candidates and we may incur significant financial harm. In addition, Auryxia and our product candidates may
compete with other products and product candidates for access to third party manufacturing facilities. A third party manufacturer may
also encounter delays brought on by sudden internal resource constraints, labor disputes, or shifting regulatory protocols. Certain of
these third party manufacturing facilities may be contractually prohibited from manufacturing our product candidates or products, due
to exclusivity provisions in agreements with our competitors. There are a limited number of manufacturers that operate under cGMP
regulations and are capable of manufacturing Auryxia and our product candidates for us.
Our current and anticipated future dependence on third parties for the manufacture of Auryxia and our product candidates may
adversely affect our ability to continue to commercialize Auryxia or any product candidates that receive marketing approval on a
timely and competitive basis and any future profit margins.
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Third party manufacturers may be unable to manufacture our product and product candidates in sufficient quality and quantity,
which would delay or prevent us from commercializing approved products and developing our product candidates.
As a result of the large quantity of materials required for Auryxia production and the large quantities of Auryxia tablets that are
required for our commercial success, the continued commercial viability of Auryxia depends on adequate supply of starting materials
that meet quality, quantity and cost standards and the ability of our contract manufacturers to continually produce drug substance and
finished drug product on a commercial scale. Failure to achieve and maintain these levels of supply can jeopardize and prevent the
successful continued commercialization of Auryxia. Moreover, issues that may arise in any scale-up and technology transfer of
Auryxia and continued commercial scale manufacture of Auryxia may lead to significant delays in our development and commercial
timelines and negatively impact our financial performance. For example, a production-related issue resulted in an interruption in the
supply of Auryxia in the third and fourth quarters of 2016. This supply interruption negatively impacted Keryx’s revenues in 2016.
Although this supply interruption was resolved and actions designed to prevent future interruptions in the supply of Auryxia have been
taken, any future supply interruptions for Auryxia or any of our product candidates for which we receive marketing approval would
negatively and materially impact our reputation and financial condition.
In addition, in order to complete our development of and commercialize, if approved, vadadustat and any other product candidates, we
will need to work with third party manufacturers to manufacture them in large quantities. Our current and future third party
manufacturers may be unable to successfully achieve commercial scale production of vadadustat or increase the manufacturing
capacity of any other product candidates for the conduct of clinical trials and commercialization in a timely or cost-effective manner,
if at all. In addition, quality issues may arise during scale-up activities. Any changes in our manufacturing processes as a result of
scaling up may result in the need to obtain additional marketing approvals. If our third party manufacturers are unable to achieve
commercial scale production or there is a need for additional marketing approvals of vadadustat or any other product candidates, or if
there are difficulties in increasing the manufacturing capacity for any other product candidates, the development, marketing approval
and commercialization of that product candidate may be delayed or infeasible, or ongoing commercialization may be unsuccessful,
any of which could significantly harm our business.
We do not know whether our third party manufacturers will be able to meet our demand, either because of the nature of our
agreements with those third party manufacturers, or, in some cases, our limited experience with those third party manufacturers or our
relative importance as a customer to those third party manufacturers. It may be difficult for us to assess their ability to timely meet our
demand in the future based on past performance. While our current third party manufacturers have generally met our demand for their
products on a timely basis in the past, they may subordinate our needs in the future to their other customers.
We depend on collaborations with third parties for the development and commercialization of vadadustat and Auryxia. If our
collaborations are not successful or if our collaborators terminate their agreements with us, we may not be able to capitalize on the
market potential of Auryxia and vadadustat, and our business could be materially harmed.
We sublicensed the rights to commercialize Riona to JT and Torii in Japan. We entered into collaboration agreements with Otsuka to
develop and commercialize vadadustat in the United States, Europe, China and certain other territories. We also entered into a
collaboration agreement with MTPC to develop and commercialize vadadustat in Japan and certain other Asian countries. We may
form or seek other strategic alliances, joint ventures, or collaborations, or enter into additional licensing arrangements with third
parties that we believe will complement or augment our commercialization efforts with respect to Auryxia and our development and
commercialization efforts with respect to vadadustat and any other product candidates. Our likely collaborators for any collaboration
arrangements include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies and
biotechnology companies.
We may not be able to maintain our collaborations and our collaborations may not be successful due to a number of important factors,
including the following:
(cid:129)
(cid:129)
(cid:129)
(cid:129)
collaborators may have significant discretion in determining the efforts and resources that they will apply to these
collaborations;
collaborations may be terminated in accordance with the terms of the collaborations and, if terminated, may make it
difficult for us to attract new collaborators or adversely affect how we are perceived in scientific and financial
communities, and may result in a need for additional capital and expansion of our internal capabilities to pursue further
development or commercialization of the applicable products and product candidates;
if permitted by the terms of the collaborations, collaborators may elect not to continue or renew development or
commercialization programs based on clinical trial results, changes in their strategic focus, availability of funding or other
external factors such as a business combination that diverts resources or creates competing priorities;
if permitted by the terms of the collaborations, 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 formulation of a product candidate for clinical testing;
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(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
a collaborator with marketing and distribution rights to our products may not commit sufficient resources to their
marketing and distribution;
if permitted by the terms of the collaboration, we and our collaborator may have a difference of opinion regarding the
development or commercialization strategy for a particular product, and our collaborator may have ultimate decision
making authority;
disputes may arise between a collaborator and us that cause the delay or termination of activities related to research,
development or commercialization of Auryxia, vadadustat and any other product candidates, or that result in costly
litigation or arbitration that diverts management attention and resources;
collaborations may not lead to development or commercialization of products and product candidates in the most efficient
manner or at all;
a significant change in the senior management team, a change in the financial condition or a change in the business
operations, including a change in control or internal corporate restructuring, of any of our collaborators, could result in
delayed timelines, re-prioritization of our programs, decreasing resources or funding allocated to support our programs, or
termination of the collaborations; and
collaborators may not comply with all applicable regulatory requirements.
If any of these events occurs, the market potential of our products and product candidates could be reduced, and our business could be
materially harmed. We also cannot be certain that, following a collaboration, the benefits of the collaboration will outweigh the
potential risks.
We may seek to establish additional collaborations and, if we are not able to establish them on commercially reasonable terms, we
may have to alter our development and commercialization plans.
We will require substantial additional cash to fund the continued commercialization of Auryxia and the development and potential
commercialization of vadadustat and any other product candidates. We may decide to enter into additional collaborations for the
development and commercialization of vadadustat or Auryxia. Any of these relationships may require us to incur non-recurring and
other charges, increase our near and long-term expenditures, issue securities that dilute our existing stockholders, or disrupt our
management and business.
We may not be successful in entering into additional collaborations as a result of many factors including the following:
(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
competition in seeking appropriate collaborators;
a reduced number of potential collaborators due to recent business combinations in the pharmaceutical industry;
inability to negotiate collaborations on acceptable terms;
inability to negotiate collaborations on a timely basis;
a potential collaborator’s evaluation of our product or product candidates;
a potential collaborator’s resources and expertise; and
restrictions due to an existing collaboration agreement.
If we are unable to enter into additional collaborations, we may have to curtail the commercialization of the product or the
development of the product candidate on which we are seeking to collaborate, reduce or delay its development program or other of our
other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase
our expenditures and undertake development or commercialization activities at our own expense. If we elect to increase our
expenditures to fund development or commercialization activities on our own, we may need to obtain additional 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 commercialize
Auryxia or develop or commercialize our product candidates.
Even if we enter into additional collaboration 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 timelines or otherwise adversely affect our business.
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We may incur losses as a result of unforeseen or catastrophic events, including the emergence of a pandemic, terrorist attacks,
extreme weather events or other natural disasters.
The occurrence of unforeseen or catastrophic events, including the emergence of a pandemic, such as the novel coronavirus disease
(COVID-19), or other widespread health emergency (or concerns over the possibility of such an emergency), terrorist attacks, extreme
terrestrial or solar weather events or other natural disasters, could create economic and financial disruptions, and could lead to
operational difficulties that could impair our ability to manage our businesses or result in reduced sales or delays in our clinical studies,
which could have a material adverse effect on our financial results. In particular, the outbreak of COVID-19 may result in closures of
CMO facilities on which we rely for the supply of our product and product candidates, which could lead to delays or disruptions in
supply. The outbreak of COVID-19 could also result in potential closures of clinical trial sites on which we rely for the completion of
our clinical trials. In addition, the spread of COVID-19 may result in quarantines and travel restrictions or disruption impacting our
employees’ travel, including the travel of our sales professionals, and causing operational difficulties. Furthermore, healthcare
facilities may limit access for non-patients, including our sales professionals, or we may advise our sales professionals to limit their
visits to healthcare facilities, which could negatively impact our access to healthcare providers and, ultimately, our sales. At this point,
the outbreak of COVID-19 has begun to have indeterminable adverse effects on general commercial activity and the world economy.
However, the extent to which COVID-19 may impact our business and operations is uncertain. If we or any of the third parties with
whom we engage were to experience shutdowns or other business disruptions, our ability to conduct our business in the manner and
on the timelines presently planned could be materially and negatively impacted, which could have a material adverse effect on our
business and our financial results.
Risks Related to our Intellectual Property
If we are unable to adequately protect our intellectual property, third parties 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 protection 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 applications in the United States and certain foreign jurisdictions. The process for
obtaining patent protection is expensive and time consuming, and we may not be able to file and prosecute all necessary or desirable
patent applications in a cost effective or timely manner. In addition, we may fail to identify patentable subject matter early enough to
obtain patent protection. Further, license agreements with third parties may not allow us to control the preparation, filing and
prosecution of patent applications, or the maintenance or enforcement of patents. Such third parties may decide not to enforce such
patents or enforce such patents without our involvement. Thus, these patent applications 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 applications may not issue as patents and may not issue in all countries in which we develop, manufacture or
potentially sell our product(s) or in countries where others develop, manufacture and potentially sell products using our technologies.
Moreover, our pending patent applications, if issued as patents, may not provide additional protection for our product.
The patent positions of pharmaceutical and biotechnology companies can be highly uncertain and involve complex legal and factual
questions. No consistent policy regarding the breadth of claims allowed in pharmaceutical and biotechnology patents has emerged to
date. Changes in the patent laws or the interpretation of the patent laws in the United States and other jurisdictions may diminish the
value of our patents or narrow the scope of our patent protection. Accordingly, the patents we own or license may not be sufficiently
broad to prevent others from practicing our technologies or from developing competing products. Furthermore, others may
independently develop similar or alternative drug products or technologies or design around our patented drug product and
technologies which may have an adverse effect on our business. If our competitors prepare and file patent applications in the United
States that claim technology also claimed by us, we may have to participate in interference or derivation proceedings in front of the
U.S. Patent and Trademark Office, or USPTO, to determine priority of invention, which could result in substantial cost, even if the
eventual outcome is favorable to us. Because of the extensive time required for development, testing and regulatory review of a
potential product, it is possible that any related patent may expire prior to, or remain in existence for only a short period following,
commercialization, thus reducing any advantage of the patent. The patents we own or license may be challenged or invalidated or may
fail to provide us with any competitive advantage. Since we have licensed or sublicensed many patents from third parties, we may not
be able to enforce such licensed patents against third party infringers without the cooperation of the patent owner and the licensor,
which may not be forthcoming. In addition, we may not be successful or timely in obtaining any patents for which we submit
applications.
Additionally, the laws of foreign countries may not protect our intellectual property rights to the same extent as do the laws of the
United States. For example, claims in a patent application directed to methods of treatment of the human body are not patentable or
are restricted in many non-U.S. countries. Further, we may not pursue or obtain patent protection in all major markets. In addition, in
jurisdictions outside the United States where we own or license patent rights, we may be unable to prevent unlicensed parties from
selling or importing products or technologies derived elsewhere using our proprietary technology.
Generally, the first to file a patent application is entitled to the patent if all other requirements of patentability are met. However, prior
to March 16, 2013, in the United States, the first to invent was entitled to the patent. Since publications of discoveries in the scientific
literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not
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published until 18 months after filing, or in some cases not at all, we cannot know with certainty whether we were the first to make the
inventions claimed in our patents or pending patent applications, or that we were the first to file for patent protection of such
inventions. Moreover, the laws enacted by the Leahy-Smith America Invents Act of 2011, or the Act, which reformed certain patent
laws in the United States, introduce procedures that permit competitors to challenge our patents in the USPTO after grant,
including inter partes review and post grant review. Similar laws exist outside of the United States. The laws of the European Patent
Convention, for example, provide for post-grant opposition procedures that permit competitors to challenge, or oppose, our European
patents administratively at the European Patent Office.
In July 2011, a third party filed an opposition to our issued European patents, European Patent No. 2044005, or the ’005 EP Patent,
which covers vadadustat. During the oral proceedings, which took place on April 10, 2013, the Opposition Division of the European
Patent Office decided to maintain certain claims of the patent directed to a compound chosen from a group of eight compounds,
including vadadustat, as well as claims to compositions and methods for treating various diseases including, but not limited to,
anemia. Both parties appealed the decision of the Opposition Division. On February 27, 2018, we withdrew the ’005 EP Patent from
appeal and filed a divisional patent application to pursue a focused claim set that includes claims for vadadustat, as well as
pharmaceutical compositions and methods of treating anemia. We cannot be assured that such claims in the divisional application will
be granted by the European Patent Office. If such claims are not granted, or the scope of the claims is significantly narrowed, we may
not be able to adequately protect our rights, provide sufficient exclusivity, or preserve our competitive advantage.
We may become involved in addressing patentability objections based on third party submission of references, or we may become
involved in defending our patent rights in oppositions, derivation proceedings, reexamination, inter partes review, post grant review,
interference proceedings or other patent office proceedings or litigation, in the United States or elsewhere, challenging our patent
rights or the patent rights of others. An adverse result in any such proceeding or litigation could reduce the scope of, or invalidate, our
patent rights, allow third parties 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 United States 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 parties from using or commercializing similar or identical products, or limit the duration
of the patent protection for our products.
In addition, patents protecting our product candidate might expire before or shortly after such candidate is commercialized. Thus, our
patent portfolio may not provide sufficient rights to exclude others from commercializing products similar or identical to ours.
We also rely on trade secrets and know-how to protect our intellectual property where we believe patent protection is not appropriate
or obtainable. Trade secrets are difficult to protect. While we require our employees, licensees, collaborators and consultants to enter
into confidentiality agreements, this may not be sufficient to adequately protect our trade secrets or other proprietary information. In
addition, we share ownership and publication rights to data relating to our drug product and technologies with our research
collaborators and scientific advisors. If we cannot maintain the confidentiality of this information, our ability to receive patent
protection or protect our trade secrets or other proprietary information will be at risk.
The intellectual property and related non-patent exclusivity that we own or have licensed relating to our product, Auryxia, is
limited, which could adversely affect our ability to compete in the market and adversely affect the value of Auryxia.
The patent rights and related non-patent exclusivity that we own or have licensed relating to Auryxia are limited in ways that may
affect our ability to exclude third parties from competing against us. For example, a third party may design around our owned or
licensed composition of matter patent claims or not market a product for methods of use covered by our owned or licensed patents.
Obtaining proof of direct infringement by a competitor for a method of use patent requires us to demonstrate that the competitors
make and market a product for the patented use(s). Alternatively, we can prove that our competitors induce or contribute to others in
engaging in direct infringement. Proving that a competitor contributes to, or induces, infringement of a patented method by another
has additional proof requirements. For example, proving inducement of infringement requires proof of intent by the competitor. If we
are required to defend ourselves against claims or to protect our own proprietary rights against others, it could result in substantial
costs to us and the distraction of our management. An adverse ruling in any litigation or administrative proceeding could prevent us
from marketing and selling Auryxia, increase the risk that a generic or other similar version of Auryxia could enter the market to
compete with Auryxia, limit our development and commercialization of Auryxia, or otherwise harm our competitive position and
result in additional significant costs. In addition, any successful claim of infringement asserted against us could subject us to monetary
damages or injunction, which could prevent us from making or selling Auryxia. We also may be required to obtain licenses to use the
relevant technology. Such licenses may not be available on commercially reasonable terms, if at all.
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Moreover, physicians may prescribe a competitive identical product for indications other than the one for which the product has been
approved, or “off-label” indications, that are covered by the applicable patents. Although such off-label prescriptions may directly
infringe or contribute to or induce infringement of method of use patents, such infringement is difficult to prevent.
In addition, any limitations of our patent protection described above may adversely affect the value of our drug product and may
inhibit our ability to obtain a collaboration partner at terms acceptable to us, if at all.
In the United States, the FDA has the authority to grant additional regulatory exclusivity protection for approved drugs where the
sponsor conducts specified testing in pediatric or adolescent populations. If granted, this pediatric exclusivity may provide an
additional six months which are added to the term of any non-patent exclusivity that has been awarded as well as to the regulatory
protection related to the term of a relevant patent, to the extent these protections have not already expired.
In addition to patent protection, we may utilize, if granted by the FDA, pediatric exclusivity or other provisions of the FDCA such as
new chemical entity, or NCE, exclusivity, or exclusivity for a new use or new formulation, to provide non-patent exclusivity for a
drug product. The FDCA provides a five-year period of non-patent exclusivity within the United States to the first applicant to gain
approval of a new drug application, or NDA, for an NCE. A drug is an NCE if the FDA has not previously approved any other new
drug containing the same active moiety, which consists of the molecule(s) or ion(s) responsible for the action of the drug substance
(but not including those portions 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 submitted by
another company for another version of such drug where the applicant does not own or have a legal right of reference to all the data
required for approval. However, an ANDA or 505(b)(2) NDA that references an NDA product with NCE exclusivity may be
submitted after four years if it contains a certification of patent invalidity or non-infringement. The FDCA also provides three years of
exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability
studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application
(for example, for new indications, dosages, or strengths of an existing drug). This three-year exclusivity covers only the conditions
associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for drugs containing the
original active agent. The three-year exclusivity period, unlike five-year exclusivity, does not prevent the submission of a competing
ANDA or 505(b)(2) NDA. Instead, it only prevents the FDA from granting final approval to such a product until expiration 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 submitted under section 505(b)(1) of the FDCA; however, an applicant
submitting a full NDA would be required to conduct all of its own studies needed to independently support a finding of safety and
effectiveness for the proposed product, or have a full right of reference to all studies not conducted by the applicant.
On August 23, 2018, Keryx submitted a Citizen Petition requesting, inter alia, that FDA recognize that Auryxia is eligible for five
years of new chemical entity, or NCE, exclusivity based on its novel active ingredient and for three years exclusivity for the IDA
Indication. On January 19, 2019, FDA responded that Auryxia is eligible for a three-year exclusivity period for the IDA Indication,
which expires on November 6, 2020. FDA, however, denied the NCE exclusivity based on its determination that Auryxia contains a
previously-approved active moiety (ferric cation). FDA’s decision on the Citizen Petition is subject to further review both within FDA
and in the courts. On February 21, 2019, we filed a Petition for Reconsideration of FDA’s decision on the NCE determination for
Auryxia.
The FDA’s determination as to whether to grant NCE exclusivity to Auryxia may also affect the timing of the 30 month stay barring
FDA from granting final approval to generic versions of Auryxia. When an ANDA applicant has provided a Paragraph IV certification
to the FDA, the applicant must also send notice of the Paragraph IV certification to the NDA and patent holders once the ANDA has
been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent infringement lawsuit in response to the
notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV
certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months after the receipt of the
Paragraph IV notice, expiration of the patent, or a decision in the infringement case that is favorable to the ANDA applicant. We have
received Paragraph IV certification notice letters regarding Abbreviated New Drug Applications, or ANDAs, submitted to the FDA,
from generic drug manufacturers requesting approval for generic versions of Auryxia tablets (210 mg iron per tablet), have filed
certain complaints for patent infringement relating to such ANDAs, and have entered into a settlement and license agreement with one
such ANDA filer. See Part I, Item 3. Legal Proceedings for further information relating to the ANDAs, lawsuits and settlement.
In cases where NCE exclusivity has been granted to a new drug product, the 30-month stay triggered by such litigation is extended by
the amount of time such that 7.5 years 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
notice of a Paragraph IV certification from the ANDA applicant.
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We cannot assure that Auryxia or any drug candidates we may acquire or in-license will obtain such pediatric exclusivity, NCE
exclusivity or any other market exclusivity in the United States, EU or any other territory, or that we will be the first to receive the
respective regulatory approval for such drugs so as to be eligible for any non-patent exclusivity protection. We also cannot assure that
Auryxia or any drug candidates we may acquire or in-license will obtain patent term extension.
Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover
them or that our trade secrets will be misappropriated or disclosed.
Because we rely on third parties to assist with research, development and manufacture of our product candidates, we must, at times,
share trade secrets with them. We seek to protect our proprietary technology in part by entering into confidentiality agreements and, if
applicable, services agreements, material transfer agreements, consulting agreements, research agreements or other similar agreements
with our advisors, employees, third party contractors, collaborators and consultants prior to beginning research or disclosing
proprietary information. These agreements typically limit the rights of the third parties to use or disclose our confidential information,
including our trade secrets. Despite the contractual provisions employed when working with third parties, the need to share trade
secrets and other confidential information increases the risk that such information becomes known by our competitors, is inadvertently
incorporated into the technology of others, or is disclosed or used in violation of these agreements. Given that our proprietary position
is based, in part, on our know-how and trade secrets, a competitor’s discovery of our trade secrets or other unauthorized use or
disclosure would impair our competitive position and may have a material adverse effect on our business.
In addition, these agreements typically restrict the ability of our advisors, employees, third party contractors, and consultants to
publish data potentially relating to our trade secrets, although our agreements may contain certain limited publication rights. For
example, any academic institution with which we may collaborate will usually expect to be granted rights to publish data arising out of
such collaboration. We often grant such rights, provided that we are notified in advance and given the opportunity to delay publication
for a limited time period in order for us to secure patent protection of intellectual property rights arising from the collaboration and
remove confidential or trade secret information from any such publication. In the future, we may also conduct joint research and
development programs that may require us to share trade secrets under the terms of our research and development or similar
agreements. Despite our efforts to protect our trade secrets, our competitors may discover our trade secrets, either through breach of
our agreements with third parties or independent development or disclosure or publication of information by any of our employees,
advisors, consultants, third party contractors or collaborators. A competitor’s discovery of our trade secrets would impair our
competitive position and have an adverse impact on our business.
Litigation or third party claims of intellectual property infringement may be costly and time consuming and may delay or harm our
drug discovery, development and commercialization efforts.
We may be forced to initiate litigation to enforce our contractual and intellectual property rights, or we may be sued by third parties
asserting claims based on contract, tort or intellectual property infringement. In addition, third parties may have or may obtain patents
in the future and claim that our product or any other technologies infringe their patents. If we are required to defend against suits
brought by third parties, or if we sue third parties to protect our rights, we may be required to pay substantial litigation costs, and our
management’s attention may be diverted from operating our business. In addition, any legal action against our licensor or us that seeks
damages or an injunction of our commercial activities relating to our product or other technologies could subject us to monetary
liability, a temporary or permanent injunction preventing the development, marketing and sale of our product or such technologies,
and/or require our licensor or us to obtain a license to continue to use our product or other technologies. We cannot predict whether
our licensor or we would prevail in any of these types of actions 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 parties. The
pharmaceutical and biotechnology industries are characterized by extensive litigation 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 litigation or other proceedings
regarding intellectual property rights with respect to our drug candidates. As the pharmaceutical and biotechnology industries expand
and more patents are issued, the risk increases that our drug 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 United States falls within the scope of the exemptions provided by 35 U.S.C.
Section 271(e), which provides that it shall not be an act of infringement to make, use, offer to sell, or sell within the United States or
import into the United States a patented invention solely for uses reasonably related to the development and submission of information
to the FDA. As a result of the Merger, our portfolio now includes a commercial product, Auryxia. Consequently, there is an increased
possibility of a patent infringement claim against us. We attempt to ensure that our product candidates and the methods we employ to
manufacture them, as well as the methods for their use which we intend to promote, do not infringe other parties’ patents and other
proprietary rights. There can be no assurance they do not, however, and competitors or other parties may assert that we infringe their
proprietary rights in any event.
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Third parties may hold or obtain patents or other intellectual property rights and allege in the future that the use of our products or
product candidates infringes these patents or intellectual property rights, or that we are employing their proprietary technology without
authorization. We do not believe that there are any currently issued U.S. patents that will prevent us from commercializing Auryxia or
vadadustat; nor do we make any admission that any of such patents are valid, enforceable or infringed. Under U.S. law, a party may be
able to patent a discovery of a new way to use a previously known compound, even if such compound itself is patented, provided the
newly discovered use is novel and nonobvious. Such a method-of-use patent, however, if valid, only protects the use of a claimed
compound for the specified methods claimed in the patent. This type of patent does not prevent persons from using the compound for
any previously known use of the compound. Further, this type of patent does not prevent persons from making and marketing the
compound for an indication that is outside the scope of the patented method. We are not aware of any valid U.S. patents issued to
FibroGen, or any other person, that claim methods of using any of our product candidates for purposes of inhibiting hypoxia-inducible
factor prolyl hydroxylases, or HIF-PHs, for the treatment of anemia due to CKD. For example, we are aware of certain patents that
have been acquired by FibroGen directed to certain heterocyclic carboxamide compounds that are described as inhibitors of prolyl-4-
hydroxylase. Those patents, however, are believed to have expired as of December 2014.
FibroGen has also filed other patent applications in the United States and other countries directed to purportedly new methods of using
such previously known heterocyclic carboxamide compounds for purposes of treating or affecting specified conditions, and some of
these applications have since issued as patents. To the extent any such patents issue or have been issued, we may initiate opposition or
other legal proceedings with respect to such patents. We discuss the status of the opposition and/or invalidation proceedings against
certain FibroGen patents in Part I, Item 3. Legal Proceedings of this Annual Report on Form 10-K.
There may be other patents of FibroGen or patents of other third parties of which we are currently unaware with claims to compounds,
materials, formulations, methods of manufacture or methods for treatment related to the use or manufacture of our drug candidates.
Also, because patent applications can take many years to issue, there may be currently pending patent applications which may later
result in issued patents that our product candidates may infringe.
Third parties, including FibroGen, may in the future claim that our product candidates and other technologies infringe upon their
patents and may challenge our ability to commercialize vadadustat. Parties making claims against us may seek and obtain injunctive or
other equitable relief, which could effectively block our ability to continue to commercialize Auryxia or further develop and
commercialize vadadustat or any other product candidates. If any third party patents were held by a court of competent jurisdiction 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 until 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 jurisdiction to cover aspects
of our formulations, processes for manufacture or our intended methods of use, including patient selection methods, 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 until 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 settle litigation or in order to resolve disputes prior to litigation. Furthermore, even in the absence of
litigation, we may need to obtain licenses from third parties to advance our research or allow commercialization 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
products or product candidates may be impaired or delayed, which could in turn significantly harm our business.
Further, defense of infringement claims, regardless of their merit, would involve substantial litigation expense and would be a
substantial diversion of employee resources from our business. In the event of a successful claim of infringement against us, we may
have to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, pay royalties or redesign our
products, which may be impossible or require substantial time and monetary expenditure.
We are currently involved in patent infringement lawsuits and opposition and invalidity proceedings and may in the future be
involved in additional lawsuits or administrative proceedings to challenge the patents of our competitors or to protect or enforce
our patents, which could be expensive, time consuming, and unsuccessful.
Competitors may infringe our patents or misappropriate our trade secrets or confidential information. To counter infringement or
unauthorized use, we may be required to file infringement or misappropriation claims, which can be expensive and time-consuming.
We may not be able to prevent infringement of our patents or misappropriation of our trade secrets or confidential information,
particularly in countries where the laws may not protect those rights as fully as in the United States. In addition, 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 question. An adverse result in any litigation or
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 applications at risk of not issuing.
In addition, there may be a challenge or dispute regarding inventorship or ownership of patents or applications currently identified as
being owned by or licensed to us. Defense of these claims, regardless of their merit, would involve substantial litigation expense and
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would be a substantial diversion of employee resources from our business. Interference proceedings provoked by third parties or
brought by the USPTO may be necessary to determine the priority of inventions with respect to our patents or patent applications.
Various administrative proceedings are also available for challenging patents, including interference, reexamination, inter partes
review, and post-grant review proceedings before the USPTO or oppositions and other comparable proceedings in foreign
jurisdictions. 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 attempt 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,
participation in interference or other administrative proceedings before the USPTO or a foreign patent office may result in substantial
costs and distract our management and other employees.
For example, we are currently involved in patent infringement lawsuits against several generic companies in the federal district courts.
In addition, we are currently involved in opposition or invalidation proceedings in the European Patent Office, the Japan Patent Office,
the Canadian Federal Court and the United Kingdom Patents Court. These proceedings may be ongoing for a number of years and
may involve substantial expense and diversion of employee resources from our business. In addition, we may become involved in
additional opposition proceedings or other legal or administrative proceedings in the future. For more information, see the other risk
factors under “Risks Related to our Intellectual Property” and Part I, Item 3. Legal Proceedings of this Annual Report on Form 10-K.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation and some
administrative proceedings, there is a risk that some of our confidential information could be compromised by disclosure during
discovery. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or
developments. If securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the
price of our common stock.
Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee
payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or
eliminated for non-compliance with these requirements.
Periodic maintenance fees on any issued patent are due to be paid to the USPTO and foreign patent agencies in several stages over the
lifetime of the patent. The USPTO and governmental patent agencies in other jurisdictions also require compliance with a number of
procedural, documentary, fee payment (such as annuities) and other similar provisions during the patent application 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 situations in which non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or
complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of a patent
or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, non-payment of
fees, and failure to properly legalize and submit formal documents. In such an event, our competitors might be able to enter the
market, which would have a material adverse effect on our business.
We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed
confidential information of third parties.
We have received confidential and proprietary information from potential collaborators, prospective licensees and other third parties.
In addition, we employ individuals who were previously employed at other biotechnology or pharmaceutical companies. We may be
subject to claims that we or our employees, consultants or independent contractors have inadvertently or otherwise used or disclosed
confidential information of these third parties or our employees’ former employers. We may also be subject to claims that former
employees, collaborators or other third parties 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 conflicting obligations of consultants or others who are involved
in developing our product candidates. Litigation may be necessary to defend against these claims. If we fail in defending any such
claims, in addition 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, litigation could result in substantial cost and be a distraction to our management and
employees.
We may not be able to protect our intellectual property rights throughout the world.
Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively
expensive. Consequently, the breadth of our intellectual property rights in some countries outside the United States may be less
extensive than those in the United States. In addition, the laws of some countries do not protect intellectual property rights to the same
extent as laws in the United States. As a result, we may not be able to prevent third parties from practicing our inventions in all
countries outside the United States, or from selling or importing products made using our inventions in and into the United States or
other countries. Competitors may use our technologies in countries where we have not obtained patent protection to develop their own
products and, further, may infringe our patents in territories where we have patent protection, but enforcement is not as strong as in the
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United States. These products may compete with our products and our patents or other intellectual property rights may not be effective
or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in certain countries.
The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets
and other intellectual property, particularly those relating to pharmaceutical and biotechnology products, which could make it difficult
for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
Proceedings to enforce our patent rights in countries outside of the United States could result in substantial costs and divert our efforts
and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our
patent applications at risk of not issuing, and could provoke third parties to assert claims against us. We may not prevail in any
lawsuits that we initiate 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
from the intellectual property that we develop or license.
Risks Related to our Business and Industry
If we fail to attract, keep and motivate senior management and key personnel, we may be unable to successfully develop vadadustat
and commercialize Auryxia.
Recruiting and retaining qualified scientific, clinical, medical, manufacturing and sales and marketing personnel is critical to our
success. We are also highly dependent on our executives, certain members of our senior management and certain members of our
commercial organization. The loss of the services of our executives, senior managers or other key employees, including employees in
our commercial organization, could impede the achievement of our research, development and commercialization objectives and
seriously harm our ability to successfully implement our business strategy. Furthermore, replacing executives, senior managers and
other key employees may be difficult and may take an extended period of time because of the limited number of individuals in our
industry with the breadth of skills and experience required to successfully develop, gain marketing approval of and commercialize
products. We may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the intense competition
among numerous biopharmaceutical companies for similar personnel, particularly in our geographic region.
We also experience competition for the hiring of personnel from universities and research institutions. In addition, we rely on
contractors, consultants and advisors, including scientific and clinical advisors, to assist us in formulating and executing our research
and development and commercialization strategy. Our contractors, consultants and advisors may become employed by companies
other than ours and may have commitments with other entities that may limit their availability to us. If we are unable to continue to
attract and retain high quality personnel, our ability to grow and pursue our business strategy will be limited.
We may expend our limited resources to pursue a particular product, product candidate or indication and fail to capitalize on
products, product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we focus on products, research programs and product candidates for
specific indications. As a result, we may forgo or delay pursuit of opportunities with other product candidates or for other indications
that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on viable
commercial products or profitable market opportunities. Our spending on current and future research and development programs and
product candidates for specific indications may not yield any commercially viable products. If we do not accurately evaluate the
commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate
through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain
sole development and commercialization rights to such product candidate.
Security breaches and unauthorized use of our IT systems and information, or the IT systems or information in the possession of
our collaborators and other third-parties, could damage the integrity of our clinical studies, impact our regulatory filings,
compromise our ability to protect our intellectual property, and subject us to regulatory actions that could result in significant fines
or other penalties.
We, our collaborators, contractors and other third-parties rely significantly upon information technology, and any failure, inadequacy,
interruption or security lapse of that technology, including any cyber security incidents, could harm our ability to operate our business
effectively. In addition, we and our collaborators, contractors and other third parties rely on information technology networks and
systems, including the Internet, to process, transmit and store clinical trial data, patient information, and other electronic information,
and manage or support a variety of business processes, including operational and financial transactions and records, personal
identifying information, payroll data and workforce scheduling information. We purchase some of our information technology from
vendors, on whom our systems depend. We rely on commercially available systems, software, tools and monitoring to provide
security for the processing, transmission and storage of company and customer information.
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In the ordinary course of our business, we and our third party contractors maintain personal and other sensitive data on our and their
respective networks, including our intellectual property and proprietary or confidential business information relating to our business
and that of our clinical trial subjects and business partners. In particular, we rely on CROs and other third parties to store and manage
information from our clinical trials. We also rely on third parties to manage patient information for Auryxia. The secure maintenance
of this sensitive information is critical to our business and reputation.
Companies and other entities and individuals have been increasingly subject to a wide variety of security incidents, cyber-attacks and
other attempts to gain unauthorized access to systems and information. These threats can come from a variety of sources, ranging in
sophistication from individual hackers to state-sponsored attacks. Cyber threats may be broadly targeted, or they may be custom-
crafted against our information systems or those of our vendors or third party service providers. A security breach, cyber-attack 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 actions,
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. protecting confidential or personal information, that could be expensive to defend and could result
in significant fines or other penalties. Cyber-attacks can include malware, computer viruses, hacking or other unauthorized access or
other significant compromise of our computer, communications and related systems. Although we take steps to manage and avoid
these risks and to be prepared to respond to attacks, our preventive and any remedial actions may not be successful and no such
measures can eliminate the possibility of the systems’ improper functioning or the improper access or disclosure of confidential or
personally identifiable information such as in the event of cyber-attacks. Security breaches, whether through physical or electronic
break-ins, computer viruses, ransomware, impersonation of authorized users, attacks by hackers or other means, can create system
disruptions or shutdowns or the unauthorized disclosure of confidential information.
Likewise, although we believe our collaborators, vendors and service providers, such as our CROs, take steps to manage and avoid
information security risks and respond to attacks, we may be vulnerable to attacks against our collaborators, vendors or service
providers, and we may not have adequate contractual remedies against such collaborators, vendors and service providers in such
event. Additionally, outside parties may attempt to fraudulently induce employees, collaborators, or other contractors to disclose
sensitive information or take other actions, including making fraudulent payments or downloading malware, by using “spoofing” and
“phishing” emails or other types of attacks. Our employees may be targeted by such fraudulent activities. Outside parties may also
subject us to distributed denial of services attacks 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. In the recent past, cyber-attacks have become more
prevalent and much harder to detect and defend against and, because the techniques used to obtain unauthorized access, disable or
degrade service, or sabotage systems change frequently and continuously become more sophisticated, often are not recognized until
launched against a target and may be difficult to detect for a long time, we may be unable to anticipate these techniques or to
implement adequate preventive or detective measures, and we might not immediately detect such incidents and the damage caused by
such incidents.
Such attacks, whether successful or unsuccessful, or other compromises with respect to our information 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 litigation, responding to regulatory inquiries or actions, paying damages or fines, or taking other
remedial steps with respect to third parties, inadvertent diversion of cash, divert the attention of our management and key information
technology resources, disrupt key business operations, harm our reputation and deter business partners from working with us. A
compromise with respect to our information security could lead to public exposure of personal information of our clinical trial
subjects, Auryxia patients and others, and negative publicity. Publicity about vulnerabilities and attempted or successful incursions
could damage the integrity of our studies or delay their completion. If a compromise to our information security were to occur and
cause interruptions in our operations, it could result in a disruption of our development programs and our business operations, whether
due to a loss of our trade secrets or other proprietary information or other similar disruptions. For example, any loss of clinical trial
data could result in delays in our regulatory approval efforts for our product candidates and significantly increase our costs to recover
or reproduce the data. In addition, such attacks could compromise our ability to protect our trade secrets and proprietary information
from unauthorized access or misappropriation and a loss of, or damage to, our data or marketing applications. Inappropriate public
disclosure of confidential or proprietary information could subject us to liability and cause delays in our product research,
development and commercialization efforts. We currently do not maintain cybersecurity insurance to protect against losses due to
security breaches.
Any failure to maintain proper functionality and security of our internal computer and information systems could result in a loss of, or
damage to, our data or marketing applications or inappropriate disclosure of confidential or proprietary information, interrupt our
operations, damage our reputation, subject us to liability claims or regulatory penalties, under a variety of federal, state or other
applicable privacy laws, such as HIPAA, the GDPR, or state data protection laws including the CCPA, harm our competitive position
and delay the further development and commercialization of our products and product candidates, or impact our relationships with
Auryxia patients.
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Our employees, independent contractors, principal investigators, CROs, consultants and vendors may engage in misconduct or
other improper activities, including non-compliance with regulatory standards and requirements and insider trading.
We are exposed to the risk that our employees, independent contractors, principal investigators, CROs, consultants and vendors may
engage in fraudulent conduct or other illegal activity. Misconduct by these parties could include intentional, reckless and/or negligent
conduct or unauthorized activities that violate applicable laws, including the following:
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the FDA and other healthcare authorities’ regulations, including those laws that require the reporting of true, complete and
accurate information to regulatory authorities, and those prohibiting the promotion of unapproved drugs or approved drugs
for an unapproved use;
quality standards, including GXP;
federal and state healthcare fraud and abuse laws and regulations and their non-U.S. equivalents;
anti-bribery and anti-corruption laws, such as the FCPA and the UK Bribery Act or country-specific anti-bribery or anti-
corruption laws, as well as various import and export laws and regulations;
laws that require the reporting of true and accurate financial information and data; and
U.S. securities laws and regulations and their non-U.S. equivalents.
We are conducting global clinical trials in countries where corruption is prevalent, and violations 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 sanctions. We are subject to complex laws that govern our international
business practices. 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 purposes of obtaining or keeping business or to obtain any
kind of advantage for the company. The FCPA also requires companies to keep accurate books and records and maintain adequate
accounting controls. A number of past and recent FCPA investigations by the Department of Justice and the U.S. Securities and
Exchange Commission have focused on the life sciences sector.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a recognized problem. Some of
the countries in which we are conducting clinical trials have a history of corruption, which increases our risks of FCPA violations. In
addition, the FCPA presents unique challenges in the pharmaceutical 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
pharmaceutical companies, or on their behalf by CROs, to hospitals in connection with clinical trials and other work have been
deemed to be improper payments to government officials and have led to FCPA enforcement actions.
Additionally, the UK Bribery Act applies to our global activities and prohibits bribery of private individuals as well as public officials.
The UK Bribery Act prohibits both the offering and accepting 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 anti-bribery
and anti-corruption laws in countries where we are conducting clinical trials, and many of these also carry the risk of significant
financial or criminal penalties.
We are also subject to trade control regulations and trade sanctions laws that restrict the movement of certain goods, currency,
products, materials, services and technology to, and certain operations in, various countries or with certain persons. Our ability to
transfer people and products among certain countries is subject to maintaining required licenses and complying with these laws and
regulations.
The internal controls, policies and procedures, and training and compliance programs we have implemented to deter prohibited
practices may not be effective in preventing our employees, contractors, consultants, agents or other representatives from violating or
circumventing such internal policies or violating applicable laws and regulations. The failure to comply with laws governing
international business practices may impact our clinical trials, result in substantial civil or criminal penalties for us and any such
individuals, including imprisonment, suspension or debarment from government contracting, withdrawal of our products, if approved,
from the market, or being delisted from The Nasdaq Global Market. In addition, we may incur significant costs in implementing
sufficient systems, controls and processes to ensure compliance with the aforementioned laws.
The laws and regulations referenced above may restrict or prohibit a wide range of pricing, discounting, marketing and promotion,
sales commission, customer incentive programs and other business arrangements. It is not always possible to identify and deter
misconduct by employees and third parties, and the precautions we take to detect and prevent this activity may not be effective in
controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits
stemming from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us, and we are not
successful in defending ourselves or asserting our rights, or if any such action is instituted against our employees, consultants, vendors
or principal investigators, those actions could have a significant impact on our business, including the imposition of civil, criminal and
administrative penalties, damages, monetary fines, possible exclusion from participation in Medicare, Medicaid and other federal
healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, curtailment of our operations,
disclosure of our confidential information and imprisonment, any of which could adversely affect our ability to operate our business
and our results of operations.
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We may encounter difficulties in managing our growth and expanding our operations successfully.
As we commercialize Auryxia and advance our product candidates through development and commercialization, we have expanded
and may need to further expand our clinical, medical, regulatory, manufacturing, marketing and sales capabilities or contract with
third parties to provide these capabilities for us. In addition, we may encounter difficulties in managing the expanded operations of a
larger and more complex company following the Merger as well as challenges associated with managing an increasingly diversified
business.
We have strategic collaborations for the commercialization of Riona and the development and commercialization of vadadustat. As
our operations expand, we expect that we will need to manage additional relationships with various strategic collaborators,
consultants, vendors, suppliers and other third parties. Future growth will impose significant added responsibilities on members of
management.
In addition, in connection with the Merger, we have experienced and may to continue to experience significant growth in our
employee base for sales, marketing, operational, managerial, financial, human resources, compliance, drug development, quality,
regulatory and medical affairs and other areas. This growth has imposed and will continue to impose significant added responsibilities
on members of management, including the need to recruit, hire, retain, motivate and integrate additional employees, including
employees who joined us in connection with the Merger. Also, our management may have to divert a disproportionate amount of its
attention away from our day-to-day activities and devote a substantial amount of time to managing these growth activities, including
the integration of Keryx’s business with our business.
Our future financial performance and our ability to commercialize Auryxia and vadadustat or any other product candidate, if
approved, and to compete effectively will depend, in part, on our ability to manage any future growth effectively. To manage our
recent and anticipated future growth, we must continue to implement and improve our managerial, operational and financial systems,
expand our facilities and continue to recruit and train additional qualified personnel. Due to our limited financial resources and the
limited experience of our management team in managing a company with such growth, we may not be able to effectively manage the
expansion of our operations or recruit and train additional qualified personnel. In addition, we may need to adjust the size of our
workforce as a result of changes to our expectations for our business, which can result in diversion of management attention,
disruptions to our business, and related expenses. The physical expansion of our operations may lead to significant costs and may
divert our management and business development resources. Any inability to manage growth could delay the execution of our
business plans or disrupt our operations. We may not be able to accomplish these tasks, and our failure to accomplish any of them
could prevent us from successfully growing our company or realizing the anticipated benefits of the Merger.
If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit
commercialization of our product and product candidates.
We face an inherent risk of product liability as a result of the use of our product commercially, and clinical testing of our product
candidates, and we will face an even greater risk if we commercialize any additional products in the future. For example, we may be
sued if our product or any of our product candidates allegedly causes injury or is found to be otherwise unsuitable during product
testing, manufacturing, marketing or sale. Any such product liability claims may include allegations 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
warranties. Claims could also be asserted under state consumer protection acts. If we cannot successfully defend ourselves against
product liability claims, we may incur substantial liabilities or be required to limit commercialization of our products and product
candidates. Even a successful defense would require significant financial and management resources. Regardless of the merits or
eventual outcome, product liability claims may result in:
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decreased demand for any product or product candidates;
injury to our reputation and significant negative media attention;
withdrawal of clinical trial participants;
delay or termination of clinical trials;
our inability to continue to develop a product candidate;
significant costs to defend the related litigation;
a diversion of management’s time and our resources;
substantial monetary awards to study subjects or patients;
product recalls or withdrawals, or labeling, marketing or promotional restrictions;
decreased demand for a product or product candidate;
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loss of revenue;
the inability to commercialize any product or product candidates; and
a decline in our stock price.
Failure to obtain and retain sufficient product liability insurance at an acceptable cost to protect against potential product liability
claims could prevent or inhibit the commercialization 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 settlement 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 negotiated in a
settlement that exceed our coverage limitations or that are not covered by our insurance, we may not have, or be able to obtain,
sufficient capital to pay such amounts. In addition, 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 additional insurance coverage that will be
adequate to cover product liability risks that may arise. Consequently, a product liability claim may result in losses that could be
material to our business.
Risks Related to our Common Stock
Our stock price has been and may continue to be volatile, which could result in substantial losses for purchasers of our common
stock and lawsuits against us and our officers and directors.
Our stock price has been and will likely continue to be volatile. The stock market in general and the market for smaller pharmaceutical
and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating
performance of particular companies. Since our initial public offering in March 2014, the price of our common stock as reported on
The Nasdaq Global Market has ranged from a low of $2.99 on November 13, 2019 to a high of $31.00 on June 20, 2014. The market
price of shares of our common stock could be subject to wide fluctuations in response to many risk factors listed in this section,
developments related to and results of our clinical studies, developments related to our regulatory submissions, developments related
to our ability to commercialize Auryxia and any other approved product candidates, announcements by us or our competitors of
significant mergers, acquisitions, licenses, strategic collaborations, joint ventures, collaborations or capital commitments, negative
publicity around Auryxia, vadadustat or any other product or product candidate, the results of competitive clinical trials, products or
technologies, regulatory or legal developments in the United States and other countries, developments or disputes concerning patent
applications, issued patents or other proprietary rights, the recruitment or departure of key personnel, the level of expenses related to
Auryxia, vadadustat or any other product or product candidate or clinical development programs, actual or anticipated changes in
estimates as to financial results, development timelines or recommendations by securities analysts, variations in our financial results or
those of companies that are perceived to be similar to us, changes in the structure of healthcare payment systems, market conditions in
the pharmaceutical and biotechnology sectors, general economic, industry and market conditions and others beyond our control. As a
result of this volatility, our shareholders may not be able to sell their common stock at or above the price at which they purchased it.
In addition, companies that have experienced volatility in the market price of their stock have frequently been the subject of securities
class action and shareholder derivative litigation. See Part I, Item 3. Legal Proceedings for information concerning securities class
action and shareholder derivative lawsuits initiated against Keryx and certain current and former directors and officers of ours and
Keryx’s. In addition, we could be the target of other such litigation in the future. Class action and shareholder derivative lawsuits,
whether successful or not, could result in substantial costs, damage or settlement awards and a diversion of our management’s
resources and attention from running our business, which could materially harm our reputation, financial condition and results of
operations.
The issuance of additional shares of our common stock or the sale of shares of our common stock by any of our directors, officers
or significant shareholders will dilute our shareholders’ 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 restriction at any time. As such, sales of a substantial number of shares
of our common stock in the public market could occur at any time. These sales, or the perception 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.
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According to the most recent filings made under Section 13(d) and 13(g) of the Securities Exchange Act of 1934, as amended, or the
Exchange Act, Baupost Group Securities, L.L.C., or Baupost, beneficially owned approximately 16% of our outstanding common
stock, and our former director Muneer Satter, beneficially owned approximately 3% of our outstanding common stock. Subject to
certain restrictions, Baupost and Mr. Satter are able to sell their shares of common stock in the public market from time to time
without registering them, subject to certain limitations on the timing, amount and method of those sales imposed by Rule 144 under
the Securities Act of 1933, as amended. In addition, pursuant to our registration rights agreement with Baupost and our Fourth
Amended and Restated Investors’ Rights Agreement, as amended, with Mr. Satter, Baupost and Mr. Satter have the right, subject to
certain conditions and with certain exceptions, to require us to file registration statements covering the shares common stock they own
or to include their shares in registration statements that we may file or in public offerings of our shares of common stock. Following
their registration and sale under the applicable registration statement, those shares would become freely tradable. By exercising their
registration rights and selling a large number of shares of common stock, Baupost and Mr. Satter could cause the price of our common
stock to decline.
We have a significant number of shares that are subject to outstanding options, restricted stock units and a warrant, and in the future
we may issue additional options, restricted stock units, warrants or other derivative securities convertible into our common stock. The
exercise or vesting of any such options, restricted stock units, warrants or other derivative securities, 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
securities in the future at a time and at a price that we deem appropriate. Also, the Merger was financed by the issuance of shares of
our common stock to shareholders of Keryx, comprising approximately 50.6% of our issued and outstanding shares of common stock,
calculated based on our fully diluted market capitalization as of the date of signing the Agreement and Plan of Merger relating to the
Merger. Keryx shareholders may decide not to hold the shares of our common stock they received in the Merger. Other Keryx
shareholders, such as funds with limitations on the amount of stock they are permitted to hold in individual issuers, may be required to
sell the shares of our common stock they received in the Merger. 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.
In addition, we currently have on file with the SEC a universal shelf registration statement, which allows us to offer and sell certain
registered securities, such as common stock, preferred stock, warrants and units, from time to time pursuant to one or more offerings
at prices and terms to be determined at the time of sale.
Sales of substantial amounts of shares of our common stock or other securities by our employees or our other shareholders or by us
under our universal shelf registration 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 securities.
Insiders and significant stockholders could cause us to take actions that may not be, or refrain from taking actions that may be, in
our best interest or in the best interest of all of our stockholders.
As of December 31, 2019, we believe that our directors and executive officers, together with their affiliates, beneficially owned, in the
aggregate, approximately 2% of our outstanding common stock. In addition, we have certain significant stockholders, including
Baupost, which beneficially owned approximately 16% of our outstanding common stock according to the most recent filings made
under Section 13(d) and 13(g) of the Exchange Act. As a result, if certain significant stockholders were to choose to act together, they
would be able to control all matters submitted to our stockholders for approval, as well as our management and affairs, such as:
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the composition of our Board of Directors;
the adoption of amendments to our Ninth Amended and Restated Certificate of Incorporation and Amended and Restated
By-Laws;
the approval of mergers or sales of substantially all of our assets;
our capital structure and financing; and
the approval of contracts between us and these shareholders or their affiliates, which could involve conflicts of interest.
This concentration of ownership could harm the market price of our common stock by:
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delaying, deferring or preventing a change in control of our company and making some transactions more difficult or
impossible without the support of these stockholders, even if such transactions are beneficial to other stockholders;
impeding a merger, consolidation, takeover or other business combination involving our company; or
entrenching our management or our Board of Directors.
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Moreover, the interests of these stockholders may conflict with the interests of other stockholders, and we may be required to engage
in transactions that may not be agreeable to or in the best interest of us or other stockholders.
We will continue to incur increased costs as a result of operating as a public company, and our management will be required to
devote substantial time to compliance initiatives and corporate governance practices.
As a public company, and particularly on and after December 31, 2019 when we ceased to be an “emerging growth company”, we will
continue to incur significant legal, accounting and other expenses. The Sarbanes-Oxley Act of 2002, or the SOX Act, the Dodd-Frank
Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq Global Market and other applicable
securities rules and regulations impose various requirements on public companies, including establishment and maintenance of
effective disclosure and financial controls and corporate governance practices. Our management and other personnel will need to
continue to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have and will
continue to increase our legal and financial compliance costs and make some activities more time-consuming and costly, especially
since, as of December 31, 2019, we are no longer an “emerging growth company” and we therefore may no longer take advantage of
certain exemptions from various reporting requirements that are applicable to public companies that are “emerging growth
companies”.
We cannot predict or estimate the amount of additional costs we may incur to continue to operate as a public company, nor can we
predict the timing of such costs. These rules and regulations are often subject to varying interpretations, in many cases due to their
lack of specificity and, as a result, their application in practice may evolve over time as new guidance is provided by regulatory and
governing bodies, which could result in continuing uncertainty regarding compliance matters and higher costs necessitated by ongoing
revisions to disclosure and governance practices.
If we are unable to satisfy the requirements of Section 404 of the Sarbanes-Oxley Act or fail to maintain an effective system of
internal control over financial reporting, we may not be able to accurately report our financial results or prevent fraud. As a result,
stockholders could lose confidence in our financial and other public reporting which would harm our business and the trading
price of our common stock.
Effective internal control over financial reporting 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 implement required new or improved controls, or
difficulties encountered in their implementation could cause us to fail to meet our reporting obligations. In addition, any testing by us,
as and when required, conducted in connection with Section 404 of the SOX Act, or Section 404, or any testing by our independent
registered public accounting firm, which became required as of December 31, 2019, may reveal deficiencies in our internal control
over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our
financial statements or identify other areas for further attention or improvement. As a larger company following the Merger,
implementing and maintaining effective controls may require more resources, and we may encounter internal control integration
difficulties. For example, as of December 31, 2019, management and our independent registered public accounting firm concluded
that our disclosure controls and procedures were not effective because of a material weakness in our internal control over financial
reporting relating to our inventory process. No adjustments to our current or prior period financial statements were required as a result
of this material weakness. Inferior internal controls could also cause investors to lose confidence in our reported financial information,
which could have a negative effect on the trading price of our common stock. Although we expect to remediate this material weakness
in the short term, we may not be successful in our efforts to do so.
We will need to continue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to
assess and document the adequacy of internal control over financial reporting, continue steps to remediate control deficiencies and
improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a
continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that we
will not be able to conclude within the prescribed timeframe that our internal control over financial reporting is effective as required
by Section 404. If we are not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act in a timely manner each
year, we could be subject to sanctions or investigations by the Securities and Exchange Commission, the Nasdaq Stock Market or
other regulatory authorities which would require additional financial and management resources and could adversely affect the market
price of our common stock. Furthermore, if we cannot provide reliable financial reports or prevent fraud, our business and results of
operations could be harmed and investors could lose confidence in our reported financial information.
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Provisions in our organizational documents and Delaware law may have anti-takeover effects that could discourage an acquisition
of us by others, even if an acquisition would be beneficial to our stockholders, and may prevent attempts by our stockholders to
replace or remove our current management.
Provisions in our Ninth Amended and Restated Certificate of Incorporation, Amended and Restated By-Laws contain provisions that
may have the effect of discouraging, delaying or preventing 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 addition, because our Board of Directors is responsible for appointing certain members of our
management team, these provisions may frustrate or prevent any attempts 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:
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authorize “blank check” preferred stock, which could be issued by our Board of Directors without stockholder approval
and may contain voting, liquidation, 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 meetings of our stockholders can be called only by our Board of Directors pursuant to a resolution
adopted by a majority of the total number of directors;
prohibit stockholder action by written consent;
establish an advance notice procedure for stockholder approvals to be brought before an annual meeting of our
stockholders, including proposed nominations of persons for election 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 entitled to vote or the majority vote of our Board of
Directors to amend our Amended and Restated By-Laws; and
require a supermajority vote of 85% of the holders of our capital stock entitled to vote to amend the classification of our
Board of Directors and to amend certain other provisions of our Ninth Amended and Restated Certificate of Incorporation.
These provisions, alone or together, could delay or prevent hostile takeovers, changes in control or changes in our management.
In addition, Section 203 of the Delaware General Corporation Law prohibits a publicly-held Delaware corporation from engaging in a
business combination with an interested stockholder, generally a person which together with its affiliates owns, or within the last three
years has owned, 15% of our voting stock, for a period of three years after the date of the transaction in which the person became an
interested stockholder, unless the business combination is approved in a prescribed manner.
Any provision of our Ninth Amended and Restated Certificate of Incorporation, our Amended and Restated By-Laws or Delaware law
that has the effect of delaying or deterring a change in control could limit the opportunity for our stockholders to receive a premium
for their shares of our common stock, and could also affect the price that some investors are willing to pay for our common stock.
Our ability to use net operating losses to offset future taxable income may be subject to certain limitations.
Under Section 382 of the Internal Revenue Code, or Section 382, a corporation that undergoes an “ownership change” is subject to
limitations on its ability to utilize its pre-change net operating losses, or NOLs, to offset future taxable income. On December 12,
2018, we completed the Merger, which we believe has resulted in a change in control under Section 382. Future changes in our stock
ownership, many of which are outside of our control, could result in an additional ownership change under Section 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
limitations, which could potentially result in increased future tax liability to us. In addition, at the state level, 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 utilize our NOLs is conditioned upon our attaining profitability and generating U.S. taxable income. As
described above under “—Risks Related to our Financial Position and Need for Additional Capital,” we have incurred significant net
losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future; thus, we do not
know whether or when we will generate the U.S. taxable income necessary to utilize our NOLs. A valuation allowance has been
provided for the entire amount of our NOLs.
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Our Ninth Amended and Restated Certificate of Incorporation designates the state or federal courts located in the State of
Delaware as the sole and exclusive forum for certain types of actions and proceedings that may be initiated 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 Ninth Amended and Restated Certificate of Incorporation provides that, subject to limited exceptions, the state and federal courts
located in the State of Delaware will be the sole and exclusive forum for (1) any derivative action or proceeding brought on our behalf,
(2) any action asserting a claim of breach of a fiduciary duty owed by any of our directors, officers or other employees to us or our
stockholders, (3) any action asserting a claim against us arising pursuant to any provision of the Delaware General Corporation Law,
our Ninth Amended and Restated Certificate of Incorporation or our Amended and Restated By-Laws, or (4) any other action asserting
a claim against us that is governed by the internal affairs doctrine. Under our Ninth Amended and Restated Certificate of
Incorporation, this exclusive forum provision will not apply to claims that are vested in the exclusive jurisdiction 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 matter jurisdiction. For instance, the provision would not apply to actions arising under federal securities laws, including suits
brought to enforce any liability or duty created by the Securities Exchange Act of 1934, as amended, or the rules and regulations
thereunder. Any person or entity purchasing or otherwise acquiring any interest in shares of our capital stock shall be deemed to have
notice of and to have consented to the provisions of our Ninth Amended and Restated Certificate of Incorporation 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. Alternatively, if a court were to find these provisions of our Ninth Amended and Restated Certificate of Incorporation
inapplicable to, or unenforceable with respect to, one or more of the specified types of actions or proceedings, we may incur additional
costs associated with resolving such matters in other jurisdictions, which could adversely affect our business and financial condition.
We are currently subject to putative securities class action litigation and other legal proceedings, which could result in substantial
costs and divert management's attention, and we could be subject to additional legal proceedings.
We are currently subject to putative securities class action litigation and other legal proceedings as described in Part I, Item 3. Legal
Proceedings. In addition, securities class action and derivative lawsuits and other legal proceedings are often brought against
companies for any of the risks described in this Annual Report on Form 10-K following a decline in the market price of their
securities. In connection with any litigation or other legal proceedings, we could incur substantial costs, and such costs and any related
settlements or judgments may not be covered by insurance. We could also suffer an adverse impact on our reputation and a diversion
of management’s attention and resources, which could have a material adverse effect on our business.
Because we do not anticipate paying any cash dividends on our capital in the foreseeable future, capital appreciation, if any, will
be our stockholders’ sole source of gain.
We have never declared or paid cash dividends on our capital stock. We currently intend to retain all of our future earnings, if any, to
finance the development and growth of our business. In addition, the terms of our current or future debt agreements may preclude us
from paying dividends. As a result, capital appreciation, 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 2.
Properties
Our corporate headquarters are located in Cambridge, Massachusetts. We currently lease approximately 65,167 square feet of office
and lab space in Cambridge, Massachusetts, and 27,300 square feet of office space in Boston, Massachusetts. Excluding renewal
options, the lease for the Cambridge, Massachusetts office space expires on September 11, 2026, the lease for the Cambridge,
Massachusetts lab space expires on November 30, 2021, and the lease for the Boston, Massachusetts office space expires on February
28, 2023. In September 2019, Keryx entered into an agreement to sublease the Boston office space to Foundation Medicine, Inc. We
believe that our existing facilities are adequate to meet our current needs, and that suitable additional alternative spaces will be
available in the future on commercially reasonable terms for our future growth.
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Item 3.
Legal Proceedings
Legal Proceedings Relating to Vadadustat
Opposition Proceedings Against Patents Covering Vadadustat
In July 2011, a third party filed an opposition to our issued European Patent No. 2044005, or the ’005 EP Patent, in the European
Patent Office, or the EPO. During the oral proceedings, which took place on April 10, 2013, the Opposition Division of the EPO
maintained the ’005 EP Patent. This decision resulted in the maintenance of a claim directed to a compound chosen from a group of
eight compounds, including vadadustat, as well as claims to compositions and methods for treating various diseases, including, but not
limited to, anemia. Both parties appealed the decision of the Opposition Division of the EPO. On February 27, 2018, we withdrew the
’005 EP Patent from appeal and filed a divisional patent application to pursue a focused claim set that includes claims for vadadustat,
as well as pharmaceutical compositions and methods of treating anemia.
In September 2018, Dr. Reddy’s Laboratories Limited filed an opposition to our issued Indian Patent No. 287720, or the ’720 IN
Patent, in the Indian Patent Office.
Opposition and Invalidity Proceedings Against FibroGen, Inc.
We filed an opposition in the EPO against FibroGen, Inc.’s, or 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 Opposition Division of
EPO ruled that the patent as granted did not meet the requirements for patentability under the European Patent Convention and,
therefore, revoked the patent in its entirety. FibroGen has appealed that decision. Likewise, we also filed an invalidity proceeding
before the Japan Patent Office, or JPO, on June 2, 2014 against certain claims of FibroGen’s Japanese Patent No. 4804131, or the ’131
JP Patent, which is the Japanese counterpart to the ’823 EP Patent, and the JPO issued a preliminary decision finding all of the
challenged claims to be invalid. FibroGen subsequently amended the claims and the JPO accepted the amendments. The resulting ’131
JP Patent does not cover vadadustat or any pyridine carboxamide compounds. To date, FibroGen has been unsuccessful in its attempts
to obtain a patent in the United States covering the same claim scope as it obtained initially in Europe and Japan in the ’823 EP Patent
and ’131 JP Patent. In the event FibroGen were to obtain such a patent in the United States, we may decide to challenge the patent as
we have done in Europe and Japan.
On May 13, 2015, May 20, 2015 and July 6, 2015, we filed oppositions to FibroGen’s European Patent Nos. 2322155, or the ’155 EP
Patent, 1633333, or the ’333 EP Patent, and 2322153, or the ’153 EP Patent in the EPO, respectively, requesting the patents be
revoked in their entirety. These related patents claim, among other things, various compounds that either stabilize HIFα or inhibit a
HIF hydroxylase or a HIF prolyl hydroxylase, or HIF-PH, for treating or preventing various conditions, including, among other things,
iron deficiency, microcytosis associated with iron deficiency, anemia of chronic disease, anemia wherein the subject has a transferrin
saturation of less than 20%, anemia refractory to treatment with exogenously administered erythropoietin and microcytosis in
microcytic anemia. Such method of use patents do not prevent persons from using the compound for other uses, including any
previously known use of the compound. In particular, these patents do not claim methods of using any of our product candidates for
purposes of inhibiting HIF-PH for the treatment of anemia due to chronic kidney disease, or CKD. While we do not believe these
patents will prevent us from commercializing vadadustat for the treatment of anemia due to CKD, we filed these oppositions to
provide us and our collaborators with maximum flexibility for developing vadadustat and our pipeline of HIF-PHI compounds.
Oppositions to the ’155 EP Patent and the ’153 EP Patent were also filed in the EPO by Glaxo Group Limited, or Glaxo, and by Bayer
Intellectual Property GmbH, Bayer Pharma Aktiengesellschaft, and Bayer Animal Health GmbH, or, collectively, Bayer.
With regard to the opposition that we filed in Europe against the ’333 EP Patent, an oral proceeding took place on December 8 and 9,
2016. Following the oral proceeding, the Opposition Division of the EPO ruled that the patent as granted did not meet the
requirements for patentability under the European Patent Convention and, therefore, revoked the patent in its entirety. On December 9,
2016, FibroGen filed a notice to appeal the decision to revoke the ’333 EP Patent.
In oral proceedings held on May 29, 2017, regarding the ’155 EP Patent, the European Opposition Division ruled that the ’155 EP
Patent as granted did not meet the requirements for patentability under the European Patent Convention and, therefore, revoked the
patent in its entirety. FibroGen filed a notice to appeal the decision to revoke the ’155 EP Patent on May 29, 2017.
Subsequently, in related oral proceedings held on May 31, 2017 and June 1, 2017 for the ’153 EP Patent, the Opposition Division of
the EPO maintained the patent after FibroGen significantly narrowed the claims to an indication for which vadadustat is not intended
to be developed. We and Glaxo separately filed notices to appeal the decision to maintain the ’153 EP Patent on November 9, 2017.
Bayer filed a notice to appeal the decision on November 14, 2017.
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On April 3, 2019, we filed oppositions to FibroGen’s European Patent Nos. 2289531, or the ’531 EP Patent, and 2298301, or the ’301
EP Patent in the EPO, respectively, requesting the patents be revoked in their entirety.
On May 21, 2018, we filed a Statement of Claim in Canadian Federal Court to challenge the validity of three of FibroGen’s HIF-
related patents in Canada: CA 2467689, CA 2468083, and CA 2526496.
On June 22, 2018, we and our collaboration partner in Japan, Mitsubishi Tanabe Pharma Corporation, or MTPC, jointly filed a
Request for Trial before the JPO to challenge the validity of one of FibroGen’s HIF-related patents in Japan, JP4845728. On July 20,
2018 and August 13, 2018, we and MTPC jointly filed a Request for Trial before the JPO to challenge the validity of two additional
FibroGen HIF-related patents in Japan, JP5474872 and JP5474741, respectively. On September 26, 2019, the JPO conducted an
invalidation trial for JP5474872 and JP4845728. On November 11, 2019, the JPO conducted an invalidation trial for JP5474741. On
February 10, 2020, the JPO issued a pre-notice of a trial decision for JP4845728, which invalidated all claims except two claims in
amended form, which we believe will not prevent our collaboration partner MTPC from launching vadadustat for the treatment of
anemia due to CKD in Japan.
On December 13, 2018, we and our collaboration partner, Otsuka Pharmaceutical Co. Ltd., or Otsuka, filed Particulars of Claim in the
Patents Court of the United Kingdom, or the UK, to challenge the validity of FibroGen’s six HIF-related patents in the UK: the ’823
EP Patent (UK), the ’333 EP Patent (UK), the ’153 EP Patent (UK), 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 Pharma
Inc., or Astellas, the exclusive licensee of FibroGen’s HIF-related patents, sued Akebia and Otsuka for patent infringement in the
Patents Court of the UK. In September 2019, we and Otsuka filed an Amended Particulars of Claim to include FibroGen’s European
Patent No. 1487472, or the ’472 EP Patent (UK). On February 28, 2020, the parties agreed to dismiss the ’472 EP Patent (UK) from
the trial. A trial is currently ongoing.
Legal Proceedings Relating to Auryxia
ANDA Litigation
On October 31, 2018, November 6, 2018, December 24, 2018 and February 4, 2019, Keryx received Paragraph IV certification notice
letters regarding Abbreviated New Drug Applications, or ANDAs, submitted to the U.S. Food and Drug Administration, or FDA, by
Lupin Atlantis Holdings SA, or Lupin, Teva Pharmaceuticals USA, Inc., or Teva, Chemo Research S.L., or Chemo, and Mylan
Pharmaceuticals Inc., or Mylan, respectively, requesting approval for generic versions of Auryxia tablets (210 mg iron per tablet). On
December 13, 2018, Keryx and its licensors, Panion & BF Biotech, Inc., or Panion, and Chen Hsing Hsu, M.D., filed a complaint for
patent infringement against Lupin and Lupin Ltd., or the Lupin Defendants, in the United States District Court for the District of
Delaware, or the Delaware District Court, arising from Lupin’s ANDA filing with the FDA. On December 19, 2018, Keryx and
Panion filed a complaint for patent infringement against Teva and Teva Pharmaceutical Industries Limited, or the Teva Defendants, in
the Delaware District Court arising from Teva’s ANDA filing with the FDA. On February 1, 2019, Keryx, Panion and Dr. Hsu filed a
complaint for patent infringement against Chemo and Insud Pharma S.A., or the Chemo Defendants, in the Delaware District Court
arising from Chemo’s ANDA filing with the FDA. On March 15, 2019, Keryx, Panion and Dr. Hsu filed a complaint for patent
infringement against Mylan in the United States District Court for the Northern District of West Virginia arising from Mylan’s ANDA
filing with the FDA. On April 18, 2019, Keryx, Panion and Dr. Hsu filed a motion with the Judicial Panel on Multidistrict Litigation
seeking to consolidate these four cases in the Delaware District Court for pretrial proceedings.
On March 29, 2019, April 2, 2019, and April 12, 2019, Keryx received Paragraph IV certification notice letters regarding ANDAs
submitted to the FDA by Lupin Ltd., Watson Laboratories, Inc., or Watson, a wholly-owned, indirect subsidiary of Teva, and Par
Pharmaceutical, Inc., or Par, an Endo International company, or Endo, respectively, requesting approval for generic versions of
Auryxia tablets (210 mg iron per tablet). On May 10, 2019, Keryx, Panion and Dr. Hsu filed a complaint for patent infringement
against Lupin Ltd. in the Delaware District Court arising from Lupin Ltd.’s ANDA filing with the FDA. On May 10, 2019, Keryx and
Panion filed a complaint for patent infringement against Watson and the Teva Defendants, or the Watson Defendants, in the Delaware
District Court arising from Watson’s ANDA filing with the FDA. On May 15, 2019, Keryx and Panion filed a complaint for patent
infringement against the Watson Defendants in the United States District Court for the District of Nevada, or the Nevada District
Court, from Watson’s ANDA filing with the FDA. On May 23, 2019, Keryx and Panion filed a complaint for patent infringement
against Par in the Delaware District Court arising from Par’s ANDA filing with the FDA. On May 24, 2019, Keryx and Panion filed a
complaint for patent infringement against Par, in the United States District Court for the Southern District of New York, or the
Southern New York District Court, arising from Par’s ANDA filing with the FDA. On June 4, 2019, Keryx and Panion filed a notice
of voluntary dismissal to dismiss the suit in the Nevada District Court in view of the Watson Defendants’ consent to venue of the
Delaware District Court. On June 26, 2019, Keryx, Panion and Dr. Hsu notified the Judicial Panel on Multidistrict Litigation of
additional actions in the Delaware District Court against the Lupin Defendants and the Watson Defendants. On July 31, 2019, the
Judicial Panel on Multidistrict Litigation issued an order to consolidate all of our ANDA cases in Delaware District Court for pretrial
proceedings. On August 26, 2019, Keryx filed an amended complaint against the Lupin Defendants in the Delaware District Court
arising from the Lupin Defendants’ ANDA filings with the FDA. On September 19, 2019, the Delaware District court set a trial date
for February 8, 2021.
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As a result of the timely filing of these lawsuits in accordance with the relevant statute, a 30-month stay of approval will be imposed
by the FDA on Lupin’s ANDA, Teva’s ANDA, Chemo’s ANDA, Mylan’s ANDA, Lupin Ltd.’s ANDA, Watson’s ANDA, and Par’s
ANDA, which stays are expected to remain in effect until April 2021, May 2021, June 2021, August 2021, September 2021, October
2021, and October 2021, respectively, absent an earlier judgment by the court in each of these lawsuits finding the patents at issue
invalid, unenforceable or not infringed. We and the other plaintiffs in each of these lawsuits are seeking, among other relief, an order
that the effective date of FDA approval of the ANDA be a date no earlier than the expiration of each of the patents at issue and
equitable relief enjoining the Lupin Defendants, the Teva Defendants, the Chemo Defendants, Mylan, and the Watson Defendants
from infringing these patents.
On July 22, 2019, Keryx received from Teva a supplemental Paragraph IV certification notice letter regarding its ANDA. On July 22,
2019, Keryx received from Watson a supplemental Paragraph IV certification notice letter regarding its ANDA. On July 31, 2019,
Keryx received from Lupin a supplemental Paragraph IV certification notice letter regarding its ANDA. On July 31, 2019, Keryx
received from Lupin Ltd. a supplemental Paragraph IV certification notice letter regarding its ANDA. On September 17, 2019, Keryx
received from Par a supplemental Paragraph IV certification notice letter regarding its ANDA. On October 16, 2019, Keryx received
from Mylan a supplemental Paragraph IV certification notice letter regarding its ANDA.
On August 2, 2019, Keryx and Panion entered into a settlement and license agreement with Par resolving patent litigation brought by
Keryx and Panion in response to Par’s ANDA seeking approval to market a generic version of Auryxia tablets prior to the expiration
of the applicable patents. Pursuant to the terms of the settlement, Keryx and Panion will grant Par a license to market a generic version
of Auryxia in the United States beginning on March 20, 2025 (subject to FDA approval), or earlier under certain circumstances
customary for settlement agreements of this nature. Additionally, in accordance with the agreement, the parties will terminate all
ongoing litigation between Keryx and Panion and Par regarding Auryxia patents pending in the Delaware District Court and the
Southern New York District Court. The settlement and license agreement is confidential and subject to review by the U.S. Federal
Trade Commission and the U.S. Department of Justice. On August 5, 2019, the parties filed a request to stay the litigation pending a
review of the settlement and license agreement by these regulatory authorities. On September 6, 2019 and September 9, 2019, the
Southern New York District Court and the Delaware District Court, respectively, entered a stipulation and order of dismissal filed by
the parties to dismiss the actions against Par.
CMS Litigation
On October 15, 2019, we filed a complaint in the United States District Court for the District of Massachusetts, or the Massachusetts
District Court, against Centers for Medicare & Medicaid Services, or CMS, the U.S. Department of Health and Human Services, Alex
M. Azar II in his official capacity as Secretary of Health and Human Services, and Seema Verma in her official capacity as
administrator for CMS challenging CMS’s decision that Auryxia would no longer be covered by Medicare for the treatment of iron
deficiency anemia, or IDA, in adult patients with CKD not on dialysis, or the IDA Indication, and CMS’s related decision that
imposed a prior authorization requirement for Auryxia in the treatment of adult patients with CKD on dialysis, or the
Hyperphosphatemia Indication. On October 29, 2019, we filed a motion for a preliminary injunction asking the court to provide relief
while the lawsuit is pending, specifically, to restore coverage for Auryxia when used for the IDA Indication, and to remove the prior
authorization requirement for Auryxia when used for the Hyperphosphatemia Indication. In the alternative, we filed a motion for
summary judgment with the court asking it to decide the case on the merits now in our favor. On February 4, 2020, the court denied
our request for a preliminary injunction. We filed an expedited appeal with the Court of Appeals for the First Circuit challenging the
district court’s denial of our motion for a preliminary injunction. The appeal is currently pending.
Shareholder Litigation Relating to Auryxia Supply
Four putative class action lawsuits were filed against Keryx Biopharmaceuticals, Inc., or Keryx, and certain of its former officers
(Gregory P. Madison, Scott A. Holmes, Ron Bentsur, and James Oliviero) and consolidated in the Massachusetts District Court,
captioned Karth v. Keryx Biopharmaceuticals, Inc., et al. (filed October 26, 2016, with an amended complaint filed on February 27,
2017). Plaintiff sought to represent all stockholders who purchased shares of Keryx common stock between May 8, 2013 and August
1, 2016. The complaint alleges that Keryx and the named individual defendants violated Sections 10(b) and/or 20(a) of the Securities
Exchange Act of 1934, as amended, or the Exchange Act, and Rule 10b-5 promulgated thereunder by making allegedly false and/or
misleading statements concerning Keryx, its supplier relationships, and future prospects, and that the allegedly misleading statements
were not made known to the market until Keryx’s August 1, 2016 announcement of an interruption in its supply of Auryxia. By order
dated July 19, 2018, the Massachusetts District Court granted in part and denied in part the defendants’ motion to dismiss the
complaint. On February 27, 2019, defendants filed a motion for judgment on the pleadings. On April 30, 2019, plaintiff filed a motion
to further amend his complaint, and also moved for class certification. The Massachusetts District Court heard oral argument on the
motions for judgment on the pleadings and class certification on June 19, 2019.
90
On September 23, 2019, the Massachusetts District Court issued a Memorandum and Order denying plaintiff’s motion for class
certification, granting defendants’ motion for judgment on the pleadings, and denying plaintiff’s motion for leave to further amend his
Complaint. That same day, the Massachusetts District Court entered a final judgment in favor of defendants on all claims. On
September 24, 2019, plaintiff filed a notice of appeal. Plaintiff tendered his appeal brief for filing on December 16, 2019 and tendered
a corrected version of such brief on December 30, 2019. The Court of Appeals for the First Circuit has not yet set a deadline for
Defendants’ appeal brief or set an oral argument date for the appeal.
Two stockholder derivative complaints also were filed on December 16, 2016 against Keryx and certain of its former officers
(Gregory P. Madison, Scott A. Holmes, Ron Bentsur and James Oliviero) certain of its former directors (Kevin J. Cameron, Daniel P.
Regan, Steven C. Gilman, Michael Rogers Michael P. Tarnok, Joseph Feczko, Jack Kaye Wyche Fowler, Jr. and John P. Butler), some
of whom are current directors and officers of ours, in the Superior Court of Massachusetts, one captioned Venkat Vara Prasad Malledi
v. Keryx Biopharmaceuticals, Inc., et al., and one captioned James Anderson v. Keryx Biopharmaceuticals, Inc., et al. Each of these
two complaints generally alleges breach of fiduciary duty, unjust enrichment, abuse of control, mismanagement and corporate waste.
On June 27, 2017, the Superior Court of Massachusetts granted the parties’ motion to consolidate and stay the derivative litigations,
and that stay remains in effect. All of the complaints seek unspecified damages, interest, attorneys’ fees, and other costs. It is expected
that such complaints would be dismissed if the above-mentioned ruling of the Massachusetts District Court entering judgment for the
defendants in the case brought under the securities laws stands; however, as discussed above, we are awaiting the outcome of the
appeal of that judgment.
We deny any allegations of wrongdoing and intend to continue vigorously defending against the shareholder lawsuits described in this
section. There is no assurance, however, that we will be successful in the defense of these lawsuits, or any associated appeals, or that
insurance will be available or adequate to fund any settlement or judgment or the litigation costs of these actions. Moreover, we are
unable to predict the outcome or reasonably estimate a range of possible losses at this time. A resolution of these lawsuits in a manner
adverse to us, however, could have a material effect on our financial position and results of operations in the period in which a
particular lawsuit is resolved.
Other Matters
On June 28, 2018, we entered into an Agreement and Plan of Merger with Keryx and Alpha Therapeutics Merger Sub, Inc., or the
Merger Sub, pursuant to which the Merger Sub would merge with and into Keryx, with Keryx becoming a wholly owned subsidiary of
ours, or the Merger. On December 12, 2018, we completed the Merger. In October and November 2018, four purported shareholders
of Keryx filed four separate putative class actions, or the Merger Securities Actions, against Keryx, a former officer and director of
Keryx (Jodie P. Morrison, who is now a director of ours), former directors of Keryx (Kevin J. Cameron, Mark J. Enyedy, Steven C.
Gilman, Michael T. Heffernan, Daniel P. Regan and Michael Rogers, some of whom are current members of our Board of Directors),
and, with respect to the Rosenblatt action discussed below, the Merger Sub and Akebia, challenging the disclosures made in
connection with the Merger.
Three of the Merger Securities Actions were filed in the Delaware District Court: Corwin v. Keryx Biopharmaceuticals, Inc., et al.
(filed October 16, 2018); Van Hulst v. Keryx Biopharmaceuticals, Inc., et al. (filed October 24, 2018); and Andreula v. Keryx
Biopharmaceuticals, Inc., et al. (filed November 1, 2018). The fourth Merger Securities Action was filed in the Massachusetts District
Court: Rosenblatt v. Keryx Biopharmaceuticals, Inc., et al. (filed October 23, 2018). On February 19, 2019, the plaintiff in the
Rosenblatt action filed a notice of voluntary dismissal of the action without prejudice. On March 27, 2019, the plaintiff in the Van
Hulst action filed a notice of voluntary dismissal of the action without prejudice.
On April 2, 2019, the Delaware District Court granted Abraham Kiswani, a member of the putative class in both the Andreula and
Corwin actions, and plaintiff John Andreula’s motion to consolidate the remaining two Merger Securities Actions pending in the
Delaware District Court and consolidated the Corwin and Andreula cases under the caption In re Keryx Biopharmaceuticals, Inc., or
the Consolidated Action. The Delaware District Court also appointed Kiswani and plaintiff Andreula as lead plaintiffs for the
Consolidated Action. On June 3, 2019, the lead plaintiffs filed a consolidated amended complaint in the Consolidated Action, or the
Consolidated Complaint. The Consolidated Complaint generally alleges that the registration statement filed in connection with the
Merger contained allegedly false and misleading statements or failed to disclose certain allegedly material information in violation of
Section 14(a) and 20(a) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and Rule 14a-9 promulgated
thereunder. The alleged misstatements or omissions relate to (i) certain financial projections for Keryx and Akebia and certain
financial analyses performed by our advisors and (ii) any alleged negotiations that may have taken place regarding the conversion of
certain convertible notes of Keryx in connection with the Merger. The Consolidated Complaint seeks compensatory and/or rescissory
damages, a declaration that the defendants violated Sections 14(a) and 20(a) of the Exchange Act and Rule 14a-9 thereunder, and an
award of lead plaintiffs’ costs, including reasonable allowance for attorneys’ fees and experts’ fees. The defendants in the
Consolidated Action moved to dismiss the Consolidated Complaint in its entirety on August 2, 2019. Briefing on the defendants’
motion to dismiss was completed on November 20, 2019, and a decision on the motion to dismiss has not yet been issued.
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On December 10, 2018, a stockholder of Keryx, Michael J. Donnelly, filed a complaint against Keryx pursuant to Section 220 of the
Delaware General Corporation Law in the Delaware Court of Chancery, captioned Donnelly v. Keryx Biopharmaceuticals, Inc., or the
Donnelly Action. The Donnelly Action sought inspection of various Keryx books and records, purportedly to investigate “possible
wrongdoing,” in connection with Keryx’s negotiation and approval of the Merger, as well as the independence of former members of
Keryx’s Board of Directors, some of whom are current members of our Board of Directors. In addition to the production of books and
records, the Donnelly Action sought costs and expenses incurred in the action, including reasonable attorneys’ fees. On January 31,
2019, Keryx answered the complaint in the Donnelly Action. The Delaware Court of Chancery entered a scheduling order to govern
the Donnelly Action on March 28, 2019. The trial for the Donnelly Action took place on July 10, 2019. On October 24, 2019, the
Delaware Chancery Court issued a written decision granting inspection, denying the plaintiff’s request for costs and expenses, and
directing the parties to confer on the proper scope of the inspection.
Item 4. Mine Safety Disclosures
Not applicable.
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PART II
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Market Information
Our common stock is traded on The Nasdaq Global Market under the symbol “AKBA”.
Holders
At March 1, 2020, there were approximately 30 holders of record of our common stock. The actual number of holders of our common
stock is greater than this number of record holders, and includes stockholders who are beneficial owners, but whose shares are held in
street name by brokers or held by other nominees. This number of holders of record also does not include stockholders whose shares
may be held in trust by other entities.
Dividends
We have never declared or paid any cash dividends on our common stock. We currently intend to retain earnings, if any, for use in our
business and do not anticipate paying cash dividends on our common stock in the foreseeable future. Payment of future dividends, if
any, on our common stock will be at the discretion of our board of directors after taking into account various factors, including our
financial condition, operating results, anticipated cash needs, and plans for expansion.
Issuer Purchases of Equity Securities
None.
Recent Sales of Unregistered Securities
None.
Purchases of Equity Securities by the Issuer and Affiliated Purchasers
None.
Comparative Stock Performance Graph
The following performance graph and related information shall not be deemed to be “soliciting material” or “filed” with the SEC or
subject to Regulation 14A or 14C, or to the liabilities of Section 18 of the Exchange Act, except to the extent that we specifically
request that this information be treated as soliciting material or we specifically incorporate it by reference into a filing under the
Securities Act of 1933, as amended, or the Exchange Act.
93
Set forth below is a graph comparing the total cumulative returns of Akebia Therapeutics, Inc., the Nasdaq Composite Index and the
Nasdaq Biotechnology Index. The graph assumes $100 was invested on December 31, 2014 in our common stock and each of the
indices and that all dividends, if any, are reinvested. The performance shown represents past performance and should not be
considered an indication of future performance.
Comparison of 60 Month Cumulative Total Return
Assumes Initial Investment of $100
December 2019
250.00
200.00
150.00
100.00
50.00
0.00
1
3
6
9
1
3
6
9
1
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9
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9
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3
1
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9
Akebia Therapeutics, Inc
NASDAQ Composite-Total Return
NASDAQ Biotechnology Index
Securities Authorized for Issuance under Equity Compensation Plans
Information about our equity compensation plans is incorporated herein by reference to Item 12, Security Ownership of Certain
Beneficial Owners and Management and Related Stockholder Matters, of this Annual Report on Form 10-K.
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Item 6.
Selected Financial Data
The selected consolidated financial data set forth below for the years ended December 31, 2019, 2018 and 2017 and as of December
31, 2019 and 2018 are derived from our audited consolidated financial statements, which are included elsewhere in this Annual Report
on Form 10-K. The selected consolidated financial data for the years ended December 31, 2016 and 2015 and as of December 31,
2017, 2016 and 2015 are derived from our audited consolidated financial statements that are not included elsewhere in this Annual
Report on Form 10-K. You should read these data together with “Management’s Discussion and Analysis of Financial Condition and
Results of Operations” and our consolidated financial statements and related notes included elsewhere in this Annual Report on Form
10-K under the captions “Financial Statements and Supplementary Data.” The selected financial data in this section are not intended to
replace our consolidated financial statements and related notes and are qualified in their entirety by the consolidated financial
statements and related notes included elsewhere in this Annual Report on Form 10-K. Our historical results for any prior period are
not necessarily indicative of results to be expected in any future period.
2019
Year Ended December 31,
2017
(in thousands, except share and per share data)
2016
2018
2015
Consolidated statements of operations data:
Revenues:
Product revenue, net
License, collaboration and other revenue
Total revenues
Cost of goods sold
Operating expenses
Loss from operations
Other income (expense), net
Benefit for income taxes
Net loss
Net loss per share applicable to common stockholders—
basic and diluted(1)
Weighted-average number of common shares used in
net loss per share applicable to common stockholders—
basic and diluted
$
111,119 $
223,882
335,001
6,824 $
200,918
207,742
— $
181,227
181,227
— $
1,535
1,535
—
—
—
145,336
475,953
(286,288)
(2)
(6,631)
7,768
378,135
(178,161)
6,235
(28,338)
(279,659) $ (143,588) $
—
257,901
(76,674)
3,003
—
—
137,995
(136,460)
713
—
(73,671) $ (135,747) $
—
61,513
(61,513)
797
—
(60,716)
(2.36) $
(2.47) $
(1.69) $
(3.60) $
(2.29)
$
$
118,395,919 58,038,252 43,500,795 37,716,949 26,469,170
(1)
See Note 2 of the notes to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for a
description of the method used to calculate basic and diluted net loss per share of common stock.
2019
2018
December 31,
2017
(in thousands)
2016
2015
Consolidated Balance Sheet Data:
Cash and cash equivalents and available for sale securities
Working capital
Total assets
Accumulated deficit
Total stockholders’ equity
$
147,694 $
101,415
771,201
(794,054)
394,757
321,640 $
202,582
996,540
(514,395)
635,928
317,792 $
217,250
364,257
(370,807)
122,574
260,343 $
182,053
300,216
(297,136)
68,120
138,454
129,149
142,940
(161,389)
130,998
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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
You should read the following discussion and analysis of our financial condition and results of operations together with our
consolidated financial statements and related notes appearing elsewhere in this Annual Report on Form 10-K. Some of the
information contained in this discussion and analysis, including information with respect to our plans and strategy for our business,
includes forward-looking statements that involve significant risks and uncertainties. As a result of many factors, including those
factors set forth in the “Risk Factors” section of this Annual Report on Form 10-K, our actual results could differ materially from the
results described in or implied by the forward-looking statements contained in the following discussion and analysis. Please also refer
to the section under the heading “Note Regarding Forward-Looking Statements.”
Operating Overview
We are a biopharmaceutical company focused on the development and commercialization of renal therapeutics for people living with
kidney disease. Our portfolio includes a late-stage product candidate and a commercial product:
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Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor, or HIF-PHI, in global Phase 3
development for two indications: (1) anemia due to chronic kidney disease, or CKD, in adult patients on dialysis, or DD-
CKD, and (2) anemia due to CKD in adult patients not on dialysis, or NDD-CKD. We believe vadadustat has the potential
to set a new oral standard of care for patients with anemia due to CKD, subject to regulatory approval. Vadadustat is
designed to mimic the physiologic effect of altitude on oxygen availability. At higher altitudes, the body responds to lower
oxygen availability with stabilization of hypoxia-inducible factor, or HIF, which can lead to red blood cell, or RBC,
production and improved oxygen delivery to tissues.
Auryxia® (ferric citrate) is approved and marketed in the United States for two indications: (1) the control of serum
phosphorus levels in adult patients with DD-CKD, or the Hyperphosphatemia Indication, and (2) the treatment of iron
deficiency anemia, or IDA, in adult patients with NDD-CKD, or the IDA Indication. Ferric citrate is also approved and
marketed in Japan as an oral treatment for the improvement of hyperphosphatemia in patients with CKD, including DD-
CKD and NDD-CKD, under the trade name Riona® (ferric citrate hydrate).
If the results of our global Phase 3 studies for vadadustat are positive, we plan to file for regulatory approval in the United States and
other regions. In connection with our plan to file for regulatory approval for vadadustat in the United States, we entered into a letter
agreement on February 14, 2020, or the Letter Agreement, with Vifor (International) Ltd., or Vifor Pharma, relating to Vifor Pharma’s
agreement with a third party to purchase a Priority Review Voucher, or the PRV, issued by the U.S. Food and Drug Administration, or
FDA, subject to satisfaction of customary closing conditions, or the PRV Purchase. A PRV entitles the holder to priority review of a
New Drug Application, or NDA, or a Biologics License Application for a new drug, which reduces the target FDA review time to six
months after official acceptance of the submission, and could lead to expedited approval. Pursuant to the Letter Agreement, we will
pay Vifor Pharma $10.0 million within fifteen business days after the closing of the PRV Purchase. Vifor Pharma is obligated to retain
all rights to, and maintain the validity of, the PRV until we and Vifor Pharma (a) enter into a definitive agreement setting forth the
financial and other terms by which Vifor Pharma will assign the PRV to us for use with our planned NDA for vadadustat for the
treatment of anemia due to CKD in both DD-CKD and NDD-CKD patients, or (b) make a mutual decision to sell the PRV and share
the proceeds based on certain terms.
We plan to commercialize vadadustat, subject to FDA approval, in the United States with our existing nephrology-focused
commercial organization, while also leveraging our collaboration with Otsuka Pharmaceutical Co. Ltd., or Otsuka, and its U.S.
commercial organization. We also granted Otsuka exclusive rights to commercialize vadadustat in Europe, China and certain other
markets, subject to marketing approvals. In Japan and certain other countries in Asia, we granted Mitsubishi Tanabe Pharma
Corporation, or MTPC, exclusive rights to commercialize vadadustat, subject to marketing approvals. In addition, we granted Vifor
Pharma an exclusive license to sell vadadustat solely to Fresenius Kidney Care Group LLC, or FKC, which manages approximately
40% of the dialysis patients in the United States, at its U.S. dialysis clinics, and to certain third party dialysis organizations in the
United States, approved by us, or Third Party Dialysis Organizations, which account for up to an additional 20% of the dialysis market
in the United States. The license granted to Vifor Pharma would be effective upon FDA approval of vadadustat in the DD-CKD
indication, the earlier of a determination by the Centers for Medicare & Medicaid Services, or CMS, that vadadustat will be included
in Medicare’s bundled reimbursement model or that vadadustat will be reimbursed using the Transitional Drug Add-On Payment
Adjustment, or TDAPA, and a milestone payment by Vifor Pharma.
We market Auryxia in the United States with our well-established, nephrology-focused commercial organization. Our Japanese
sublicensee, Japan Tobacco, Inc., or JT, and its subsidiary, Torii Pharmaceutical Co., Ltd., or Torii, commercialize Riona in Japan.
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Auryxia is our only product approved for sale in the United States and it generated approximately $111.1 million in revenue from U.S.
product sales during the year ended December 31, 2019. We have funded our operations primarily through equity offerings, strategic
collaborations and debt.
We have never been profitable and have incurred net losses in each year since inception. Our net losses were $279.7 million, $143.6
million and $73.7 million for the years ended December 31, 2019, 2018 and 2017, respectively. Substantially all of our net losses
resulted from costs incurred in connection with our development efforts relating to vadadustat, including preparing for and conducting
clinical studies of vadadustat, providing general and administrative support for these operations and protecting our intellectual
property.
We expect to continue to incur significant expenses and operating losses for the foreseeable future. The amount of our future net
losses will depend, in part, on the rate of our future expenditures, and our financial position will depend, in part, on our product
revenue from Auryxia and, if approved, vadadustat, and our ability to obtain additional funding. We expect to continue to incur
significant expenses if and as we:
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conduct our development program of vadadustat for the treatment of anemia due to CKD, including PRO2TECT and
INNO2VATE and other ongoing or planned studies with respect to vadadustat, and develop plans for and conduct the
preclinical and clinical development of any other potential product candidates;
continue our commercialization activities for Auryxia and plan for the commercialization of vadadustat, if approved, and
any other product or product candidate, including those that may be in-licensed or acquired;
continue our integration activities as a result of our merger, or the Merger, with Keryx Biopharmaceuticals, Inc., or Keryx;
seek marketing approvals for our product candidates that successfully complete clinical studies, and maintain marketing
approvals for Auryxia and any product candidate for which we obtain marketing approval, including complying with any
post-marketing regulatory requirements;
have our product candidates manufactured for clinical trials and for commercial sale;
initiate any post-marketing approval studies, Phase 4 studies or any other clinical trials for Auryxia or any other product,
including those that may be in-licensed or acquired;
seek to discover additional product candidates;
engage in transactions, including strategic, merger, collaboration, acquisition and licensing transactions, pursuant to which
we would market and develop commercial products, or develop and commercialize other product candidates and
technologies;
make royalty, milestone or other payments under our license agreements and any future license agreements;
maintain, protect and expand our intellectual property portfolio;
attract and retain skilled personnel;
continue to create additional infrastructure and expend additional resources to support our operations as a public company,
including any additional infrastructure and resources necessary to support the transition from our prior status as an
emerging growth company; and
experience any delays or encounter issues with any of the above.
We have one product approved for commercial sale but have not generated, and may not generate, enough product revenue from the
sale of Auryxia to realize net profits from product sales. We have no manufacturing facilities, and all of our manufacturing activities
are contracted out to third parties. Additionally, we currently utilize contract research organizations, or CROs, to carry out our clinical
development activities. If we obtain marketing approval for any of our product candidates, and as we continue to commercialize
Auryxia, we expect to incur significant commercialization expenses related to product sales, marketing, manufacturing and
distribution. If and until we can generate a sufficient amount of revenue from product sales, we expect to finance future cash needs
through public or private equity or debt transactions, payments from our collaborators, royalty transactions, strategic transactions, or a
combination of these approaches. If we are unable to raise additional capital in sufficient amounts when needed or on terms acceptable
to us, we may have to significantly delay, scale back or discontinue the development or commercialization of our product or one or
more of our product candidates. Any of these events could significantly harm our business, financial condition and prospects.
97
From inception through December 31, 2019, we raised approximately $494.6 million of net proceeds from the sale of equity including
$377.4 million from various underwritten public offerings, $67.2 million from at-the-market offerings, or ATM offerings, pursuant to
sales agreements with Cantor Fitzgerald & Co and $50.0 million from the sale of 3,571,429 shares of common stock to Vifor Pharma.
In addition, on November 11, 2019, we entered into a loan agreement, or the Loan Agreement, with funds managed by Pharmakon
Advisors LP, or Pharmakon, pursuant to which term loans in an aggregate principal amount of $100.0 million were made available to
us in two tranches, subject to certain terms and conditions, or the Term Loans. On November 25, 2019, we drew down the first tranche
of $80.0 million from the Term Loans and received net proceeds of $77.3 million. Subsequent to December 31, 2019 and through
February 4, 2020, we raised $56.7 million from ATM offerings. At inception of our collaboration agreements with Otsuka and MTPC,
our collaborators committed to an aggregate of approximately $573.0 million or more in cost-share funding, which we generally
continue to receive on a quarterly prepaid basis, and license payments. Of these commitments, we received approximately $272.0
million at the onset of the collaboration agreements.
Financial Overview
Revenue
To date, our revenues have been derived from collaboration revenues, which include license and milestone payments and cost-sharing
revenue, generated through collaboration and license agreements with partners for the development and commercialization of
vadadustat and, following the Merger, commercial sales of Auryxia and royalty revenue from sales of Riona in Japan. Cost-sharing
revenue represents amounts reimbursed by our collaboration partners for expenses incurred by us for research and development
activities and, potentially, co-promotion activities, under our collaboration agreements.
We expect our revenue to continue to be generated primarily from our collaborations with Otsuka and MTPC and any other
collaborations into which we may enter, as well as commercial sales of Auryxia in the United States, and royalty revenue from JT and
Torii.
Cost of Goods Sold
Cost of goods sold includes direct costs to manufacture commercial drug substance and drug product for Auryxia, as well as indirect
costs including costs for packaging, shipping, insurance and quality assurance, idle capacity charges, write-offs for inventory that fails
to meet specifications or is otherwise no longer suitable for commercial sale, and royalties due to the licensor of Auryxia related to the
U.S. product sales recognized during the period.
As a result of the Merger and the application of purchase accounting, costs of goods sold also includes amortization expense
associated with the fair value of the developed product rights for Auryxia, which is being amortized over nine years, as well as
expense associated with the fair value inventory step-up, which we expect to incur over approximately two and a half years from the
date of the Merger.
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for the development of our product candidates, which include:
(cid:129)
(cid:129)
(cid:129)
(cid:129)
(cid:129)
personnel-related expenses, including salaries, benefits, recruiting fees, travel and stock-based compensation expense of
our research and development personnel;
expenses incurred under agreements with CROs and investigative sites that conduct our clinical studies;
the cost of acquiring, developing and manufacturing clinical study materials through contract manufacturing
organizations, or CMOs;
facilities, depreciation and other expenses, which include direct and allocated expenses for rent and maintenance of
facilities, insurance and other supplies; and
costs associated with preclinical, clinical and regulatory activities.
Research and development costs are expensed as incurred. Costs for certain development activities are recognized based on an
evaluation of the progress to completion of specific tasks using information and data provided to us by our vendors and our clinical
sites.
98
We cannot determine with certainty the duration and completion costs of current or future clinical studies of our product candidates or
if, when, or to what extent we will generate revenue from the commercialization and sale of any of our product candidates that obtain
marketing approval. We may never succeed in achieving marketing approval for any of our product candidates.
The duration, costs and timing of clinical studies and development of our product candidates will depend on a variety of factors
including, but not limited to, those described in Part I, Item 1A. Risk Factors. A change in the outcome of any of these variables with
respect to the development of a product candidate could mean a significant change in the costs and timing associated with the
development of that product candidate. For example, if the FDA, the European Medicines Agency, or the EMA, or other regulatory
authorities were to require us to conduct clinical studies in addition to or different from those that we currently anticipate, or if we
experience delays in any of our clinical studies, we could be required to expend significant additional financial resources and time on
the completion of clinical development.
From inception through December 31, 2019, we have incurred $1,076.8 million in research and development expenses. We expect to
have significant research and development expenditures for the foreseeable future as we continue the development of vadadustat and
any other product candidates.
Our direct research and development expenses consist principally of external costs, such as fees paid to clinical trial sites, consultants,
central laboratories and CROs in connection with our clinical studies, and drug substance and drug product manufacturing for clinical
studies.
We currently have four clinical trials for our global Phase 3 clinical program for vadadustat to which the majority of our research and
development costs are attributable. A significant portion of our research and development costs have been external costs, which we
track on a program-by-program basis. These external costs include fees paid to investigators, consultants, central laboratories and
contract research organizations in connection with our clinical trials, and costs related to acquiring and manufacturing clinical trial
materials. Our internal research and development costs are primarily personnel-related costs, depreciation and other indirect costs. We
do not track our internal research and development expenses on a program-by-program basis as they are deployed across multiple
projects under development.
Prior to 2019, we did not track or record our external research and development expenses on a program-by-program basis. The
following table summarizes our external research and development expenses by program, as well as expenses not allocated to
programs, for the year ended December 31, 2019:
Vadadustat external costs
External costs for other programs
Total external research and development expenses
Headcount, consulting, facilities and other
Total research and development expenses
Year ended December 31,
2019
(in thousands)
253,259
20,311
273,570
49,399
322,969
$
$
Selling, General and Administrative Expenses
Selling, general and administrative expenses consist primarily of salaries and related costs for personnel, including stock-based
compensation and travel expenses for our commercial personnel, including our field sales force and other commercial support
personnel, as well as personnel in executive and other administrative or non-research and development functions. Other selling,
general and administrative expenses include facility-related costs, fees for directors, accounting and legal services fees, recruiting fees
and expenses associated with obtaining and maintaining patents.
99
Results of Operations
Comparison of the Years Ended December 31, 2019 and 2018
Revenues:
Product revenue, net
License, collaboration and other revenue
$
Total revenues
Cost of goods sold:
Product
Amortization of intangible assets
Total cost of goods sold
Operating expenses:
Research and development
Selling, general and administrative
License expense
Total operating expenses
Operating loss
Other income (expense), net
Net loss before income taxes
Benefit from income taxes
Net loss
$
Year ended December 31,
2019
2018
(In Thousands)
Increase
(Decrease)
111,119 $
223,882
335,001
108,935
36,401
145,336
322,969
149,455
3,529
475,953
(286,288)
(2)
(286,290)
(6,631)
(279,659) $
6,824 $
200,918
207,742
6,251
1,517
7,768
291,007
87,061
67
378,135
(178,161)
6,235
(171,926)
(28,338)
(143,588) $
104,295
22,964
127,259
102,684
34,884
137,568
31,962
62,394
3,462
97,818
108,127
(6,237)
114,364
(21,707)
136,071
Product Revenue, Net. Net product revenue is derived from sales of our sole commercial product, Auryxia. We distribute our product
principally through a limited number of wholesale distributors as well as certain specialty pharmacy providers. We began recording
product revenue on sales of Auryxia in the United States on December 12, 2018 following the consummation of the Merger. Net
product revenue was $111.1 million for the year ended December 31, 2019 and $6.8 million for the period from December 12, 2018
through December 31, 2018. This increase as compared to the period from December 12, 2018 through December 31, 2018 was due to
net product revenue associated with Auryxia, as there was no comparable net product revenue in the period from January 1, 2018
through December 11, 2018 prior to the Merger.
In September 2018, the Centers for Medicare & Medicaid Services, or CMS, decided that Auryxia would not be covered by Medicare
for the IDA Indication. While this decision does not impact CMS coverage of the Hyperphosphatemia Indication, it requires all
Auryxia prescriptions for Medicare patients to undergo a prior authorization to ensure their use in the Hyperphosphatemia Indication.
On October 15, 2019, we filed a complaint in the United States District Court for the District of Massachusetts against CMS and the
U.S. Department of Health and Human Services challenging CMS’s decision that Auryxia would no longer be covered by Medicare
for the IDA Indication and CMS’s related decision that imposed a prior authorization requirement for Auryxia in the
Hyperphosphatemia Indication. See Part I, Item 3. Legal Proceedings for further information. While we believe that the vast majority
of the Medicare prescriptions written for Auryxia today are for the Hyperphosphatemia Indication and therefore will continue to be
covered by Medicare with prior authorization, the prior authorization requirement and the CMS decision have had and will continue to
have an adverse impact on the sales of Auryxia for the Hyperphosphatemia Indication and the IDA Indication, and ultimately on the
timing and number of prescriptions and Auryxia product revenue. Sales of Auryxia for the Hyperphosphatemia Indication and the IDA
Indication have been negatively impacted, and may continue to be negatively affected, as a result of the CMS decision. Even if we are
successful in overturning the CMS decision, the negative impact that the original decision had on the growth of sales of Auryxia for
the Hyperphosphatemia Indication and the IDA Indication will continue, although less significantly than if the CMS decision is not
overturned.
100
License, collaboration and other revenue. License, collaboration and other revenue was $223.9 million for the year ended December
31, 2019, compared to $200.9 million for the year ended December 31, 2018. We recognized $216.9 million in collaboration revenue
for the year ended December 31, 2019 from our cost sharing arrangement under the Otsuka collaboration agreement for the U.S., or
the Otsuka U.S. Agreement, the Otsuka collaboration agreement for certain territories outside the U.S., or the Otsuka International
Agreement, as well as revenue recognized in connection with our collaboration agreement with MTPC, or the MTPC Agreement. We
recognized $200.5 million in collaboration revenue for the year ended December 31, 2018 from our cost sharing arrangement under
the Otsuka U.S. Agreement, the Otsuka International Agreement, as well as revenue recognized in connection with the MTPC
Agreement. The increase in revenue between the two periods was primarily attributable to an additional $15.7 million of revenue
recognized under both the Otsuka U.S. Agreement and Otsuka International Agreement and an additional $0.7 million of revenue
recognized in connection with the MTPC Agreement. The remaining variance is primarily due to an increase in license revenue
relating to our sublicense agreement with JT and Torii and includes license fees and royalties on net product sales of Riona in Japan.
We expect our collaboration revenue to decrease in the near term as our PRO2TECT and INNO2VATE studies near completion.
Cost of Goods Sold - Product. Cost of goods sold of $108.9 million for the year ended December 31, 2019 consists primarily of costs
associated with the manufacturing of Auryxia and a $70.4 million charge related to the fair-value inventory step-up from the
application of purchase accounting. Cost of goods sold of $6.3 million for the period from December 12, 2018 through December 31,
2018 consists primarily of costs associated with the manufacturing of Auryxia and a $4.8 million charge related to the fair-value
inventory step-up from the application of purchase accounting. This increase as compared to the period from December 12, 2018
through December 31, 2018 was due to costs associated with Auryxia, as there were no comparable costs in the period from January 1,
2018 through December 11, 2018 prior to the Merger.
Cost of Goods Sold - Amortization of Intangibles. Amortization of intangibles relates to the acquired developed product rights for
Auryxia. This intangible asset is being amortized over its estimated useful life of approximately nine years using a straight-line
method. Amortization of intangibles for the years ended December 31, 2019 and 2018 was $36.4 million and $1.5 million,
respectively.
Research and Development Expenses. Research and development expenses were $323.0 million for the year ended December 31,
2019, compared to $291.0 million for the year ended December 31, 2018. The net increase of $32.0 million was due to the following:
Vadadustat development expenses
Headcount, consulting and facilities
Other research and development
Total net increase
(in millions)
(5.3)
24.1
13.2
32.0
$
The decrease in the costs related to the development of vadadustat is primarily attributable to a decrease in external costs related
to other supporting clinical and preclinical activities, as well as regulatory activities, and a decrease in costs for the Japan Phase 2
studies, which were completed in 2018. There was also a decrease in external costs for the PRO2TECT and INNO2VATE Phase 3
program and a decrease in costs related to the manufacture of drug substance and drug product. The overall increase in research and
development expenses is primarily impacted by increases in headcount and consulting costs to support our research and development
programs. Although we expect our research and development expenses in 2020 to decrease as PRO2TECT and INNO2VATE near top
line data readout, we will continue to incur significant research and development expenses in future periods in support of our global
Phase 3 program and other studies for vadadustat and development of our other product candidates.
Selling, General and Administrative Expenses. Selling, general and administrative expenses were $149.5 million for the year ended
December 31, 2019, compared to $87.1 million for the year ended December 31, 2018. The increase of $62.4 million was primarily
due to commercialization costs associated with Auryxia as there were no comparable commercialization costs during the first eleven
months of 2018, and an increase in costs to support our research and development programs. In 2020, we expect our selling, general
and administrative expenses for our ongoing commercialization of Auryxia and our ongoing research and development and potential
commercialization of vadadustat and other product candidates to be relatively consistent with 2019.
License Expenses. License expense related to royalties due to Auryxia relating to sales of Riona in Japan were $3.5 million for the
year ended December 31, 2019, compared to $67,000 for the year ended December 31, 2018. The increase of $3.4 million was
primarily due to no license expense in the period from January 1, 2018 through December 11, 2018 prior to the Merger.
Other Expense, Net. Other expense, net, was $2,000 for the year ended December 31, 2019, compared to $6.2 million of other income,
net for the year ended December 31, 2018. The change to other expense, net was primarily due to interest expense associated with our
Line of Credit with Silicon Valley Bank, or SVB, in the first quarter of 2019 and interest expense associated to our Term Loans in the
fourth quarter of 2019 offset by interest income from investment balances during the year ended December 31, 2019. We did not have
similar expenses during the year ended December 31, 2018.
101
Benefit for Income Taxes. Benefit for income taxes was $6.6 million for the year ended December 31, 2019 due to a decrease in our
net deferred tax liabilities, or DTLs. During the year ended December 31, 2019, there was an increase in deferred tax assets associated
with the state net operating loss generated during the period. This increase in deferred tax assets reduced our net DTLs which created a
benefit from income taxes for the year ended December 31, 2019.
Comparison of the Years Ended December 31, 2018 and 2017
Revenues:
Product revenue, net
$
License, collaboration and other revenue
Total revenues
Cost of goods sold:
Product
Amortization of intangibles
Total cost of goods sold
Operating expenses:
Research and development
Selling, general and administrative
License expense
Total operating expenses
Operating loss
Other income, net
Net loss before income taxes
Benefit from income taxes
Net loss
$
Year ended December 31,
2018
2017
(In Thousands)
Increase
(Decrease)
6,824 $
200,918
207,742
— $
181,227
181,227
6,251
1,517
7,768
291,007
87,061
67
378,135
(178,161)
6,235
(171,926)
(28,338)
(143,588) $
—
—
—
230,893
27,008
—
257,901
(76,674)
3,003
(73,671)
—
(73,671) $
6,824
19,691
26,515
6,251
1,517
7,768
60,114
60,053
67
120,234
(101,487)
3,232
(98,255)
(28,338)
(69,917)
Revenue. Net product revenue is derived from sales of our sole commercial product, Auryxia. We began recording product revenue on
sales of Auryxia in the United States on December 12, 2018 following the consummation of the Merger. During the period from
December 12, 2018 through December 31, 2018 we recorded approximately $6.8 million of net product revenue.
License, collaboration and other revenue was $200.9 million for the year ended December 31, 2018, compared to $181.2 million for
the year ended December 31, 2017. We recognized $200.5 million in collaboration revenue for the year ended December 31, 2018
from our cost sharing arrangement under the Otsuka U.S. Agreement, the Otsuka International Agreement, as well as revenue
recognized in connection with the MTPC Agreement. We recognized $181.2 million in collaboration revenue for the year ended
December 31, 2017 from our cost sharing arrangement under the Otsuka U.S. Agreement, which commenced in December 2016, the
Otsuka International Agreement, which commenced in April 2017, and the MTPC Agreement, for which the revenue recognition
criteria, as required under ASC 606, began to be satisfied in the fourth quarter of 2017. The increase in revenue between the two
periods was primarily attributable to an additional $52.9 million of revenue recognized under both the Otsuka U.S. Agreement and
Otsuka International Agreement, partially offset by a decrease of $33.6 million of revenue recognized in connection with the MTPC
Agreement. The remaining variance was primarily due to an increase in license revenue relating to our sublicense agreement with JT
and Torii and included license fees and royalties on net product sales of Riona in Japan.
Cost of Goods Sold - Product. Cost of goods sold of $6.3 million during the period from December 12, 2018 through December 31,
2018 consisted primarily of costs associated with the manufacturing of Auryxia and a $4.8 million charge related to the fair-value
inventory step-up from the application of purchase accounting.
Cost of Goods Sold - Amortization of Intangibles. Amortization of intangibles related to the acquired developed product rights for
Auryxia. This intangible asset is being amortized over its estimated useful life of approximately 9 years using a straight-line method.
Amortization of intangibles for the year ended December 31, 2018 was $1.5 million.
102
Research and Development Expenses. Research and development expenses were $291.0 million for the year ended December 31,
2018, compared to $230.9 million for the year ended December 31, 2017. The increase of $60.1 million was due to the following:
PRO2TECT and INNO2VATE Phase 3 program
Manufacture of drug substance and drug product
Regulatory activities and other clinical and preclinical activities
FO2RWARD-2 and TRILO2GY-2 studies1
Japan Phase 2 studies
Total increase related to the continued development of vadadustat
Headcount, consulting and facilities
Other research
Janssen license fee
Fair value of warrants issued for Janssen license
Other
Total net increase
(in millions)
27.9
16.1
15.2
(2.9)
(9.6)
46.7
17.1
0.8
(1.0)
(3.4)
(0.1)
60.1
$
$
(1)
Includes costs from the FO2RWARD, FO2RWARD-2, TRIL2OGY, and TRILO2GY-2 studies.
The increase in the costs related to the development of vadadustat was primarily attributable to an increase in external costs related to
the continued advancement of the PRO2TECT and INNO2VATE Phase 3 program, including ongoing enrollment, manufacture of drug
substance and drug product in support of the global Phase 3 program, and regulatory activities as well as other clinical and preclinical
activities. This increase in costs related to the development of vadadustat was partially offset by a decrease in costs related to the
FO2RWARD, TRILO2GY, and Japan Phase 2 studies. The increase in research and development expenses were further impacted by
increases in headcount and consulting costs to support our expanding research and development programs.
Selling, General and Administrative Expenses. Selling, general and administrative expenses were $87.1 million for the year ended
December 31, 2018, compared to $27.0 million for the year ended December 31, 2017. The increase of $60.1 million was primarily
due to an increase in legal and other professional fees related to the Merger, including $13.4 million attributed to the fair value of the
4,000,000 Additional Shares issued to Baupost, and an increase in costs to support our research and development programs, including
headcount and compensation-related costs.
License Expenses. For the year ended December 31, 2018, we recognized approximately $67,000 in license expense related to
royalties from sales of Riona in Japan.
Other Income, Net. Other income, net, was $6.2 million for the year ended December 31, 2018, compared to $3.0 million for the year
ended December 31, 2017. Other income, net for the year ended December 31, 2018, was primarily comprised of interest income
caused by higher average interest rates on our investments during 2018.
Benefit for Income Taxes. Benefit for income taxes was $28.3 million for the year ended December 31, 2018 due to the release of a
portion of our valuation allowance as the DTLs recorded as part of purchase accounting will provide a source of income that allowed
us to conclude that certain of our deferred tax assets are realizable. The release of valuation allowance creates a tax benefit in the
consolidated statement of operations and comprehensive loss.
Liquidity and Capital Resources
We have incurred losses and cumulative negative cash flows from operations since our inception in February 2007, and as of
December 31, 2019, we had an accumulated deficit of $794.1 million. We anticipate that we will continue to incur losses for the
foreseeable future. We expect to continue to incur additional research and development and selling, general and administrative
expenses and, as a result, we will need additional capital to fund our operations, which we expect to raise through public or private
equity or debt transactions, payments from our collaborators, royalty transactions, strategic transactions, or a combination of these
approaches.
We have funded our operations principally through sales of our common stock, payments received from our collaboration partners, debt,
and following the Merger, product sales. As of December 31, 2019, we had cash and cash equivalents and available for sale securities
of approximately $147.7 million. Cash in excess of immediate requirements is invested in accordance with our investment policy,
primarily with a view to liquidity and capital preservation. Accordingly, available for sale securities, consisting principally of
corporate and government debt securities stated at fair value, are also available as a source of liquidity.
103
Cash Flows
The following table sets forth the primary sources and uses of cash for each of the periods set forth below:
Net cash provided by (used in):
Operating activities
Investing activities
Financing activities
Net increase/(decrease) in cash, cash equivalents and
restricted cash
2019
Year ended December 31,
2018
(In Thousands)
2017
$
(257,441) $
211,176
88,970
(97,494) $
36,594
96,562
(56,159)
(177,260)
116,240
$
42,705
$
35,662
$
(117,179)
Operating Activities. Net cash used in operating activities in all periods resulted primarily from our net losses adjusted for non-cash
charges and changes in the components of working capital. Net cash used in operating activities during the year ended December 31,
2019 of $257.4 million was largely driven by timing of payments on our Phase 3 development program for vadadustat, payments for
inventory and merger-related liabilities. These payments were partially offset by adjustments for non-cash items, including the fair
value write-up of inventory sold of $70.4 million, amortization of intangibles of $36.4 million, and stock-based compensation expense
of $11.9 million. Net cash used in operating activities during the year ended December 31, 2018 of $97.5 million was largely driven
by our Phase 3 development program for vadadustat, partially offset by receipt of cash from collaboration agreements. Net cash used
in operating activities during the year ended December 31, 2017 of $56.2 million was largely driven by our Phase 3 development
program for vadadustat, partially offset by receipt of cash from collaboration agreements, including a $73.0 million up-front payment
under the Otsuka International Agreement.
Investing Activities. During the year ended December 31, 2019, net cash provided by investing activities of $211.2 million was
comprised primarily of proceeds from the maturities of available for sale securities of $153.1 million and proceeds from the sales of
available for sale securities of $64.7 million, partially offset by purchases of equipment of $6.7 million. Net cash provided by
investing activities during the year ended December 31, 2018 of $36.6 million was comprised primarily from the sale and maturities of
available for sale securities, partially offset by purchases of available for sale securities, purchases of equipment and acquisition of the
business, net of cash acquired. Net cash used in investing activities during the year ended December 31, 2017 of $177.3 million was
comprised primarily from the purchases of available for sale securities of $330.6 million, partially offset by sale of and maturities of
available for sale securities and purchases of equipment.
Financing Activities. During the years ended December 31, 2019, 2018 and 2017 our net cash provided by financing activities was
$89.0 million, $96.6 million and $116.2 million, respectively. Net cash provided by financing activities for the years ended
December 31, 2019, 2018 and 2017 consisted primarily of net proceeds from the issuance of debt, net proceeds from the public
issuance of common stock, proceeds from the exercise of stock options and proceeds from the sale of stock under our employee stock
purchase plan, partially offset by payments on loans payable.
Operating Capital Requirements
We have one product, Auryxia, approved for commercial sale, but have not generated, and may not generate, enough product revenue
from the sale of Auryxia to realize net profits from product sales. We anticipate that we will continue to generate losses for the
foreseeable future, and we expect the losses to increase as we continue the development of, and seek marketing approvals for, our
product candidates. We are subject to all risks incident to the development and commercialization of novel therapeutics, and we may
encounter unforeseen expenses, difficulties, complications, delays and other unknown factors that may adversely affect our business.
We expect to continue to incur additional costs associated with operating as a public company and we anticipate that we will need
substantial additional funding in connection with our continuing operations.
We ended 2019 with cash, cash equivalents and available for sale securities of $147.7 million. At the inception of our collaboration
agreements with Otsuka and MTPC, our collaborators committed to an aggregate of approximately $573.0 million or more in cost-
share funding, of which we received approximately $272.0 million at the onset of the collaborations, and the remainder of which we
generally continue to receive on a quarterly prepaid basis, and through license payments. We expect our cash resources and the receipt
of a $15.0 million regulatory milestone from MTPC, assuming approval of vadadustat in Japan, to fund our current operating plan
well into 2021.
104
We will require additional capital for the development and potential commercialization of our existing product candidates, further
commercialization of Auryxia and would need to raise additional funds to pursue development activities related to additional product
candidates. If and until we can generate a sufficient amount of product revenue, we expect to finance future cash needs through public
or private equity or debt transactions, payments from our collaborators, royalty transactions, strategic transactions, or a combination of
these approaches. We have based these estimates on assumptions that may prove to be wrong, and we could use our available capital
resources sooner than we currently expect. Furthermore, our development and regulatory milestones may not be achieved, we may not
receive the anticipated funding from our collaboration partners, and we may not secure other sources of financing. Additional funds
may not be available to us on acceptable terms or at all. If we are unable to raise additional capital in sufficient amounts or on terms
acceptable to us, we may have to significantly delay, scale back or discontinue the commercialization of our product or the
development or commercialization of one or more of our product candidates. If we raise additional funds through the issuance of
additional debt or equity securities, it could result in dilution to our existing stockholders or increased fixed payment obligations, and
any such securities may have rights senior to those of our common stock. Any of these events could significantly harm our business,
financial condition and prospects.
Our forecast of the period of time through which our financial resources will be adequate to support our operations is a forward-
looking statement and involves risks and uncertainties, and actual results could vary as a result of a number of factors. We have based
this estimate on assumptions that may be substantially different than actual results, and we could utilize 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.
If we cannot expand our operations or otherwise capitalize on our business opportunities because we lack sufficient capital, our
business, financial condition and results of operations could be materially adversely affected.
Contractual Obligations and Commitments
At December 31, 2019, our future contractual obligations are as follows:
Payments due by period
(in thousands)
Less than 1
year
Total
1-3 years
3-5 years
More than 5
years
Operating Lease Obligations
Manufacturing Agreements
Debt Obligations
Total
$
$
39,648 $
196,092 $
110,208
345,948 $
6,568 $
44,351 $
7,727
58,646 $
13,799 $
83,008 $
20,608
117,415 $
10,463 $
35,733 $
81,873
128,069 $
8,818
33,000
—
41,818
Leases
We lease approximately 65,167 square feet of office and lab space in Cambridge, Massachusetts under a lease which was most
recently amended in April 2018, collectively the Cambridge Lease. Under the Third Amendment to the Cambridge Lease, or the Third
Amendment, executed in July 2016, total monthly lease payments under the initial base rent were approximately $242,000 and are
subject to annual rent escalations. In addition to such annual rent escalations, base rent payments for a portion of said premises
commenced on January 1, 2017 in the monthly amount of approximately $22,000. The Fourth Amendment to the Cambridge Lease,
executed in May 2017, provided additional storage space to us and did not impact rent payments. In April 2018, we entered into a
Fifth Amendment to the Cambridge Lease, or the Fifth Amendment, for an additional 19,805 square feet of office space on the 12th
floor. Monthly lease payments for the existing 45,362 square feet of office and lab space, under the Third Amendment, remain
unchanged. The new space leased by us was delivered in September 2018 and additional monthly lease payments of approximately
$135,000 commenced in February 2019 and are subject to annual rent escalations, which commenced in September 2019.
Additionally, as a result of the Merger, we have a lease for 27,300 square feet of office space in Boston, Massachusetts, or the Boston
Lease, which expires on February 27, 2023. The total monthly lease payments under the base rent are approximately $136,000 and are
subject to annual rent escalations.
In September 2019, Keryx entered into an agreement to sublease the Boston office space to Foundation Medicine, Inc., or Foundation.
The sublease is subject and subordinate to the Boston Lease between Keryx and the landlord. The term of the sublease commenced on
October 16, 2019, upon receipt of the required consent from the landlord for the sublease agreement, and expires on February 27,
2023. Foundation is obligated to pay Keryx rent that approximates the rent due from us to Keryx’s landlord with respect to the Boston
Lease. Keryx continues to be obligated for all payment terms pursuant to the Boston Lease, and we will guaranty Keryx’s obligations
under the sublease.
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Term Loans
On November 11, 2019, Akebia, with Keryx as guarantor, entered into a loan agreement, or the 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,
collectively with the Collateral Agent, Pharmakon, pursuant to which term loans in an aggregate principal amount of $100.0 million
were made available to us in two tranches, subject to certain terms and conditions, or the Term Loans. The first tranche of $80.0
million, or Tranche A, was drawn on November 25, 2019, or the Tranche A Funding Date. The second tranche, available until
December 31, 2020, allows us to borrow, at our option, an additional $20.0 million, or Tranche B, subject to the satisfaction of
customary conditions. The date on which Tranche B is drawn, the Tranche B Funding Date, and each of the Tranche A Funding Date
and the Tranche B Funding Date, a Funding Date.
Proceeds from the Term Loans may be used for general corporate purposes. We and Keryx entered into a Guaranty and Security
Agreement with the Collateral Agent, or the Guaranty and Security Agreement, on the Tranche A Funding Date. Pursuant to the
Guaranty and Security Agreement, our obligations under the Term Loans are unconditionally guaranteed by Keryx, or the Guarantee.
Additionally, our and Keryx’s obligations under the Term Loans and the Guarantee are secured by a first priority lien on certain assets
of ours and Keryx’s, including Auryxia and certain related assets, cash, and certain equity interests held by us and Keryx, collectively
the Collateral.
The Term Loans bear interest at a floating rate per annum equal to the three-month LIBOR rate plus 7.50%, subject to a 2.00%
LIBOR floor and a 3.35% LIBOR cap, payable quarterly in arrears. The Term Loans will mature on the fifth anniversary of the
Tranche A Funding Date, or the Maturity Date. We will repay the principal under the Term Loans in equal quarterly payments starting
on the 33rd-month anniversary of the applicable Funding Date or, if certain conditions are met, it will have the option to repay the
principal in equal quarterly payments starting on the 48th-month anniversary of the applicable Funding Date, or collectively the
Amortization Schedule. Under certain circumstances, unless certain liquidity conditions are met, the Maturity Date may decrease by
up to one year, and the Amortization Schedule may correspondingly commence up to one year earlier.
On the Tranche A Funding Date, we paid to Pharmakon a facility fee equal to 2.00% of the aggregate principal amount of the Term
Loans, or $2.0 million, in addition to other expenses incurred by Pharmakon and reimbursed by us, or Lender Expenses. The Tranche
A draw was $77.3 million, net of facility fee, Lender Expenses and issuance costs. The Loan Agreement permits voluntary
prepayment at any time in whole or in part, subject to a prepayment premium. The prepayment premium would be 2.00% of the
principal amount being prepaid prior to the third anniversary of the applicable Funding Date, 1.00% on or after the third anniversary,
but prior to the fourth anniversary, of the applicable Funding Date, and 0.50% on or after the fourth anniversary of the applicable
Funding Date but prior to the Maturity Date, and a make-whole premium on or prior to the second anniversary of the applicable
Funding Date in an amount equal to foregone interest through the second anniversary of the applicable Funding Date. A change of
control triggers a mandatory prepayment of the Term Loans.
The Loan Agreement contains customary representations, warranties, events of default and covenants of ours and our subsidiaries,
including maintaining, on an annual basis, a minimum liquidity threshold starting in 2021, and on a quarterly basis, a minimum net
sales threshold for Auryxia starting in the fourth quarter of 2020. If an event of default occurs and is continuing under the Loan
Agreement, the Collateral Agent is entitled to take enforcement action, including acceleration of amounts due under the Loan
Agreement. Under certain circumstances, a default interest rate will apply on all outstanding obligations during the occurrence and
continuance of an event of default. As of December 31, 2019, we determined that no events of default had occurred.
We assessed the terms and features of the Loan Agreement in order to identify any potential embedded features that would require
bifurcation or any beneficial conversion feature. As part of this analysis, we assessed the economic characteristics and risks of the
Loan Agreement, including put and call features. The terms and features assessed include a potential extension to the interest-only
period dependent on both no event of default having occurred and continuing and on us achieving certain regulatory and revenue
conditions. We also assessed the acceleration of the obligations under the Loan Agreement under an event of default. In addition,
under certain circumstances, a default interest rate will apply on all outstanding obligations during the occurrence and continuance of
an event of default. In accordance with ASC 815, we concluded that these features are not clearly and closely related to the host
instrument, and represent a single compound derivative that is required to be re-measured at fair value on a quarterly basis.
The foregoing description of the Loan Agreement does not purport to be complete and is qualified in its entirety by reference to the
Loan Agreement, a copy of which is filed as an exhibit to this Annual Report on Form 10-K for the year ending December 31, 2019.
Manufacturing Agreements
As a result of the Merger, our contractual obligations include Keryx’s commercial supply agreements with BioVectra Inc., or
BioVectra, and Siegfried Evionnaz SA, or Siegfried, to supply commercial drug substance for Auryxia.
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Pursuant to the Manufacture and Supply Agreement with BioVectra and the Product Manufacture and Supply and Facility
Construction Agreement with BioVectra, collectively the BioVectra Agreement, we have agreed to purchase a minimum quantity of
drug substance of Auryxia at predetermined prices. The price per kilogram will decrease with an increase in quantity above the
minimum purchase quantity. In addition, the BioVectra Agreement contained contingent milestone payments for capital developments
in connection with construction of an expansion of the site of the BioVectra production facility for the manufacture of drug substance
for Auryxia. These milestone payments were achieved by BioVectra and paid and fully recorded prior to the Merger. The term of the
BioVectra Agreement expires in late 2026, after which, it automatically renews for specified terms until terminated. We have the right
to terminate the BioVectra Agreement prior to the contract term, which could result in an early termination fee. As of December 31,
2019, we are required to purchase a minimum quantity of drug substance for Auryxia annually at a total cost of approximately $135.3
million through the year ended December 31, 2026.
As part of purchase accounting, we identified an executory contract in the supply agreement between Keryx and BioVectra, which
includes future firm purchase commitments. This executory contract was deemed to have an off-market element related to the amount
of purchase commitments that exceed the current forecast. As a result, we recorded a liability of $29.5 million in purchase accounting
as of the acquisition date for the preliminary fair value of the off-market element. Through December 31, 2019, we recorded $0.7
million in accretion expense related to the present value discount associated with this liability.
Pursuant to the Siegfried Master Manufacturing Services and Supply Agreement, or the Siegfried Agreement, we have agreed to
purchase a minimum quantity of drug substance of Auryxia at predetermined prices. The price per kilogram will decrease with an
increase in quantity above the minimum purchase quantity. The term of the Siegfried Agreement expires on December 31, 2021, after
which, it automatically renews for one-year terms until terminated. The Siegfried Agreement provides us with certain termination
rights prior to December 31, 2021. As of December 31, 2019, we are required to purchase a minimum quantity of drug substance for
Auryxia annually at a total cost of approximately $60.8 million through the year ended December 31, 2021.
On April 9, 2019, we entered into a Supply Agreement with Esteve Química, S.A., or Esteve, or the Esteve Agreement. The Esteve
Agreement includes the terms and conditions under which Esteve will manufacture vadadustat drug substance, or API, for commercial
use.
Pursuant to the Esteve Agreement, we shall provide rolling forecasts to Esteve on a quarterly basis, or the Forecast. The Forecast shall
reflect our needs for API produced by Esteve over a certain number of months, represented as a quantity of API per calendar quarter.
The parties have agreed to a volume-based pricing structure under the Esteve Agreement. The Esteve Agreement has an initial term of
four years, beginning April 9, 2019 and ending April 9, 2023. Subsequent to December 31, 2019, we have a minimum commitment
with Esteve for $5.8 million through the first quarter of 2021.
Other Third Party Contracts
Under our agreement with IQVIA to provide contract research organization services for the PRO2TECT and INNO2VATE programs,
the total remaining contract costs as of December 31, 2019 were approximately $34.9 million, of which Otsuka reimburses a
significant portion back to us. The estimated period of performance for the committed work with IQVIA is through the end of 2020.
We also contract with various other organizations to conduct research and development activities with remaining contract costs to us
of approximately $61.4 million as of December 31, 2019. The scope of the services under these research and development contracts
can be modified and the contracts cancelled by us upon written notice, and therefore not included in the table of contractual
obligations and commitments. In some instances, the contracts may be cancelled by the third party upon written notice.
Off-Balance Sheet Arrangements
As of December 31, 2019, we did not have any off-balance sheet arrangements as defined in the rules and regulations of the SEC.
Critical Accounting Policies and Significant Judgments and Estimates
Our management’s discussion and analysis of our financial condition and results of operations are based on our consolidated financial
statements, which have been prepared in accordance with U.S. generally accepted accounting principles. The preparation of these
consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities,
and expenses and the disclosure of contingent assets and liabilities in our consolidated financial statements. On an ongoing basis, we
evaluate our estimates and judgments, including those related to revenue, prepaid and accrued research and development expenses and
stock-based compensation. We base our estimates on historical experience, known trends and events, and various other factors that are
believed to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values
of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different
assumptions or conditions. In making estimates and judgments, management employs critical accounting policies.
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While our significant accounting policies are described in more detail in the notes to our consolidated financial statements appearing
elsewhere in this Annual Report on Form 10-K, we believe the following accounting policies to be most critical to the judgments and
estimates used in the preparation of our consolidated financial statements.
Derivative Financial Instruments
We account for warrants and other derivative financial instruments as either equity or liabilities in accordance with ASC Topic 815,
Derivatives and Hedging, or ASC 815, based upon the characteristics and provisions of each instrument. Warrants classified as equity
are recorded at fair value as of the date of issuance on our consolidated balance sheets and no further adjustments to their valuation are
made. Warrants classified as derivative liabilities and other derivative financial instruments that require separate accounting as
liabilities are recorded on our consolidated balance sheets at their fair value on the date of issuance and will be revalued on each
subsequent balance sheet date until such instruments are exercised or expire, with any changes in the fair value between reporting
periods recorded as other income or expense. The warrant issued by us in connection with the Janssen Pharmaceutica NV Research
and License Agreement, the Janssen Agreement, is classified as equity in our consolidated balance sheet. (See Note 12 to our
consolidated financial statements in Part 2, Item 8. Financial Statements and Supplementary Data). The derivative liability recorded in
connection with the Loan Agreement with Pharmakon is classified as a liability in our consolidated balance sheet. (See Note 11 to our
consolidated financial statements in Part 2, Item 8. Financial Statements and Supplementary Data).
Inventory
We value our inventories at the lower-of-cost or net realizable value. We determine the cost of our inventories, which includes
amounts related to materials and manufacturing overhead, on a first-in, first-out basis. We classify inventory costs as long-term, in
other assets in our consolidated balance sheets, when we expect to utilize the inventory beyond our normal operating cycle.
Prior to the regulatory approval of our product candidates, we incur expenses for the manufacture of material that could potentially be
available to support the commercial launch of our products. Until the first reporting period when regulatory approval has been
received or is otherwise considered probable and the future economic benefit is expected to be realized, we record all such costs as
research and development expense. Inventory used in clinical trials is also expensed as research and development expense, when
selected for such use. Inventory that can be used in either the production of clinical or commercial products is expensed as research
and development costs when identified for use in a clinical manufacturing campaign.
We perform an assessment of the recoverability of capitalized inventory during each reporting period, and write down any excess and
obsolete inventory to our net realizable value in the period in which the impairment is first identified. Such impairment charges,
should they occur, are recorded as a component of cost of product sales in the consolidated statements of operations and
comprehensive loss. The determination of whether inventory costs will be realizable requires the use of estimates by management. If
actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required.
Additionally, our product is subject to strict quality control and monitoring that we perform throughout the manufacturing process. In
the event that certain batches or units of product no longer meet quality specifications, we will record a charge to cost of product sales
to write-down any unmarketable inventory to its estimated net realizable value. In all cases, product inventory is carried at the lower
of cost or its estimated net realizable value.
Debt
We perform an assessment of all embedded features of a debt instrument to determine if (1) such features should be bifurcated and
separately accounted for, and (2) if bifurcation requirements are met, whether such features should be classified and accounted for as
equity or liability instruments. If the embedded feature meets the requirements to be bifurcated and accounted for as a liability, the fair
value of the embedded feature is measured initially, included as a liability on the consolidated balance sheet, and re-measured to fair
value at each reporting period. Any changes in fair value are recorded in the consolidated statement of operations. We monitor, on an
ongoing basis, whether events or circumstances could give rise to a change in the classification of embedded features.
Revenue
We generate revenues primarily from sales of Auryxia, see Note 3 to our consolidated financial statements in Part II, Item 8. Financial
Statements and Supplementary Data, and from our collaborations with MTPC and Otsuka, see Note 4 to our consolidated financial
statements in Part II, Item 8. Financial Statements and Supplementary Data. We recognize revenue in accordance with ASC 606,
which applies to all contracts with customers, except for contracts that are within the scope of other standards. Under ASC 606, we
recognize revenue when our customer obtains control of promised goods or services, in an amount that reflects the consideration
which the entity expects to receive in exchange for those goods or services. To determine revenue recognition for arrangements that
we determine are within the scope of ASC 606, we perform the following five steps:
(i)
identify the contract(s) with a customer;
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(ii)
identify the performance obligations in the contract;
(iii) determine the transaction price;
(iv)
allocate the transaction price to the performance obligations in the contract; and
(v)
recognize revenue when (or as) the entity satisfies a performance obligation.
We only apply the five-step model to contracts when it is probable that the entity will collect the consideration we are entitled to in
exchange for the goods or services we transfer to the customer. At contract inception, once the contract is determined to be within the
scope of ASC 606, we assess the goods or services promised within each contract and determine those that are performance
obligations, and assess whether each promised good or service is distinct. We then recognize as revenue the amount of the transaction
price that is allocated to the respective performance obligation when (or as) the performance obligation is satisfied.
Product Revenue, Net
We sell Auryxia in the United States, primarily to wholesale distributors as well as certain specialty pharmacy providers, collectively
the Customers. These Customers resell our product to health care providers and patients. In addition to distribution agreements with
Customers, we enter into arrangements with health care providers and payors that provide for government-mandated and/or privately-
negotiated rebates, chargebacks, and discounts with respect to the purchase of our product.
We recognize revenue on product sales when the Customer obtains control of our product, which occurs at a point in time, typically
upon delivery to the Customer. We expense incremental costs of obtaining a contract as and when incurred if the expected
amortization period of the asset that we would have recognized is one year or less.
Reserves for Variable Consideration
Revenue from product sales is recorded at the net sales price (transaction price), which includes estimates of variable consideration for
which reserves are established and which result from discounts, returns, chargebacks, rebates, co-pay assistance and other allowances
that are offered within contracts between us and our Customers, health care providers, payors and other indirect customers relating to
our sales of our products. These reserves are based on the amounts earned or to be claimed on the related sales and are classified as
reductions of accounts receivable (if the amount will be credited to the Customer) or a current liability (if the amount is payable to a
Customer or a party other than a Customer). When appropriate, these estimates take into consideration a range of possible outcomes
which are probability-weighted in accordance with the expected value method in ASC 606 for relevant factors such as our historical
experience, current contractual and statutory requirements, specific known market events and trends, industry data, and forecasted
customer buying and payment patterns. Overall, these reserves reflect our best estimates of the amount of consideration to which we
are entitled based on the terms of the respective underlying contracts.
The amount of variable consideration that is included in the transaction 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 cumulative revenue recognized will not occur in a
future period. Actual amounts of consideration ultimately received may differ from our estimates. If actual results in the future vary
from our estimates, we will adjust these estimates, which would affect net product revenue and earnings in the period such variances
become known.
Trade Discounts and Allowances: We generally provide Customers with discounts that include incentive fees that are explicitly stated
in our contracts and are recorded as a reduction of revenue in the period the related product revenue is recognized. In addition, we
compensate (through trade discounts and allowances) our Customers for sales order management, data, and distribution services.
However, we have determined such services received to date are not distinct from our sale of products to the Customer and, therefore,
these payments have been recorded as a reduction of revenue within the statement of operations and comprehensive loss
through December 31, 2019. We record a corresponding reduction to accounts receivable (if the trade discount and/or allowance will
be credited to the Customer) or an increase to accrued expense (if the trade discount and/or allowance is payable to a Customer) on the
consolidated balance sheets.
Product Returns: Consistent with industry practice, we generally offer Customers a limited right of return which allows for product
return when the product expiry is within an allowable window. This right of return lapses once provided to a patient. We estimate the
amount of our product sales that may be returned by our Customers and record this estimate as a reduction of revenue in the period the
related product revenue is recognized. We currently estimate product return reserve using available industry data and our own
historical sales information, including our visibility into the inventory remaining in the distribution channel.
Provider Chargebacks and Discounts: Chargebacks for fees and discounts to providers represent the estimated obligations resulting
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 ultimate selling price to the qualified healthcare providers. These reserves are established in the same period that the related
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revenue is recognized, resulting in a reduction of product revenue and accounts receivable. Chargeback amounts are generally
determined at the time of resale to the qualified healthcare provider by Customers, and we generally issue credits for such amounts
within a few weeks of the Customer’s resale of the product. Reserves for chargebacks consist of credits that we expect to issue for
units that remain in the distribution channel at each reporting 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 organizations, primarily health insurance
companies and pharmacy benefit managers, for the payment of rebates with respect to utilization of our products. We estimate the
rebates for commercial and Medicare Part D payors based upon (i) our contracts with the payors and (ii) information obtained from
our Customers and other third parties regarding the payor mix for Auryxia. We estimate these rebates and record such estimates in the
same period the related revenue is recognized, resulting in a reduction of product revenue and the establishment of a current liability.
Other Government Rebates: We are subject to discount obligations under state Medicaid programs and other government
programs. We estimate Medicaid and other government programs rebates based upon a range of possible outcomes that are
probability-weighted for the estimated payor mix. These reserves are recorded in the same period the related revenue is recognized,
resulting in a reduction of product revenue and the establishment of a current liability which is included in accrued expenses and other
current liabilities on the consolidated balance sheets. For Medicare, we also estimate the number of patients in the prescription drug
coverage gap for whom we will owe an additional 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, estimates
of claims for the current quarter, and estimated future claims that will be made for product that has been recognized as revenue, but
which remains in the distribution channel at the end of each reporting period.
Other Incentives: Other incentives that we offer include voluntary patient assistance programs such as our co-pay assistance program,
which are intended to provide financial assistance to qualified commercially insured patients with prescription drug co-payments
required by payors. The calculation of the accrual for co-pay assistance is based on actual claims processed during a given period, as
well as historical utilization data to estimate the amount we expect to receive associated with product that has been recognized as
revenue, but remains in in the distribution channel at the end of each reporting period.
Collaboration Revenues
We enter into out-license and collaboration agreements which are within the scope of ASC 606, under which we license certain rights
to our product candidates to third parties. The terms of these arrangements typically include payment to us of one or more of the
following: non-refundable, up-front license fees; development, regulatory, and commercial milestone payments; payments for
manufacturing supply services we provide through our contract manufacturers; and royalties on net sales of licensed products. Each of
these payments may result in license, collaboration and other revenue, except for revenues from royalties on net sales of licensed
products, which are classified as royalty revenues.
In determining the appropriate amount of revenue to be recognized as we fulfill our obligations under each of our agreements, we
implement the five-step model noted above. As part of the accounting for these arrangements, we must develop assumptions that
require judgment to determine whether the individual promises represent separate performance obligations or as a combined
performance obligation, and to determine the stand-alone selling price for each performance obligation identified in the contract. A
deliverable represents a separate performance obligation if both of the following criteria are met: (i) the customer can benefit from the
good or service either on our own or together with other resources that are readily available to the customer, and (ii) the entity’s
promise to transfer the good or service to the customer is separately identifiable from other promises in the contract. We use key
assumptions to determine the stand-alone selling price, which may include forecasted revenues, development timelines,
reimbursement rates for personnel costs, discount rates, and probabilities of technical and regulatory success. With regard to the
MTPC and Otsuka collaboration agreements, we recognize revenue related to amounts allocated to the identified performance
obligation on a proportional performance basis as the underlying services are performed.
Licenses of Intellectual Property
If the license to our intellectual property is determined to be distinct from the other performance obligations identified in an out-
license and collaboration arrangement, we recognize 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, we utilize judgment to assess the nature of the combined performance obligation to determine whether the combined
performance obligation is satisfied over time or at a point in time and, if over time, the appropriate method of measuring progress for
purposes of recognizing revenue from non-refundable, up-front fees. We evaluate the measure of progress each reporting period and,
if necessary, adjust the measure of performance and related revenue recognition.
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Milestone Payments
At the inception of each arrangement that includes development milestone payments, we evaluate whether the milestones are
considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount
method. We evaluate factors such as the scientific, clinical, regulatory, commercial, and other risks that must be overcome to assess
the milestone as probable of being achieved. There is considerable judgment involved in determining whether a milestone is probable
of being reached at each specific reporting period. Milestone payments that are not within our control or the customer, such as
regulatory approvals, are not considered probable of being achieved until those approvals are received. If it is probable that a
significant revenue reversal would not occur, the associated milestone value is included in the transaction price. The transaction price
is then allocated to each performance obligation on a relative stand-alone selling price basis, for which we recognize revenues as, or
when, the performance obligations under the contract are satisfied. At the end of each subsequent reporting period, we will re-evaluate
the probability of achievement of such development milestones and any related constraint, and if necessary, adjust our estimate of the
overall transaction price. Any such adjustments are recorded on a cumulative catch-up basis, which would affect collaboration revenue
in the period of adjustment.
Manufacturing Supply Services
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 discretion are generally considered as options. We assess if these options provide a material right
to the licensee and if so, they are accounted for as separate performance obligations. If we are entitled to additional payments when the
licensee exercises these options, any additional payments are recorded in license, collaboration and other revenues when the licensee
obtains control of the goods, which is upon delivery.
Royalties
We will recognize sales-based royalties, including milestone payments based on the level of sales, at the later of (i) when the related
sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or
partially satisfied). We receive royalty payments from JT and Torii, based on net sales of Riona in Japan.
Collaborative Arrangements
We record the elements of our collaboration agreements that represent joint operating activities in accordance with ASC Topic 808,
Collaborative Arrangements (ASC 808). Accordingly, the elements of the collaboration agreements that represent activities in which
both parties are active participants and to which both parties are exposed to the significant risks and rewards that are dependent on the
commercial success of the activities are recorded as collaborative arrangements. We consider the guidance in ASC 606-10-15,
Revenue from Contracts with Customers – Scope and Scope Exceptions, in determining the appropriate treatment for the transactions
between us and our collaborative partner and the transactions between us and third parties. Generally, the classification of transactions
under the collaborative arrangements is determined based on the nature and contractual terms of the arrangement along with the nature
of the operations of the participants. Therefore, we recognize our allocation of the shared costs incurred with respect to the jointly
conducted medical affairs and commercialization and non-promotional activities under the Otsuka U.S. Agreement as a component of
the related expense in the period incurred. During the years ended December 31, 2019 and 2018, we incurred approximately $1.8 million
and $1.2 million, respectively, of costs related to the cost-sharing provisions of the Otsuka U.S. Agreement, as defined below in Note 4 to
our consolidated financial statements in Part II, Item 8. Financial Statements and Supplementary Data, of which approximately $0.7
million and $0.5 million are reimbursable by Otsuka and recorded as a reduction to research and development expense during each of the
years ended December 31, 2019 and 2018, respectively. During the year ended December 31, 2019 and 2018, Otsuka incurred
approximately $1.9 million and $1.1 million, respectively, of costs related to the cost-sharing provisions of the Otsuka U.S.
Agreement, of which approximately $1.0 million and $0.5 million are reimbursable by us and recorded as an increase to research and
development expense during the years ended December 31, 2019 and 2018. To the extent product revenue is generated from the
collaboration, we recognize our share of the net sales on a gross basis if it is deemed to be the principal in the transactions with
customers, or on a net basis if it is instead deemed to be the agent in the transactions with customers, consistent with the guidance in
ASC 606.
Intangible Assets
We maintain a definite-lived intangible asset related to developed product rights for Auryxia, which was acquired on December 12,
2018 as part of the Merger.
Intangible assets are initially recorded at fair value and stated net of accumulated amortization and impairments. We amortize our
intangible assets that have finite lives using either the straight-line method, or if reliably determinable, based on the pattern in which
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the economic benefit of the asset is expected to be utilized. Amortization for our intangible asset is recorded over its estimated useful
life of nine years.
We review intangible assets subject to amortization to determine if any adverse conditions exist or a change in circumstances has
occurred that would indicate impairment or a change in the remaining useful life. If an impairment indicator exists, we perform a
recoverability test by comparing the sum of the estimated undiscounted cash flows of the intangible asset and asset group to its
carrying value on the consolidated balance sheet. If the carrying value of the intangible asset exceeds the undiscounted cash flows
used in the recoverability test, we will write the carrying value down to the fair value in the period identified. We calculate the fair
value of intangible assets as the present value of estimated future cash flows expected to be generated from the intangible asset using a
risk-adjusted discount rate. In determining estimated future cash flows associated with our intangible assets, we use market participant
assumptions pursuant to ASC Topic 820, Fair Value Measurements and Disclosures (ASC 820).
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. We recognize deferred tax assets and liabilities for the expected future tax consequences of events that
have been included in the financial statements or tax returns. Deferred tax assets and liabilities are determined based on the difference
between the financial statement and tax bases of assets and liabilities using enacted tax rates in effect for the year in which the
differences are expected to reverse. Valuation 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, 2019 and 2018 are
classified as noncurrent within the income tax provision (see Note 14 to our consolidated financial statements in Part 2, Item 8.
Financial Statements and Supplementary Data).
We account for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist, we
recognize the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The determination as to
whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position, as well as
consideration of the available facts and circumstances. As of December 31, 2019 and 2018, we do not have any significant uncertain
tax positions. We recognize interest and penalties related to uncertain tax positions in income tax expense.
Stock-Based Compensation
We account for stock-based compensation awards in accordance with ASC Topic 718, Compensation—Stock Compensation, or ASC
718. ASC 718 requires all stock-based payments to employees and non-employees, including grants of stock options, restricted stock,
restricted stock units, or RSUs, and modifications to existing stock awards, to be recognized in the statements of operations and
comprehensive loss based on their fair values. Our stock-based awards are comprised of stock options and RSUs. We estimate the fair
value of options granted using the Black-Scholes option pricing model. We use a blend of our stock price and the quoted market price
of comparable public companies to determine the fair value of restricted stock awards and common stock awards.
The Black-Scholes option pricing model requires the input of certain subjective assumptions, including (a) the expected stock price
volatility, (b) the calculation of expected term of the award, (c) the risk-free interest rate and (d) expected dividends. Due to the lack of
company-specific historical and implied volatility data for trading our stock in the public market, we have based our estimate of
expected volatility on the historical volatility of a group of similar companies that are publicly traded. The historical volatility is
calculated based on a period of time commensurate with the expected term assumption. The computation of expected volatility is
based on the historical volatility of a representative group of companies with similar characteristics to us, including stage of product
development and life science industry focus. During 2017, we began to estimate our volatility by using a blend of our stock price
history for the length of time we have market data for our stock and the historical volatility of similar public companies for the
expected term of each grant. We are a commercial-stage biopharmaceutical company and the representative group of companies has
certain similar characteristics to us. We believe the group selected has sufficient similar economic and industry characteristics and
includes companies that are most representative of us. We use the simplified method as prescribed by the SEC Staff Accounting
Bulletin No. 107, Share-Based Payment, to calculate the expected term for options granted to employees as it does not have sufficient
historical exercise data to provide a reasonable basis upon which to estimate the expected term. The expected term is applied to the
stock option grant group as a whole, as we do not expect substantially different exercise or post-vesting termination behavior among
our employee population. For options granted to non-employees, we utilize the contractual term of the arrangement as the basis for the
expected term assumption. The risk-free interest rate is based on a treasury instrument whose term is consistent with the expected life
of the stock options. The expected dividend yield is assumed to be zero as we have never paid dividends and have no current plans to
pay any dividends on our common stock, which is similar to our peer group.
Our stock-based awards are subject to either service- or performance-based vesting conditions. Compensation expense related to
awards to employees and non-employees with service-based vesting conditions is recognized on a straight-line basis based on the
112
grant date fair value over the associated service period of the award, which is generally the vesting term, and is adjusted for pre-
vesting forfeitures in the period in which the forfeitures occur. Compensation expense related to awards to employees and non-
employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period
using the accelerated attribution method to the extent achievement of the performance condition is probable.
For awards with performance conditions in which the award does not vest unless the performance condition is met, we recognize
expense if, and to the extent that, we estimate that achievement of the performance condition is probable. If we conclude that vesting
is probable, we recognize expense from the date we reach this conclusion through the estimated vesting date.
Recent Accounting Pronouncements
For additional discussion of recent accounting pronouncements, please refer to New Accounting Pronouncements – Recently Adopted
and New Accounting Pronouncements – Not Yet Adopted included within Note 2 to our consolidated financial statements in Part 2,
Item 8. Financial Statements and Supplementary Data.
Item 7A. Quantitative and Qualitative Disclosures about Market Risk
We are exposed to market risk related to changes in interest rates. As of December 31, 2019 and 2018, we had cash and cash
equivalents and available for sale securities of $147.7 million and $321.6 million, respectively, primarily money market mutual funds
consisting of U.S. government debt securities, certificates of deposit and corporate debt securities. Our primary exposure to market
risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because our
investments are primarily in short-term securities. Our investments are subject to interest rate risk and will fall in value if market
interest rates increase. Due to the short-term duration of our investment portfolio and the low risk profile of our investments, an
immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our portfolio.
113
Item 8.
Financial Statements and Supplementary Data
Akebia Therapeutics, Inc.
Table of Contents
Report of Independent Registered Public Accounting Firm ............................................................................................................... 115
Financial Statements
Consolidated Balance Sheets..................................................................................................................................................... 116
Consolidated Statements of Operations and Comprehensive Loss ........................................................................................... 117
Consolidated Statements of Stockholders’ Equity .................................................................................................................... 118
Consolidated Statements of Cash Flows ................................................................................................................................... 119
Notes to Consolidated Financial Statements ............................................................................................................................. 120
Page
114
Report of Independent Registered Public Accounting Firm
The Board of Directors and Shareholders of Akebia Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Akebia Therapeutics, Inc. (the “Company”) as of December 31,
2019 and 2018, the related consolidated statements of operations and comprehensive loss, stockholders' equity and cash flows for each
of the three years in the period ended December 31, 2019, and the related notes (collectively referred to as the “consolidated financial
statements”). In our opinion, the consolidated financial statements present fairly, in all material respects, the financial position of the
Company at December 31, 2019 and 2018, and the results of its operations and its cash flows for each of the three years in the period
ended December 31, 2019, in conformity with U.S. generally accepted accounting principles.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(PCAOB), the Company's internal control over financial reporting as of December 31, 2019, based on criteria established in Internal
Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework)
and our report dated March 12, 2020 expressed an adverse opinion thereon.
Adoption of ASU No. 2016-02
As discussed in Note 2 to the consolidated financial statements, the Company changed its method of accounting for leases in the year
ended December 31, 2019 due to the adoption of ASU No. 2016-02, Leases (Topic 842), and the related amendments.
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 accounting firm registered with the PCAOB and are required to
be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities 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 evaluating the accounting principles used
and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe
that our audits provide a reasonable basis for our opinion.
/s/ Ernst & Young LLP
We have served as the Company’s auditor since 2013.
Boston, Massachusetts
March 12, 2020
115
AKEBIA THERAPEUTICS, INC.
Consolidated Balance Sheets
(in thousands, except share and per share data)
Assets
Current assets:
Cash and cash equivalents
Available for sale securities
Inventory
Accounts receivable, net
Prepaid expenses and other current assets
Total current assets
Property and equipment, net
Operating lease assets
Goodwill
Other intangible assets, net
Other assets
Total assets
Liabilities and stockholders' equity
Current liabilities:
Accounts payable
Accrued expenses
Current portion of long-term debt
Short-term deferred revenue
Total current liabilities
Deferred rent, net of current portion
Deferred revenue, net of current portion
Operating lease liabilities, net of current portion
Deferred tax liabilities
Derivative liability
Long-term debt, net
Other non-current liabilities
Total liabilities
Commitments and contingencies (Note 16)
Stockholders' equity:
Preferred stock $0.00001 par value, 25,000,000 shares authorized at December 31,
2019 and 2018; 0 shares issued and outstanding at December 31, 2019 and 2018
Common stock: $0.00001 par value; 175,000,000 shares authorized at December 31,
2019 and 2018; 121,674,568 and 116,887,518 shares issued and outstanding at
December 31, 2019 and 2018, respectively
Additional paid-in capital
Accumulated other comprehensive loss
Accumulated deficit
Total stockholders' equity
Total liabilities and stockholders' equity
December 31,
2019
December 31,
2018
147,449 $
245
116,349
38,864
6,626
309,533
10,380
29,038
55,053
291,212
75,985
771,201 $
39,217 $
129,071
—
39,830
208,118
—
33,120
27,528
—
1,650
75,805
30,223
376,444
104,644
216,996
114,245
16,666
15,724
468,275
8,023
—
55,053
328,153
137,036
996,540
42,796
150,917
15,000
56,980
265,693
3,006
55,709
—
6,631
—
—
29,573
360,612
—
—
1
1,188,810
—
(794,054)
394,757
771,201 $
1
1,150,583
(261)
(514,395)
635,928
996,540
$
$
$
$
See accompanying notes to consolidated financial statements.
116
AKEBIA THERAPEUTICS, INC.
Consolidated Statements of Operations and Comprehensive Loss
(in thousands, except share and per share data)
Revenues:
Product revenue, net
License, collaboration and other revenue
Total revenues
Cost of goods sold:
Product
Amortization of intangible assets
Total cost of goods sold
Operating expenses:
Research and development
Selling, general and administrative
License expense
Total operating expenses
Operating loss
Other income (expense):
Interest income, net
Other income (expense)
Net loss before income taxes
Benefit from income taxes
Net loss
Net loss per share - basic and diluted
Weighted-average number of common shares - basic and diluted
Comprehensive loss:
Net loss
Other comprehensive gain (loss) - unrealized gain (loss) on
securities
Total comprehensive loss
2019
Year Ended
December 31,
2018
2017
$
111,119 $
223,882
335,001
6,824 $
200,918
207,742
—
181,227
181,227
108,935
36,401
145,336
6,251
1,517
7,768
—
—
—
322,969
149,455
3,529
475,953
(286,288)
291,007
87,061
67
378,135
(178,161)
230,893
27,008
—
257,901
(76,674)
792
(794)
(286,290)
(6,631)
(279,659) $
(2.36) $
118,395,919
6,154
81
(171,926)
(28,338)
(143,588) $
(2.47) $
58,038,252
2,799
204
(73,671)
—
(73,671)
(1.69)
43,500,795
$
$
$
(279,659) $
(143,588) $
(73,671)
261
(279,398) $
181
(143,407) $
(400)
(74,071)
$
See accompanying notes to consolidated financial statements.
117
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B
AKEBIA THERAPEUTICS, INC.
Consolidated Statements of Cash Flows
(in thousands)
Operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
2019
Year ended December 31,
2018
2017
$
(279,659) $
(143,588) $
(73,671)
Depreciation and amortization
Amortization of intangible assets
Amortization of premium/discount on investments
Non-cash interest expense
Non-cash operating lease expense
Write-off of property and equipment
Non-cash merger expense(1)
Fair value write-up of inventory sold
Write-down of inventory
Stock-based compensation
Deferred income taxes
Fair value of warrants issued for license
Changes in operating assets and liabilities:
Accounts receivable
Inventory
Prepaid expenses and other current assets
Other long-term assets
Accounts payable
Accrued expense
Operating lease liabilities
Deferred revenue
Deferred rent
Net cash used in operating activities
Investing activities:
Acquisition of business, net of acquired cash and restricted cash
Purchase of property and equipment
Proceeds from the maturities of available for sale securities
Proceeds from sales of available for sale securities
Purchase of available for sale securities
Net cash provided by (used in) investing activities
Financing activities:
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 stock options
Retirement of treasury stock
Proceeds from the issuance of debt, net
Payments on debt
Payments on capital lease obligations
Net cash provided by financing activities
Increase (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
Non-cash financing activities
Fair value of shares and equity awards issued in acquisition
$
$
2,245
36,401
(819)
786
(2,229)
2,053
—
70,444
7,112
11,925
(6,631)
—
(22,198)
(29,142)
10,541
4,917
1,372
(27,351)
2,531
(39,739)
—
(257,441)
—
(6,655)
153,110
64,721
—
211,176
25,785
383
560
(426)
77,668
(15,000)
—
88,970
42,705
107,099
149,804 $
899
1,522
(1,232)
28
—
—
13,386
4,771
—
19,040
(28,338)
—
33,384
26
(977)
903
13,717
55,482
—
(66,935)
418
(97,494)
6,147
(1,606)
243,269
13,000
(224,216)
36,594
95,452
482
647
—
—
—
(19)
96,562
35,662
71,437
107,099 $
617
—
610
—
—
—
—
—
—
8,867
—
3,413
(393)
—
(4,193)
(991)
4,959
21,974
—
(17,665)
314
(56,159)
—
(1,622)
149,998
5,000
(330,636)
(177,260)
114,580
353
1,312
—
—
—
(5)
116,240
(117,179)
188,616
71,437
— $
527,754 $
—
(1) Relates to non-cash expense associated with the fair value of the Baupost additional shares (see Note 5).
See accompanying notes to consolidated financial statements.
119
Akebia Therapeutics, Inc.
Notes to Consolidated Financial Statements
1. Nature of Organization and Operations
Akebia Therapeutics, Inc., referred to as Akebia or the Company, was incorporated in the State of Delaware in 2007. Akebia is a
biopharmaceutical company focused on the development and commercialization of renal therapeutics for people living with kidney
disease. Akebia’s lead investigational product candidate, vadadustat, is an oral therapy in Phase 3 development. The Company
believes vadadustat has the potential to set a new standard of care in the treatment of anemia due to CKD, acting via a novel hypoxia
inducible factor, or HIF, pathway. HIF is the primary regulator of the production of red blood cells, or RBCs, in the body, as well as
other important metabolic functions. The Company’s commercial product, Auryxia is currently approved by the United States Food
and Drug Administration, or FDA, and marketed for two indications in the United States, the control of serum phosphorus levels in
adult patients with chronic kidney disease, or CKD, on dialysis, or DD-CKD, and the treatment of iron deficiency anemia, or IDA, in
adult patients with CKD not on dialysis, or NDD-CKD. Ferric citrate is also approved and marketed in Japan as an oral treatment for
the improvement of hyperphosphatemia in patients with DD-CKD and NDD-CKD under the trade name Riona.
On November 11, 2019, the Company, with Keryx Biopharmaceuticals, Inc., or Keryx, as guarantor, entered into a loan agreement, or
the Loan Agreement, with Biopharma Credit plc as collateral agent and lender, or the Collateral Agent, and Biopharma Credit
Investments V (Master) LP as lender, or collectively with the Collateral Agent, Pharmakon, pursuant to which term loans in an
aggregate principal amount of $100.0 million are available to the Company in two tranches, subject to certain terms and conditions, or
the Term Loan. The first tranche of $80.0 million, or Tranche A, was drawn on November 25, 2019. The second tranche under
the Term Loan allows the Company to borrow an additional $20.0 million until December 31, 2020, subject to the satisfaction of
customary conditions. Refer to Note 11 to our consolidated financial statements in Part II, Item 8 – Financial Statements and
Supplementary Data for additional details on the Loan Agreement.
On December 12, 2018, the Company completed a merger with Keryx Biopharmaceuticals, Inc., or Keryx, or the Merger. Pursuant to
the terms and conditions of the Agreement and Plan of Merger, or the Merger Agreement, each share of Keryx common stock, or
Keryx Share, issued and outstanding immediately prior to the effective time of the Merger, or the Effective Time, was cancelled and
converted into 0.37433, or the Exchange Multiplier, fully paid and non-assessable shares of Akebia common stock, or Akebia Shares,
resulting in the issuance of an aggregate of 59,270,410 Akebia Shares.
Since inception, the Company has devoted most of its resources to research and development, including its preclinical and clinical
development activities, raising capital, and providing general and administrative support for these operations. The Company began
recording revenue from the U.S. sales of Auryxia and revenue from sublicensing rights to Auryxia in Japan to the Company’s
Japanese partners Japan Tobacco, Inc. and its subsidiary Torii Pharmaceutical Co., Ltd., collectively JT and Torii, on December 12,
2018. The Company has not generated a profit to date and may never generate profits from product sales. The Company’s product
candidates are subject to long development cycles, and the Company may be unsuccessful in its efforts to develop, obtain marketing
approval for or market its product candidates. If the Company does not successfully commercialize any of its products or product
candidates, it may be unable to achieve profitability.
The Company is subject to a number of risks including, but not limited to, risks relating to integration following the Merger, the need
to obtain adequate additional funding, including the resources necessary to fund the continued commercialization of Auryxia, the
global Phase 3 program for vadadustat in NDD-CKD, called PRO2TECT, and DD-CKD, called INNO2VATE, and post-approval
studies with respect to Auryxia, risks relating to market acceptance, coverage and reimbursement of Auryxia, risks related to
maintaining the Company’s commercial organization and capabilities, risks relating to potential generic entrants, risks of clinical trial
failures, the risk of relying on third parties, the risk that the Company never achieves profitability, protection of proprietary technology,
compliance with governmental regulations, and dependence on key personnel, and the impact of legal, regulatory and administrative
proceedings. Overall, the PRO2TECT and INNO2VATE Phase 3 programs have enrolled 7,436 patients. In August 2016, the first patient
was dosed in INNO2VATE. The Company completed enrollment of INNO2VATE in April 2019. The Company anticipates reporting
top-line data for the INNO2VATE studies in the second quarter of 2020. The first patient was dosed in PRO2TECT in December 2015.
The Company completed enrollment of PRO2TECT in August 2019. The Company anticipates reporting top-line data for the
PRO2TECT studies in mid-2020.
120
In December 2015, the Company entered into a collaboration agreement with Mitsubishi Tanabe Pharma Corporation, or MTPC, to
develop and commercialize vadadustat in Japan and certain other countries in Asia, collectively, the MTPC Territory, for total
payments of up to $245.0 million, comprised of a $20.0 million upfront payment, up to $50.0 million in specified development and
regulatory milestones, and up to $175.0 million in specified commercial milestones, as well as tiered double-digit royalty payments up
to 20% on sales of vadadustat in the MTPC Territory, subject to a reduction upon launch of a generic product on a country-by-country
basis (Note 4).
In December 2016, the Company entered into a collaboration and license agreement with Otsuka Pharmaceutical Co. Ltd., or Otsuka,
to develop and commercialize vadadustat in the United States. In December 2016, the Company received $125.0 million upfront
payment, and in March 2017, Otsuka reimbursed the Company approximately $33.8 million for global expenses previously incurred
by us for its ongoing global development program for vadadustat in DD-CKD and NDD-CKD patients. The agreement also provides
for additional funding for the global development program for vadadustat, totaling $266.8 million or more, depending on the actual
global development costs incurred. In addition, Akebia is eligible to receive from Otsuka up to $190.0 million in specified
development and regulatory milestones and up to $575.0 million in specified commercial milestones. The Company will share with
Otsuka the costs of developing and commercializing vadadustat in the United States and the profits from sales of vadadustat in the
United States after approval by the FDA and commercial launch (Note 4).
In April 2017, the Company entered into a collaboration and license agreement with Otsuka to develop and commercialize vadadustat
in Europe, Russia, China, Canada, Australia, the Middle East and certain other territories. In April 2017, the Company received a
$73.0 million upfront payment and $0.2 million for global expenses previously incurred by the Company in implementing the current
global Phase 3 development plan for vadadustat in DD-CKD and NDD-CKD patients in excess of a specified threshold during the
quarter-ended March 31, 2017. The agreement also provides for additional funding for the global development program for
vadadustat, totaling $214.0 million or more, depending on the actual global development costs incurred. In addition, Akebia is eligible
to receive from Otsuka up to $132.0 million in specified development and regulatory milestones and up to $525.0 million in specified
commercial milestones (Note 4).
From inception through December 31, 2019, the Company has raised approximately $494.6 million of net proceeds from the sale of
equity, including $377.4 million from several underwritten public offerings, $67.2 million from at-the-market offerings, or ATM
offerings, pursuant to sales agreements with Cantor Fitzgerald & Co. and $50.0 million from the sale of 3,571,429 shares of common
stock to Vifor (International) Ltd., or Vifor Pharma. In November 2019, the Company also received net proceeds of $77.3 million
from Tranche A of the Loan Agreement with Pharmakon. Subsequent to December 31, 2019 and through February 4, 2020, the
Company raised $56.7 million from ATM offerings. At inception of the Company’s collaboration agreements with Otsuka and MTPC,
they committed to an aggregate of approximately $573.0 million or more in cost-share funding, of which the Company received
approximately $272.0 million at the onset of the collaborations, and the remainder of which the Company generally continues to
receive on a quarterly prepaid basis, and via license payments.
Management of the Company completed its going concern assessment in accordance with ASC 205-40. The Company believes that its
cash resources will be sufficient to allow the Company to fund its current operating plan through at least the next twelve months from
the filing of the Company’s 2019 Annual Report on Form 10-K, as required by ASC 205-40. There can be no assurance, however, that
the current operating plan will be achieved in the time frame anticipated by the Company, or that its cash resources will fund the
Company’s operating plan for the period anticipated by the Company or that additional funding will be available on terms acceptable
to the Company, or at all. The Company will require additional capital for the further commercialization of Auryxia and continued
development and potential commercialization of the Company’s existing product candidates and would need to raise additional funds
to pursue development activities related to any additional product candidates. If and until the Company can generate a sufficient
amount of product revenue, the Company expects to finance future cash needs through public or private equity or debt transactions,
payments from its collaborators, royalty transactions, strategic transactions, or a combination of these approaches. However, adequate
additional financing may not be available to the Company on acceptable terms, or at all. If the Company is unable to raise capital
when needed or on attractive terms, it may be forced to delay, reduce or eliminate its research and development programs or any
commercialization efforts.
2. Summary of Significant Accounting Policies
Basis of Presentation
The accompanying consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries. All
intercompany balances and transactions have been eliminated in consolidation. These consolidated financial statements have been
prepared in conformity with accounting principles generally accepted in the United States of America (U.S. GAAP). Any reference in
these notes to applicable guidance is meant to refer to the authoritative U.S. GAAP as found in the Accounting Standards Codification
(ASC) and Accounting Standards Update (ASU) of the Financial Accounting Standards Board (FASB).
121
New Accounting Pronouncements – Recently Adopted
In February 2016, the FASB issued ASU 2016-02, Leases (Topic 842), which supersedes the existing guidance for lease accounting,
Leases (Topic 840). ASU 2016-02 requires entities to recognize right-of-use assets and lease liabilities for leases with lease terms of
more than 12 months on their balance sheets and provide enhanced disclosures. In 2018, the FASB issued additional ASUs related to
Topic 842, or ASC 842, that clarified various aspects of the new lease guidance, including how to record certain transition
adjustments, as well as other improvements and practical expedients. The Company adopted this new standard on January 1, 2019
using the modified retrospective approach for all leases existing at, or entered into after, the date of initial application, and has elected
to use the following practical expedients that are permitted under the rules of the adoption:
(cid:129)
(cid:129)
The Company elected the package of transition practical expedients, which allows it to retain the lease classification and
initial direct costs for any leases that existed prior to the adoption of this new standard.
The Company will not reassess whether any contracts completed prior to the adoption are leases.
The Company adopted ASC 842 using the modified retrospective approach, as of January 1, 2019, with no restatements of prior
periods or a cumulative effect of the adoption of ASC 842 in retained earnings. On January 1, 2019, the Company recognized
additional operating lease liabilities, net of deferred rent, of approximately $37.1 million based on the present value of the remaining
minimum lease payments, a corresponding right of use assets of approximately $33.4 million, and $0.9 million to prepaid expenses
and other current assets related to leasehold improvement allowances that had yet to be incurred as of the date of adoption, but for
which the Company was reasonably certain to incur costs at least equal to the maximum level of leasehold improvement allowance.
The adoption of ASC 842 did not have an impact on the Company’s consolidated statement of operations. Prior periods are presented
in accordance with ASC 840, Leases.
The Company made an accounting policy election not to recognize leases with an initial term of 12 months or less within its
consolidated balance sheets and to recognize those lease payments on a straight-line basis in its consolidated statements of operations.
The Company also made the accounting policy election 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 inception. An arrangement is determined to contain a lease if the contract
conveys the right to control the use of an identified property, plant, or equipment for a period of time in exchange for consideration. 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 multiple underlying assets are identified, the lease
consideration is allocated to the various components based on each of the component’s relative fair value.
Operating lease assets represent the Company’s right to use an underlying asset for the lease term and operating lease liabilities
represent its obligation to make lease payments arising from the leasing arrangement. Operating lease assets and operating lease
liabilities 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 estimate of its incremental borrowing rate when the implicit rate is not
readily determinable based upon the available information at the commencement date of lease inception. The incremental borrowing
rate is determined using a credit rating scoring model to estimate the Company’s credit rating, adjusted for collateralization. The
calculation of the operating lease assets includes any lease payments made and excludes any lease incentives. The Company’s lease
terms may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option.
The Company’s operating leases are reflected in prepaid expenses and other current assets, operating lease assets, accrued expenses
and operating lease liabilities, net of current portion in its consolidated balance sheets. Lease expense for minimum lease payments is
recognized on a straight-line basis over the lease term.
In January 2017, the FASB issued ASU 2017-04, Intangibles-Goodwill and Other (Topic 350): Simplifying the Test for Goodwill
Impairment, which simplifies how companies calculate goodwill impairments by eliminating Step 2 of the impairment test. Step 2
measures a goodwill impairment loss by comparing the implied fair value of a reporting unit’s goodwill with the carrying amount of
that goodwill. ASU 2017-04 requires companies to compare the fair value of a reporting unit to its carrying amount and recognize an
impairment charge for the amount by which the carrying amount exceeds the reporting unit's fair value; however, the loss recognized
should not exceed the total amount of goodwill allocated to the related reporting unit. This ASU is effective for annual periods
beginning after December 15, 2019, and is applicable to the Company in fiscal year 2020. Early adoption is allowed, and the
Company adopted ASU 2017-04 in the first quarter of fiscal year 2019. The Company conducted its initial goodwill impairment test
as of October 1, 2019 and will continue to do so annually hereafter, or more frequently if indicators of impairment are present or
changes in circumstances suggest that an impairment may exist.
122
New Accounting Pronouncements – Not Yet Adopted
In June 2016, the FASB issued ASU 2016-13, Financial Instruments-Credit Losses (Topic 326): Measurement of Credit Losses on
Financial Instruments, which requires that financial assets measured at amortized cost be presented at the net amount expected to be
collected. Currently, U.S. GAAP delays recognition of the full amount of credit losses until the loss is probable of occurring. Under
this ASU, the income statement will reflect an entity’s current estimate of all expected credit losses. The measurement of expected
credit losses will be based upon historical experience, current conditions, and reasonable and supportable forecasts that affect the
collectability of the reported amount. Credit losses relating to available-for-sale debt securities will be recorded through an allowance
for credit losses rather than as a direct write-down of the security. Additionally, credit losses for trade receivables will be also be
recorded through an allowance that reflects the Company’s current estimate of credit losses expected to be incurred. This ASU is
effective for annual periods beginning after December 15, 2019, and is applicable to the Company in fiscal year 2020. Early adoption
is permitted. The Company is currently evaluating the impact of the adoption of ASU 2016-13 on its consolidated financial position
and results of operations. Based on the composition of the Company’s available-for-sale debt securities, trade receivables, and other
financial assets, and also taking into account current market conditions and historical credit loss activity, the Company does not expect
that the adoption of this standard will have a material impact on the Company’s consolidated financial statements and related
disclosures.
In August 2018, the FASB issued ASU 2018-13, Fair Value Measurement (Topic 820): Disclosure Framework-Changes to the
Disclosure Requirements for Fair Value Measurement, which modifies the disclosure requirements for fair value measurements. This
ASU is effective for annual periods beginning after December 15, 2019, and is applicable to the Company in fiscal year 2020. Early
adoption is permitted. The Company is currently evaluating the impact the adoption of the standard will have on its consolidated
financial statements and related disclosures.
In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes. This
ASU is effective for fiscal years beginning after December 15, 2020, including interim periods therein, and is applicable to the
Company in fiscal year 2021. Early adoption is permitted. The Company does not expect that the adoption of this standard will have a
material impact on the Company’s consolidated financial statements and related disclosures.
Segment Information
Operating segments are defined as components of an enterprise about which separate discrete information is available for evaluation
by the chief operating decision maker, or decision-making group, in deciding how to allocate resources and in assessing performance.
The Company views its operations and manages its business in one operating segment, which is the business of developing and
commercializing novel therapeutics for people with kidney disease.
Derivative Financial Instruments
The Company accounts for warrants and other derivative financial instruments as either equity or liabilities in accordance with ASC
Topic 815, Derivatives and Hedging, or ASC 815, based upon the characteristics and provisions of each instrument. Warrants
classified as equity are recorded at fair value as of the date of issuance on the Company’s consolidated balance sheets and no further
adjustments to their valuation are made. Warrants classified as derivative liabilities and other derivative financial instruments that
require separate accounting as liabilities are recorded on the Company’s consolidated balance sheets at their fair value on the date of
issuance and will be revalued on each subsequent balance sheet date until such instruments are exercised or expire, with any changes
in the fair value between reporting periods recorded as other income or expense. The warrant issued by the Company in connection
with the Janssen Pharmaceutica NV Research and License Agreement, the Janssen Agreement, is classified as equity in the
Company’s consolidated balance sheet. (See Note 12). The derivative liability recorded in connection with the Company’s Loan
Agreement with Pharmakon is classified as a liability in the Company’s consolidated balance sheet. (See Note 11).
Use of Estimates
The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that
affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the date of the financial
statements and the reported amounts of revenues and expenses during the reporting period. Actual results may differ from those
estimates. Management considers many factors in selecting appropriate financial accounting policies and controls, and in developing
the estimates and assumptions that are used in the preparation of these financial statements. Management must apply significant
judgment in this process. In addition, other factors may affect estimates, including expected business and operational changes,
sensitivity and volatility associated with the assumptions used in developing estimates, and whether historical trends are expected to
be representative of future trends. The estimation process often may yield a range of potentially reasonable estimates of the ultimate
future outcomes, and management must select an amount that falls within that range of reasonable estimates. Estimates are used in the
following areas, among others: prepaid and accrued research and development expense, operating lease assets and liabilities,
derivative liabilities, other non-current liabilities, stock-based compensation expense, product and collaboration revenues including
various rebates and reserves related to product sales, inventories, income taxes, intangible assets and goodwill.
123
Cash, Cash Equivalents, and Restricted Cash
Cash and cash equivalents consist of all cash on hand, deposits and funds invested in available for sale securities with original
maturities of three months or less at the time of purchase. Cash equivalents are reported at fair value. At December 31, 2019, the
Company’s cash is primarily in money market funds. The Company may maintain balances with its banks in excess of federally
insured limits.
Restricted cash represents amounts required for security deposits under the Company’s office and lab space lease agreements and, at
December 31, 2018, cash balances held as collateral for the Company’s employee credit card program. Restricted cash is included in
“prepaid expenses and other current assets” and “other assets” in the consolidated balance sheets.
The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported in the consolidated balance sheet
that sum to the total of the amounts reported in the consolidated statement of cash flows (in thousands):
Cash and cash equivalents
Prepaid expenses and other current assets
Other assets
Total cash, cash equivalents, and restricted cash shown
in the statement of cash flows
Investments
December 31, 2018
December 31, 2017
December 31, 2019
$
147,449 $
263
2,092
104,644 $
—
2,455
70,156 $
—
1,281
December 31, 2016
187,335
—
1,281
$
149,804 $
107,099 $
71,437 $
188,616
Management determines the appropriate classification of securities at the time of purchase and reevaluates such designation as of each
balance sheet date. Currently, the Company classifies all securities as available for sale which are included in current assets as they are
intended to fund current operations. The Company carries available for sale securities at fair value. The Company conducts periodic
reviews to identify and evaluate each investment that has an unrealized loss, in accordance with the meaning of other-than-temporary
impairment and its application to certain investments. When assessing whether a decline in the fair value of a security is other-than-
temporary, the Company considers the fair market value of the security, the duration of the security’s decline, and prospects for the
underlying business. Based on these considerations, the Company did not identify any other-than-temporary unrealized losses at
December 31, 2019. Unrealized losses on available for sale securities that are determined to be temporary, and not related to credit
loss, are recorded in accumulated other comprehensive loss, a component of stockholders’ equity. The amortized cost of debt
securities in this category reflects amortization of premiums and accretion of discounts to maturity computed under the effective
interest method. The Company includes this amortization in the caption “Interest income, net” within the consolidated statements of
operations and comprehensive loss. The Company also includes in net investment income, realized gains and losses and declines in
value determined to be other than temporary. The Company bases the cost of securities sold upon the specific identification method
and includes interest and dividends on securities in interest income.
Accounts Receivable
The Company’s accounts receivable represent amounts due to the Company from product sales (see Note 3) and from its collaboration
agreements with MTPC and Otsuka (see Note 4). 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
wholesale distributors as well as certain specialty pharmacy providers, or collectively, Customers. The Company deducts trade
allowances for prompt payment, among other discounts, 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
collection becomes doubtful. Provisions are made based upon a specific review of all significant outstanding invoices and the overall
quality and age of those invoices not specifically reviewed as well as historical payment patterns and existing economic factors. The
Company believes that credit risks associated with its Customers and collaboration partners are not significant. The Company did not
have an allowance for doubtful accounts as of December 31, 2019 and 2018.
Concentrations of Credit Risk and Off-Balance Sheet Risk
Cash, cash equivalents, investments, and accounts receivable are the only financial instruments that potentially subject the Company
to concentrations of credit risk. The Company maintains its cash, cash equivalents, and investments with high quality, accredited
financial institutions and, accordingly, such funds are subject to minimal credit risk. The Company’s investment policy includes
guidelines on the quality of the institutions and financial instruments and defines allowable investments that the Company believes
minimizes the exposure to concentration of credit risk. The Company has no significant off-balance sheet concentrations of credit risk,
such as foreign currency exchange contracts, option contracts or other hedging arrangements.
124
Accounts receivable represent amounts due from the Company’s Customers and collaboration partners. As part of its credit
management policy, the Company performs ongoing credit evaluations of its Customers and generally does not require collateral from
any customer. The Company also monitors economic conditions of its collaboration partners to identify facts or circumstances that
may indicate that any of its accounts receivable are at risk of collection.
Gross revenues and accounts receivable from each of the Company’s Customers or collaboration 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:
Otsuka Pharmaceutical Co. Ltd.
Fresenius Medical Care Rx
AmerisourceBergen Drug Corporation
Otsuka Pharmaceutical Co. Ltd. (1)
AmerisourceBergen Drug Corporation
Cardinal Health, Inc.
Fresenius Medical Care Rx (2)
McKesson Corporation
Percent of Total Gross Revenues
Years Ended December 31,
2018
2017
2019
45%
21%
10%
90%
—
—
Percent of Gross Accounts Receivable
As of December 31,
2019
2018
35%
16%
15%
15%
11%
76%
—
—
—
11%
13%
42%
22%
(1)
(2)
Accounts receivable from Otsuka Pharmaceutical Co. Ltd. did not represent greater than 10% of gross accounts receivable
at December 31, 2018 due to timing of payments and costs incurred. As such, the Company did not have an accounts
receivable balance for Otsuka as of December 31, 2018.
The change in accounts receivable for Fresenius Medical Care Rx as of December 31, 2018 to December 31, 2019 was due
to timing of payments received. Fresenius was the Company’s largest commercial customer in 2019 by total gross revenue,
as seen in the Percent of Total Gross Revenues table above.
Property and Equipment
Property and equipment is stated at cost, less accumulated depreciation. Assets under capital lease are included in property and
equipment. Property and equipment is depreciated using the straight-line method over the estimated useful lives of the assets,
generally three to seven years. Such costs are periodically reviewed for recoverability when impairment indicators are present. Such
indicators include, among other factors, operating losses, unused capacity, market value declines and technological obsolescence.
Recorded values of asset groups of equipment that are not expected to be recovered through undiscounted future net cash flows are
written down to current fair value, which generally is determined from estimated discounted future net cash flows (assets held for use)
or net realizable value (assets held for sale).
The following is the summary of property and equipment and related accumulated depreciation as of December 31, 2019 and 2018.
Computer equipment and software
Furniture and fixtures
Equipment
Leasehold improvements
Office equipment under capital lease
Less accumulated depreciation
Net property and equipment
Useful Life
December 31, 2019
December 31, 2018
3
5-7
7
Shorter of the
useful life or
remaining
lease term
(10 years)
3
$
$
(in thousands)
1,010 $
2,086
2,451
8,497
—
14,044
(3,664)
10,380 $
1,593
1,170
1,780
5,324
114
9,981
(1,958)
8,023
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Depreciation expense was approximately $2.2 million, $0.9 million and $0.6 million for the years ended December 31, 2019, 2018
and 2017, respectively. For the year ended December 31, 2019, approximately $2.1 million of certain leasehold improvements were
written off in connection with the sublease of the Boston office.
Inventory
The Company values its inventories at the lower-of-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. The Company classifies its
inventory costs as long-term, in other assets in its consolidated balance sheets, when it expects to utilize the inventory beyond their
normal operating cycle.
Prior to the regulatory approval of its product candidates, the Company incurs expenses for the manufacture of material that could
potentially be available to support the commercial launch of its products. Until the first reporting period when regulatory approval has
been received or is otherwise considered probable and the future economic benefit is expected to be realized, the Company records all
such costs as research and development expense. Inventory used in clinical trials is also expensed as research and development
expense, when selected for such use. Inventory that can be used in either the production of clinical or commercial products is
expensed as research and development costs when identified for use in a clinical manufacturing campaign.
The Company performs an assessment of the recoverability of capitalized inventory during each reporting period, and writes down
any excess and obsolete inventory to its net realizable value in the period in which the impairment is first identified. Such impairment
charges, should they occur, are recorded as a component of cost of product sales in the consolidated statements of operations and
comprehensive loss. The determination of whether inventory costs will be realizable requires the use of estimates by management. If
actual market conditions are less favorable than projected by management, additional write-downs of inventory may be required.
Additionally, the Company’s product is subject to strict quality control and monitoring that it performs throughout the manufacturing
process. In the event that certain batches or units of product no longer meet quality specifications, the Company will record a charge to
cost of product sales to write-down any unmarketable inventory to its estimated net realizable value. In all cases, product inventory is
carried at the lower of cost or its estimated net realizable value.
Debt
The Company performs an assessment of all embedded features of a debt instrument to determine if (1) such features should be
bifurcated and separately accounted for, and (2) if bifurcation requirements are met, whether such features should be classified and
accounted for as equity or liability instruments. If the embedded feature meets the requirements to be bifurcated and accounted for as a
liability, the fair value of the embedded feature is measured initially, included as a liability on the consolidated balance sheet, and re-
measured to fair value at each reporting period. Any changes in fair value are recorded in the consolidated statement of operations.
The Company monitors, on an ongoing basis, whether events or circumstances could give rise to a change in the classification of
embedded features.
Revenue Recognition
The Company generates revenues primarily from sales of Auryxia, see Note 3, and from its collaborations with MTPC and Otsuka,
see Note 4. The Company recognizes revenue in accordance with 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 consideration which the entity expects to receive in exchange for
those goods or services. To determine revenue recognition for arrangements that the Company determines are within the scope of ASC
606, it performs the following five steps:
(i)
(ii)
identify the contract(s) with a customer;
identify the performance obligations in the contract;
(iii) determine the transaction price;
(iv)
allocate the transaction price to the performance obligations in the contract; and
(v)
recognize revenue when (or as) the entity satisfies a performance obligation.
The Company only applies the five-step model to contracts when it is probable that the entity will collect the consideration it is
entitled to in exchange for the goods or services it transfers to the customer. At contract inception, 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 obligations, and assesses whether each promised good or service is distinct. The Company then recognizes as revenue
the amount of the transaction price that is allocated to the respective performance obligation when (or as) the performance obligation
is satisfied.
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The Company does not include a financing component to its estimated transaction price at contract inception unless it estimates that
certain performance obligations will not be satisfied within one year. Additionally, the Company recognizes the incremental costs of
obtaining a contract as an expense when incurred if the amortization period of the asset that the Company otherwise would have
recognized is one year or less.
Product Revenue, Net
The Company sells Auryxia in the United States, or U.S., primarily to wholesale distributors as well as certain specialty pharmacy
providers, collectively, Customers. These Customers resell the Company’s product to health care providers and patients. In addition to
distribution agreements with Customers, the Company enters into arrangements with health care providers and payors that provide for
government-mandated and/or privately-negotiated rebates, chargebacks, and discounts with respect to the purchase of the Company’s
product.
The Company recognizes revenue on product sales when the Customer obtains control of the Company’s product, which occurs at a
point in time, typically upon delivery to the Customer. The Company expenses incremental costs of obtaining a contract as and when
incurred if the expected amortization period of the asset that it would have recognized is one year or less.
Reserves for Variable Consideration
Revenue from product sales is recorded at the net sales price (transaction price), which includes estimates of variable consideration for
which reserves are established and which result from discounts, returns, chargebacks, rebates, co-pay assistance and other allowances
that are offered within contracts between the Company and its Customers, health care providers, payors and other indirect customers
relating to the Company’s sales of its products. These reserves are based on the amounts earned or to be claimed on the related sales
and are classified as reductions of accounts receivable (if the amount will be credited to the Customer) or as a current liability (if the
amount is payable to a Customer or a party other than a Customer). When appropriate, these estimates take into consideration 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 patterns. Overall, these reserves reflect the Company’s best estimates of
the amount of consideration to which it is entitled based on the terms of the respective underlying contracts.
The amount of variable consideration that is included in the transaction 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 cumulative revenue recognized will not occur in a
future period. Actual amounts of consideration ultimately received may differ from the Company’s estimates. If actual results in the
future vary from the Company’s estimates, the Company will adjust these estimates, which would affect net product revenue and
earnings in the period such variances become known.
Trade Discounts and Allowances: The Company generally provides Customers with discounts that include incentive fees that are
explicitly stated in the Company’s contracts and are recorded as a reduction of revenue in the period the related product revenue is
recognized. In addition, the Company compensates (through trade discounts and allowances) its Customers for sales order
management, data, and distribution services. However, the Company has determined such services received to date are not distinct
from the Company’s sale of products to the Customer and, therefore, these payments have been recorded as a reduction of revenue
within the statement of operations and comprehensive loss through December 31, 2019. The Company records a corresponding
reduction of accounts receivable (if the trade discount and/or allowance will be credited to the Customer) or an increase in accrued
expense (if the trade discount and/or allowance is payable to a Customer) on the consolidated balance sheets.
Product Returns: Consistent with industry practice, 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. This right of return lapses once the product is
provided to a patient. The Company estimates the amount of its product sales that may be returned by its Customers and records this
estimate as a reduction of revenue in the period the related product revenue is recognized. The Company currently estimates product
return reserve using available industry data and its own historical sales information, including its visibility into the inventory
remaining in the distribution channel.
Provider Chargebacks and Discounts: Chargebacks for fees and discounts to providers represent the estimated obligations resulting
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 ultimate selling price to the qualified healthcare providers. These reserves are established in the same
period that the related revenue is recognized, resulting in a reduction of product revenue and accounts receivable. Chargeback amounts
are generally determined at the time 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
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the Company expects to issue for units that remain in the distribution channel at each reporting 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 organizations, primarily health
insurance companies and pharmacy benefit managers, for the payment of rebates with respect to utilization of its products. The
Company estimates the rebates for commercial and Medicare Part D payors based upon (i) its contracts with the payors and (ii)
information obtained from its Customers and other third parties regarding the payor mix for Auryxia. The Company estimates these
rebates and records such estimates in the same period the related revenue is recognized, resulting in a reduction of product revenue
and the establishment of a current liability.
Other Government Rebates: The Company is subject to discount obligations under state Medicaid programs and other government
programs. The Company estimates its Medicaid and other government programs rebates based upon a range of possible outcomes that
are probability-weighted for the estimated payor mix. These reserves are recorded in the same period the related revenue is recognized,
resulting in a reduction of product revenue and the establishment of a current liability which is included in accrued expenses and other
current liabilities on the consolidated balance sheets. For Medicare, the Company also estimates the number of patients in the
prescription drug coverage gap for whom the Company will owe an additional 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, estimates of claims for the current quarter, and estimated future claims that will be made for
product that has been recognized as revenue, but which remains in the distribution channel at the end of each reporting period.
Other Incentives: Other incentives that the Company offers include voluntary patient assistance programs such as the Company’s co-
pay assistance program, which are intended to provide financial assistance to qualified commercially insured patients with prescription
drug co-payments required by payors. The calculation of the accrual for co-pay assistance is based on actual claims processed during
a given period, as well as historical utilization data to estimate the amount the Company expects to receive associated with product
that has been recognized as revenue, but remains in in the distribution channel at the end of each reporting period.
Collaboration Revenues
The Company enters into out-license and collaboration agreements which are within the scope of ASC 606, under which it licenses
certain rights to its product candidates to third parties. The terms of these arrangements typically include payment to the Company of
one or more of the following: non-refundable, up-front license fees; development, regulatory, and commercial milestone payments;
payments for manufacturing supply services the Company provides through its contract manufacturers; and royalties on net sales of
licensed products. Each of these payments may result in license, collaboration and other revenue, except for revenues from royalties
on net sales of licensed products, which are classified as royalty revenues.
In determining the appropriate amount of revenue to be recognized as the Company fulfills its obligations under each of its agreements,
the Company implements the five-step model noted above. As part of the accounting for these arrangements, the Company must
develop assumptions that require judgment to determine whether the individual promises should be accounted for as separate
performance obligations or as a combined performance obligation, and to determine the stand-alone selling price for each performance
obligation identified in the contract. A deliverable represents a separate performance obligation 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 entity’s promise to transfer the good or service to the customer is separately identifiable from other
promises in the contract. The Company uses key assumptions to determine the stand-alone selling price, which may include forecasted
revenues, development timelines, reimbursement rates for personnel costs, discount rates, and probabilities of technical and regulatory
success. With regard to the MTPC and Otsuka collaboration agreements, the Company recognizes revenue related to amounts
allocated to the identified performance obligation on a proportional performance basis as the underlying services are performed.
Licenses of Intellectual Property
If the license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in
an out-license and collaboration 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 utilizes judgment to assess the nature of the combined performance obligation to
determine whether the combined performance obligation is satisfied over time or at a point in time and, if over time, 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 reporting period and, if necessary, adjust the measure of performance and related revenue recognition.
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Milestone Payments
At the inception of each arrangement that includes development milestone payments, the Company evaluates whether the milestones
are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely
amount method. The Company evaluates factors such as the scientific, clinical, regulatory, commercial, and other risks that must be
overcome to assess the milestone as probable of being achieved. There is considerable judgment involved in determining whether a
milestone is probable of being reached at each specific reporting 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 until those approvals are
received. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the
transaction price. The transaction price is then allocated to each performance obligation on a relative stand-alone selling price basis,
for which the Company recognizes revenues as, or when, the performance obligations under the contract are satisfied. At the end of
each subsequent reporting period, the Company re-evaluates the probability of achievement of such development milestones and any
related constraint, and if necessary, adjusts its estimate of the overall transaction price. Any such adjustments are recorded on a
cumulative catch-up basis, which would affect collaboration revenue in the period of adjustment.
Manufacturing Supply Services
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 discretion are generally considered as options. The Company assesses if these options provide a
material right to the licensee and if so, they are accounted for as separate performance obligations. If the Company is entitled to
additional payments when the licensee exercises these options, any additional payments are recorded in license, collaboration and
other revenues when the licensee obtains control of the goods, which is upon delivery.
Royalties
The Company will recognize sales-based royalties, including milestone payments based on the level of sales, at the later of (i) when
the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been
satisfied (or partially satisfied). The Company receives royalty payments from JT and Torii, based on net sales of Riona in Japan.
Collaborative Arrangements
The Company records the elements of its collaboration agreements that represent joint operating activities in accordance with ASC
Topic 808, Collaborative Arrangements (ASC 808). Accordingly, the elements of the collaboration agreements that represent
activities in which both parties are active participants and to which both parties are exposed to the significant risks and rewards that
are dependent on the commercial success of the activities are recorded as collaborative arrangements. The Company considers the
guidance in ASC 606-10-15, Revenue from Contracts with Customers – Scope and Scope Exceptions, in determining the appropriate
treatment for the transactions between the Company and its collaborative partner and the transactions between the Company and third
parties. Generally, the classification of transactions under the collaborative arrangements is determined based on the nature and
contractual terms of the arrangement along with the nature of the operations of the participants. Therefore, the Company recognizes its
allocation of the shared costs incurred with respect to the jointly conducted medical affairs and commercialization and non-
promotional activities under the U.S. collaboration with Otsuka as a component of the related expense in the period incurred. During
the years ended December 31, 2019 and 2018, the Company incurred approximately $1.8 million and $1.2 million, respectively, of costs
related to the cost-sharing provisions of the Otsuka U.S. Agreement, as defined below in Note 4, of which approximately $0.7 million and
$0.5 million are reimbursable by Otsuka and recorded as a reduction to research and development expense during the years ended
December 31, 2019 and 2018, respectively. During the years ended December 31, 2019 and 2018, Otsuka incurred approximately $1.9
million and $1.1 million, respectively, of costs related to the cost-sharing provisions of the Otsuka U.S. Agreement, of which
approximately $1.0 million and $0.5 million are reimbursable by the Company and recorded as an increase to research and
development expense during the years ended December 31, 2019 and 2018, respectively. To the extent product revenue is generated
from the collaboration, the Company recognizes its share of the net sales on a gross basis if it is deemed to be the principal in the
transactions with customers, or on a net basis if it is instead deemed to be the agent in the transactions with customers, consistent with
the guidance in ASC 606.
Business Combinations
The Company accounts for the acquisition of a business in accordance with ASC Topic 805, Business Combinations, or ASC 805.
Amounts paid for each acquisition are allocated to the assets acquired and liabilities assumed based on their fair values at the date of
acquisition. The Company determines the fair value of acquired intangible assets based on detailed valuations that use certain
information and assumptions provided by management, which is considered management’s best estimate of inputs and assumptions
that a market participant would use. The Company allocates any excess purchase price over the fair value of the net tangible and
intangible assets acquired to goodwill.
129
Under ASC 805, transaction costs are not included as a component of consideration transferred and are expensed as incurred.
Additionally, in accordance with ASC 805, a transaction entered into by or on behalf of the acquirer or primarily for the benefit of the
acquirer or the combined entity, rather than primarily for the benefit of the acquiree (before the combination), is treated as separate
transaction.
Intangible Assets
The Company maintains a definite-lived intangible asset related to developed product rights for Auryxia, which was acquired on
December 12, 2018 as part of the Merger.
Intangible assets are initially recorded at fair value and stated net of accumulated amortization and impairments. The Company
amortizes its intangible assets that have finite lives using either the straight-line method, or if reliably determinable, based on the
pattern in which the economic benefit of the asset is expected to be utilized. Amortization for the Company’s intangible asset is
recorded over its estimated useful life of nine years.
The Company reviews intangible assets subject to amortization to determine if any adverse conditions exist or a change in
circumstances has occurred that would indicate impairment or a change in the remaining useful life. If an impairment indicator exists,
the Company performs a recoverability test by comparing the sum of the estimated undiscounted cash flows of the intangible asset and
asset group to its carrying value on the consolidated balance sheet. If the carrying value of the intangible asset exceeds the
undiscounted cash flows used in the recoverability test, the Company will write the carrying value down to the fair value in the period
identified. The Company calculates the fair value of intangible assets as the present value of estimated future cash flows expected to
be generated from the intangible asset using a risk-adjusted discount rate. In determining estimated future cash flows associated with
its intangible assets, the Company uses market participant assumptions pursuant to ASC Topic 820, Fair Value Measurements and
Disclosures (ASC 820).
Goodwill
The Company allocates any excess purchase price over the fair value of the net tangible and intangible assets acquired in a business
combination to goodwill. Goodwill is evaluated for impairment on an annual basis as of October 1, and more frequently if indicators
are present or changes in circumstances suggest that impairment may exist.
The Company compares the fair value of its reporting unit to its carrying value. If the carrying value of the net assets assigned to the
reporting unit exceeds the fair value of its reporting unit, the Company would record an impairment loss equal to the difference. As
described above, the Company operates in one operating segment which the Company considers to be the only reporting unit.
Fair Value of Financial Instruments
The Company is required to disclose information on all assets and liabilities reported at fair value that enables an assessment of the
inputs used in determining the reported fair values. ASC 820 establishes a hierarchy of inputs used in measuring fair value that
maximizes the use of observable inputs and minimizes the use of unobservable inputs by requiring that the observable inputs be used
when available.
Observable inputs are inputs that market participants would use in pricing the asset or liability based on market data obtained from
sources independent of the Company. Unobservable inputs are inputs that reflect the Company’s assumptions about the inputs that
market participants would use in pricing the asset or liability, and are developed based on the best information available in the
circumstances. The fair value hierarchy applies only to the valuation inputs used in determining the reported fair value of the
investments, and is not a measure of the investment credit quality. The three levels of the fair value hierarchy are described below:
(cid:129)
(cid:129)
(cid:129)
Level 1 – Valuations based on unadjusted quoted prices in active markets for identical assets or liabilities that the
Company has the ability to access at the measurement date.
Level 2 – Valuations based on quoted prices for similar assets or liabilities in markets that are not active, or for which all
significant inputs are observable, either directly or indirectly.
Level 3 – Valuations that require inputs that reflect the Company’s own assumptions that are both significant to the fair
value measurement and unobservable.
To the extent that valuation is based on models or inputs that are less observable or unobservable in the market, the determination of
fair value requires more judgment. Accordingly, the degree of judgment exercised by the Company in determining fair value is
130
greatest for instruments categorized in Level 3. A financial instrument’s level within the fair value hierarchy is based on the lowest
level of any input that is significant to the fair value measurement.
Items measured at fair value on a recurring basis include available for sale securities and derivative liabilities (see Note 7). The
carrying amounts of prepaid expenses and other current assets, accounts payable and accrued expenses approximate their fair values
due to their short-term maturities.
Items measured at fair value on a nonrecurring basis include property and equipment, intangible assets and goodwill. The Company
remeasures the fair value of these assets upon the occurrence of certain events. There were no remeasurements to property and
equipment for the year ended December 31, 2019, other than the write-off of certain leasehold improvements in connection with the
sublease of the Boston office. There were no impairments to assets measured using Level 3 inputs during the years ended December
31, 2019 or 2018, respectively.
The Company’s other financial instruments mainly consists of debt (see Note 11). The carrying amount for the Company’s Loan
Agreement with Pharmakon approximates fair value because the interest rate is variable and reflects current market rates.
Research and Development Costs
Research and development costs are expensed as incurred. Research and development expenses are comprised of costs incurred in
providing research and development activities, including salaries and benefits, facilities costs, overhead costs, contract research and
development services, and other outside costs. Nonrefundable advance payments for goods and services that will be used in future
research and development activities are expensed when the activity has been performed or when the goods have been received rather
than when the payment is made.
External research and development expenses associated with the Company’s programs include clinical trial site costs, research
compounds and clinical manufacturing costs, costs incurred for consultants and other outside services, such as data management and
statistical analysis support, and materials and supplies used in support of the clinical and preclinical programs. Internal costs of the
Company’s clinical program include salaries, benefits, stock-based compensation, and an allocation of the Company’s facility costs.
When third-party service providers’ billing terms do not coincide with the Company’s period-end, the Company is required to make
estimates of its obligations to those third parties, including clinical trial and pharmaceutical development costs, contractual services
costs and costs for supply of its drug candidates, incurred in a given accounting period and record accruals at the end of the period.
The Company bases its estimates on its knowledge of the research and development programs, services performed for the period, past
history for related activities and the expected duration of the third-party service contract, where applicable.
Advertising Expenses
The costs of advertising are expensed as incurred and included in selling, general and administrative expenses in the consolidated
statements of operations and comprehensive loss. For the years ended December 31, 2019 and 2018, advertising expenses totaled $6.0
million and $0.5 million, respectively. Advertising expenses relate to advertising for Auryxia. The Company incurred advertising
expenses throughout the entire fiscal year 2019 compared to the period from December 12, 2018 through December 31, 2018 in fiscal
year 2018. The Company did not incur any advertising expenses for the year ended December 31, 2017.
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 liabilities for the expected future tax consequences of
events that have been included in the financial statements or tax returns. Deferred tax assets and liabilities are determined based on the
difference between the financial statement and tax bases of assets and liabilities using enacted tax rates in effect for the year in which
the differences are expected to reverse. Valuation 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, 2019 and 2018 are
classified as noncurrent within the income tax provision (see Note 14).
The Company accounts for uncertain tax positions in accordance with the provisions of ASC 740. When uncertain tax positions exist,
the Company recognizes the tax benefit of tax positions to the extent that the benefit will more likely than not be realized. The
determination as to whether the tax benefit will more likely than not be realized is based upon the technical merits of the tax position,
as well as consideration of the available facts and circumstances. As of December 31, 2019 and 2018, the Company does not have any
significant uncertain tax positions. The Company recognizes interest and penalties related to uncertain tax positions in income tax
expense.
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Stock-Based Compensation
The Company accounts for its stock-based compensation awards in accordance with ASC Topic 718, Compensation—Stock
Compensation, or ASC 718. ASC 718 requires all stock-based payments to employees and non-employees, including grants of stock
options, restricted stock, restricted stock units, or RSUs, and modifications to existing stock awards, to be recognized in the statements
of operations and comprehensive loss based on their fair values. The Company’s stock-based awards are comprised of stock options
and RSUs. The Company estimates the fair value of options granted using the Black-Scholes option pricing model. The Company uses
a blend of its stock price and the quoted market price of comparable public companies to determine the fair value of restricted stock
awards and common stock awards.
The Black-Scholes option pricing model requires the input of certain subjective assumptions, including (a) the expected stock price
volatility, (b) the calculation of expected term of the award, (c) the risk-free interest rate and (d) expected dividends. Due to the lack of
company-specific historical and implied volatility data for trading the Company’s stock in the public market, the Company has based
its estimate of expected volatility on the historical volatility of a group of similar companies that are publicly traded. The historical
volatility is calculated based on a period of time commensurate with the expected term assumption. The computation of expected
volatility is based on the historical volatility of a representative group of companies with similar characteristics to the Company,
including stage of product development and life science industry focus. During 2017, the Company began to estimate its volatility by
using a blend of its stock price history for the length of time it has market data for its stock and the historical volatility of similar
public companies for the expected term of each grant. The Company is a commercial-stage biopharmaceutical company and the
representative group of companies has certain similar characteristics to the Company. The Company believes the group selected has
sufficient similar economic and industry characteristics and includes companies that are most representative of the Company. The
Company uses the simplified method as prescribed by the SEC Staff Accounting Bulletin No. 107, Share-Based Payment, to calculate
the expected term for options granted to employees as it does not have sufficient historical exercise data to provide a reasonable basis
upon which to estimate the expected term. The expected term is applied to the stock option grant group as a whole, as the Company
does not expect substantially different exercise or post-vesting termination behavior among its employee population. For options
granted to non-employees, the Company utilizes the contractual term of the arrangement as the basis for the expected term
assumption. The risk-free interest rate is based on a treasury instrument whose term is consistent with the expected life of the stock
options. 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, which is similar to the Company’s peer group.
The Company’s stock-based awards are subject to either service- or performance-based vesting conditions. Compensation expense
related to awards to employees and non-employees with service-based vesting conditions 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 vesting term, and is adjusted for pre-
vesting forfeitures in the period in which the forfeitures occur. Compensation expense related to awards to employees and non-
employees with performance-based vesting conditions is recognized based on the grant date fair value over the requisite service period
using the accelerated attribution method to the extent achievement of the performance condition is probable.
For awards with performance conditions in which the award does not vest unless the performance condition is met, the Company
recognizes expense if, and to the extent that, the Company estimates that achievement of the performance condition is probable. If the
Company concludes that vesting is probable, it recognizes expense from the date it reaches this conclusion through the estimated
vesting date.
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
consideration for common stock equivalents. Diluted net loss per share is calculated by adjusting weighted-average shares outstanding
for the dilutive effect of common stock equivalents outstanding for the period, determined using the treasury-stock method. For
purposes of the diluted net loss per share calculation, preferred stock, stock options, warrants, restricted stock and RSUs are
considered to be common stock equivalents, but have been excluded from the calculation of diluted net loss per share, as their effect
would be anti-dilutive 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 dilutive effect from outstanding options, warrants, restricted stock and RSUs using the treasury stock method.
132
3. Product Revenue, Net
To date, the Company’s only source of product revenue has been from the U.S. sales of Auryxia, which it began recording on
December 12, 2018 following the consummation of the Merger. Total net product revenue was $111.1 million for the year ended
December 31, 2019 and $6.8 million for the period from December 12, 2018 to December 31, 2018. The following table summarizes
activity in each of the product revenue allowance and reserve categories for the period from December 12, 2018 to December 31, 2018
and for the year ended December 31, 2019 (in thousands):
Balance at December 12, 2018
Provisions related to sales
Credits/payments made relating to sales
Balance at December 31, 2018
Current provisions related to sales in current year
Adjustments related to prior year sales
Credits/payments made
Balance at December 31, 2019
Chargebacks
and
Discounts
Rebates, Fees
and other
Deductions
Returns
$
$
466
415
(365)
516
7,822
—
(7,600)
$
21,247
3,869
(2,255)
22,861
110,866
1,149
(104,324)
$
738 $
30,552 $
418 $
(58)
—
360
2,008
—
(2,115)
253 $
Total
22,131
4,226
(2,620)
23,737
120,696
1,149
(114,039)
31,543
Chargebacks, discounts and returns are recorded as a direct reduction of revenue on the consolidated statement of operations with a
corresponding reduction to accounts receivable on the consolidated balance sheets. Rebates, distribution-related fees, and other sales-
related deductions are recorded as a reduction in revenue on the consolidated statement of operations with a corresponding increase to
accrued liabilities or accounts payable on the consolidated balance sheets.
Accounts receivable, net related to product sales was approximately $23.0 million and $15.1 million as of December 31, 2019 and
2018, respectively.
4. License, Collaboration and Other Significant Agreements
During the years ended December 31, 2019, 2018 and 2017, the Company recognized the following revenues from its license,
collaboration and other significant agreements and had the following deferred revenue balances as of December 31, 2019:
License, Collaboration and Other Revenue:
MTPC Agreement
Otsuka U.S. Agreement
Otsuka International Agreement
Total Proportional Performance Revenue
JT and Torii
MTPC Other Revenue
Total License, Collaboration and Other Revenue
Deferred Revenue:
Otsuka U.S. Agreement
Otsuka International Agreement
Vifor Agreement
Total
2019
For the Year Ended December 31,
2018
(in thousands)
2017
10,000 $
131,314
75,614
216,928 $
5,882
1,072
223,882 $
9,281 $
103,870
87,320
200,471 $
112
335
200,918 $
42,918
85,971
52,307
181,196
—
31
181,227
December 31, 2019
Short-Term
Long-Term
Total
(in thousands)
23,530 $
16,300
—
39,830 $
20,641 $
7,800
4,679
33,120 $
44,171
24,100
4,679
72,950
$
$
$
$
$
133
The following table presents changes in the Company’s contract assets and liabilities during the years ended December 31, 2019 and
2018 (in thousands):
Twelve Months Ended December 31, 2019
Contract assets:
Other current assets
Accounts receivable(1)
Contract liabilities:
Deferred revenue
Accounts payable
Twelve Months Ended December 31, 2018
Contract assets:
Other current assets
Accounts receivable(1)
Contract liabilities:
Deferred revenue
Accounts payable
Balance at
Beginning of
Period
Additions
Deductions
Balance at End
of Period
$
$
$
$
$
$
$
$
— $
1,587 $
10,000
172,614
112,689 $
13,492 $
167,189
—
— $
34,186 $
531
146,267
179,624 $
— $
133,537
17,919
$
$
$
$
$
$
$
$
(10,000)
(158,379)
(206,928)
(13,492)
(531)
(178,866)
(200,472)
(4,427)
$
$
$
$
$
$
$
$
—
15,822
72,950
—
—
1,587
112,689
13,492
(1)
Excludes accounts receivable from other services related to clinical and regulatory activities performed by the Company on
behalf of MTPC that are not included in the performance obligations identified under the MTPC Agreement as of December 31,
2019 and 2018. Also excludes accounts receivable related to amounts due to the Company from product sales which are
included in the accompanying consolidated balance sheets as of December 31, 2019 and 2018.
During the years ended December 31, 2019, 2018 and 2017, the Company recognized the following revenues as a result of changes in
the contract asset and contract liability balances in the respective periods (in thousands):
Revenue Recognized in the Period from:
Amounts included in deferred revenue at the beginning of the period
Performance obligations satisfied in previous periods
For the Year Ended December 31,
2018
2017
2019
$
$
80,634
45,592
$
$
137,726
6,659
$
$
124,454
275
Mitsubishi Tanabe Pharma Corporation Collaboration Agreement
Summary of Agreement
On December 11, 2015, the Company and MTPC entered into a collaboration agreement, or the MTPC Agreement, providing MTPC
with exclusive development and commercialization rights to vadadustat in Japan and certain other Asian countries, collectively, the
MTPC Territory. In addition, the Company will supply vadadustat for both clinical and commercial use in the MTPC Territory,
subject to MTPC’s option to manufacture commercial drug product in the MTPC Territory.
The Company and MTPC agreed that, instead of including Japanese patients in the Company’s global Phase 3 program for vadadustat,
MTPC would be the sponsor of a Phase 3 program for vadadustat in Japan. MTPC reported top-line data for the two Phase 3 pivotal
trials and data from the two supportive Phase 3 studies in March 2019 and 52-week data for the two Phase 3 pivotal trials in
November 2019. MTPC is responsible for the costs of the Phase 3 program in Japan and other studies required in Japan, and will make
no funding payments for the global Phase 3 program. In July 2019, MTPC submitted a Japanese New Drug Application, or JNDA, to
the Ministry of Health, Labor and Welfare in Japan for manufacturing and marketing approval of vadadustat, as a treatment for anemia
due to CKD, which triggered a $10.0 million regulatory milestone payment to the Company.
MTPC has sole responsibility for the commercialization of vadadustat in the MTPC Territory as well as for Medical Affairs (as
defined in the MTPC Agreement) in the MTPC Territory. Akebia is responsible for manufacturing and supplying vadadustat for
clinical use in the MTPC Territory.
134
The Company and MTPC have established a joint steering committee pursuant to the MTPC Agreement to oversee development and
commercialization of vadadustat in the MTPC Territory, including approval of any development or commercialization plans. Unless
earlier terminated, the MTPC Agreement will continue in effect on a country-by-country basis until the later of the following:
expiration of the last-to-expire patent covering vadadustat in such country in the MTPC Territory; expiration of marketing or
regulatory exclusivity in such country in the MTPC Territory; or ten years after the first commercial sale of vadadustat in such country
in the MTPC Territory. MTPC may terminate the MTPC Agreement upon twelve months’ notice at any time after the second
anniversary of the effective 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 time period or upon the insolvency of the other party.
MTPC is required to make certain milestone payments to the Company aggregating up to approximately $225.0 million upon the
achievement of specified development, regulatory and commercial events. More specifically, the Company received $10.0 million in
development milestone payments and is eligible to receive up to $40.0 million in regulatory milestone payments, of which the
Company received $10.0 million in relation to the JNDA filing in the third quarter of 2019 and is eligible to receive an additional
$15.0 million upon regulatory approval of vadadustat in Japan, and up to $175.0 million in commercial milestone payments associated
with aggregate sales of all products. In consideration for the exclusive license and other rights contained in the MTPC Agreement,
MTPC also made a $20.0 million upfront payment as well as a payment of $20.5 million for Phase 2 studies in Japanese patients
completed by the Company and reimbursed by MTPC. Additionally, if vadadustat is commercialized, the Company would be entitled
to receive tiered double-digit royalty payments of up to 20% on sales of vadadustat in the MTPC Territory. Royalty payments are
subject to certain reductions, including upon the introduction of competitive products in certain instances. Royalties are due on a
country-by-country basis from the date of first commercial sale of a licensed product in a country until the last to occur of: (i) the
expiration of the last to expire valid claim within the intellectual property covering the licensed product, (ii) the expiration of
marketing or regulatory exclusivity in such country, or (iii) the tenth anniversary of the first commercial sale of such licensed product
in such country. Due to the uncertainty of pharmaceutical development and the high historical failure rates associated with drug
development, although the Company has received $10.0 million in development milestones and a $10.0 million regulatory milestone,
for which payment was received in the third quarter of 2019, no additional milestone or royalty payments may ever be received from
MTPC.
In September 2017, the Company provided MTPC with an option to use data from the Company’s global Phase 3 vadadustat program
to obtain regulatory approval for vadadustat in Japan. If exercised, MTPC would make payments to the Company of up to $25.0
million, which is in addition to the milestone payments described above.
Revenue Recognition
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’s arrangement with MTPC contains the following material promises under
the contract at inception: (i) license under certain of the Company’s intellectual property to develop and commercialize vadadustat (the
License Deliverable) in the MTPC Territory, (ii) clinical supply of vadadustat (the Clinical Supply Deliverable), (iii) knowledge
transfer, (iv) Phase 2 dosing study research services (the Research Deliverable), and (v) rights to future know-how.
The Company has identified two performance obligations in connection with its material promises under the MTPC Agreement as
follows: (i) License, Research and Clinical Supply Performance Obligation and (ii) Rights to Future Know-How Performance
Obligation. Factors considered in making the assessment of which material promises will be accounted for as separate performance
obligations included, among other things, the capabilities of the collaboration partner, whether any other vendor sells the item
separately, whether the good or service is highly interdependent or highly interrelated to the other elements in the arrangement, and
whether there are other vendors that can provide the items. Additionally, the MTPC Agreement does not include a general right of
return.
The Company allocates the transaction price to each performance obligation based on the Company’s best estimate of the relative
standalone selling price. The Company developed a best estimate of the standalone selling price for the Rights to Future Know-How
Performance Obligation primarily based on the likelihood that additional intellectual property covered by the license conveyed will be
developed during the term of the arrangement. The Company did not develop a best estimate of standalone selling price for the
License, Research and Clinical Supply Performance Obligation because the estimate of standalone selling price associated with the
Rights to Future Know-How Performance Obligation was determined to be immaterial. The Company has concluded that a change in
the key assumptions used to determine the best estimate of standalone selling price for each performance obligation would not have a
significant impact on the allocation of arrangement consideration. The deliverables associated with the License, Research and Clinical
Supply Performance Obligation were satisfied as of June 30, 2018.
135
The transaction price at inception was comprised of: (i) the up-front payment, (ii) the estimated cost for the Phase 2 studies, (iii) a
non-substantive milestone associated with the first patient enrolled in the NDD-CKD Phase 3 study, and (iv) the cost of all clinical
supply provided to MTPC for the Phase 3 studies. No other development and no regulatory milestones were included in the
transaction price at inception, as all other milestone amounts were fully constrained. As part of its evaluation of the constraint, the
Company considered numerous factors, including that receipt of the milestones is outside the control of the Company and contingent
upon success in future clinical trials and the licensee’s efforts. The total aggregate amount of development milestones is $10.0 million
and the total aggregate amount of the regulatory milestones is up to $40.0 million. The total aggregate amount of sales milestones is
up to $175.0 million. Any consideration related to sales-based milestones (including royalties) will be recognized when the related
sales occur as they were determined to relate predominantly to the license granted to MTPC and therefore have also been excluded
from the transaction price. The Company re-evaluates the transaction price in each reporting period and as uncertain events are
resolved or other changes in circumstances occur.
As of December 31, 2019, the transaction price is 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, comprised of a $6.0 million and a $4.0 million development milestone, and (v) the $10.0 million
regulatory milestone relating to the JNDA filing. As of December 31, 2019, all development milestones have been achieved and, other
than the $10.0 million regulatory milestone received by the Company related to the filing of the JNDA that was achieved, no other
regulatory milestones have been assessed as probable of being achieved and as a result have been fully constrained. Revenue for the
License, Research and Clinical Supply Performance Obligation for the MTPC Agreement is being recognized using a proportional
performance method. Accordingly, the Company recognized the $10.0 million regulatory milestone for the filing of the JNDA as
revenue during the year ended December 31, 2019 as the regulatory milestone was both deemed probable of being achieved and the
required performance obligations had been satisfied as of December 31, 2019. The Company recognized approximately $9.3 million
and $42.9 million during the years ended December 31, 2018 and 2017, respectively. The revenue is classified as collaboration
revenue in the accompanying consolidated statements of operations. As of December 31, 2019, there is no deferred revenue, no
accounts receivable, and no contract assets. There were no asset or liability balances classified as long-term in the consolidated
balance sheet as of December 31, 2019.
U.S. Collaboration and License Agreement with Otsuka Pharmaceutical Co. Ltd.
Summary of Agreement
On December 18, 2016, the Company entered into a collaboration and license agreement with Otsuka, or the Otsuka U.S. Agreement.
The collaboration is focused on the development and commercialization of vadadustat in the United States. Under the terms of the
Otsuka U.S. Agreement, the Company is responsible for leading the development of vadadustat, including the ongoing Phase 3
development program. The Company and Otsuka will co-commercialize vadadustat in the United States, subject to the approval of
vadadustat by the FDA.
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 activities and to conduct non-promotional
and commercialization activities related to vadadustat in accordance with the associated plans. The co-exclusive license relates to
activities that will be jointly conducted by the Company and Otsuka pursuant to the terms of the Otsuka U.S. Agreement.
Additionally, the parties agreed not to promote, market or sell any competing product in the territory covered by the agreement.
The Company is responsible for performing all activities related to the development of vadadustat as outlined in the current global
development plan. The current global development plan encompasses all activities with respect to the ongoing PRO2TECT and
INNO2VATE clinical programs through the filing for marketing approval, as well as certain other studies. Under the Otsuka U.S.
Agreement, the Company controls and retains final decision-making authority with respect to certain matters. The Company’s
obligations related to the conduct of the current global development plan include the associated manufacturing and supply services for
vadadustat.
Under the Otsuka U.S. Agreement, the parties jointly conduct, and have equal responsibility for, all medical affairs, commercialization
and non-promotional activities pursuant to underlying plans as agreed to by the parties. If approved by the FDA, the Company plans to
provide vadadustat to Otsuka for commercialization pursuant to a separate supply agreement to be negotiated.
The activities under the Otsuka U.S. Agreement are governed by a joint steering committee, or JSC, formed by an equal number of
representatives from the Company and Otsuka. The JSC coordinates and monitors the parties’ activities under the collaboration.
Among other responsibilities, the JSC manages the overall strategic alignment between the parties, oversees the current global
development plan and reviews other detailed plans setting forth the parties’ activities under the arrangement, including the medical
affairs plan and commercialization and non-promotional activities plan. Additionally, the parties established a joint development
committee, or JDC, which is comprised of an equal number of representatives from the Company and Otsuka. Among other
responsibilities, the JDC shares information related to, and reviews and discusses activities and progress under, the current global
136
development plan and any other development that may be conducted pursuant to the collaboration. The Company and Otsuka also
established a joint manufacturing committee, or JMC, which is comprised of an equal number of representatives from each of the
parties. Among other responsibilities, the JMC oversees the manufacturing plan and related manufacturing activities. In support of the
potential commercialization of vadadustat, the parties established a joint commercialization committee, or JCC, which is comprised of
an equal number of representatives from the Company and Otsuka. Among other responsibilities, the JCC oversees the activities and
progress under the commercialization and non-promotional activities plan and all other sales and marketing activities. The Company
has retained final decision-making authority with respect to certain matters, including U.S. pricing strategy and certain other key
commercialization matters.
Under the terms of the Otsuka U.S. Agreement, the Company received a $125.0 million up-front, non-refundable, non-creditable cash
payment in December 2016. In March 2017, the Company received a payment of approximately $33.8 million, which represented
reimbursement for Otsuka’s share of costs previously incurred by the Company in implementing the current global development plan
through December 31, 2016. Commencing in the third quarter of 2017, whereupon the Company had incurred a specified amount of
incremental costs, Otsuka began to contribute, as required by the Otsuka U.S. Agreement, a percentage of the remaining costs incurred
under the current global development plan. The Company estimates that Otsuka’s funding of the current global development plan
costs subsequent to December 31, 2016 will total $266.8 million or more, depending on the actual costs incurred toward the current
global development plan. The costs associated with the performance of any development activities in addition to those outlined in the
current global development plan will be subject to a cost sharing or reimbursement mechanism as set forth in the Otsuka U.S.
Agreement or to be determined by the parties. Costs incurred with respect to medical affairs and commercialization and non-
promotional activities will generally be shared equally by the parties. In addition, due to the costs incurred in completing the activities
under the current global development plan exceeding a certain threshold in the second quarter of 2019, the Company elected to require
Otsuka to increase the aggregate percentage of current global development costs it funds under the Otsuka U.S. Agreement and the
Otsuka International Agreement, as defined below, from 52.5% to 80%, or the Otsuka Funding Option. The Company estimates the
additional funding as a result of exercising the Otsuka Funding Option, or the Additional Funding, to total approximately $104.2
million or more, depending on the actual costs incurred toward the current global development plan. The Additional Funding is fully
creditable against future payments due to the Company under the arrangement, provided that future payments due to the Company
may not be reduced by more than 50% in any calendar year and any remaining creditable amount above 50% in any calendar year will
be applied to subsequent future payments until fully credited. As of December 31, 2019, the Additional Funding was $43.7 million.
In addition, Otsuka is required to make certain milestone payments to the Company upon the achievement of specified development,
regulatory and commercial events. More specifically, the Company is eligible to receive up to $125.0 million in development
milestone payments and up to $65.0 million in regulatory milestone payments for the first product to achieve the associated event.
Moreover, the Company is eligible for up to $575.0 million in commercial milestone payments associated with aggregate sales of
licensed products, subject to reduction as a result of the Company’s exercise of the Otsuka Funding Option, as described above, the
Additional Funding for which, as of December 31, 2019, totaled $43.7 million. Due to the uncertainty of pharmaceutical development
and the high historical failure rates associated therewith, no milestone payments may ever be received from Otsuka.
Under the Otsuka U.S. Agreement, the Company and Otsuka share the costs of developing and commercializing vadadustat in the
United States and the profits from the sales of vadadustat after approval by the FDA. In connection with the profit share calculation,
net sales include gross sales to third-party customers net of discounts, rebates, chargebacks, taxes, freight and insurance charges and
other applicable deductions. Shared costs generally include costs attributable or reasonably allocable to the manufacture of vadadustat
for commercialization purposes and the performance of medical affairs activities, non-promotional activities and commercialization
activities.
Unless earlier terminated, the Otsuka U.S. Agreement will expire in the United States on a product-by-product basis on the date that
one or more generic versions of vadadustat first achieves 90% market penetration. Either party may terminate the Otsuka U.S.
Agreement in its entirety upon an uncured breach or insolvency on the part of the other party. Otsuka may terminate the Otsuka U.S.
Agreement in its entirety upon 12 months’ prior written notice at any time after the release of the first topline data from the global
Phase 3 development program for vadadustat. In the event of termination of the Otsuka U.S. Agreement, all rights and licensees
granted to Otsuka under the Otsuka U.S. Agreement will automatically terminate and the licenses granted to the Company will
become freely sublicensable. In addition, the upfront payment, all development costs and milestone payments received by the
Company prior to such termination will not be refunded to Otsuka.
Revenue Recognition
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, is a customer. The Company’s arrangement with Otsuka contains the following material promises
under the contract at inception: (i) license under certain of the Company’s intellectual property to develop, perform medical affairs
activities with respect to and conduct non-promotional and commercialization activities related to vadadustat and products containing
or comprising vadadustat (the License Deliverable), (ii) development services to be performed pursuant to the current global
development plan (the Development Services Deliverable), (iii) rights to future intellectual property (the Future IP Deliverable), and
(iv) joint committee services (the Committee Deliverable).
137
The Company has identified three performance obligations in connection with its obligations under the Otsuka U.S. Agreement.
Factors considered in making the assessment of which material promises will be accounted for as separate performance obligations
included, among other things, the capabilities of the collaboration partner, whether any other vendor sells the item separately, whether
the good or service is highly interdependent or highly interrelated to the other elements in the arrangement, and whether there are
other vendors that can provide the items. Additionally, the Otsuka U.S. Agreement does not include a general right of return. The three
performance obligations identified in connection with the Company’s obligations under the Otsuka U.S. Agreement are as follows:
(i)
License and Development Services Combined (License Performance Obligation)
The License Deliverable is not distinct from the Development Services Deliverable, due to the limitations inherent in the
license conveyed. More specifically, the license conveyed to Otsuka does not provide Otsuka with the right to
manufacture vadadustat and products containing or comprising vadadustat. However, the manufacturing and supply
services that are conducted as part of the services to be performed pursuant to the current global development plan are
necessary for Otsuka to fully exploit the associated license for its intended purpose. The value of the rights provided
through the license conveyed will be realized when the underlying products covered by the intellectual property progress
through the development cycle, receive regulatory approval and are commercialized. Products containing or comprising
vadadustat cannot be commercialized until the development services under the current global development plan are
completed. Accordingly, Otsuka must obtain the manufacturing and supply of the associated products that are included
within the development services to be performed pursuant to the current global development plan from the Company in
order to derive benefit from the license, which significantly limits the ability for Otsuka to utilize the License Deliverable
for its intended purpose in a way that generates economic benefits.
(ii)
Rights to Future Intellectual Property (Future IP Performance Obligation)
The License and Development Services deliverables combined are distinct from the Future IP Deliverable because Otsuka
can obtain the value of the license using the clinical trial materials implicit in the development services without the receipt
of any other intellectual property that may be discovered or developed in the future. The Future IP Deliverable is distinct
from the Committee Deliverable because the joint committee services have no bearing on the value to be derived from the
rights to potential future intellectual property. As a result, the Future IP Deliverable qualifies as a separate performance
obligation.
(iii)
Joint Committee Services (Committee Performance Obligation)
The License and Development Services deliverables combined are distinct from the Committee Deliverable because
Otsuka can obtain the value of the license using the clinical trial materials implicit in the development services without the
joint committee services. The Committee Deliverable also is distinct from the rights to Future IP Deliverable because the
joint committee services have no bearing on the value to be derived from the rights to potential future intellectual property.
As a result, the Committee Deliverable qualifies as a separate performance obligation.
The Company allocates the transaction price to each performance obligation based on the Company’s best estimate of the relative
standalone selling price. The Company developed a best estimate of standalone selling price for the Committee Performance
Obligation after considering the nature of the services to be performed and estimates of the associated effort and rates applicable to
such services that would be expected to be realized under similar contracts. The Company developed a best estimate of standalone
selling price for the Future IP Performance Obligation primarily based on the likelihood that additional intellectual property covered
by the license conveyed will be developed during the term of the arrangement. The Company did not develop a best estimate of
standalone selling price for the License Performance Obligation due to the following: (i) the best estimates of standalone selling price
associated with the Future IP Performance Obligation was determined to be immaterial and (ii) the period of performance and pattern
of recognition for the License Performance Obligation and the Committee Performance Obligation was determined to be similar. The
Company has concluded that a change in the key assumptions used to determine the best estimate of standalone selling price for each
performance obligation would not have a significant impact on the allocation of arrangement consideration.
The transaction price at inception was comprised of: (i) the up-front payment, (ii) the cost share payment with respect to amounts
incurred by the Company through December 31, 2016, and (iii) an estimate of the cost share payments to be received with respect to
amounts incurred by the Company subsequent to December 31, 2016. No development or regulatory milestones were included in the
transaction price at inception, as all milestone amounts were fully constrained. As part of its evaluation of the constraint, the Company
considered numerous factors, including that receipt of the milestones is outside the control of the Company and contingent upon
success in future clinical trials and the licensee’s efforts. Any consideration related to sales-based milestones will be recognized when
the related sales occur as they were determined to relate predominantly to the license granted to Otsuka and therefore have also been
excluded from the transaction price.
138
The Company re-evaluates the transaction price in each reporting period and as uncertain events are resolved or other changes in
circumstances occur. The Company determined that under ASC 606, the contract was modified in the second quarter of 2019 when the
Otsuka Funding Option became effective and the Company became eligible to receive the Additional Funding amount. In connection
with the modification, the Company adjusted the transaction price to include the Additional Funding amount as additional variable
consideration. The Company constrains the variable consideration to an amount for which a significant revenue reversal is not
probable.
No amounts were allocated to the Future IP Performance Obligation because the associated best estimate of standalone selling price
was determined to be immaterial. Due to the similar performance period and recognition pattern between the License Performance
Obligation and the Committee Performance Obligation, the transaction price has been allocated to the License Performance Obligation
and the Committee Performance Obligation on a combined basis. Accordingly, the Company will recognize revenue related to the
allocable arrangement consideration on a proportional performance basis as the underlying development services are performed
pursuant to the current global development plan which is commensurate with the period and consistent with the pattern over which the
Company’s obligations are satisfied for both the License Performance Obligation and the Committee Performance Obligation.
Effectively, the Company has treated the arrangement as if the License Performance Obligation and the Committee Performance
Obligation are a single performance obligation.
As of December 31, 2019, the transaction price totaling $425.6 million is comprised of: (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, (iii) the
estimate of the cost base share payments to be received of approximately $209.1 million with respect to amounts incurred by the
Company subsequent to December 31, 2016, and (iv) the estimate of the Additional Funding of approximately $57.7 million related to
incremental cost share payments under the Otsuka Funding Option described above. As of December 31, 2019, no development or
regulatory milestones have been assessed as probable of being reached and thus have been fully constrained.
During the years ended December 31, 2019, 2018 and 2017, the Company recognized revenue totaling approximately $131.3 million,
$103.9 million and $86.0 million, respectively, with respect to the Otsuka U.S. Agreement. The revenue is classified as collaboration
revenue in the accompanying consolidated statements of operations. As of December 31, 2019, there is approximately $44.2 million of
deferred revenue related to the Otsuka U.S. Agreement of which $23.6 million is classified as current and $20.6 million is classified as
long-term in the accompanying consolidated balance sheet based on the performance period of the underlying obligations. Additionally,
as of December 31, 2019, there is approximately $8.9 million in accounts receivable in the accompanying consolidated balance sheet. As
of December 31, 2018, there was approximately $7.2 million in contract liabilities (included in accounts payable) in the consolidated
balance sheet.
The Company determined that the medical affairs, commercialization and non-promotional activities elements of the Otsuka U.S.
Agreement represent joint operating activities in which both parties are active participants and of which both parties are exposed to
significant risks and rewards that are dependent on the success of the activities. Accordingly, the Company is accounting for the joint
medical affairs, commercialization and non-promotional activities in accordance with ASC No. 808, Collaborative Arrangements
(ASC 808). Additionally, the Company has determined that in the context of the medical affairs, commercialization and non-
promotional activities, Otsuka does not represent a customer as contemplated by ASC 606-10-15, Revenue from Contracts with
Customers – Scope and Scope Exceptions. As a result, the activities conducted pursuant to the medical affairs, commercialization and
non-promotional activities plans will be accounted for as a component of the related expense in the period incurred. During the years
ended December 31, 2019 and 2018, the Company incurred approximately $1.8 million and $1.2 million, respectively, of costs related to
the cost-sharing provisions of the Otsuka U.S. Agreement of which approximately $0.7 million and $0.5 million are reimbursable by
Otsuka and recorded as a reduction to research and development expense during each of the years ended December 31, 2019 and 2018,
respectively. During the years ended December 31, 2019 and 2018, Otsuka incurred approximately $1.9 million and $1.1 million,
respectively, of costs related to the cost-sharing provisions of the Otsuka U.S. Agreement, of which approximately $1.0 million and
$0.5 million are reimbursable by the Company and recorded as an increase to research and development expense during the years
ended December 31, 2019 and 2018.
International Collaboration and License Agreement with Otsuka Pharmaceutical Co. Ltd.
Summary of Agreement
On April 25, 2017, the Company entered into a collaboration and license agreement with Otsuka, or the Otsuka International
Agreement. The collaboration is focused on the development and commercialization of vadadustat in Europe, Russia, China, Canada,
Australia, the Middle East and certain other territories, collectively, the Otsuka International Territory. Under the terms of the Otsuka
International Agreement, the Company is responsible for leading the development of vadadustat, including the ongoing global Phase 3
development program. Otsuka has the sole responsibility, at its own cost, for the commercialization of vadadustat in the Otsuka
International Territory, subject to the approval by the relevant regulatory authorities.
Under the terms of the Otsuka International Agreement, the Company granted to Otsuka an exclusive, sublicensable license under
certain intellectual property controlled by the Company to develop and commercialize vadadustat and products containing or
comprising vadadustat in the Otsuka International Territory.
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Pursuant to the terms of the Otsuka International Agreement, the Company is responsible for performing all activities related to the
development of vadadustat as outlined in the current global development plan; however, the parties may agree to allocate certain
responsibilities to Otsuka. Under the Otsuka International Agreement, the Company controls and retains final decision-making
authority with respect to certain matters. Per the terms of the Otsuka International Agreement, Otsuka is generally responsible for the
conduct of any development activities that may be required for marketing approvals in the Otsuka International Territory or otherwise
performed with respect to the Otsuka International Territory that are incremental to those included in the current global development
plan. The Company’s obligations related to the conduct of the current global development plan include the associated manufacturing
and supply services for vadadustat.
Under the Otsuka International Agreement, Otsuka is to be solely responsible for the conduct of all medical affairs and
commercialization activities in the Otsuka International Territory pursuant to underlying plans as reviewed and discussed by the
parties. If approved by the relevant jurisdictional regulatory health authorities in the Otsuka International Territory, the Company will
provide vadadustat to Otsuka for commercialization pursuant to a separate supply agreement to be negotiated. Additionally, the parties
agreed not to promote, market or sell any competing product in the territory covered by the agreement.
The activities under the Otsuka International Agreement are governed by a JSC formed by an equal number of representatives from
the Company and Otsuka. The JSC coordinates and monitors the parties’ activities under the collaboration. Among other
responsibilities, the JSC manages the overall strategic alignment between the parties, oversees the current global development plan
and reviews other detailed plans setting forth any other development activities that may be conducted under the arrangement.
Additionally, the parties established a JDC, which is comprised of an equal number of representatives from the Company and Otsuka.
Among other responsibilities, the JDC shares information related to, and reviews and discusses activities and progress under, the
current global development plan and any other development that may be conducted pursuant to the collaboration. The Company and
Otsuka also established a JMC, which is comprised of an equal number of representatives from each of the parties. Among other
responsibilities, the JMC oversees the manufacturing plan and related manufacturing activities. In support of the potential
commercialization of vadadustat, the parties established a JCC, which is comprised of an equal number of representatives from the
Company and Otsuka. Among other responsibilities, the JCC manages the activities and progress under the commercialization and
non-promotional activities plan and all other sales and marketing activities. The Company has retained final decision-making authority
with respect to certain matters. Otsuka has retained final decision-making authority with respect to all commercialization matters,
other than decisions related to certain marketing matters.
Under the terms of the Otsuka International Agreement, the Company received a $73.0 million up-front, non-refundable, non-
creditable cash payment. The Company also received a payment of approximately $0.2 million which represents reimbursement for
Otsuka’s share of costs previously incurred by the Company in implementing the current global development plan in excess of a
specified threshold during the quarter ended March 31, 2017. Commencing in the second quarter of 2017, Otsuka began to contribute,
as required by the Otsuka International Agreement, a percentage of the remaining costs incurred under the current global development
plan. The Company estimates that Otsuka’s funding of the current global development plan costs subsequent to March 31, 2017 will
total roughly $214.0 million or more, depending on the actual current global development plan costs incurred. The costs associated
with the performance of any mutually agreed upon development activities in addition to those outlined in the current global
development plan will be subject to a cost sharing or reimbursement mechanism as set forth in the Otsuka International Agreement or
to be determined by the parties. Otsuka may elect to conduct additional studies of vadadustat in the EU, subject to the Company’s
right to delay such studies based on its objectives outside the Otsuka International Territory. Otsuka will pay a percentage of the costs
of any such studies, and the Company will pay its portion of the costs in the form of a credit against future amounts due to the
Company under the Otsuka International Agreement. The costs incurred related to any other development activities, which are
pursued solely for obtaining or maintaining marketing approval in the Otsuka International Territory or otherwise performed solely
with respect to the Otsuka International Territory that are incremental to the development activities included in the current global
development plan, will be borne in their entirety by Otsuka. Otsuka will pay costs incurred with respect to medical affairs and
commercialization activities in the Otsuka International Territory.
In addition, Otsuka would be required to make certain milestone payments to the Company upon the achievement of specified
development, regulatory and commercial events. More specifically, the Company is eligible to receive up to $80.0 million in
development milestone payments and up to $52.0 million in regulatory milestone payments for the first licensed product to achieve the
associated event. Moreover, the Company is eligible for up to $525.0 million in commercial milestone payments associated with
aggregate sales of all licensed products. Additionally, to the extent vadadustat is commercialized, the Company would be entitled to
receive tiered royalty payments ranging from the low double digits to the low thirties based on a percentage of net sales. Royalties are
due on a country-by-country basis from the date of the first commercial sale of a licensed product in a country until the latest to occur
of: (i) the expiration date in such country of the last to expire valid claim within the intellectual property covering the licensed
product, (ii) the date of expiration of data or regulatory exclusivity in such country or (iii) the tenth anniversary of the first commercial
sale of such licensed product in such country. Due to the uncertainty of pharmaceutical development and the high historical failure
rates associated therewith, no milestone or royalty payments may ever be received from Otsuka. There are no cancellation, termination
or refund provisions in the Otsuka International Agreement that contain material financial consequences to the Company.
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Unless earlier terminated, the Otsuka International Agreement will expire upon the expiration of the royalty term in the last country in
the Otsuka International Territory. Either party may terminate the Otsuka International Agreement in its entirety upon an uncured
material breach or insolvency on the part of the other party. Otsuka may terminate the Otsuka International Agreement in its entirety
or for a specific region in the Otsuka International Territory upon 12 months’ prior written notice at any time after the release of the
first topline data from either the PRO2TECT Phase 3 development program or the INNO2VATE Phase 3 development program,
whichever comes first. In the event of termination of the Otsuka International Agreement, all rights and licensees granted to Otsuka
under the Otsuka International Agreement will automatically terminate, and the licenses granted to the Company will become freely
sublicensable, but potentially subject to a future royalty. In addition, the upfront payment, all development costs and milestone
payments received by the Company prior to such termination will not be eligible for refund to Otsuka.
Revenue Recognition
The Company has accounted for the Otsuka International Agreement separately from the collaboration arrangement with Otsuka with
respect to the U.S. due to the lack of interrelationship and interdependence of the elements and payment terms within each of the
contracts as they relate to the respective territories. Accordingly, the Company has applied the guidance in ASC 606 solely in
reference to the terms and conditions of the Otsuka International Agreement, while the Otsuka U.S. Agreement has continued to be
accounted for as a discrete agreement in its own right. The Company evaluated the Otsuka International Agreement in accordance
with the provisions of ASC 606 and concluded that the contract counterparty, Otsuka, is a customer. The Company’s arrangement
with Otsuka related to the Otsuka International Territory contains the following material promises under the contract at inception: (i)
license under certain of the Company’s intellectual property to develop and commercialize (including the associated packaging)
vadadustat and products containing or comprising vadadustat and development services to be performed pursuant to the current global
development plan (the License and Development Services Deliverable), (ii) rights to future intellectual property (the Future IP
Deliverable) and (iii) joint committee services (the Committee Deliverable).
The Company has identified three performance obligations in connection with its obligations under the Otsuka International
Agreement. Factors considered in making this assessment of which material promises will be accounted for as a separate performance
obligation included, among other things, the capabilities of the collaboration partner, whether any other vendor sells the item
separately, whether the good or service is highly interdependent or highly interrelated to the other elements in the arrangement, and
whether there are other vendors that can provide the items. Additionally, the Otsuka International Agreement does not include a
general right of return. The three performance obligations identified in connection with the Company’s obligations under the Otsuka
International Agreement are as follows:
(i)
License and Development Services Combined (License Performance Obligation)
The Company has determined that the license granted to Otsuka pursuant to the Otsuka International Agreement will be
accounted for as component of the development services as opposed to a separately identified promise. Although the
rights granted under the license are effective throughout the entire term of the arrangement, the Company will not be
providing significant additional contributions of study data, regulatory submissions and regulatory approvals beyond the
point that services under the current global development plan are conducted. Therefore, the period and pattern of
recognition would be the same for both the license and the development services. Consequently, the Company has
concluded that the license will effectively be treated as an inherent part of the associated development services promise
instead of as a separate promise. As a result, the License and Development Services Deliverable will be treated as a single
performance obligation (the License Performance Obligation).
(ii)
Rights to Future Intellectual Property (Future IP Performance Obligation)
The License and Development Services Deliverable is distinct from the Future IP Deliverable because Otsuka can obtain
the value of the license using the clinical trial materials implicit in the development services without the receipt of any
other intellectual property that may be discovered or developed in the future. The Future IP Deliverable is distinct from
the Committee Deliverable because the Committee Deliverable has no bearing on the value to be derived from the rights
to potential future intellectual property. As a result, the Future IP Deliverable qualifies as a separate performance
obligation.
(iii)
Joint Committee Services (Committee Performance Obligation)
The License and Development Services Deliverable is distinct from the Committee Deliverable because Otsuka can obtain
the value of the license using the clinical trial materials implicit in the development service without the joint committee
services. The Committee Deliverable is distinct from the Future IP Deliverable because the Committee Deliverable has no
bearing on the value to be derived from the rights to potential future intellectual property. As a result, the Committee
Deliverable qualifies as a separate performance obligation.
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The Company allocates the transaction price to each performance obligation based on the Company’s best estimate of the relative
standalone selling price. The Company developed a best estimate of standalone selling price for the Committee Performance
Obligation after considering the nature of the services to be performed and estimates of the associated effort and rates applicable to
such services that would be expected to be realized under similar contracts. The Company developed a best estimate of standalone
selling price for the Future IP Performance Obligation primarily based on the likelihood that additional intellectual property covered
by the license conveyed will be developed during the term of the arrangement. The Company did not develop a best estimate of
standalone selling price for the License Performance Obligation due to the following: (i) the best estimates of standalone selling price
associated with the Future IP Performance Obligation was determined to be immaterial and (ii) the period of performance and pattern
of recognition for the License Performance Obligation and the Committee Performance Obligation was determined to be similar. The
Company has concluded that a change in the key assumptions used to determine the best estimate of standalone selling price for each
performance obligation would not have a significant impact on the allocation of arrangement consideration.
The transaction price at inception was comprised of: (i) the up-front payment, (ii) the cost share payment with respect to amounts
incurred by the Company during the quarter ended March 31, 2017, and (iii) an estimate of the cost share payments to be received
with respect to amounts incurred by the Company subsequent to March 31, 2017. No development or regulatory milestones were
included in the transaction price at inception, as all milestone amounts were fully constrained. As part of its evaluation of the
constraint, the Company considered numerous factors, including whether the receipt of the milestone payment is outside the control of
the Company and contingent upon success in future clinical trials and the licensee’s efforts. Any consideration related to sales-based
milestones (including royalties) will be recognized when the related sales occur as they were determined to relate predominantly to the
license granted to Otsuka and therefore have also been excluded from the transaction price. The Company re-evaluates the transaction
price in each reporting period and as uncertain events are resolved or other changes in circumstances occur.
No amounts were allocated to the Future IP Performance Obligation because the associated best estimate of standalone selling price
was determined to be immaterial. Due to the similar performance period and recognition pattern between the License Performance
Obligation and the Committee Performance Obligation, the transaction price has been allocated to the License Performance Obligation
and the Committee Performance Obligation on a combined basis. Accordingly, the Company will recognize revenue related to the
allocable arrangement consideration on a proportional performance basis as the underlying development services are performed
pursuant to the current global development plan which is commensurate with the period and consistent with the pattern over which the
Company’s obligations are satisfied for both the License Performance Obligation and the Committee Performance Obligation.
Effectively, the Company has treated the arrangement as if the License Performance Obligation and the Committee Performance
Obligation are a single performance obligation.
As of December 31, 2019, the transaction price totaling $287.2 million is comprised of: (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) an estimate of the cost share payments to be received with respect to amounts incurred by the Company subsequent to March
31, 2017 of $214.0 million. As of December 31, 2019, no development or regulatory milestones have been assessed as probable of
being reached and thus have been fully constrained.
During the years ended December 31, 2019, 2018 and 2017, the Company recognized revenue totaling approximately $75.6 million,
$87.3 million, and $52.3 million, respectively, with respect to the Otsuka International Agreement. The revenue is classified as
collaboration revenue in the accompanying consolidated statements of operations. As of December 31, 2019, there is approximately $24.1
million of deferred revenue related to the Otsuka International Agreement of which $16.3 million is classified as current and $7.8 million
is classified as long-term in the accompanying consolidated balance sheet based on the performance period of the underlying obligations.
Additionally, as of December 31, 2019, there is approximately $4.0 million in accounts receivable in the accompanying consolidated
balance sheet. As of December 31, 2018, there was approximately $6.3 million in contract liabilities (included in accounts payable) in the
consolidated balance sheet.
Janssen Pharmaceutica NV Research and License Agreement
Summary of Agreement
On February 9, 2017, the Company entered into a Research and License Agreement, the Janssen Agreement, with Janssen
Pharmaceutica NV, or Janssen, a subsidiary of Johnson & Johnson, pursuant to which Janssen granted the Company an exclusive
license under certain intellectual property rights to develop and commercialize worldwide certain HIF prolyl hydroxylase targeted
compounds.
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Under the terms of the Janssen Agreement, Janssen granted to the Company a license for a three-year research term to conduct
research on the HIF compound portfolio, which research term is now expired. During the research term, the Company could designate
one or more compounds as candidates for development and commercialization. Once a compound was designated for development
and commercialization, the Company was to be solely responsible for the development and commercialization of the compound
worldwide at its own cost and expense.
Under the terms of the Janssen Agreement, the Company made an upfront payment of $1.0 million in cash to Janssen and issued a
warrant to purchase 509,611 shares of the Company’s common stock. In addition, Janssen could be eligible to receive up to an
aggregate of $16.5 million from the Company in specified development milestone payments on a product-by-product basis. Janssen
will also be eligible to receive up to $215.0 million from the Company in specified commercial milestones as well as tiered, escalating
royalties ranging from a low to mid-single digit percentage of net sales, on a product-by-product basis, and subject to reduction upon
expiration of patent rights or the launch of a generic product in the territory.
Unless earlier terminated, the Janssen Agreement will expire on a product-by-product and country-by-country basis upon the
expiration of the last royalty term, which ends upon the longer of the expiration of the patents licensed under the Janssen Agreement,
the expiration of regulatory exclusivity for such product, or 10 years from first commercial sale of such product. The Company may
terminate the Janssen Agreement in its entirety or only with respect to a particular licensed compound or product upon 180 days’ prior
written notice to Janssen. The parties also have customary termination rights, subject to a cure period, in the event of the other party’s
material breach of the Janssen Agreement or in the event of certain additional circumstances.
As discussed above, the Company issued a Common Stock Purchase Warrant, or the Warrant, to Johnson & Johnson Innovation –
JJDC, Inc., or JJDC, an affiliate of Janssen, for 509,611 shares of the Company’s common stock at an exercise price of $9.81 per share.
The Warrant is exercisable by JJDC, in whole or in part, at any time prior to February 9, 2022. The Warrant and the shares issuable
upon exercise of the Warrant will be sold and issued without registration under the Securities Act of 1933, as amended, or the
Securities Act. The Company recorded the fair value of the Warrant in the amount of $3.4 million to additional paid-in capital and
research and development expense in March 2017.
Vifor Pharma License Agreement
Summary of Agreement
On May 12, 2017, the Company entered into a License Agreement, or the Vifor Agreement, with Vifor (International) Ltd., or Vifor
Pharma, pursuant to which the Company granted Vifor Pharma an exclusive license to sell vadadustat solely to Fresenius Kidney Care
Group LLC, or FKC, an affiliate of Fresenius Medical Care North America, or FMCNA, in the United States. On April 8, 2019, the
Company and Vifor Pharma entered into an Amended and Restated License Agreement, or the Vifor Amended Agreement, which
amends and restates in full the Vifor Agreement.
Pursuant to the Vifor Amended Agreement, the Company granted Vifor Pharma an exclusive license to sell vadadustat to FKC and to
certain third party dialysis organizations approved by the Company, or Third Party Dialysis Organizations, in the United States.
The license granted under the Vifor Amended Agreement will become effective upon (i) the approval of vadadustat for DD-CKD
patients by the FDA, (ii) the earlier of a determination by the Centers for Medicare & Medicaid Services that vadadustat will be
reimbursed using Medicare’s bundled reimbursement model or that vadadustat will be reimbursed using the Transitional Drug Add-
On Payment Adjustment, and (iii) payment by Vifor Pharma of a $25.0 million milestone upon the occurrence of (i) and (ii).
The Vifor Amended Agreement is structured as a profit share arrangement between the Company and Vifor Pharma in which the
Company will receive a majority of the profit, after deduction of certain amounts relating to Vifor Pharma’s costs, from Vifor
Pharma’s sales of vadadustat to FKC and the Third Party Dialysis Organizations in the United States. The Company will share the
milestone payment and the revenue from the profit share with Otsuka pursuant to the Otsuka U.S. Agreement. The Company currently
retains rights to commercialize vadadustat for use in the NDD-CKD market and in other dialysis organizations in the United States,
which will be done in collaboration with Otsuka following FDA approval.
The Vifor Amended Agreement provides that the Company and Vifor Pharma will enter into a commercial supply agreement for
vadadustat pursuant to which the Company will supply all of Vifor Pharma’s requirements for vadadustat in the United States. In
addition, Vifor Pharma will enter into supply arrangements with FKC and the Third Party Dialysis Organizations that will govern the
terms pursuant to which Vifor Pharma will supply vadadustat to FKC and the Third Party Dialysis Organizations for use in patients at
its dialysis centers in the United States. During the term of the Vifor Amended Agreement, Vifor Pharma is not permitted to sell any
HIF product that competes with vadadustat in the United States to FKC or its affiliates or to any Third Party Dialysis Organization,
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and the Company may not directly supply vadadustat to FKC or any other affiliate of FMCNA or any Third Party Dialysis
Organization.
Unless earlier terminated, the Vifor Amended Agreement will expire upon the later of the expiration of all patents that claim or cover
vadadustat or expiration of marketing or regulatory exclusivity for vadadustat in the United States. Vifor Pharma may terminate the
Vifor Amended Agreement in its entirety upon 12 months’ prior written notice after the release of the first topline data in the
vadadustat global Phase 3 program for DD-CKD patients. In addition, either party may, subject to a cure period, terminate the Vifor
Amended Agreement in the event of the other party’s uncured material breach or bankruptcy. The Company may terminate the Vifor
Amended Agreement (or suspend the license) upon the occurrence of certain events, such as for specific violations of the Vifor
Amended Agreement, Vifor Pharma’s failure to achieve certain sales levels, or if there are changes in Vifor Pharma’s relationship
with FKC or in applicable laws and regulations related to the reimbursement of drugs like vadadustat at dialysis clinics, or if Vifor
Pharma contests the validity or enforceability of any patent controlled by the Company that covers vadadustat. The Vifor Amended
Agreement also includes a standstill provision and customary representations and warranties.
Investment Agreement
In connection with the Vifor Agreement, in May 2017, the Company and Vifor Pharma entered into an investment agreement, or the
Investment Agreement, pursuant to which the Company sold an aggregate of 3,571,429 shares of the Company’s common stock, or
the Shares, to Vifor Pharma at a price per share of $14.00 for a total of $50.0 million. The amount representing the premium over the
closing stock price of $12.69 on the date of the transaction, totaling $4.7 million, was determined by the Company to represent
consideration related to the Vifor Agreement. As the parties’ rights under the Vifor Agreement are conditioned upon (a) the approval of
vadadustat for DD-CKD patients by the FDA; (b) the earlier of a determination by the Centers for Medicare & Medicaid Services that
vadadustat will be reimbursed using Medicare’s bundled reimbursement model or that vadadustat will be reimbursed using the
Transitional Drug Add-On Payment Adjustment; and (c) payment by Vifor Pharma of a $25.0 million milestone upon the occurrence
of (a) and (b), in accordance with ASC 606, the Company has determined that the full transaction price is fully constrained. As part of
its evaluation of the constraint, the Company considered numerous factors, including clinical and regulatory risks that must be
overcome in order for the parties’ rights to become effective and the probability of the $25.0 million milestone being achieved.
Accordingly, the $4.7 million continues to be recorded as deferred revenue in the accompanying consolidated balance sheets. Upon
the satisfaction of the aforementioned conditions, revenue will be recognized as the Company supplies vadadustat to Vifor Pharma
using a proportional performance method.
Vifor Pharma agreed to a lock-up restriction such that it agrees not to sell the Shares for a period of time following the effective date
of the Investment Agreement as well as a customary standstill agreement. In addition, the Investment Agreement contains voting
agreements made by Vifor Pharma with respect to the Shares. The Shares have not been registered pursuant to the Securities Act, and
were issued and sold in reliance upon the exemption from registration contained in Section 4(a)(2) of the Securities Act and Rule 506
promulgated thereunder.
Priority Review Voucher Letter Agreement
On February 14, 2020, we entered into a letter agreement, or the Letter Agreement, with Vifor Pharma relating to Vifor Pharma’s
agreement with a third party to purchase a Priority Review Voucher, or the PRV, issued by the FDA, subject to satisfaction of
customary closing conditions, or the PRV Purchase. A PRV entitles the holder to priority review of a New Drug Application, or NDA,
or a Biologics License Application for a new drug, which reduces the target FDA review time to six months after official acceptance
of the submission, and could lead to expedited approval. Pursuant to the Letter Agreement, Akebia will pay Vifor Pharma $10.0
million within fifteen business days after the closing of the PRV Purchase. Vifor Pharma is obligated to retain all rights to, and
maintain the validity of, the PRV until Akebia and Vifor Pharma (a) enter into a definitive agreement setting forth the financial and
other terms by which Vifor Pharma will assign the PRV to Akebia for use with Akebia’s planned NDA for vadadustat for the
treatment of anemia due to CKD in both dialysis-dependent and non-dialysis dependent patients, or (b) make a mutual decision to sell
the PRV and share the proceeds based on certain terms.
License Agreement with Panion & BF Biotech, Inc.
As a result of the Merger, the Company had a license agreement, which was amended from time to time, with Panion & BF Biotech,
Inc., or Panion, under which Keryx, the Company’s wholly owned subsidiary, was the contracting party, or the Panion License
Agreement, Keryx in-licensed the exclusive worldwide rights, excluding certain Asian-Pacific countries, or the Licensor Territory, for
the development and commercialization of ferric citrate.
On April 17, 2019, the Company and Panion entered into a second amended and restated license agreement, or the Panion Amended
License Agreement, which amends and restates in full the Panion License Agreement, effective as of April 17, 2019. The Panion
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Amended License Agreement provides Keryx 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 the Licensor
Territory. The Panion Amended License Agreement also provides Panion with an exclusive license under Keryx-owned patents
covering the rights to sublicense (with the Company’s written 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 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 expiration of each of the Company’s and Panion’s obligations to pay
royalties thereunder. In addition, the Company may terminate the Panion Amended License Agreement (i) in its entirety or (ii) with
respect to one or more countries in the Company’s licensed territory, in either case upon 90 days’ notice. 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, until the second anniversary of the expiration of the obligation
of the Company or Panion, as applicable, to pay royalties in a country in which such party has ferric citrate for sale on the date of such
expiration, 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 distribution in such country.
The Panion Amended License Agreement includes customary terms relating to, among others, indemnification, confidentiality,
remedies, and representations and warranties.
During the year ended December 31, 2019 and the period from December 12, 2018 to December 31, 2018, the Company incurred
approximately $10.2 million and $0.4 million, respectively, in royalty payments due to Panion relating to the Company’s sales of
Auryxia in the United States and JT and Torii’s net sales of Riona in Japan, as the Company is required to pay a mid-single digit
percentage of net sales of ferric citrate in the Company’s licensed territories to Panion under the terms of the Panion Amended License
Agreement.
Sublicense Agreement with Japan Tobacco, Inc. and its subsidiary, Torii Pharmaceutical Co., Ltd.
Summary of Agreement
As a result of the Merger, the Company has an Amended and Restated Sublicense Agreement, which was amended in June 2013, with
JT and Torii, or the JT and Torii Sublicense Agreement, under which Keryx, the Company’s wholly owned subsidiary, remains the
contracting party. Under the JT and Torii Sublicense Agreement, JT and Torii obtained the exclusive sublicense rights for the
development and commercialization of ferric citrate hydrate in Japan. JT and Torii are responsible for the future development and
commercialization costs in Japan.
Ferric citrate hydrate is currently approved by the Japanese Ministry of Health, Labour and Welfare for manufacturing and marketing
in Japan for the treatment of hyperphosphatemia in patients with CKD. Ferric citrate hydrate is being marketed in Japan by Torii,
under the brand name Riona. JT and Torii are currently conducting a Phase 3 clinical program evaluating Riona for the treatment of
IDA in adult patients in Japan. JT and Torii have stated that, upon successful completion of its Phase 3 program, they expect to file an
application for approval of IDA as an additional indication for Riona in Japan. The Company is eligible to receive royalty payments
based on a tiered double-digit percentage of net sales of Riona in Japan escalating up to the mid-teens, subject to certain reductions
upon expiration or termination of the Amended and Restated License Agreement between Keryx and Panion, by which Keryx in-
licensed the exclusive worldwide rights, excluding certain Asian-Pacific countries, for the development and commercialization of
ferric citrate. The Company is entitled to receive up to an additional $55.0 million upon the achievement of certain annual net sales
milestones.
The sublicense under the JT and Torii Sublicense Agreement terminates upon the expiration 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 written notice to
us. Additionally, either party may terminate the JT and Torii Sublicense Agreement for cause upon 60 days’ prior written notice after
the breach of any uncured material provision of the JT and Torii Sublicense Agreement, or after certain insolvency events.
145
Revenue Recognition
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’s arrangement with JT and Torii contains the
following material promises under the contract at inception: (i) exclusive license to develop and commercialize ferric citrate hydrate in
Japan (the License Deliverable), (ii) supply of ferric citrate hydrate until JT and Torii could secure their own source (the Supply
Deliverable), (iii) knowledge transfer, and (iv) rights to future know-how.
The Company identified two performance obligations in connection with its obligations under the JT and Torii Sublicense Agreement:
(i) License and Supply Performance Obligation and (ii) Rights to Future Know-How Performance Obligation. The Company allocated
the transaction price to each performance obligation based on the Company’s best estimate of the relative standalone selling price. The
Company developed a best estimate of the standalone selling price for the Rights to Future Know-How Performance Obligation
primarily based on the likelihood that additional 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 estimate of standalone selling
price for the License and Supply Performance Obligation and allocated the entire transaction price to this performance obligation.
Additionally, as of the consummation of the Merger, the services associated with the License and Supply Performance Obligation
were completed and JT and Torii had secured their own source to manufacture ferric citrate hydrate. As such, any initial 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 consideration that may be payable to the Company under the terms of the sublicense
agreement are either quarterly royalties on net sales or payments due upon the achievement of sales-based milestones. In accordance
with ASC 606, the Company recognizes sales-based royalties, including 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 obligation is satisfied, or the related sales occur.
During the year ended December 31, 2019 and the period from December 12, 2018 to December 31, 2018, the Company recognized
$5.9 million and $0.1 million, respectively, in license revenue related to royalties 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.
5. Business Combination
On December 12, 2018, the Company completed the Merger with Keryx. Keryx’s proprietary product, Auryxia, is approved by the
FDA for two indications: (1) the control of serum phosphorus levels in adult patients with DD-CKD and (2) the treatment of iron
deficiency anemia in adult patients with NDD-CKD.
Akebia was determined to be the accounting acquirer and has accounted for the transaction as a business combination using the
acquisition method of accounting under ASC 805. Accordingly, the results of Keryx’s operations are included in our consolidated
financial statements from December 12, 2018, the date the Merger was completed. Keryx’s revenues and net loss from December 12,
2018 to December 31, 2018 were $6.9 million and $3.8 million, respectively.
Pursuant to the terms and conditions of the Merger Agreement, each outstanding Keryx Share, excluding the Baupost Additional
Shares, as defined below, and each outstanding Keryx equity award were converted into Akebia Shares and substantially similar
Akebia equity awards, respectively, at an exchange ratio of 0.37433 for a total fair value consideration of $527.8 million consisting of
the following (in thousands):
Fair value of 57,773,090 Akebia Shares
Fair value of 602,752 Akebia RSUs
Fair value of 3,967,290 Akebia stock options
Total consideration
$
$
516,492
304
10,958
527,754
The fair value of the Akebia common stock and Akebia awards issued was calculated using $8.94 per share, the closing price of
Akebia common stock on December 12, 2018. The portion of the fair value relating to the Akebia RSUs and stock options represents
the fair value attributable to precombination employee services. The fair value relating to future employee service will be expensed as
stock-based compensation on a straight-line basis over the remaining service periods of those awards.
146
Additionally, immediately prior to the Merger, Baupost Group Securities, L.L.C., or Baupost, agreed to convert its $164.7 million of
Keryx’s Convertible Notes into 35,582,335 Keryx Shares, in accordance with the terms of the governing indenture agreement, in
exchange for an additional 4,000,000 Keryx Shares, or the Baupost Additional Shares. The aggregate 39.6 million Keryx Shares were
then converted into Akebia Shares at the 0.37433 exchange ratio. The fair value of the Baupost Additional Shares, on an as-converted
basis, of $13.4 million has been excluded from the purchase price and recorded within selling, general and administrative expenses in
the Company’s consolidated financial statements, as the issuance of those shares by Keryx is considered to be a separate transaction
under ASC 805, since it was entered into by or on behalf of the acquirer or primarily for the benefit of the acquirer or the combined
entity.
The Company allocated the $527.8 million purchase price to the identifiable assets acquired and liabilities assumed in the business
combination at their fair values as of December 12, 2018 as follows (in thousands):
Cash and cash equivalents
Inventory
Trade accounts receivable, net
Prepaid expenses and other current assets
Goodwill
Intangible assets:
Developed product rights for Auryxia
Other intangible assets
Property and equipment, net
Other assets
Accounts payable
Accrued expenses
Deferred tax liability
Debt
Fair value of unfavorable executory contract
Total purchase price
$
$
5,257
235,597
15,834
8,399
55,053
329,130
545
3,646
14,441
(17,570)
(42,972)
(35,096)
(15,000)
(29,510)
527,754
In performing the purchase price allocation, the Company considered, among other factors, the intended future use of acquired assets,
analysis of historical financial performance and estimates of future performance of Keryx’s business.
As part of the purchase price allocation, the Company identified developed product rights for Auryxia as the primary intangible asset.
The fair value of the developed product rights for Auryxia was determined using the multi-period excess earnings method which is a
variation of the income approach, and is a valuation technique that provides an estimate of the fair value of an asset based on the
principle that the value of an intangible asset is equal to the present value of the incremental after-tax cash flows attributable to the
asset, after taking charges for the use of other assets employed by the business. Key estimates and assumptions used in this model
were projected revenues and expenses related to the asset, estimated contributory asset charges, and a risk-adjusted discount rate of
20.0% used to calculate the present value of the future expected cash inflows from the asset. The intangible asset is being amortized
on a straight-line basis over its estimated useful life, which for Auryxia is nine years.
The Company also identified an executory contract in the supply agreement between Keryx and BioVectra Inc., or BioVectra, which
includes future firm purchase commitments. This executory contract was deemed to have an off-market element related to the amount
of purchase commitments that exceed the current forecast and as such, the Company recorded a liability in purchase accounting. As of
the acquisition date, the fair value of the off-market element was $29.5 million.
The goodwill represents the excess of the purchase price over the estimated fair value of net assets acquired. The factors contributing
to the recognition of goodwill were based on several strategic and synergistic benefits that were expected to be realized from the
Merger. These benefits included the expectation that the combined company would establish itself as a leading renal company with
enhanced position and large market opportunity, synergistic utilization of Keryx’s commercial organization, and strengthening the
combined company’s financial profile. Such goodwill is not deductible for tax purposes.
In connection with the Merger, the Company identified a deferred tax liability of $35.1 million as a result of the difference in the book
basis and tax basis related to the identifiable inventory, other intangible assets, net and other liability. In determining the deferred tax
liability to be recorded the Company elected to first consider the recoverability of the deferred tax assets acquired in the acquisition
before considering the recoverability of the acquirer’s existing deferred tax assets.
147
In connection with the Merger, the Company incurred $23.1 million of direct transaction costs, which along with the expense
associated with the Baupost Additional Shares, is recorded within general and administrative expenses in our consolidated financial
statements for the year ended December 31, 2018.
6. Available For Sale Securities
Available for sale securities at December 31, 2019 and 2018 consist of the following:
December 31, 2019
Cash and cash equivalents
Available for sale securities:
Certificates of deposit
Total available for sale securities
Total cash, cash equivalents, and available for sale securities
December 31, 2018
Cash and cash equivalents
Available for sale securities:
Certificates of deposit
U.S. government debt securities
Corporate debt securities
Total available for sale securities
Total cash, cash equivalents, and available for sale securities
Gross
Gross
Unrealized
Unrealized
Amortized Cost
Gains
Losses
Fair Value
(in thousands)
$
$
$
$
147,449 $
— $
— $
147,449
245
245 $
147,694 $
—
— $
— $
— $
— $
— $
245
245
147,694
Gross
Gross
Unrealized
Unrealized
Amortized Cost
Gains
Losses
Fair Value
(in thousands)
$
$
$
$
104,644 $
— $
— $
104,644
245
158,518
58,494
217,257 $
321,901 $
—
1
—
1 $
1 $
— $
(198)
(64)
(262) $
(262) $
245
158,321
58,430
216,996
321,640
The estimated fair value of the Company’s available for sale securities balance at December 31, 2019, by contractual maturity, is as
follows (in thousands):
Due in one year or less
Due after one year
Total available for sale securities
$
$
245
—
245
There were no realized gains or losses on available for sale securities for the years ended December 31, 2019 or 2018. Additionally,
the Company did not have any available for sale securities that were in an unrealized loss position as of December 31, 2019. The
following table summarizes the Company’s available for sale securities that were in a continuous unrealized loss position, but were
not deemed to be other-than-temporarily impaired, as of December 31, 2018:
Unrealized Loss for
Less Than 12 Months
Gross
Unrealized
Losses
Estimated
Fair Value
Gross
Unrealized
Losses
Unrealized Loss for
12 Months or More
Total
Gross
Estimated Unrealized
Fair Value
Losses
Estimated
Fair Value
December 31, 2018
Available for sale securities:
U.S. government debt securities
Corporate debt securities
Total
(in thousands)
$
$
(159) $ 116,026 $
58,430
(64)
(223) $ 174,456 $
(39) $
—
(39) $
29,934 $
—
29,934 $
(198) $ 145,960
58,430
(64)
(262) $ 204,390
148
As noted above, there were no securities as of December 31, 2019 that were in an unrealized loss position. There were 51 securities as
of December 31, 2018 that were in an unrealized loss position. The Company considered the decline in the market value of these
securities to be primarily attributable to current economic conditions. The contractual terms of these securities do not permit the issuer
to settle the securities at a price less than the amortized cost basis of the investment.
7. Fair Value of Financial Instruments
The Company utilizes a portfolio management company for the valuation of the majority of its investments. This company is an
independent, third-party vendor recognized to be an industry leader with access to market information that obtains or computes fair
market values from quoted market prices, pricing for similar securities, recently executed transactions, cash flow models with yield
curves and other pricing models. For valuations obtained from the pricing service, the Company performs due diligence to understand
how the valuation was calculated or derived, focusing on the valuation technique used and the nature of the inputs.
Based on the fair value hierarchy, the Company classifies its cash equivalents and available for sale securities within Level 1 or
Level 2. This is because the Company values its cash equivalents and available for sale securities using quoted market prices or
alternative pricing sources and models utilizing market observable inputs.
Assets measured or disclosed at fair value on a recurring basis as of December 31, 2019 and 2018 are summarized below:
December 31, 2019
Assets:
Cash and cash equivalents
Certificates of deposit
Liabilities:
Derivative liability
December 31, 2018
Assets:
Cash and cash equivalents
Certificates of deposit
U.S. government debt securities
Corporate debt securities
Fair Value Measurements Using
Level 1
Level 2
Level 3
Total
(in thousands)
$
$
$
$
$
$
147,449 $
—
147,449 $
— $
245
245 $
— $
—
— $
147,449
245
147,694
— $
— $
— $
— $
1,650 $
1,650 $
1,650
1,650
Fair Value Measurements Using
Level 1
Level 2
Level 3
Total
(in thousands)
104,644 $
—
—
—
104,644 $
— $
245
158,321
58,430
216,996 $
— $
—
—
—
— $
104,644
245
158,321
58,430
321,640
The corporate debt securities held by the Company were all investment grade.
The Company’s Loan Agreement with Pharmakon (see Note 11) contains certain provisions that change the underlying cash flows of
the debt instrument, including a potential extension to the interest-only period dependent on both no event of default having occurred
and continuing and on the Company achieving certain regulatory and revenue conditions. The Company also assessed the acceleration
of the obligations under the Loan Agreement under an event of default. In addition, under certain circumstances, a default interest rate
will apply on all outstanding obligations during the occurrence and continuance of an event of default. In accordance with ASC 815,
the Company concluded that these features are not clearly and closely related to the host instrument, and represent a single compound
derivative that is required to be re-measured at fair value on a quarterly basis.
149
The events of default include a minimum liquidity threshold starting in 2021. At November 25, 2019, the Company recorded a
derivative liability related to the Company’s Loan Agreement with Pharmakon of $1.7 million. The Company determined that the
change in fair value from November 25, 2019 to December 31, 2019 was immaterial. The Company classified the derivative liability
as a non-current liability on the balance sheet at December 31, 2019. The estimated fair value of the derivative liability was
determined using a scenario-based approach and discounted cash flow model that includes principal and interest payments under
various scenarios involving clinical development success for vadadustat and various cash flow assumptions. Probabilities surrounding
clinical development success were derived using industry benchmarks. Should the Company’s assessment of the probabilities around
these scenarios change, there could be a change to the fair value of the derivative liability.
The Company had no other assets or liabilities measured at fair value on a recurring basis using significant unobservable inputs
(Level 3) at December 31, 2019 and December 31, 2018.
Investment securities are exposed to various risks such as interest rate, market and credit risks. Due to the immaterial balance of
investments held at December 31, 2019, the Company does not believe that changes in risks in the near term would result in material
changes in the fair value of investments.
8. Inventory
The components of inventory, inclusive of step-up as a result of bringing Keryx’s inventory onto Akebia’s books in connection with
the Merger, are summarized as follows:
December 31,
2019
December 31,
2018
(in thousands)
Raw materials
Work in process
Finished goods
Total inventory
$
2,278 $
1,880
215,122
18,182
$ 182,232 $ 235,184
137,858
42,096
Long-term inventory, which primarily consists of raw materials and work in process, is included in other assets in the Company’s
consolidated balance sheets.
Balance Sheet Classification:
Inventory
Other assets
Total inventory
December 31,
2019
December 31,
2018
(in thousands)
$ 116,349
65,883
$ 114,245
120,939
$ 182,232 $ 235,184
Inventory amounts written down as a result of excess, obsolescence, scrap or other reasons and charged to cost of goods sold totaled
$7.1 million during the year ended December 31, 2019. There were no inventory write-offs during the period from December 12, 2018
through December 31, 2018. If future sales of Auryxia are lower than expected, the Company may be required to write-down the value
of such inventories. Inventory write-downs and losses on purchase commitments are recorded as a component of cost of sales in the
consolidated statement of operations.
150
9. Intangible Assets and Goodwill
Intangible Assets
The following table presents the Company’s intangible assets (in thousands):
Acquired intangible assets:
Developed product rights for Auryxia
Favorable lease
Total
Acquired intangible assets:
Developed product rights for Auryxia
Favorable lease
Total
December 31, 2019
Gross
Carrying
Value
Accumulated
Amortization
ASC 842
Adjustment
Total
Estimated
useful life
$ 329,130 $
545
$ 329,675 $
(37,918) $
(5)
(37,923) $
— $ 291,212
-
(540)
(540) $ 291,212
9 Years
N/A
December 31, 2018
Gross
Carrying
Value
Accumulated
Amortization
Total
Estimated useful
life
$
$
329,130 $
545
329,675 $
(1,517) $
(5)
(1,522) $
327,613
540
328,153
9 Years
4 years
On December 12, 2018, the Company completed the Merger, whereby it acquired certain definite-lived intangible assets, including the
developed product rights for Auryxia and a favorable lease. The Company amortizes its definite-lived intangible assets acquired as
part of the Merger using the straight-line method, which is considered the best estimate of economic benefit, over its estimated useful
life. As a result of the adoption of ASC 842 on January 1, 2019, the Company reclassed the remaining balance of the favorable lease
intangible asset into the operating lease asset. The Company recorded $36.4 million and $1.5 million in amortization expense related
to the developed product rights for Auryxia during the years ended December 31, 2019 and 2018. Estimated future amortization
expense for the intangible asset as of December 31, 2019 is as follows (in thousands):
2020
2021
2022
2023
2024
Thereafter
Goodwill
Goodwill was $55.1 million as of December 31, 2019 and 2018, derived as follows (in thousands):
Total Merger consideration
Less: Fair value of identified acquired assets and liabilities, net
Goodwill
$
$
$
$
Total
36,402
36,401
36,402
36,401
36,402
109,204
291,212
527,754
(472,701)
55,053
Goodwill is evaluated for impairment on an annual basis as of October 1, and more frequently if indicators are present or changes in
circumstances suggest that an impairment may exist.
151
10. Accrued Expenses
Accrued expenses are as follows:
Accrued clinical
Product revenue allowances
Accrued payroll
Lease liability
Professional fees
Royalties
Accrued commercial manufacturing
Accrued severance
Merger costs
Accrued other
Total accrued expenses
11. Debt
December 31, 2019
December 31, 2018
(in thousands)
$
$
61,815 $
30,552
12,604
4,989
3,444
2,713
2,680
725
—
9,549
129,071 $
71,881
22,861
12,880
—
2,367
2,430
6,383
3,962
16,071
12,082
150,917
Future principal payments on the Term Loans (as defined below) as of December 31, 2019 are as follows (in thousands):
2020
2021
2022
2023
2024
Thereafter
Total before unamortized discount and issuance costs
Less: unamortized discount and issuance costs
Total term loans
Principal
Payments
(in thousands)
—
—
7,140
30,354
42,506
—
80,000
(4,195)
75,805
$
$
Term Loans
On November 11, 2019, the Company, with Keryx as guarantor, entered into a loan agreement, or the 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, collectively with the Collateral Agent, Pharmakon, pursuant to which term loans in an aggregate principal amount of $100.0
million are made available to the Company in two tranches, subject to certain terms and conditions, or the Term Loans. The first
tranche of $80.0 million, or Tranche A, was drawn on November 25, 2019, or the Tranche A Funding Date. The second tranche,
available until December 31, 2020, allows the Company to borrow, at its option, an additional $20.0 million, or Tranche B, subject to
the satisfaction of customary conditions. The date on which Tranche B is drawn, the Tranche B Funding Date, and each of the Tranche
A Funding Date and the Tranche B Funding Date, a Funding Date.
Proceeds from the Term Loans may be used for general corporate purposes. The Company and Keryx entered into a Guaranty and
Security Agreement with the Collateral Agent, or the Guaranty and Security Agreement, on the Tranche A Funding Date. Pursuant to
the Guaranty and Security Agreement, the Company’s obligations under the Term Loans are unconditionally guaranteed by Keryx, or
the Guarantee. Additionally, the obligations of the Company and Keryx under the Term Loans and the Guarantee are secured by a first
priority lien on certain assets of the Company and Keryx, including Auryxia and certain related assets, cash, and certain equity
interests held by the Company and Keryx, collectively the Collateral.
152
The Term Loans bear interest at a floating rate per annum equal to the three-month LIBOR rate plus 7.50%, subject to a 2.00%
LIBOR floor and a 3.35% LIBOR cap, payable quarterly in arrears. The Term Loans will mature on the fifth anniversary of the
Tranche A Funding Date, or the Maturity Date. The Company will repay the principal under the Term Loans in equal quarterly
payments starting on the 33rd-month anniversary of the applicable Funding Date or, if certain conditions are met, it will have the
option to repay the principal in equal quarterly payments starting on the 48th-month anniversary of the applicable Funding Date, or
collectively the Amortization Schedule. Under certain circumstances, unless certain liquidity conditions are met, the Maturity Date
may decrease by up to one year, and the Amortization Schedule may correspondingly commence up to one year earlier.
On the Tranche A Funding Date, the Company paid to Pharmakon a facility fee equal to 2.00% of the aggregate principal amount of
the Term Loans, or $2.0 million, in addition to other expenses incurred by Pharmakon and reimbursed by the Company, or Lender
Expenses. The Tranche A draw was $77.3 million, net of facility fee, Lender Expenses and issuance costs. The Loan Agreement
permits voluntary prepayment at any time in whole or in part, subject to a prepayment premium. The prepayment premium would be
2.00% of the principal amount being prepaid prior to the third anniversary of the applicable Funding Date, 1.00% on or after the third
anniversary, but prior to the fourth anniversary, of the applicable Funding Date, and 0.50% on or after the fourth anniversary of the
applicable Funding Date but prior to the Maturity Date, and a make-whole premium on or prior to the second anniversary of the
applicable Funding Date in an amount equal to foregone interest through the second anniversary of the applicable Funding Date. A
change of control triggers a mandatory prepayment of the Term Loans.
The Loan Agreement contains customary representations, warranties, events of default and covenants of the Company and its
subsidiaries, including maintaining, on an annual basis, a minimum liquidity threshold starting in 2021, and on a quarterly basis, a
minimum net sales threshold for Auryxia starting in the fourth quarter of 2020. If an event of default occurs and is continuing under
the Loan Agreement, the Collateral Agent is entitled to take enforcement action, including acceleration of amounts due under the Loan
Agreement. Under certain circumstances, a default interest rate will apply on all outstanding obligations during the occurrence and
continuance of an event of default. As of December 31, 2019, the Company determined that no events of default had occurred.
The Company assessed the terms and features of the Loan Agreement in order to identify any potential embedded features that would
require bifurcation or any beneficial conversion feature. As part of this analysis, the Company assessed the economic characteristics
and risks of the Loan Agreement, including put and call features. The terms and features assessed include a potential extension to the
interest-only period dependent on both no event of default having occurred and continuing and on the Company achieving certain
regulatory and revenue conditions. The Company also assessed the acceleration of the obligations under the Loan Agreement under an
event of default. In addition, under certain circumstances, a default interest rate will apply on all outstanding obligations during the
occurrence and continuance of an event of default. In accordance with ASC 815, the Company concluded that these features are not
clearly and closely related to the host instrument, and represent a single compound derivative that is required to be re-measured at fair
value on a quarterly basis.
The events of default include a minimum liquidity threshold starting in 2021. At November 25, 2019, the Company recorded a
derivative liability related to the Company’s Loan Agreement with Pharmakon of $1.7 million. The Company determined that the
change in fair value from November 25, 2019 to December 31, 2019 was immaterial. The Company classified the derivative liability
as a non-current liability on the balance sheet at December 31, 2019.
During the year ended December 31, 2019, the Company recognized approximately $0.9 million of interest expense related to the
Loan Agreement.
Revolving Line of Credit
Keryx, the Company’s wholly owned subsidiary following the Merger, had a $40.0 million revolving line of credit, or the Line of
Credit, under its Loan and Security Agreement with Silicon Valley Bank, or SVB. On July 31, 2019, Keryx entered into a Waiver and
First Amendment to Loan and Security Agreement, or the Loan Amendment. Pursuant to the Loan Amendment, certain revisions were
made to the Loan and Security Agreement, including requiring Keryx to maintain, from and after December 31, 2019, subject to
certain exceptions, a certain amount of funds to which the Company had unrestricted access in one or more asset management
accounts with SVB or SVB’s affiliate and revising certain of the representations and warranties and covenants in the Loan and
Security Agreement. In addition, pursuant to the Loan Amendment, SVB waived the then-existing events of default.
153
On August 7, 2019, the Company executed and delivered to SVB an Unconditional Guaranty, or the Guaranty, pursuant to which the
Company guaranteed the prompt and complete payment and performance when due of all of the obligations and liabilities of Keryx
under the Loan and Security Agreement, as amended by the Loan Amendment, or the Amended Loan Agreement. In addition, the
Company entered into a Security Agreement with SVB effective August 7, 2019, or the Security Agreement, pursuant to which the
Company granted to SVB a continuing first priority security interest in substantially all of the Company’s personal property, other
than the Company’s intellectual property, to secure the payment and performance of the Company’s obligations under the Guaranty.
The Company’s obligations under the Guaranty were independent of Keryx’s obligations, and separate actions were able to be brought
against the Company.
Availability under the Line of Credit was subject to a borrowing base comprised of eligible receivables and eligible inventory of
Keryx as set forth in the Loan and Security Agreement. As of December 31, 2019 and 2018, there was $0 and $15.0 million
outstanding, respectively, under the Line of Credit and the Company had $0 in available borrowing base as of December 31, 2019, as
the Line of Credit was terminated in November 2019.
The principal amount outstanding under the Loan and Security Agreement bore interest at a floating rate per annum equal to the
greater of (i) 2.0% above the “prime rate,” as reported in The Wall Street Journal and (ii) 6.75%, which interest was payable monthly.
Principal amounts borrowed under the Line of Credit were able to be repaid and, prior to the maturity date, re-borrowed, subject to the
terms and conditions set forth in the Loan and Security Agreement. Upon entry into the Loan and Security Agreement (payable in
installments and subject to certain conditions), and at the one year anniversary of the effective date of the Loan and Security
Agreement (or, if earlier, upon termination of or an event of default under the Loan and Security Agreement), Keryx paid to SVB a fee
equal to 1.00% of the Line of Credit. Keryx was also required to pay on a quarterly basis a fee equal to 0.25% per annum of the
average unused portion of the Line of Credit. Pursuant to the terms of the Loan and Security Agreement, Keryx was required to pay a
termination fee of 2.00% of the Line of Credit, if the Loan and Security Agreement was terminated prior to the maturity date, subject
to certain exceptions. The Company terminated the Loan and Security Agreement, the Unconditional Guaranty, and the Security
Agreement on November 7, 2019, and Keryx paid SVB a termination fee of $0.8 million.
During the year ended December 31, 2019 and the period from December 12, 2018 through December 31, 2018, the Company
recognized approximately $0.5 million and $65,000, respectively, of interest expense related to the Line of Credit. The Company did
not incur any amortization expense related to the origination fee and other additional fees noted above as such fees were included in
the fair value of the Line of Credit as of December 12, 2018, the date on which the Merger was consummated, in accordance with
ASC 805.
12. Warrant
In connection with the Janssen Agreement, in February 2017, the Company issued a warrant to purchase 509,611 shares of the
Company’s common stock at an exercise price of $9.81 per share. The warrant was fully vested upon issuance and exercisable in
whole or in part, at any time prior to February 9, 2022. The warrant satisfied the equity classification criteria of ASC 815, and is
therefore classified as an equity instrument. The fair value at issuance of $3.4 million was calculated using the Black-Scholes option
pricing model and was charged to research and development expense as it represented consideration for a license for which the
underlying intellectual property was deemed to have no alternative future use. As of December 31, 2019, the warrant remains
outstanding and expires on February 9, 2022.
13. Stockholders’ Equity
Authorized and Outstanding Capital Stock
As of December 31, 2019, the authorized capital stock of the Company included 175,000,000 shares of common stock, par value
$0.00001 per share, of which 121,674,568 and 116,887,518 shares were issued and outstanding at December 31, 2019 and 2018,
respectively; and 25,000,000 shares of undesignated preferred stock, par value $0.00001 per share, of which 0 shares were issued and
outstanding at December 31, 2019 and December 31, 2018.
Retired Shares
In April 2019, the Company repurchased and retired 55,324 shares of common stock from certain officers of the Company. The
proceeds from the disposition of these shares were used by certain officers of the Company to cover tax liabilities associated with
previously vested RSUs.
154
At-the-Market Facility
In May 2016, the Company established an at-the-market, or ATM, equity offering program pursuant to which it was able to offer and
sell up to $75.0 million its common stock at the then current market prices from time to time. Through December 31, 2018, the
Company sold 1,775,214 shares of common stock under this program with net proceeds of $22.6 million, of which 694,306 shares
were sold in the year ended December 31, 2018 for net proceeds of approximately $10.5 million. Additionally, the Company sold
1,384,520 shares in the six months ended June 30, 2019 for net proceeds (after deducting commissions and other offering expenses) of
approximately $9.4 million.
On November 12, 2019, the Company entered into an Amended and Restated Controlled Equity OfferingSM Sales Agreement with
Cantor Fitzgerald & Co. for the offer and sale of common stock at the then current market prices in amounts to be determined from
time to time. Also, on November 12, 2019, the Company filed a prospectus supplement pursuant to which it was able to offer and sell
up to $75.0 million its common stock at the then current market prices from time to time. In December 2019, the Company
commenced sales under this program. Through December 31, 2019, the Company sold 2,684,392 shares of common stock under this
program with net proceeds (after deducting commissions and other offering expenses) of $16.8 million. Subsequent to December 31,
2019 and through February 4, 2020, the Company sold 7,973,967 shares of common stock under this program with net proceeds (after
deducting commissions and other offering expenses) of $56.7 million.
Equity Offering
In March 2018, the Company completed a follow-on public equity offering, whereby the Company sold 8,500,000 shares of common
stock at a public offering price of $10.50 per share. The aggregate net proceeds received by the Company from the offering were
approximately $84.8 million, net of underwriting discounts and commissions and estimated offering expenses payable by the
Company. The Company did not have any follow-on public equity offerings during the year ended December 31, 2019.
Shares Issued and Awards Assumed in Connection with Business Combination
On December 12, 2018, the Company completed the Merger. Pursuant to the terms and conditions of the Merger Agreement, each
Keryx Share issued and outstanding as of the Effective Time was cancelled and converted into 0.37433 fully paid and non-assessable
Akebia Shares. As a result, in December 2018, the Company issued 57,773,090 shares of common stock to Keryx shareholders, and
1,497,320 shares issued as part of the Baupost Additional Shares which has been excluded from the business combination purchase
price (see Note 5).
Additionally, in connection with the Merger, the Company converted outstanding and unexercised options to purchase Keryx Shares
into 3,967,290 options to purchase Akebia Shares, as adjusted to the reflect the Exchange Multiplier, of which 3,733,336 are service-
based stock options and 233,954 are performance-based stock options. The Company also converted outstanding Keryx Restricted
Shares into 602,752 Akebia RSUs, of which 486,709 are service-based RSUs and 116,043 are performance-based RSUs.
Acceleration of Equity Awards
In connection with the closing of the Merger, certain executives of Keryx were terminated and as a result, the Company accelerated in
full the vesting of all of the outstanding equity awards for each such executive, consistent with his or her existing employment
agreements. Additionally, subject to limited exceptions, all outstanding equity awards held by certain officers of Akebia also had the
vesting of their outstanding equity awards accelerated in full upon consummation of the Merger as a result of the change in control
provision included in each such officer’s award agreements and their Executive Severance Agreements. As a result, the Company
recognized $9.7 million of stock-based compensation expense related to the acceleration of awards during the year ended December
31, 2018.
Equity Plans
On February 28, 2014, the Company’s Board of Directors adopted its 2014 Incentive Plan and its 2014 Employee Stock Purchase
Plan, or the 2014 ESPP, which were subsequently approved by its shareholders and became effective upon the closing of the
Company’s initial public offering on March 25, 2014. The Company’s 2014 Incentive Plan was subsequently amended on December
11, 2018, which amendment did not require shareholder approval. The Company’s 2014 Incentive Plan, as amended, is referred to as
the 2014 Plan. The 2014 Plan replaced the Company’s Amended and Restated 2008 Equity Incentive Plan, or the 2008 Plan; however,
options or other awards granted under the 2008 Plan prior to the adoption of the 2014 Plan that have not been settled or forfeited
remain outstanding and effective. On June 6, 2019, the Company’s shareholders approved the Amended and Restated 2014 Employee
Stock Purchase Plan, or the ESPP. In May 2016, the Company’s Board of Directors approved an inducement award program that was
separate from the Company’s equity plans and which, consistent with Nasdaq Listing Rule 5635(c)(4), did not require shareholder
approval, or the Inducement Award Program. For 2019, the Company authorized the issuance of up to 3,150,000 shares for the
purpose of granting options to purchase shares of the Company’s common stock to new hires under the Inducement Award Program,
of which 1,505,300 options to purchase Akebia Shares were granted during the year ended December 31, 2019, of which 1,412,550
options to purchase Akebia Shares remained outstanding at December 31, 2019.
155
The 2014 Plan allows for the granting of stock options, stock appreciation rights, or SARs, restricted stock, unrestricted stock, RSUs,
performance awards and other awards convertible into or otherwise based on shares of the Company’s common stock. Dividend
equivalents may also be provided in connection with an award under the 2014 Plan. The Company’s employees, officers, directors and
consultants and advisors are eligible to receive awards under the 2014 Plan. The Company initially reserved 1,785,000 shares of its
common stock for the issuance of awards under the 2014 Plan. The 2014 Plan provides that the number of shares reserved and
available for issuance under the 2014 Plan will automatically increase annually on January 1 of each calendar year, by an amount
equal to three percent (3%) of the number of Akebia Shares outstanding on a fully diluted basis as of the close of business on the
immediately preceding December 31, or the 2014 Plan Evergreen Provision. The Company’s Board of Directors may act prior to
January 1 of any year to provide that there will be no automatic increase in the number of Akebia Shares available for grant under the
2014 Plan for that year (or that the increase will be less than the amount that would otherwise have automatically been made). On
December 12, 2018, in connection with the consummation of the Merger, the Company assumed outstanding and unexercised options
to purchase Keryx Shares, as adjusted by the Exchange Multiplier pursuant to the terms of the Merger Agreement, under the following
Keryx equity plans, or the Keryx Equity Plans: the Keryx 1999 Share Option Plan, the Keryx 2004 Long-Term Incentive Plan, the
Keryx 2007 Incentive Plan, the Keryx Amended and Restated 2013 Incentive Plan, and the Keryx 2018 Equity Incentive Plan, or the
Keryx 2018 Plan. In addition, the number of Keryx Shares available for issuance under the Keryx 2018 Plan, as adjusted by the
Exchange Multiplier pursuant to the terms of the Merger Agreement, may be used for awards granted by the Company under its 2014
Plan, or the Assumed Shares, provided that the Company uses the Assumed Shares for individuals who were not employees or
directors of the Company prior to the consummation of the Merger. During the year ended December 31, 2019, the Company granted
2,028,625 options to purchase Akebia Shares to employees under the 2014 Plan, 1,505,300 options to purchase Akebia Shares to
employees under the Inducement Award Program, 4,485,895 Akebia RSUs to employees under the 2014 Plan, 180,900 options to
purchase Akebia Shares to directors under the 2014 Plan, and 123,300 Akebia RSUs to directors under the 2014 Plan.
The ESPP provides for the issuance of options to purchase shares of the Company’s common stock to participating employees at a
discount to their fair market value. As noted above, the Company’s stockholders approved the ESPP, which amended and restated the
Company’s 2014 ESPP, on June 6, 2019. The maximum aggregate number of shares at December 31, 2019 of the Company’s
common stock available for future issuance under the ESPP is 5,715,992. Under the ESPP, each offering period is six months, at the
end of which employees may purchase shares of the Company’s common stock through payroll deductions made over the term of the
offering. The per-share purchase price at the end of each offering period is equal to the lesser of eighty-five percent (85%) of the
closing price of the Company’s common stock at the beginning or end of the offering period.
Shares Reserved for Future Issuance
The Company has reserved for future issuance the following number of shares of common stock:
Common stock options and RSUs outstanding (1)
Shares available for issuance under Akebia equity plans (2)
Warrant to purchase common stock
Shares available for issuance under the ESPP (3)
Total
December 31, 2019
12,195,031
2,983,256
509,611
5,715,992
21,403,890
December 31, 2018
9,309,204
4,526,563
509,611
603,522
14,948,900
(1)
(2)
(3)
Includes awards granted under the 2014 Plan and the Inducement Award Program and awards issued in connection with the
Merger.
On January 1, 2020, January 1, 2019 and January 1, 2018, the shares reserved for future grants under the 2014 Plan increased by
4,031,376, 3,801,198 and 1,575,329 shares, respectively, pursuant to the 2014 Plan Evergreen Provision. On December 12,
2018, the shares reserved for future grants under the 2014 Plan increased by 2,323,213 shares as a result of the Company’s
addition of the Assumed Shares to the 2014 Plan. On December 19, 2017, the Company’s Board of Directors approved 750,000
shares for issuance as option awards in fiscal year 2018 under the Inducement Award Program. On January 30, 2019, the
Company’s Board of Directors approved 3,150,000 shares for issuance as option awards in fiscal year 2019 under the
Inducement Award Program.
On June 6, 2019, the shares reserved for future issuance under the ESPP increased by 5,200,000 shares upon shareholder
approval of the Amended and Restated 2014 Employee Stock Purchase Plan. On February 28, 2018 and February 28, 2017, the
shares reserved for future issuance under the ESPP remained unchanged. There were no increases in the shares reserved for
future issuance pursuant to the evergreen provision under the 2014 ESPP in 2017 and 2018 as the maximum aggregate number
of shares available for purchase under the 2014 ESPP had reached its cap of 739,611 on February 28, 2016.
156
Stock-Based Compensation
Stock Options
Service-Based Stock Options
On February 28, 2019, as part of the Company’s annual grant of equity, the Company issued 2,028,625 stock options to employees. In
addition, the Company issues stock options to directors, new hires and occasionally to other employees not in connection with the
annual grant process. Options granted by the Company vest over periods of between 12 and 48 months, subject, in each case, to the
individual’s continued service through the applicable vesting date. Options 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 after the one year
anniversary of the grant date, subject to the individual’s continuous service with the Company. Options generally expire ten years after
the date of grant. The Company recorded approximately $5.4 million, $11.9 million and $6.5 million of stock-based compensation
expense related to stock options granted during fiscal years 2019, 2018 and 2017, respectively.
On December 12, 2018, pursuant to the Merger Agreement, each outstanding and unexercised option to acquire Keryx Shares granted
under a Keryx equity plan converted into an option to acquire Akebia Shares, with the number of shares and exercise price adjusted by
the Exchange Multiplier. As a result, the Company assumed 3,733,336 service-based options related to the Merger. The vesting
schedule for these options is consistent with the vesting schedule noted above.
The assumptions used in the Black-Scholes pricing model to estimate the grant date fair value of options granted under the 2014 Plan
are as follows:
Risk-free interest rate
Dividend yield
Volatility
Expected term (years)
Year ended December 31,
2019
2018
2017
1.42% - 2.57%
2.54% - 3.01%
1.81% - 2.27%
0.00%
0.00%
0.00%
61.40% - 64.10%
61.65% - 77.04%
78.57% - 85.81%
5.51 - 6.25
5.51 - 6.25
5.51 - 6.25
The following table summarizes the Company’s stock option activity, excluding performance-based options, for the year ended
December 31, 2019:
Outstanding, December 31, 2018
Granted
Exercised
Forfeited
Expired/cancelled
Outstanding, December 31, 2019
Options exercisable, December 31, 2019
Vested and expected to vest,
December 31, 2019
Weighted-Average
Shares
8,144,752 $
3,714,825 $
(362,796) $
(3,842,588) $
(30,084) $
7,624,109 $
3,759,075 $
7,624,109 $
Exercise Price
13.57
6.38
1.54
15.26
18.09
9.77
12.74
9.77
Weighted-Average
Contractual Life
(in years)
Aggregate
Intrinsic Value
$
$
$
7.84 $
6.45 $
2,351,316
1,273,757
67,753
3,173,101
983,273
The weighted-average grant date fair values of options granted in the years ended December 31, 2019, 2018, and 2017 were $3.85,
$7.12, and $8.47 per share, respectively. The total intrinsic value of options exercised during the years ended December 31, 2019,
2018, and 2017 were $1.3 million, $1.2 million, and $2.7 million, respectively. The fair value of options that vested during the years
ended December 31, 2019, 2018, and 2017 were $4.3 million, $13.6 million, and $5.6 million, respectively. As of December 31, 2019,
there was approximately $13.5 million of unrecognized compensation cost related to stock options under the Company’s 2014 Plan or
made pursuant to the Inducement Award Program, which is expected to be recognized over a weighted average period of 2.83 years.
157
Performance-Based Stock Options
On December 12, 2018, pursuant to the Merger Agreement, each outstanding and unexercised performance-based option to acquire
Keryx Shares granted under a Keryx equity plan converted into a service-based option or performance-based option to acquire Akebia
Shares, with the number of shares and exercise price adjusted by the Exchange Multiplier. As a result, the Company issued 233,954
performance-based options related to the Merger. The Company did not have any performance based-options outstanding in fiscal
year 2018 prior to the Merger. The Company did not issue any performance-based options during the year ended December 31, 2019
and 2018 besides those issued related to the Merger in 2018. As of December 31, 2019, the Company had 46,790 performance-based
options outstanding. The potential range of shares issuable pursuant to the Company’s performance-based options range from 0% to
100% of the target shares based on financial measures. Performance-based options vest up to 50% upon achievement of performance
condition and up to 50% one year following achievement of the performance condition.
The following table summarizes the Company’s performance-based option activity for the year ended December 31, 2019:
Outstanding, December 31, 2018
Granted
Exercised
Forfeited/cancelled
Outstanding, December 31, 2019
Shares
Weighted-Average
Exercise Price
Weighted-Average
Contractual Life
(in years)
Aggregate
Intrinsic Value
202,136 $
— $
— $
(155,346) $
46,790 $
19.82
—
—
21.04
15.77
7.42 $
$
6.83 $
—
—
—
The Company did not record any stock-based compensation expense related to performance-based options during 2019, 2018 and
2017. There were 46,790 performance-based options that vested during fiscal year 2019 and no performance-based options that vested
during fiscal years 2018 or 2017. As of December 31, 2019, there were no unrecognized compensation costs related to performance-
based stock options under the Company’s 2014 Plan.
Restricted Stock Units
On February 28, 2019, as part of the Company’s annual grant of equity, the Company issued 1,384,775 restricted stock units, or RSUs,
to employees. In addition, the Company occasionally issues RSUs not in connection with the annual grant process to employees. On
September 30, 2019, the Company issued 2,979,400 restricted stock units to employees. RSUs granted by the Company vest in one of
the following ways: (i) 100% of each RSU grant vests on either the first or the third anniversary of the grant date, or (ii) one third of
each RSU grant vests on the first, second and third anniversaries of the grant date, subject, in each case, to the individual’s continued
service through the applicable vesting date, or (iii) 50% of each RSU grant vests on the first anniversary and 25% of each RSU grant
vests in 6 months increment after the one year anniversary of the grant date. The expense recognized for these awards is based on the
grant date fair value of the Company’s common stock multiplied by the number of units granted and recognized on a straight-line
basis over the vesting period. The Company recorded approximately $6.2 million, $5.8 million and $2.0 million of stock-based
compensation expense related to employee RSUs in 2019, 2018 and 2017, respectively.
On December 12, 2018, pursuant to the Merger Agreement, each Keryx Share that was subject to a Keryx restricted share award, other
than those Keryx restricted shares that accelerated or lapsed as a result of the completion of the Merger, was converted into an RSU
award of Akebia, covering the number of Akebia Shares determined in accordance with the Exchange Multiplier. As a result, the
Company issued 486,709 service-based RSUs in substitution for Keryx restricted share awards in connection with the Merger. These
RSUs vest either (i) in 3 equal annual installments beginning after the one-year anniversary of the grant date or (ii) one third on the
one year anniversary of the grant date with the remaining RSUs vesting on the first day of each calendar quarter over the next two
years thereafter.
A following table summarizes the Company’s RSU activity for the year ended December 31, 2019:
Unvested balance, December 31, 2018
Granted
Vested
Forfeited
Unvested balance, December 31, 2019
158
Shares
Weighted-
Average Grant
Date Fair Value
846,273 $
4,609,195 $
(323,136) $
(621,302) $
4,511,030 $
9.16
4.97
8.32
6.90
5.25
The total amount of RSUs that vested during 2019, 2018 and 2018 (measured on the date of vesting) was $2.7 million, $7.4 million,
and $0.2 million, respectively. As of December 31, 2019, there was approximately $17.8 million of unrecognized compensation cost
related to RSUs, which is expected to be recognized over a weighted average period of 1.82 years.
There are 13,102 performance-based RSUs, issued in connection with the Merger, outstanding at December 31, 2019.
Employee Stock Purchase Plan
The first offering period under the ESPP opened on January 2, 2015. The Company issued 87,530 shares during the year ended
December 31, 2019. The Company recorded approximately $0.3 million, $0.2 million and $0.2 million of stock-based compensation
expense related to the ESPP during 2019, 2018 and 2017, respectively.
Compensation Expense Summary
The Company has classified its stock-based compensation expense related to share-based awards as follows:
Research and development
Selling, general and administrative
Total
Compensation expense by type of award:
Stock options
Restricted stock
Restricted stock units
Employee stock purchase plan
Warrant
Total
$
$
$
$
2019
Years ended December 31,
2018
2017
(in thousands)
3,544 $
8,381
11,925 $
5,755 $
13,285
19,040 $
6,496
5,784
12,280
2019
Years ended December 31,
2018
2017
(in thousands)
5,421 $
—
6,240
264
—
11,925 $
12,114 $
—
6,731
195
—
19,040 $
6,512
158
2,021
176
3,413
12,280
Included in the compensation expense of stock options and RSUs for the year ended December 31, 2018, is approximately $1.1
million related to awards assumed under the Merger and acceleration of the vesting for awards of certain officers of Keryx.
14. 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 year ended December 31, 2017 due to the
Company’s net losses and increases in its valuation allowance against its deferred tax assets. At December 31, 2018 the Company
recorded a tax benefit of $28.3 million as a result of the Merger with Keryx. As part of purchase accounting, the Company recorded a
deferred tax liability that is a source of income for which the Company can benefit from its tax attributes. The use of the Company’s
tax attributes resulted in a release of the corresponding valuation allowance associated with this benefit. At December 31, 2019 the
company has recorded an additional tax benefit of $6.6 million as a result of additional losses incurred during the year.
159
The provision for income taxes for each of the years ended December 31, 2019, 2018 and 2017 consisted of the following:
Current:
Federal
State
Foreign
Total Current:
Deferred:
Federal
State
Foreign
Total Deferred:
Total Income Taxes
Year ended December 31,
2018
2017
2019
—
—
—
—
23
104
—
127
—
(6,631)
—
(6,631)
(6,631)
(16,383)
(12,082)
—
(28,465)
(28,338)
—
—
—
—
—
—
—
—
—
Our effective income tax rate differs from the statutory federal income tax rate as follows for the years ended December 31, 2019,
2018 and 2017:
Federal tax at statutory rate
State and local tax at statutory rate
Research and development tax credits
Equity compensation
Alternative minimum tax
Change in valuation allowance
Impact of US tax reform
Non-deductible transaction costs
Other permanent differences
Reduction in deferred tax assets for change in ownership
Effect of rate changes
Other
Effective tax rate
Year ended December 31,
2018
2017
2019
21.0%
5.5
2.0
—
—
(22.4)
—
—
(0.3)
(1.6)
(1.4)
(0.5)
2.3%
21.0%
4.1
5.0
—
—
16.3
—
(3.1)
(0.7)
(26.1)
—
—
16.5%
34.0%
3.8
11.9
(0.6)
(1.3)
6.9
(54.7)
—
—
—
—
—
0.0%
For the year ended December 31, 2017, the Company had taxable income primarily due to timing differences. The income was fully
offset with available net operating losses, or NOLs, for regular federal and state tax purposes. The Company did have a tax liability
that was based on the Alternative Minimum Tax and resulted in approximately $0.8 million of Federal Tax, however due to tax reform,
the amount is fully refundable through 2021 and thus the net result is that the Company recorded an income tax receivable of
approximately $0.8 million rather than a tax expense for the year ended December 31, 2017.
160
Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
financial reporting purposes and the amounts used for income tax purposes. When realization of the deferred tax asset is more likely
than not to occur, the benefit related to the deductible temporary differences attributable to operations is recognized as a reduction of
income tax expense. A valuation 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 valuation allowance against the Company’s otherwise recognizable net
deferred tax assets. The Company continues to maintain the underlying tax benefits to offset future taxable income and to monitor the
need for a valuation allowance based on the profitability of its future operations. The valuation allowance increased by approximately
$64.0 million and $23.3 million, during the years ended December 31, 2019 and 2018, respectively. Significant components of the
Company’s deferred tax assets and liabilities are as follows:
Deferred tax assets:
Accrued expenses
Deferred revenue
Stock based compensation
Research and development credits
Other non-current liabilities
Net operating loss carryforward
ASC 842 lease liability
Fixed assets
Other
Total deferred tax assets
Less valuation allowance
Total deferred tax assets, net of valuation allowance
Deferred tax liabilities:
Fixed assets
Intangible assets
Inventory
ASC 842 ROU asset
Derivative liability
Total deferred tax liabilities
Net deferred tax liability
December 31,
2019
2018
(in thousands)
2,933 $
18,678
10,136
9,601
8,049
242,167
8,382
806
4,018
304,770
(195,418)
109,352
—
(75,940)
(25,494)
(7,495)
(423)
(109,352)
— $
4,993
28,533
9,514
2,899
7,567
189,842
—
—
853
244,201
(131,424)
112,777
(121)
(81,847)
(37,440)
—
—
(119,408)
(6,631)
$
$
At December 31, 2019 and 2018, the Company has approximately $0.5 million (after amortization of $1.4 million) and $0.6 million (after
amortization of $1.3 million), respectively, of start-up expenses capitalized for income tax purposes with amortization available to offset
future federal, state and local income tax.
As of December 31, 2019 and 2018, the Company has approximately $1,014.8 million and $790.0 million, respectively, of federal NOL
carry-forwards which expire through 2037. Included in the $1,014.8 million of federal NOLs are losses of $432.8 million that will carry
forward indefinitely as a result of the Tax Cuts and Jobs Act. Additionally, at December 31, 2019 and 2018, the Company has
approximately $1,374.0 million and $442.4 million, respectively, of state NOL carry-forwards which expired through 2039. The
Company also has approximately $5.8 million of federal research and development tax credit carryforwards which expire through 2039
and $4.9 million of state research and development tax credit carryforwards which expire through 2038.
Under the provisions of the Internal Revenue Code, the net operating losses and tax credit carry-forwards are subject to review and
possible adjustment by the Internal Revenue Service and state tax authorities. Net operating losses and tax credit carryforwards may
become subject to an annual limitation under Internal Revenue Code 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
evaluation of its ownership changes and concluded that an ownership change did occur on December 12, 2018 for both Akebia and
Keryx in connection with the Merger. As a consequence of this ownership change, the Company’s NOL’s and tax credit carryforwards
allocable to the tax periods preceding the ownership change became subject to limitation under Section 382. The Company reduced its
associated deferred tax assets by $44.9 million as a result of the limitation.
The Company generated research credits but has not conducted a formal study to document its qualified activities. This study may
result in an adjustment to the Company’s research and development credit carryforwards; however, until a study is completed and any
161
adjustment is known, no amounts are being presented as an uncertain tax position. A valuation allowance has been provided against
the Company’s research and development credits and, if an adjustment is required, this adjustment would be offset by an adjustment to
the deferred tax asset established for the research and development credit carry-forwards and the valuation allowance.
The Company files income tax returns in the U.S. federal and various state and local jurisdictions. For federal and state income tax
purposes, the 2018, 2017 and 2016 tax years remain open for examination under the normal three-year statute of limitations. The
statute of limitations for income tax audits in the United States will commence upon utilization of net operating losses and will expire
three years from the filing of the tax return the loss was utilized on.
There was no accrual for uncertain tax positions or for interest and penalties related to uncertain tax positions for 2019, 2018 and 2017.
The Company does not believe that there will be a material change in its unrecognized tax positions over the next twelve months. All
of the unrecognized tax benefits, if recognized, would be offset by the valuation allowance.
15. Employee Retirement Plan
During 2008, the Company established a retirement plan, or the Plan, authorized by Section 401(k) of the Internal Revenue Code. In
accordance with the Plan, all employees who have attained the age of 21 are eligible to participate in the Plan as of the first Entry
Date, as defined, following their date of employment. Each employee can contribute a percentage of compensation up to a maximum
of the statutory limits per year. Company contributions are discretionary and contributions in the amount of approximately $1.3
million, $0.3 million and $0.2 million were made during the years ended December 31, 2019, 2018 and 2017, respectively.
16. Commitments and Contingencies
Leases
The Company leases approximately 65,167 square feet of office and lab space in Cambridge, Massachusetts under a lease which was
most recently amended in April 2018, collectively the Cambridge Lease. Under the Third Amendment to the Cambridge Lease, or the
Third Amendment, executed in July 2016, total monthly lease payments under the initial base rent were approximately $242,000 and
are subject to annual rent escalations. In addition to such annual rent escalations, base rent payments for a portion of said premises
commenced on January 1, 2017 in the monthly amount of approximately $22,000. The Fourth Amendment to the Cambridge Lease,
executed in May 2017, provided additional storage space to the Company and did not impact rent payments. In April 2018, the
Company entered into a Fifth Amendment to the Cambridge Lease, or the Fifth Amendment, for an additional 19,805 square feet of
office space on the 12th floor. Monthly lease payments for the existing 45,362 square feet of office and lab space, under the Third
Amendment, remain unchanged. The new space leased by the Company was delivered in September 2018 and additional monthly
lease payments of approximately $135,000 commenced in February 2019 and are subject to annual rent escalations, which
commenced in September 2019.
Additionally, as a result of the Merger, the Company now has a lease for 27,300 square feet of office space in Boston, Massachusetts,
or the Boston Lease, which expires in February 2023. The total monthly lease payments under the base rent are approximately
$136,000 and are subject to annual rent escalations.
The term of the Cambridge Lease with respect to the office space expires on September 11, 2026, with one five-year extension option
available. The term of the Cambridge Lease with respect to the lab space expires on November 30, 2021, with an extension option for
one additional period of two years. The term of the Boston Lease office space expires on February 28, 2023, with an extension option
for one additional five-year extension option available. The renewal options in the Company’s real estate leases were not included in
the calculation of the operating lease assets and operating lease liabilities as the renewal is not reasonably certain. The lease
agreements do not contain residual value guarantees. Operating lease costs for the year ended December 31, 2019 were $6.6 million
and cash paid for amounts included in the measurement of operating lease liabilities for the year ended December 31, 2019 were $6.9
million.
In September 2019, Keryx entered into an agreement to sublease the Boston office space to Foundation Medicine, Inc., or Foundation.
The sublease is subject and subordinate to the Boston Lease between Keryx and the landlord. The term of the sublease commenced on
October 16, 2019, upon receipt of the required consent from the landlord for the sublease agreement, and expires on February 27,
2023. Foundation is obligated to pay Keryx rent that approximates the rent due from Keryx to its landlord with respect to the Boston
Lease. Sublease rental income is recorded to other income. Keryx continues to be obligated for all payment terms pursuant to the
Boston Lease, and the Company will guaranty Keryx’s obligations under the sublease. Keryx received $0.2 million in rent payments
from Foundation during the year ended December 31, 2019.
The Company has not entered into any material short-term leases or financing leases as of December 31, 2019.
162
The total security deposit in connection with the Cambridge Lease is $1.6 million as of December 31, 2019. Additionally, the
Company recorded $0.8 million for the security deposit under the Boston Lease. Both the Cambridge Lease and the Boston Lease
have their security deposits in the form of a letter of credit, all of which are included in prepaid expenses and other current assets in
the Company’s consolidated balance sheet as of December 31, 2019.
As of December 31, 2019, undiscounted minimum rental commitments under non-cancelable leases, for each of the next five years
and total thereafter are as follows:
2020
2021
2022
2023
2024
Thereafter
Total
Operating
Leases
(in thousands)
Lease Payments
to be Received
from Sublease
Net Operating
Lease Payments
$
$
6,568 $
7,064
6,735
5,347
5,116
8,818
39,648 $
1,769 $
1,797
1,824
307
5,697 $
4,799
5,267
4,911
5,040
5,116
8,818
33,951
In arriving at the operating lease liabilities, the Company applied incremental borrowing rates ranging from 5.91% to 6.94%, which
were based on the remaining lease term at the date of adoption of ASC 842. As of December 31, 2019, the remaining lease terms
ranged from 1.92 years to 6.70 years. As of December 31, 2019, the following represents the difference between the remaining
undiscounted minimum rental commitments under non-cancelable leases and the operating lease liabilities:
Undiscounted minimum rental commitments
Present value adjustment using incremental borrowing rate
Operating lease liabilities
Operating
Leases
(in thousands)
Total
$
$
39,648
(7,133)
32,515
At December 31, 2018, the Company’s future minimum payments required under these leases are as follows:
2019
2020
2021
2022
2023
Thereafter
Total
Operating
Lease
(in thousands)
6,777
7,008
7,064
6,735
5,347
13,934
46,865
$
$
The Company recorded approximately $3.7 million and $3.2 million in rent expense for the years ended December 31, 2018 and 2017,
respectively.
Manufacturing Agreements
As part of the Merger, the Company retained Keryx’s commercial supply agreements with BioVectra and Siegfried Evionnaz SA, or
Siegfried, to supply commercial drug substance for Auryxia.
163
Pursuant to the Manufacture and Supply Agreement with BioVectra and the Product Manufacture and Supply and Facility
Construction Agreement with BioVectra, collectively the BioVectra Agreement, the Company has agreed to purchase a minimum
quantity of drug substance of Auryxia at predetermined prices. The price per kilogram will decrease with an increase in quantity above
the minimum purchase quantity. In addition, the BioVectra Agreement contained contingent milestone payments for capital
developments in connection with construction of an expansion of the site of the BioVectra production facility for the manufacture of
drug substance for Auryxia. These milestone payments were achieved by BioVectra and fully recorded prior to the Merger. These
milestone payments are recorded in other assets and amortized into drug substance as inventory is released to the Company. The term
of the BioVectra Agreement expires in late 2026, after which, it automatically renews for specified terms until terminated. The
Company may terminate the BioVectra Agreement prior to the expiration of the contract term, which could result in early termination
fee. As of December 31, 2019, the Company is required to purchase a minimum quantity of drug substance for Auryxia annually at a
total cost of approximately $135.3 million through the end of the contract term.
As part of purchase accounting, the Company identified an executory contract in the BioVectra Agreement, which includes future firm
purchase commitments. This executory contract was deemed to have an off-market element related to the amount of purchase
commitments that exceed the current forecast. As a result, the Company recorded a liability of $29.5 million in purchase accounting,
as of the acquisition date for the fair value of the off-market element. Through December 31, 2019, the Company recorded $0.7
million in accretion expense related to the present value discount associated with this liability.
Pursuant to the Siegfried Master Manufacturing Services and Supply Agreement, or the Siegfried Agreement, the Company has
agreed to purchase a minimum quantity of drug substance of Auryxia at predetermined prices. The price per kilogram will decrease
with an increase in quantity above the minimum purchase quantity. The term of the Siegfried Agreement expires on December 31,
2021, after which, it automatically renews for one-year terms until terminated. The Siegfried Agreement provides for certain
termination rights prior to December 31, 2021 for the Company. As of December 31, 2019, the Company is required to purchase a
minimum quantity of drug substance for Auryxia annually at a total cost of approximately $60.8 million through the year ending
December 31, 2021.
On April 9, 2019, the Company entered into a Supply Agreement with Esteve Química, S.A., or Esteve, or the Esteve Agreement. The
Esteve Agreement includes the terms and conditions under which Esteve will manufacture vadadustat drug substance, or API, for
commercial use.
Pursuant to the Esteve Agreement, the Company shall provide rolling forecasts to Esteve on a quarterly basis, or the Forecast. The
Forecast shall reflect the Company’s needs for API produced by Esteve over a certain number of months, represented as a quantity of
API per calendar quarter. The parties have agreed to a volume-based pricing structure under the Esteve Agreement. The Esteve
Agreement has an initial term of four years, beginning April 9, 2019 and ending April 9, 2023. Subsequent to December 31, 2019, the
Company has a minimum commitment with Esteve for $5.8 million through the first quarter of 2021.
Other Third Party Contracts
Under the Company’s agreement with IQVIA to provide contract research organization services for the PRO2TECT and INNO2VATE
programs, the total remaining contract costs as of December 31, 2019 were approximately $34.9 million, of which Otsuka reimburses
a significant portion back to the Company. The estimated period of substantive performance for the committed work with IQVIA is
through the end of 2020. The Company also contracts with various other organizations to conduct research and development activities
with remaining contract costs to the Company of approximately $61.4 million at December 31, 2019. The scope of the services under
these research and development contracts can be modified and the contracts cancelled by the Company upon written notice. In some
instances, the contracts may be cancelled by the third party upon written notice.
164
17. Net Loss per Share
The shares in the table below were excluded from the calculation of diluted net loss per share, prior to the use of the treasury stock
method, due to their anti-dilutive effect:
Warrants
Outstanding stock options
Unvested restricted stock units
Total
18. Quarterly Results (unaudited)
Product revenue, net
License, collaboration and other revenue
Cost of goods sold
Operating expenses
Loss from operations
Other income (expense), net
Benefit for income taxes
Net loss
Net loss per share:
basic and diluted
Weighted-average number of common shares:
basic and diluted
Product revenue, net
License, collaboration and other revenue
Cost of goods sold
Operating expenses
Loss from operations
Other income, net
Benefit for income taxes
Net loss
Net loss per share:
basic and diluted
Weighted-average number of common shares:
basic and diluted
Year ended December 31,
2018
2019
509,611
7,670,899
4,524,132
12,704,642
509,611
8,346,888
962,316
9,818,815
2017
509,611
3,660,014
728,738
4,898,363
Three Months Ended
March 31,
2019
June 30,
2019
September 30,
December 31,
2019
2019
(in thousands, except per share data)
(unaudited)
23,111 $
49,555 $
31,257 $
117,378 $
(75,969) $
791 $
(2,757) $
(72,421) $
29,089 $
71,714 $
37,669 $
122,657 $
(59,523) $
508 $
(845) $
(58,170) $
30,004 $
61,973 $
38,263 $
109,619 $
(55,905) $
43 $
(1,277) $
(54,585) $
28,915
40,640
38,147
126,299
(94,891)
(1,344)
(1,752)
(94,483)
(0.62) $
(0.49) $
(0.46) $
(0.79)
$
$
$
$
$
$
$
$
$
117,063,352 118,268,832 118,863,063 119,358,081
Three Months Ended
March 31,
2018
June 30,
2018
September 30,
December 31,
2018
2018
(in thousands, except per share data)
(unaudited)
— $
48,793 $
— $
84,455 $
(35,662) $
1,593 $
— $
(34,069) $
— $
53,169 $
— $
81,012 $
(27,843) $
1,796 $
— $
(26,047) $
— $
45,930 $
— $
70,428 $
(24,498) $
1,080 $
— $
(23,418) $
6,824
53,026
7,768
142,240
(90,158)
1,766
(28,338)
(60,054)
(0.48) $
(0.60) $
(0.46) $
(0.87)
$
$
$
$
$
$
$
$
$
48,613,565 56,890,295 57,027,598 69,404,187
165
Item 9.
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Management’s Evaluation of our Disclosure Controls and Procedures
We maintain disclosure controls and procedures that are designed to ensure that information required to be disclosed in the reports that
we file or submit under the Exchange Act is (1) recorded, processed, summarized, and reported within the time periods specified in the
SEC’s rules and forms and (2) accumulated and communicated to our management, including our Chief Executive Officer and Chief
Financial Officer, to allow timely decisions regarding required disclosure.
As of December 31, 2019, our management, with the participation of Chief Executive Officer and Chief Financial Officer, evaluated
the effectiveness of our disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act. Our
management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable
assurance of achieving their objectives, and management necessarily applies its judgment in evaluating the cost-benefit relationship of
possible controls and procedures. Our Chief Executive Officer and Chief Financial Officer have concluded based upon the evaluation
described below that, as of December 31, 2019, our disclosure controls and procedures were not effective because of a material
weakness in our internal control over financial reporting relating to our inventory process which is described in more detail below.
Management’s Annual Report on Internal Control over Financial Reporting
Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, is responsible for establishing and
maintaining adequate internal control over financial reporting. Internal control over financial reporting is defined in Rule 13a-15(f) or
15d-15(f) promulgated under the Securities Exchange Act of 1934 as a process designed by, or under the supervision of, the
Company’s Chief Executive Officer and Chief Financial Officer and effected by the Company’s board of directors, management and
other personnel to provide reasonable assurance regarding the reliability of our financial reporting and the preparation of financial
statements for external purposes in accordance with accounting principles generally accepted in the United States of America and
includes those policies and procedures that:
(1)
(2)
(3)
Pertain to the maintenance of records that in reasonable detail accurately and fairly reflect the transactions and
dispositions of the assets;
Provide reasonable assurance that transactions are recorded as necessary to permit preparation of consolidated financial
statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the issuer
are being made only in accordance with authorizations of management and directors; and
Provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of
the Company's assets that could have a material effect on the Company’s consolidated financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of
any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in
conditions, or that the degree of compliance with policies or procedures may deteriorate.
Management conducted an assessment of the effectiveness of our internal control over financial reporting based on the criteria set
forth in Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway
Commission, or COSO. Based on the assessment, management has concluded that our internal control over financial reporting as of
December 31, 2019 was not effective due to the following material weakness: the Company did not design and maintain effective
controls over the completeness, accuracy and presentation and disclosure of inventory. A material weakness is a deficiency, or
combination of deficiencies, in internal control over financial reporting, 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 timely basis.
Specifically, we did not maintain effective controls related to (i) the review of inventory unit and valuation reconciliations, (ii) the
annual validation of the inventory costing and (iii) the periodic assessment of inventory expiry and related reserves.
166
No adjustments to the Company’s current or prior period financial statements were required as a result of the aforementioned
deficiencies in internal controls. Management is currently taking actions to remediate the deficiencies in its internal controls over
financial reporting and is implementing additional processes and controls designed to address the underlying causes associated with
the above-mentioned material weakness. Management is committed to remediating the deficiencies described above and their internal
control remediation efforts are expected to include the following: (i) providing training to individuals with internal control
responsibilities including review documentation requirements, (ii) evaluating alignment of resources and enhancing management
review and monitoring of inventory controls, (iii) review current inventory processes and procedures to identify opportunities to
enhance their design and operation, (iv) design controls that address the completeness and accuracy of any key reports utilized in the
execution of internal controls and (v) perform control testing throughout the year to validate the operating effectiveness of internal
controls over financial reporting to gain assurance that such controls are present and functioning as designed.
Management will monitor the progress of the remediation plan and report regularly to the audit committee on the progress and results
of the remediation plan, including the identification, status and resolution of internal control deficiencies.
Changes in Internal Control over Financial Reporting
Except as noted in the preceding paragraphs, there have been no changes in the Company’s internal control over financial reporting
during the fourth quarter of 2019, as such term is 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 reporting.
Ernst & Young, LLP, the Company’s independent registered public accounting firm, has issued an auditor’s report on management’s
assessment of the effectiveness of the Company’s internal control over financial reporting as of December 31, 2019. This report is
included below.
167
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Akebia Therapeutics, Inc.
Opinion on Internal Control Over Financial Reporting
We have audited Akebia Therapeutics, Inc.’s internal control over financial reporting as of December 31, 2019, based on criteria
established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations 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 objectives of the control criteria, Akebia Therapeutics, Inc. (the “Company”) has not maintained effective
internal control over financial reporting as of December 31, 2019, based on the COSO criteria.
A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting, 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 timely basis. The following material weakness has been identified and included in management’s assessment.
Specifically, the Company did not maintain effective controls related to (i) the review of inventory unit and valuation reconciliations,
(ii) the annual validation of the inventory costing and (iii) the periodic assessment of inventory expiry and related reserves.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB),
the consolidated balance sheets of the Company as of December 31, 2019 and 2018, the related consolidated statements of operations
and comprehensive loss, stockholders’ equity and cash flows for each of the three years in the period ended December 31, 2019, and
the related notes. This material weakness was considered in determining the nature, timing and extent of audit tests applied in our
audit of the 2019 consolidated financial statements, and this report does not affect our report dated March 12, 2020, which expressed
an unqualified opinion thereon.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of
the effectiveness of internal control over financial reporting included in the accompanying Management’s Annual Report on Internal
Control over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over financial
reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be independent with
respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities
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 effective internal control over financial reporting was maintained in all material respects.
Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness
exists, testing and evaluating the design and operating effectiveness 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.
Definition and Limitations of Internal Control Over Financial Reporting
A company’s internal control over financial reporting is a process designed 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. A company’s internal control over financial reporting includes those policies and procedures that (1) pertain to the
maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the
company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in
accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in
accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding
prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect
on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections
of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in
conditions, or that the degree of compliance with the policies or procedures may deteriorate.
/s/ Ernst & Young LLP
Boston, Massachusetts
March 12, 2020
168
Item 9B. Other Information
Commercial Supply Agreement
On March 11, 2020, Akebia entered into a Supply Agreement (“Patheon Supply Agreement”) with Patheon Inc. (“Patheon”). The
Patheon Supply Agreement includes the terms and conditions under which Patheon will manufacture vadadustat drug product for
commercial use.
Pursuant to the Patheon Supply Agreement, Akebia will provide Patheon a long-term forecast on an annual basis, as well as short-term
forecasts on a quarterly basis. The forecasts shall reflect Akebia’s needs for commercial supply of vadadustat drug product produced
by Patheon, represented as a quantity of drug product per calendar quarter. The parties have agreed to a volume-based pricing
structure under the Patheon Supply Agreement. Pursuant to the Patheon Supply Agreement, Akebia agreed to purchase a certain
percentage of its or its affiliates’ global demand for vadadustat drug product for commercial purposes from Patheon.
The initial term of the Patheon Supply Agreement is March 11, 2020 to June 30, 2023. The Patheon Supply Agreement will
automatically renew for successive one-year terms, unless either party gives prior written notice of its intent to terminate. The Patheon
Supply Agreement allows either party to terminate in the event of a material breach.
The Patheon Supply Agreement includes customary indemnification, intellectual property protection, confidentiality, remedies, and
warranties terms, as well as certain quality requirements.
The foregoing description of the Patheon Supply Agreement is a summary, is not complete, and is qualified in its entirety by the terms
and conditions of the Patheon Supply Agreement, which will be filed as an exhibit to our Quarterly Report on Form 10-Q for the
quarter ending March 31, 2020.
169
PART III
Item 10. Director, Executive Officers and Corporate Governance
The information required by this Item 10 will be included in our Definitive Proxy Statement to be filed with the Securities and
Exchange Commission, or SEC, with respect to our 2020 Annual Meeting of Stockholders and is incorporated herein by reference.
Item 11.
Executive Compensation
The information required by this Item 11 will be included in our Definitive Proxy Statement to be filed with the SEC with respect to
our 2020 Annual Meeting of Stockholders and is incorporated herein by reference.
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information relating to security ownership of certain beneficial owners of our common stock and information relating to the
security ownership of our management required by this Item 12 will be included in our Definitive Proxy Statement to be filed with the
SEC with respect to our 2020 Annual Meeting of Stockholders and is incorporated herein by reference.
Equity Compensation Plan Information
The following table sets forth information as of December 31, 2019 regarding shares of our common stock that may be issued under
our equity compensation plans, consisting of our Amended and Restated 2008 Equity Incentive Plan, our 2014 Incentive Plan, as
amended, and our Amended and Restated 2014 Employee Stock Purchase Plan, and our inducement award program. As of the closing
of our initial public offering, no additional equity awards were made under our Amended and Restated 2008 Equity Incentive Plan.
Our Amended and Restated 2008 Equity Incentive Plan, our 2014 Incentive Plan, as amended, and our Amended and Restated 2014
Employee Stock Purchase Plan were approved by our shareholders. The inducement award program was approved by our Board of
Directors in May 2016 exclusively for the grant of equity awards to individuals who were not previously an employee or non-
employee director of the Company, or following a bona fide period of non-employment, as an inducement material to such
individual’s entering into employment with the Company, pursuant to Rule 5635(c)(4) of the Nasdaq Listing Rules.
Plan Category
options, warrants and rights
(a)
Number of securities
to be issued upon
exercise of outstanding
Weighted-average
exercise price of
outstanding
options, warrants
and rights($)
(b)
Number of securities
remaining
available for future issuance
under equity compensation
plans (excluding securities
reflected in column (a))
(c)
Equity compensation plans
approved by security holders
Equity compensation plans not
approved by security holders (4)
Total
10,006,118 (1)
5.90 (2)
8,699,248 (3)
2,188,913
12,195,031
7.41
6.17
—
8,699,248
(1) Includes 5,481,986 shares of Common Stock issuable upon the exercise of outstanding options and 4,524,132 shares of our
common stock issuable upon the vesting of restricted stock units, or RSUs.
(2) Does not include purchase rights accruing under the Amended and Restated 2014 Employee Stock Purchase Plan because the
purchase right, and therefore the number of shares to be purchased, will not be determined until the end of the purchase
period. In addition, RSUs issued under our equity compensation plans do not require payment by the recipient to us at the
time of vesting. As such, the weighted-average exercise price does not take these awards into account
(3) As of December 31, 2019, there were 2,983,256 shares of our common stock available for grant under the 2014 Incentive
Plan, as amended, and 5,715,992 shares of our common stock available for grant under the Amended and Restated 2014
Employee Stock Purchase Plan.
(4) This amount is under the inducement award program.
170
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this Item 13 will be included in our Definitive Proxy Statement to be filed with the SEC with respect to
our 2020 Annual Meeting of Stockholders and is incorporated herein by reference.
Item 14.
Principal Accountant Fees and Services
The information required by this Item 14 will be included in our Definitive Proxy Statement to be filed with the SEC with respect to
our 2020 Annual Meeting of Stockholders and is incorporated herein by reference.
171
PART IV
Item 15.
Exhibits, Financial Statement Schedules
(a) Documents filed as part of this Annual Report on Form 10-K.
(1) Consolidated Financial Statements
Report of Independent Registered Public Accounting Firm
Consolidated Balance Sheets
Consolidated Statements of Operations and Comprehensive Loss
Consolidated Statements of Stockholders’ Equity (Deficit)
Consolidated Statements of Cash Flows
Notes to Consolidated Financial Statements
(2) Schedules
Schedules have been omitted as all required information has been disclosed in the financial statements and related footnotes.
(3) Exhibits
The Exhibits listed below are filed as part of this Annual Report on Form 10-K.
Exhibit
Number
2.1**
2.2
3.1
3.2
4.1
4.2
4.3#
4.4#
4.5
Description of Exhibit
Agreement and Plan of Merger, dated as of June 28, 2018, by and among Akebia Therapeutics, Inc., Alpha Therapeutics
Merger Sub, Inc., and Keryx Biopharmaceuticals, Inc. (incorporated by reference to Exhibit 2.1 to the Company’s
Current Report on Form 8-K, filed on June 28, 2018)
First Amendment to Agreement and Plan of Merger, dated as of October 1, 2018, by and among Akebia Therapeutics,
Inc., Alpha Therapeutics Merger Sub, Inc. and Keryx Biopharmaceuticals, Inc. (incorporated by reference to Exhibit 2.1
to the Company’s Current Report on Form 8-K, filed on October 1, 2018)
Ninth Amended and Restated Certificate of Incorporation (incorporated by reference to Exhibit 3.1 to the Company’s
Current Report on Form 8-K, filed on March 28, 2014)
Amended and Restated Bylaws (incorporated by reference to Exhibit 3.2 to the Company’s Current Report on Form 8-K,
filed on March 28, 2014)
Form of Common Stock Certificate (incorporated by reference to Exhibit 4.1 to the Company’s Registration Statement
on Form S-1/A (333-193969), filed on March 4, 2014)
Fourth Amended and Restated Investors’ Rights Agreement, dated March 5, 2014 (incorporated by reference to Exhibit
4.4 to the Company’s 10-K for the year ending December 31, 2014 and filed on March 4, 2015)
Common Stock Purchase Warrant between Akebia Therapeutics, Inc. and Janssen Pharmaceutica NV, dated February 9,
2017 (incorporated by reference to Exhibit 4.1 to the Company’s Quarterly Report on Form 10-Q, filed on May 9, 2017)
Investment Agreement between Akebia Therapeutics, Inc. and Vifor (International) Ltd., dated May 12, 2017
(incorporated by reference to Exhibit 4.1 to the Company’s Quarterly Report on Form 10-Q, filed on August 8, 2017)
Amendment No. 1 to Fourth Amended and Restated Investors’ Rights Agreement, dated June 28, 2017 (incorporated by
reference to Exhibit 4.5 to the Company’s Annual Report on Form 10-K, filed on March 12, 2018)
4.6*
Description of Registrant’s Securities
172
Exhibit
Number
10.1†
10.2
10.3
10.4
10.5
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†
Description of Exhibit
Form of Director and Officer Indemnification Agreement (incorporated by reference to Exhibit 10.1 to the Company’s
Annual Report on Form 10-K, filed on March 12, 2018)
Office Lease Agreement Between MA-Riverview/245 First Street, L.L.C. and Akebia Therapeutics, Inc., dated
December 3, 2013 (incorporated by reference to Exhibit 10.2 to the Company’s Registration Statement on Form S-1
(333-193969), filed on February 14, 2014)
First Amendment to Office Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeutics,
Inc., dated December 15, 2014 (incorporated by reference to Exhibit 10.3 to the Company’s 10-K for the year ending
December 31, 2014 and filed on March 4, 2015)
Second Amendment to Office Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeutics,
Inc., dated November 23, 2015 (incorporated by reference to Exhibit 10.4 to the Company’s 10-K for the year ending
December 31, 2015 and filed on March 14, 2016)
Third Amendment to Office Lease Agreement Between Jamestown Premier 245 First, LLC and Akebia Therapeutics,
Inc., dated July 25, 2016 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q,
filed on November 9, 2016)
Fourth Amendment to Office Lease Agreement Between CLPF-Cambridge Science Center, LLC and Akebia
Therapeutics, Inc., dated May 1, 2017 (incorporated by reference to Exhibit 10.6 to the Company’s 10-K for the year
ending December 31, 2017, filed on March 12, 2018)
Fifth Amendment to Office Lease Agreement Between CLPF-Cambridge Science Center, LLC and Akebia Therapeutics,
Inc. dated April 9, 2018 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q,
filed on August 8, 2018)
One Marina Park Drive Office Lease dated April 29, 2015, by and between Keryx Biopharmaceuticals, Inc. and Fallon
Cornerstone One MPD LLC (incorporated by reference to Exhibit 10.29 to Keryx Biopharmaceuticals, Inc.’s Annual
Report on Form 10-K, filed on March 1, 2017)
Sublease, dated as of September 9, 2019, by and between Keryx Biopharmaceuticals, Inc. and Foundation Medicine, Inc.
(incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q, filed on November 12,
2019)
Amended and Restated 2008 Equity Incentive Plan (incorporated by reference to Exhibit 10.5 to the Company’s
Registration Statement on Form S-1 (333-193969), filed on February 14, 2014)
Amendment No. 1 to Amended and Restated 2008 Equity Incentive Plan (incorporated by reference to Exhibit 10.6 to
the Company’s Registration Statement on Form S-1 (333-193969), filed on February 14, 2014)
Executive Employment Agreement with John P. Butler, dated September 16, 2013 (incorporated by reference to Exhibit
10.7 to the Company’s Registration Statement on Form S-1 (333-193969), filed on February 14, 2014)
Executive Employment Agreement with Jason A. Amello, dated September 23, 2013 (incorporated by reference to
Exhibit 10.8 to the Company’s Registration Statement on Form S-1 (333-193969), filed on February 14, 2014)
Form of Non-Statutory Stock Option Agreement for officers (incorporated by reference to Exhibit 10.24 to the
Company’s Registration Statement on Form S-1/A (333-193969), filed on March 4, 2014)
Form of Non-Statutory Stock Option Agreement for non-employee directors (incorporated by reference to Exhibit 10.25
to the Company’s Registration Statement on Form S-1/A (333-193969), filed on March 4, 2014)
Amended and Restated Non-Employee Director Compensation Program, effective January 1, 2018 (incorporated by
reference to Exhibit 10.13 to the Company’s 10-K for the year ending December 31, 2017 and filed on March 12, 2018)
Amended and Restated Non-Employee Director Compensation Program, effective January 30, 2019 (incorporated by
reference to Exhibit 10.31 to the Company’s Annual Report on Form 10-K, filed on March 26, 2019)
Form of Executive Severance Agreement for officers (incorporated by reference to Exhibit 10.27 to the Company’s
Registration Statement on Form S-1/A (333-193969), filed on March 4, 2014)
2014 Incentive Plan (incorporated by reference to exhibit 10.29 to the Company’s Registration Statement on Form S-1/A
(333-193969), filed on March 4, 2014)
173
Exhibit
Number
10.20†
10.21†
10.22†
10.23†
10.24†
10.25†
10.26†
10.27†
10.28†
10.29†
10.30†
10.31†
10.32†
10.33†
10.34†
10.35†
10.36†
10.37†
10.38†
Description of Exhibit
Amendment No. 1 to the Akebia Therapeutics, Inc. 2014 Incentive Plan (incorporated by reference to Exhibit 4.4 to the
Company’s Registration Statement on Form S-8, filed on January 25, 2019)
2014 Employee Stock Purchase Plan (incorporated by reference to Exhibit 10.30 to the Company’s Registration
Statement on Form S-1/A (333-193969), filed on March 4, 2014)
Amended and Restated 2014 Employee Stock Purchase Plan (incorporated by reference to Appendix A to the
Company’s Definitive Proxy Statement, filed with the Securities and Exchange Commission on April 26, 2019)
Cash Incentive Plan (incorporated by reference to Exhibit 10.31 to the Company’s Registration Statement on Form S-
1/A (333-193969), filed on March 4, 2014)
Form of Officer Restricted Stock Unit Award Agreement under 2014 Incentive Plan (incorporated by reference to
Exhibit 10.18 to the Company’s Annual Report on Form 10-K, filed on March 12, 2018)
Form of Officer Restricted Stock Unit Award Agreement under 2014 Incentive Plan (incorporated by reference to
Exhibit 10.29 to the Company’s Annual Report on Form 10-K, filed on March 26, 2019)
Form of Officer Inducement Award Non-Statutory Stock Option Agreement (incorporated by reference to Exhibit 4.4 to
the Company’s Registration Statement on Form S-8 (333-222728), filed on January 26, 2018)
Form of Inducement Award Non-Statutory Stock Option Agreement for non-officers (incorporated by reference to
Exhibit 4.5 to the Company’s Registration Statement on Form S-8 (333-222728), filed on January 26, 2018)
Keryx Biopharmaceuticals, Inc. 1999 Stock Option Plan (incorporated by reference to Exhibit 10.2 to Keryx
Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q, filed on March 21, 2003)
Keryx Biopharmaceuticals, Inc. 2004 Long-Term Incentive Plan (incorporated by reference to Annex C to Keryx
Biopharmaceuticals, Inc.’s Definitive Proxy Statement on Schedule 14A, filed on April 29, 2004)
Amendment to the Keryx Biopharmaceuticals, Inc. 2004 Long-Term Incentive Plan dated April 11, 2006 (incorporated
by reference to Exhibit 10.1 to Keryx Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q, filed on August 9,
2006)
Keryx Biopharmaceuticals, Inc. 2007 Incentive Plan, (incorporated by reference to Annex D to Keryx
Biopharmaceuticals, Inc.’s Definitive Proxy Statement on Schedule 14A, filed on April 30, 2007)
Keryx Biopharmaceuticals, Inc. Amended and Restated 2013 Incentive Plan (incorporated by reference to Exhibit 10.1
to Keryx Biopharmaceuticals, Inc.’s Current Report on Form 8-K, filed on May 27, 2016)
Keryx Biopharmaceuticals, Inc. 2018 Equity Incentive Plan (incorporated by reference to Exhibit 99.1 to Keryx
Biopharmaceuticals, Inc.’s Registration Statement on Form S-8, filed on June 29, 2018)
Form of Indemnification Agreement between Keryx Biopharmaceuticals, Inc. and its directors and officers (incorporated
by reference to Exhibit 10.1 to Keryx Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q, filed on November 9,
2016)
Form of Employee Agreement (Confidentiality, Non-Competition, Non-Solicitation and Development Agreement)
applicable to officers (incorporated by reference to Exhibit 10.56 to the Company’s Annual Report on Form 10-K, filed
on March 26, 2019)
Keryx Biopharmaceuticals, Inc. Fourth Amended and Restated Directors Equity Compensation Plan (incorporated by
reference to Exhibit 10.2 to Keryx Biopharmaceuticals, Inc.’s Current Report on Form 8-K, filed on May 27, 2016)
Keryx Biopharmaceuticals, Inc. Third Amended and Restated Directors Equity Compensation Plan (incorporated by
reference to Exhibit 10.1 to Keryx Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q for the quarter ended June
30, 2014, filed on August 7, 2014)
Keryx Biopharmaceuticals, Inc. Director Non-Statutory Stock Option Award Terms and Conditions under the Third
Amended and Restated Directors Equity Compensation Plan (incorporated by reference to Exhibit 10.59 to the
Company’s Annual Report on Form 10-K, filed on March 26, 2019)
174
Exhibit
Number
10.39†
10.40#
10.41#
10.42#
10.43#
10.44#
10.45#
10.46#
10.47
10.48
10.49
Description of Exhibit
Master Consulting Services Agreement, dated as of June 10, 2019, by and between Akebia Therapeutics, Inc. and Scott
A. Canute (incorporated by reference to Exhibit 10.4 to the Company’s Quarterly Report on Form 10-Q, filed on August
8, 2019)
Master Services Agreement, between Akebia Therapeutics, Inc., and Quintiles, Inc., dated as of June 8, 2015
(incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q, filed on August 11, 2015)
Collaboration Agreement between Akebia Therapeutics, Inc. and Mitsubishi Tanabe Pharma Corporation, dated
December 11, 2015 (incorporated by reference to Exhibit 10.29 to the Company’s 10-K for the year ending December
31, 2015 and filed on March 14, 2016)
Letter Agreement between Akebia Therapeutics, Inc. and Mitsubishi Tanabe Pharma Corporation, dated September 26,
2017 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q, filed on November 8,
2017)
Collaboration and License Agreement, between Akebia Therapeutics, Inc. and Otsuka Pharmaceutical Co. Ltd., dated
December 18, 2016 (incorporated by reference to Exhibit 10.26 to the Company’s 10-K for the year ending December
31, 2016 and filed on March 6, 2017)
Collaboration and License Agreement between Akebia Therapeutics, Inc. and Otsuka Pharmaceutical Co. Ltd., dated
April 25, 2017 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q, filed on
August 8, 2017)
Research and License Agreement between Akebia Therapeutics, Inc. and Janssen Pharmaceutica NV, dated February 9,
2017 (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q, filed on May 9,
2017)
Amended and Restated License Agreement, dated April 8, 2019, by and between Akebia Therapeutics, Inc. and Vifor
(International) Ltd. (incorporated by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q, filed
on August 8, 2019)
Amended and Restated Controlled Equity OfferingSM Sales Agreement, dated November 12, 2019, by and between
Akebia Therapeutics, Inc. and Cantor Fitzgerald & Co. (incorporated by reference to Exhibit 1.1 to the Company’s
Current Report on Form 8-K, filed on November 12, 2019)
Registration Rights Agreement, dated December 12, 2018, by and between Akebia Therapeutics, Inc. and Baupost
Group Securities, L.L.C. (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K, filed
on December 13, 2018)
Notes Conversion Agreement, dated as of June 28, 2018, by and among Akebia Therapeutics, Inc., Keryx
Biopharmaceuticals, Inc. and Baupost Group Securities, L.L.C. (incorporated by reference to Exhibit 10.1 to the
Company’s Current Report on Form 8-K, filed on June 28, 2018)
10.50#
Second Amended and Restated License Agreement dated April 17, 2019, by and between Akebia Therapeutics, Inc. and
Panion & BF Biotech, Inc. (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q,
filed on August 8, 2019)
10.51
Reserved
10.52
Reserved
10.53#
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 Biopharmaceuticals, Inc., Japan Tobacco, Inc. and Torii Pharmaceutical Co., Ltd
(incorporated by reference to Exhibit 10.1 to Keryx Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q, filed on
November 7, 2017)
175
Exhibit
Number
10.54#
10.55#
10.56#
10.57#
10.58#
10.59#
10.60#
10.61#
10.62!*
10.63!*
21.1*
23.1*
31.1*
31.2*
32.1*
Description of Exhibit
Master Manufacturing Services Agreement by and between Keryx Biopharmaceuticals, 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 (incorporated by reference to Exhibit 10.12 to Keryx
Biopharmaceuticals, Inc.’s Annual Report on Form 10-K, filed on March 1, 2017)
Product Agreement, dated August 29, 2017, by and between Keryx Biopharmaceuticals, Inc. and Patheon Inc. (an
affiliate of Patheon Manufacturing Services LLC) related to the Master Manufacturing Services Agreement by and
between Keryx Biopharmaceuticals, Inc. and Patheon Manufacturing Services LLC and certain of its affiliates dated
November 12, 2016 (incorporated by reference to Exhibit 10.2 to Keryx Biopharmaceuticals, Inc.’s Quarterly Report on
Form 10-Q, filed on November 7, 2017)
Product Manufacture and Supply and Facility Construction Agreement, dated December 11, 2017, by and between
Keryx Biopharmaceuticals, Inc. and BioVectra Inc. (incorporated by reference to Exhibit 10.12 to Keryx
Biopharmaceuticals, Inc.’s Annual Report on Form 10-K, filed on February 21, 2018)
Master Manufacturing Services and Supply Agreement, dated December 20, 2017, by and between Keryx
Biopharmaceuticals, Inc. and Siegfried Evionnaz SA (incorporated by reference to Exhibit 10.13 to Keryx
Biopharmaceuticals, Inc.’s Annual Report on Form 10-K, filed on February 21, 2018)
Amendment No. 1 to the Product Manufacture and Supply and Facility Construction Agreement, dated May 5, 2018, by
and between Keryx Biopharmaceuticals, Inc. and BioVectra Inc. (incorporated by reference to Exhibit 10.6 to Keryx
Biopharmaceuticals, Inc.’s Quarterly Report on Form 10-Q, filed on August 9, 2018)
Exclusive Distribution Agreement between Keryx Biopharmaceuticals, Inc. and Cardinal Health 105, Inc., dated October
16, 2014 and Amendment to Exclusive Distribution Agreement between Keryx Biopharmaceuticals, Inc. and Cardinal
Health 105, Inc., dated April 14, 2015 (incorporated by reference to Exhibit 10.60 to the Company’s Annual Report on
Form 10-K, filed on March 26, 2019)
Manufacture and Supply Agreement between Keryx Biopharmaceuticals, Inc. and BioVectra Inc., dated May 26, 2017
and Amendment to Manufacture and Supply Agreement between Keryx Biopharmaceuticals, Inc. and BioVectra Inc.,
dated December 11, 2017 (incorporated by reference to Exhibit 10.61 to the Company’s Annual Report on Form 10-K,
filed on March 26, 2019)
Supply Agreement, dated as of April 9, 2019, by and between Akebia Therapeutics, Inc. and Esteve Química, S.A.
(incorporated by reference to Exhibit 10.3 to the Company’s Quarterly Report on Form 10-Q, filed on August 8, 2019)
Loan Agreement, dated November 11, 2019, by and among the Company, Keryx Biopharmaceuticals, Inc., Biopharma
Credit plc and Biopharma Credit Investments V (Master) LP
Guaranty and Security Agreement, dated November 25, 2019, by and between the Company, Keryx Biopharmaceuticals,
Inc. and Biopharma Credit plc
List of Subsidiaries
Consent of Ernst & Young LLP
Certification of Principal Executive Officer Required Under Rule 13a-14(a) of the Securities Exchange Act of 1934, as
amended
Certification of Principal Financial Officer Required Under Rule 13a-14(a) of the Securities Exchange Act of 1934, as
amended
Certification of Principal Executive Officer and Principal Financial Officer Required Under Rule 13a-14(b) of the
Securities Exchange Act of 1934, as amended, and 18 U.S.C. 1350
101.INS*
XBRL Instance Document
101.SCH* XBRL Taxonomy Extension Schema Document
101.CAL* XBRL Taxonomy Extension Calculation Linkbase Document
101.DEF* XBRL Taxonomy Extension Definition Linkbase Document
101.LAB* XBRL Taxonomy Extension Labels Linkbase Document
176
Exhibit
Number
101.PRE* XBRL Taxonomy Extension Presentation Linkbase Document
Description of Exhibit
*
†
#
!
**
Filed, or submitted electronically, herewith
Indicates management contract or compensatory plan
Indicates portions of the exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment
Indicates portions of the exhibit (indicated by asterisks) have been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K
The schedules to the Agreement and Plan of Merger have been omitted pursuant to Item 601(b)(2) of Regulation S-K. The Company will
furnish copies of such schedules to the Securities and Exchange Commission upon request by the Commission
Item 16.
Form 10-K Summary
None.
177
Pursuant to the requirements of Section 13 or 15(d) of the Securities 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 12, 2020
AKEBIA THERAPEUTICS, INC.
By: /s/ John P. Butler
John P. Butler
President and Chief Executive Officer
Pursuant to the requirements of the Securities Exchange Act of 1934, this report was signed by the following persons on behalf of the
registrant and in the capacities and on the date indicated.
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
Date: March 12, 2020
By: /s/ John P. Butler
John P. Butler
Director, President and Chief Executive Officer
(Principal Executive Officer)
By: /s/ Jason A. Amello
Jason A. Amello
Senior Vice President, Chief Financial Officer and
Treasurer (Principal Financial and Accounting
Officer)
By: /s/ Adrian Adams
Adrian Adams
Chairman
By: /s/ Mark J. Enyedy
Mark J. Enyedy
Director
By: /s/ Steven C. Gilman
Steven C. Gilman
Director
By: /s/ Maxine Gowen
Maxine Gowen
Director
By: /s/ Michael T. Heffernan
Michael T. Heffernan
Director
By: /s/ Jodie P. Morrison
Jodie P. Morrison
Director
By:
/s/ Michael Rogers
Michael Rogers
Director
By:
/s/ Cynthia Smith
Cynthia Smith
Director
178
Exhibit 23.1
Consent of Independent Registered Public Accounting Firm
We consent to the incorporation by reference in the following Registration Statements:
(1) Registration Statement (Form S-3 No. 333-223585) of Akebia Therapeutics, Inc.,
(2) Registration Statement (Form S-8 No. 333-196748) pertaining to the Amended and Restated 2008 Equity
Incentive Plan, the 2014 Incentive Plan, and the 2014 Employee Stock Purchase Plan of Akebia Therapeutics,
Inc.,
(3) Registration Statement (Form S-8 No. 333-209469) pertaining to the 2014 Incentive Plan and the 2014
Employee Stock Purchase Plan of Akebia Therapeutics, Inc.,
(4) Registration Statement (Form S-8 No. 333-216475) pertaining to the 2014 Incentive Plan and the 2016
Inducement Award Program of Akebia Therapeutics, Inc.,
(5) Registration Statement (Form S-8 No. 333-222728) pertaining to the 2014 Incentive Plan and the 2016
Inducement Award Program of Akebia Therapeutics, Inc.,
(6) Registration Statement (Form S-4 No. 333-227622) of Akebia Therapeutics, Inc.,
(7) Registration Statement (Form S-8 No. 333-228772) pertaining to the 2014 Incentive Plan of Akebia
Therapeutics, Inc. and the 1999 Share Option Plan, 2004 Long-Term Incentive Plan, 2007 Incentive Plan,
Amended and Restated 2013 Incentive Plan, and 2018 Equity Incentive Plan of Keryx Biopharmaceuticals,
Inc., and
(8) Registration Statement (Form S-8 No. 333-229366) pertaining to the 2014 Incentive Plan, the 2014 Employee
Stock Purchase Plan, and the Inducement Grants (January 2018 – December 2018) of Akebia Therapeutics,
Inc.
(9) Registration Statement (Form S-8 No. 333-229366) pertaining to the 2014 Incentive Plan, the 2014 Employee
Stock Purchase Plan, and the Inducement Grants (January 2018 – December 2018) of Akebia Therapeutics,
Inc.,
(10) Registration Statement (Form S-8 No. 333-233140) pertaining to the amended and restated 2014 Employee
Stock Purchase Plan of Akebia Therapeutics, Inc.,
(11) Registration Statement (Form S-8 No. 333-236060) pertaining to the 2014 Incentive Plan and the Inducement
Grant Awards (January 2019 – December 2019) of Akebia Therapeutics, Inc.,
of our reports dated March 12, 2020, with respect to the consolidated financial statements of Akebia Therapeutics, Inc.
and the effectiveness of internal control over financial reporting of Akebia Therapeutics, Inc. included in this Annual
Report (Form 10-K) of Akebia Therapeutics, Inc. for the year ended December 31, 2019.
/s/ Ernst & Young LLP
Boston, Massachusetts
March 12, 2020
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) 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;
(b) 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;
(c)
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
(d) 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) 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
(b) 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 12, 2020
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, Jason A. Amello, 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) 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;
(b) 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;
(c)
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
(d) 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) 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
(b) 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 12, 2020
By: /s/ Jason A. Amello
Jason A. Amello
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. (the Company) on Form 10-K for the fiscal year
ended December 31, 2019 (the Report), I, John P. Butler, as Chief Executive Officer and President of the Company, and I,
Jason A. Amello, 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.
2.
The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
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 12, 2020
Date: March 12, 2020
By:
By:
/s/ John P. Butler
John P. Butler
President, Chief Executive Officer and Director
(Principal Executive Officer)
/s/ Jason A. Amello
Jason A. Amello
Senior Vice President, Chief Financial Officer
and Treasurer
(Principal Financial Officer)