MeiraGTx
Annual Report 2022

Plain-text annual report

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-38520 MEIRAGTX HOLDINGS PLC (Exact name of registrant as specified in its charter) Cayman Islands (State or other jurisdiction of incorporation or organization) 450 East 29th Street, 14th Floor New York, NY (Address of principal executive offices) 98-1448305 (I.R.S. Employer Identification No.) 10016 (Zip Code) (646) 860-7985 (Registrant’s telephone number, including area code) Securities registered pursuant to Section 12(b) of the Act: Title of each class Ordinary Shares, $0.00003881 par value per share Trading Symbol(s) MGTX Name of exchange on which registered The Nasdaq Global Select 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 Section 15(d) of the Exchange 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, 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 Non-accelerated filer ☐ ☒ Accelerated filer Smaller reporting company 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. ☐ Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐ If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐ Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐ Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒ As of June 30, 2022, the last business day of the registrant's most recently completed second fiscal quarter, the aggregate market value of the registrant’s ordinary shares held by non-affiliates of the registrant was approximately $242,659,643 (based upon the closing sale price of the registrant’s ordinary shares on that date on the Nasdaq Global Select Market). As of March 8, 2023, the registrant had 48,666,263 ordinary shares outstanding. DOCUMENTS INCORPORATED BY REFERENCE Portions of the registrant’s definitive Proxy Statement relating to its 2023 annual shareholder meeting to be filed with the SEC within 120 days after the end of the fiscal year ended December 31, 2022 are incorporated herein by reference in Part III of this Annual Report on Form 10-K. Table of Contents PART I CONTENTS Business Item 1. 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 Reserved Management’s Discussion And Analysis Of Financial Condition And Results Of Operations Item 6. Item 7. Item 7A. Quantitative And Qualitative Disclosures About Market Risk Item 8. Item 9. Item 9A. Controls And Procedures Item 9B. Other Information Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections Financial Statements And Supplementary Data Changes In And Disagreements With Accountants On Accounting And Financial Disclosure PART III Item 10. Directors, Executive Officers And Corporate Governance Item 11. Item 12. Executive Compensation 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. Item 16. Exhibits and Financial Statement Schedules Form 10-K Summary Page 4 4 47 106 107 107 107 108 108 108 108 123 F-1 124 124 125 125 126 126 126 126 127 127 128 128 132 Table of Contents SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K (the “Form 10-K”) contains forward-looking statements that can involve substantial risks and uncertainties. All statements other than statements of historical facts contained in this Form 10-K, including statements regarding our future results of operations and financial position, business strategy, financing arrangements, prospective products, product approvals, research and development costs, future revenue, timing and likelihood of success, plans and objectives of management for future operations, future results of anticipated products and prospects, plans and objectives of management are forward-looking statements. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential,” “would” or “continue” or the negative of these terms or other similar expressions. The forward-looking statements in this Form 10-K are only predictions. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our business, financial condition and results of operations. These forward-looking statements speak only as of the date of this Form 10-K and are subject to a number of risks, uncertainties and assumptions described under the sections in this Form 10-K entitled “Item 1A. Risk Factors” and “Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations” and elsewhere in this Form 10-K. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Thus, one should not assume that our silence over time means that actual events are bearing out as expressed or implied in such forward-looking statements. You should read this Form 10-K and the documents that we reference in this Form 10-K and have filed as exhibits to this Form 10-K, completely and with the understanding that our actual future results may be materially different from what we expect. In addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this Form 10-K, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all relevant information. These statements are inherently uncertain and investors are cautioned not to unduly rely upon these statements. These statements should not be relied upon as representing our views as of any date subsequent to the date of this Form 10-K. 1 Table of Contents RISK FACTOR SUMMARY We are providing the following summary of the principal risk factors contained in this Form 10-K to enhance the readability and accessibility of our risk factor disclosures. We encourage you to carefully review in their entirety the full risk factors set forth in the section of this Form 10-K captioned “Item 1A. Risk Factors” for additional information regarding the material factors that make an investment in our ordinary shares speculative or risky. These risks and uncertainties include, among others, the following: ● We have incurred significant losses since inception and anticipate that we will incur continued losses for the foreseeable future, and may never achieve or maintain profitability. ● We will require additional capital to fund our operations, which may not be available on acceptable terms, if at all. ● We may not have sufficient cash flows or cash on hand to satisfy our debt obligations or covenants under our financing arrangements, or we may not be able to effectively manage our business in compliance with such covenants. ● We are heavily dependent on the success of our Most Advanced Product Candidates (as defined in “Item 1A. Risk Factors”), which are still in development, and if none of them receive regulatory approval or are successfully commercialized, our business may be harmed. ● COVID-19 has impacted and may continue to impact our business, and any other pandemic, epidemic or outbreak of an infectious disease may materially and adversely impact our business, including our preclinical studies, clinical trials, manufacturing capabilities and regulatory approvals. ● It is difficult to predict the time and cost of product candidate development on our novel gene therapy platform. Very few gene therapies have been approved in the United States or in Europe. ● Because gene therapy is novel and the regulatory landscape that governs any product candidates we may develop is uncertain and may change, we cannot predict the time and cost of obtaining regulatory approval, if we receive it at all, for any product candidates we may develop. ● Clinical trials are expensive, time-consuming, difficult to design and implement, and involve an uncertain outcome. Further, we may encounter substantial delays in our clinical trials. ● The affected populations for our product candidates may be smaller than we or third parties currently project, which may affect the addressable markets for our product candidates. ● We and our contract manufacturers for plasmid are subject to significant regulation with respect to manufacturing our products. Our manufacturing facilities and the third-party manufacturing facilities which we rely on may not continue to meet regulatory requirements and have limited capacity. ● Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and may affect the prices we may set. ● We are subject to government regulation and other legal obligations relating to privacy and data protection. Compliance with these requirements is complex and costly. Failure to comply could materially harm our business. 2 Table of Contents ● We face significant competition in an environment of rapid technological change, and there is a possibility that our competitors may achieve regulatory approval before us or develop therapies that are safer or more advanced or effective than ours, which may harm our financial condition and our ability to successfully market or commercialize any product candidates we may develop. ● We depend on proprietary technology licensed from others. If we lose our existing licenses or are unable to acquire or license additional proprietary rights from third parties, we may not be able to continue developing our product candidates. ● If we are unable to obtain and maintain patent protection for our technology and product candidates or if the scope of the patent protection obtained is not sufficiently broad, we may not be able to compete effectively in our markets. ● We may need to expand our organization, and we may experience difficulties in managing this growth, which could disrupt our operations. ● Our future success depends on our ability to retain our key personnel and to attract, retain and motivate qualified personnel. BASIS OF PRESENTATION Unless the context otherwise requires, references in this Form 10-K to “Meira,” “MeiraGTx,” “we,” “us”, “our” or “the Company” refer to MeiraGTx Holdings plc and its subsidiaries. We have proprietary rights to trademarks, trade names and service marks appearing in this Form 10-K that are important to our business. Solely for convenience, the trademarks, trade names and service marks may appear in this Form 10-K without the ® and TM symbols, but any such references are not intended to indicate, in any way, that we forgo or will not assert, to the fullest extent under applicable law, our rights or the rights of the applicable licensors to these trademarks, trade names and service marks. All trademarks, trade names and service marks appearing in this Form 10-K are the property of their respective owners. INDUSTRY AND OTHER DATA We obtained the industry, market and competitive position data in this Form 10-K from our own internal estimates and research as well as from industry and general publications and research, surveys and studies conducted by third parties. Industry publications, studies and surveys generally state that they have been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. While we believe that each of these studies and publications is reliable, we have not independently verified market and industry data from third-party sources. While we believe our internal company research as to such matters is reliable and the market definitions are appropriate, neither such research nor these definitions have been verified by any independent source. 3 Table of Contents ITEM 1. BUSINESS Overview PART I We are a vertically integrated, clinical stage gene therapy company with six programs in clinical development and a broad pipeline of preclinical and research programs. We have core capabilities in viral vector design and optimization and gene therapy manufacturing, as well as a potentially transformative gene regulation platform technology that allows precise, dose responsive control of gene expression by oral small molecules with dynamic range that can exceed 5000-fold. Led by an experienced management team, we have taken a portfolio approach by licensing, acquiring and developing technologies that give us depth across both product candidates and indications. The Company’s initial focus is on three distinct areas of unmet medical need: ocular diseases, including both inherited retinal diseases as well as large degenerative ocular diseases, neurodegenerative diseases and severe forms of xerostomia. Though initially focusing on the eye, central nervous system and salivary gland, we intend to expand our focus in the future to develop additional gene therapy treatments for patients suffering from a range of serious diseases. We own and operate a flexible and scalable viral vector manufacturing facility in London, United Kingdom that we expect can supply our current ophthalmology, neurodegenerative disease and salivary gland clinical and preclinical programs through regulatory approval and, should they be approved, provide sufficient capacity for commercial production. Completed in early 2018 and designed to meet global regulatory requirements, including the current good manufacturing practices, or cGMP, required by the U.S. Food and Drug Administration, or FDA, our 29,000 square foot facility has two cell production suites, three independent viral vector production suites providing multi-product and multi- viral vector manufacturing capabilities and an integrated, flexible fill-and-finish suite. In May 2018, we were granted a license to manufacture gene therapy product candidates in our cGMP compliant manufacturing facility by the United Kingdom’s Medicines and Healthcare products Regulatory Agency, or MHRA. The MHRA re-certified the facility in the second quarter of 2020. We have expanded our manufacturing capabilities with our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland. Coming online in 2022 and stretching over 150,000 square feet, it is the first commercial-scale gene therapy manufacturing site in Ireland and is unique in its scale and integrated capabilities. The site contains three facilities, one built to be flexible and scalable for viral vector production for clinical and commercial supply, in addition, a facility to manufacture plasmid DNA – the critical starting material for producing gene therapy products – and thirdly, a Quality Control (QC) hub performing advanced biochemical quality control testing for MeiraGTx clinical and commercial programs. We completed the acquisition of the facilities in January 2021. We believe the completion of our second viral vector manufacturing facility and bringing cGMP plasmid and DNA production in-house will provide greater flexibility and efficiency as we advance our product candidates through development, and should they be approved, commercial production. We have also established a comprehensive platform for the efficient clinical development of the next generation of gene therapies and manufacturing in accordance with cGMP. Our deep understanding of disease models informs our development of potency assays for the cGMP production of our product candidates, and our teams experienced in viral vector design and optimization work closely with our process development team to design viral vectors and develop proprietary production cell lines for efficient scaling of manufacturing processes. Our wholly-owned facilities have now produced GMP clinical trial material for six different indications, using multiple AAV serotypes, including administration into the eye, salivary gland and central nervous system. We are also developing a potentially transformative technology to precisely and specifically control gene therapy expression levels via dose-response to orally delivered small molecules. The aim of this gene regulation platform technology is to transform gene therapy into a generalizable delivery mechanism for biologic drugs using a 4 Table of Contents small molecule “switch” for temporal control. We believe the capacity for temporal control of gene therapy products has the potential to transform the gene therapy landscape by opening up new treatment possibilities. Our Pipeline Our initial focus is on three distinct areas of unmet medical need: ocular diseases, including inherited retinal diseases, or IRDs, as well as large degenerative ocular diseases, severe forms of xerostomia and neurodegenerative diseases. Utilizing our product development platform, we have assembled a pipeline of gene therapies to treat these serious diseases. Our criteria for selecting our initial product candidates included: ● unmet medical need; ● high potential for meaningful clinical benefit; ● promising preclinical data using multiple animal models as well as human stem cell derived organoids; ● compartmentalized anatomy of target tissue and the partially immune protected nature of target tissue; and ● understanding of the disease state from natural history studies and detailed long-term characterization of patients prior to entry into gene therapy treatment studies. A summary of our product candidates and the status of such product candidates as of March 1, 2023 is described below. We retain worldwide development and commercialization rights to all of our product candidates, with the exception of AAV-CNGB3, AAV-CNGA3 and botaretigene sparoparvovec, formerly referred to as AAV-RPGR, which are subject to a strategic Collaboration, Option and License Agreement (the “Collaboration Agreement”) that we executed with Janssen Pharmaceuticals, Inc. (“Janssen”), one of the Janssen Pharmaceutical Companies of Johnson & Johnson, on January 30, 2019. 5 Table of Contents In addition to these clinical and preclinical programs, we have preclinical and research programs in other indications and novel molecular technologies that we aim to advance into clinical development, including: ● gene regulation—use of our proprietary RNA shape regulation cassette to switch gene therapy expression on and off with small molecules, potentially transforming gene therapy technology into a delivery mechanism for a broad array of biologic drugs; ● geographic atrophy age related macular degeneration, or dry AMD—use of gene therapy technology to introduce light sensitive molecules into rod photoreceptors in order to restore some aspects of vision lost in this disease; ● other ocular conditions—glaucoma and uveitis; ● Alzheimer’s disease—targeting endosomal trafficking, which is a central mechanism that we believe underlies Alzheimer’s disease; ● central nervous systems/peripheral nervous system diseases—brain-derived neurotrophic factor gene therapy for treatment of genetic obesity disorders, as well as the development of gene therapy product candidates for other central nervous system diseases; and ● inflammatory/autoimmune diseases—use of gene therapy technology for the local delivery of immunomodulatory therapeutics, including osteoarthritis, gout and certain rare inflammatory disorders. Our Ophthalmology Programs Eye diseases are our first area of clinical focus and we aim to provide treatments with durable, long-term clinical benefit that will halt vision loss in patients. We are actively dosing patients in our Phase 3 Lumeos clinical trial for botaretigene sparoparvovec for the treatment of X-linked retinitis pigmentosa related to mutations in the RPGR gene, or XLRP-RPGR. We also have three Phase 1/2 clinical programs targeting IRDs, including AAV-CNGB3 and AAV-CNGA3 for the treatment of achromatopsia, or ACHM, related to mutations in CNGB3 and CNGA3 genes, respectively, and AAV- RPE65 for retinal dystrophy related to mutations in the RPE65 gene, or RPE65 deficiency. We have completed enrollment and dosing in all three of these programs. In addition to these four programs, AAV-AIPL1 has been manufactured and released for compassionate use under an MHRA specials license in the United Kingdom, or UK, to treat patients with Leber congenital amaurosis 4, or LCA4, caused by mutations in the AIPL1 gene. In addition to these clinical programs in IRDs, we have preclinical programs that apply novel approaches to both wet and dry AMD, glaucoma and uveitis, as well as several other IRDs including retinol dehydrogenase 12, or RDH12, mutation-associated retinal dystrophy. We chose diseases of the eye as our first area of clinical focus because we believe the eye is ideally suited for gene therapy for the following reasons. ● The eye is easily accessible and has highly compartmentalized anatomy, which allows for accurate delivery of vectors to specific tissues using direct visualization and microsurgical techniques. ● The structure of the eye allows for efficient delivery to specific cell subtypes with small volumes of vector, making the dose per patient much lower than is needed for systemic treatment. ● Anatomical barriers and unique structure of the eye make the immune response to the intraocular administration of vectors more attenuated than systemic administration. 6 Table of Contents ● Largely non-dividing cell populations in the eye make good targets for potentially stable, long-term gene delivery and expression. ● The retina, a structure in the back of the eye, is visible and there are many well validated structural and functional readouts allowing the detailed assessment of the therapeutic impact of the gene therapy treatment. Our strategy for developing gene therapies targeting eye diseases is to begin with a number of monogenic IRDs that are good candidates for gene replacement therapies and expand to more common eye diseases over time. We have taken a portfolio approach to the development of IRDs because, while some of these genetic defects are rare, IRDs as a class are one of the most common causes of blindness in working age adults and there are multiple synergies at the clinical, regulatory and commercial levels between many of these diseases caused by different gene mutations. The deep scientific and clinical understanding of IRDs driving our approach to gene therapy development helps us to optimize our product candidates for each specific genetic mutation and phenotype. We develop our viral vectors by selecting and modifying proprietary cell specific promoters, selecting appropriate capsids for transfection of target cells and refining the vector for efficient production and scalable manufacturing. Not only does this allow us to synergistically target a portfolio of inherited eye conditions, we also believe it has potential to be applied to the development of gene therapies for other diseases. Our longstanding relationships with leading institutions in retinal disease treatment, including the Moorfields Eye Hospital in London, the University of Michigan Kellogg Eye Center, Massachusetts Eye and Ear, the Medical College of Wisconsin & Froedtert Hospital and the Casey Eye Institute at the Oregon Health & Science University, provide us with access to experts whose guidance and insight informs our development strategy, as well potential patients for our clinical trials. We intend to leverage our platform to take advantage of the many synergies across our ophthalmology programs, including identification, diagnosis and characterization of patients, specialized surgical techniques, clinical and regulatory process, vector production and cGMP manufacturing. Botaretigene Sparoparvovec for the Treatment of X-Linked Retinitis Pigmentosa Associated with Mutations in the RPGR Gene Retinitis pigmentosa, or RP, is a group of IRDs which represent the most common genetic cause of blindness. The condition is characterized by progressive retinal degeneration and vision loss that ends in complete blindness. RP initially presents as nighttime blindness during childhood or early adulthood, progressing to peripheral visual field loss and “tunnel vision,” central visual impairment, reduced visual acuity and, ultimately, complete blindness. RP may be caused by mutations in any of over 100 different genes. The most severe forms of RP are X-linked, or XLRP, with onset in early childhood and rapid progression to blindness generally by the time patients reach 30 to 40 years old. The most frequent mutation causing XLRP is in the retinitis pigmentosa GTPase regulator gene, or RPGR. XLRP associated with a mutation in RPGR, or XLRP-RPGR, accounts for more than 70% of cases of XLRP. There are estimated to be approximately 20,000 XLRP-RPGR patients in the United States (U.S.), Japan and Germany, France, Spain, Italy and the UK, or the EU5, with a little less than 50% of those patients being under the age of 40 and approximately 200 new cases being diagnosed annually. We believe the availability of a therapeutic option may increase patient identification and the estimated prevalence of XLRP-RPGR. 7 Table of Contents There are currently no approved treatments for XLRP. Clinical Development of Botaretigene Sparoparvovec We have an ongoing natural history study in XLRP-RPGR including approximately 100 patients, which allows us to collect structural and functional data for up to five years on prospectively defined endpoints, including functional tests, retinal imaging and electrophysiological assessments. We believe access to this large population of XLRP-RPGR patients has enabled us to efficiently enroll appropriate patients into our XLRP clinical development program. Since XLRP-RPGR is a progressive disease in which the retina gradually degenerates starting in the outer, or peripheral, regions of the retina and initially causing “tunnel vision” with final degeneration of the central retina resulting in the complete loss of visual acuity and blindness that generally occurs by the time patients are 30 to 40 years old, we believe that the central region of the retina, including the macula and fovea, must be preserved to prevent the ultimate degeneration to blindness and to retain visual acuity. To this end, we aim to deliver botaretigene sparoparvovec to this central region of the retina. We conducted a Phase 1/2 clinical trial of botaretigene sparoparvovec in XLRP patients. Botaretigene sparoparvovec was delivered via subretinal injection of up to 1mL with the potential for the surgeon to use multiple retinotomies targeting the region of the central retina, including the macula and fovea. In the dose escalation portion of the Phase 1/2 trial, we enrolled 13 patients, including 10 young adults and 3 children. After we completed dosing patients in the dose escalation portion of the study, we enrolled patients in the randomized, controlled, extension portion of the Phase 1/2 trial. We disclosed six-month data from the dose escalation portion of the study as a late-breaker at the American Society of Retina Specialists 2020 Virtual Annual Meeting in July 2020, nine-month data at EURETINA 2020 Virtual Congress in October 2020 and twelve-month data at the American Academy of Ophthalmology, or AAO, 2020 Virtual Annual Meeting in November 2020. Data from each time point revealed that patients treated with low (n=3) and intermediate (n=4) dose botaretigene sparoparvovec experienced statistically significant improvement in retinal sensitivity. Nine-month data also indicated significant improvement in vision-guided mobility, and at 12-months, six of seven patients continued to show improved or stable vision in the treated eye. Each patient was treated with subretinal delivery of botaretigene sparoparvovec in one eye and the patient’s other eye served as an untreated control. The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at pre-specified timepoints post-treatment. Baseline values were determined in triplicate. We disclosed additional twelve-month clinical data from the dose escalation portion of the Phase 1/2 trial as part of an oral presentation at the EURETINA 2021 Virtual Congress in September 2021. The retinal function of ten adult males aged 18-30 years with RPGR-associated XLRP was assessed twelve months post-treatment. For the intermediate dose-escalation dose cohort (n=4), intervention with botaretigene sparoparvovec in the poorer-seeing eye altered the course of natural disease progression. At twelve months post-intervention, mean retinal sensitivity (MS) and volumetric analysis of the central 30 degrees of the retinal field (V30) in the treated eye were similar to levels observed twenty-four months pre-intervention, while the untreated eye showed a continued downward trajectory. We also disclosed positive data from the Phase 1/2 clinical trial at the AAO 2022 Annual Meeting in October 2022. Treatment with botaretigene sparoparvovec was found to be generally safe and well-tolerated, with no dose-limiting events. Adverse events profile was anticipated and manageable, with most adverse events related to the surgical delivery procedure, transient and resolved without intervention. A total of three serious adverse events were observed in the overall Phase 1/2 clinical study; two serious adverse events, which were previously reported, were observed in the dose-escalation phase of the study (n=10; one retinal detachment and one panuveitis in the low dose cohort), and a single additional serious adverse event of increased intraocular pressure was observed in the dose escalation phase and resolved with treatment. Sustained or increased functional improvements were demonstrated at six months post-treatment in multiple endpoints across each of the three domains of vision -- retinal function, visual function, and functional vision -- 8 Table of Contents in patients treated with botaretigene sparoparvovec when compared to the randomized untreated control arm of the study. We are actively dosing patients in our Phase 3 Lumeos clinical trial, a randomized, controlled study of botaretigene sparoparvovec for the treatment of XLRP associated with variants in the RPGR gene. The FDA has granted Fast Track and orphan drug designations to botaretigene sparoparvovec. Competent authorities in the European Union, or EU, have granted Priority Medicines, or PRIME, advanced therapy medicinal product, or ATMP, and orphan drug designations to botaretigene sparoparvovec. AAV-RPE65 for the Treatment of RPE65-Associated Retinal Dystrophy We are developing AAV-RPE65 for the treatment of retinal dystrophy associated with mutations in the RPE65 gene. RPE65-associated retinal dystrophy causes rod photoreceptor dysfunction and impaired vision from birth. Absence of RPE65 results in severe dysfunction of rods and causes impaired vision in dim lighting conditions. Although cone photoreceptors are generally preserved during childhood in RPE65-deficient patients, the lack of function and degeneration of the rods eventually results in the loss of cones and degeneration of the whole retina over time. Consequently, most RPE65-associated retinal dystrophy patients experience central vision loss progressing to complete blindness by early adulthood. Based on an estimated prevalence of approximately one in 500,000 people in the United States suffering from Leber congenital amaurosis, or LCA, related to mutations in the RPE65 gene, and approximately one in 70,000 people in the United States having RP due to mutations in the RPE65 gene, RPE65-deficiency occurs in approximately one in 125,000 people in the United States. There are estimated to be approximately 6,000 RPE65-deficiency patients in the United States, Japan and EU5, with almost 30% of those patients being under the age of 30 and approximately 50 new cases being diagnosed annually. We have developed a gene therapy candidate optimized for safety and potency for the treatment of RPE65-associated retinal dystrophy, AAV-RPE65. AAV-RPE65 is an AAV2/5 viral vector, in which a codon optimized RPE65 gene is driven by a novel synthetic retinal pigment epithelium cell specific promoter. The FDA has approved the first gene treatment for RPE65-associated retinal dystrophy, Luxturna, a commercially available product developed by Spark Therapeutics, Inc., which was purchased by Roche. While RPE65-associated retinal dystrophy primarily causes a loss of rod function initially leading to impaired vision in dim light, these patients ultimately experience complete blindness because of degeneration of the cone rich fovea. To prevent blindness, therefore, we believe it is critical to treat the central retina in order to maintain structural integrity in this region and save central vision. We aim to treat as extensive an area of the central retina as possible, including the cone rich fovea. Thus, in addition to improving rod function, we aim to provide sufficient RPE65 protein to the cells in the central retina to prevent the degeneration of both rods and cones in this region, and thereby prevent the progression to complete blindness. Clinical Development of AAV-RPE65 We have an ongoing natural history study in patients with RPE65-associated retinal dystrophy with approximately 30 patients enrolled that allows us to collect structural and functional data on prospectively defined endpoints, including functional tests, retinal imaging, and electrophysiological assessments. Our Phase 1/2 clinical trial enrolled RPE65-associated retinal dystrophy patients in the UK and U.S. Dosing in the Phase 1/2 clinical trial was completed in June 2018. The primary endpoint of this open-label, dose-escalation clinical trial is safety. Secondary endpoints include the outcomes of a range of functional tests, detailed structural analysis of the retina and quality of life measures. A total of 15 patients were treated in this clinical trial, including nine adult patients in three dose escalation cohorts and six pediatric patients in the pediatric extension arm of the trial. 9 Table of Contents In May 2019, we announced positive topline safety and efficacy data from the Phase 1/2 trial of AAV-RPE65. Additional data from this study were presented at the Retina Subspecialty Day of the American Academy of Ophthalmology Annual Meeting in October 2019. AAV-RPE65 met the study’s primary endpoint of safety and tolerability. Additionally, AAV-RPE65 demonstrated statistically significant improvement across several secondary endpoints assessing clinical activity. Significant improvement in vision was demonstrated at six months after AAV-RPE65 treatment, as measured by assessments of vision- guided mobility, retinal sensitivity, visual acuity and contrast sensitivity. Larger improvements from baseline in functional vision were observed between treated and control eyes at lower light levels. We believe these outcomes address the core functional manifestation of RPE65-associated retinal dystrophy, which typically causes vision impairment beginning in early childhood that is most pronounced in low-light conditions, and is consistent with the proposed mechanism of action of AAV-RPE65. We continue to evaluate the initiation of a Phase 3 clinical trial for AAV-RPE65. The FDA and European Medicines Agency, or EMA, each granted orphan status to AAV-RPE65 for the treatment of LCA caused by mutations in the RPE65 gene. The FDA also granted AAV-RPE65 rare pediatric disease designation for the treatment of inherited retinal dystrophy due to biallelic RPE65 mutations. AAV-CNGB3 and AAV-CNGA3 for the Treatment of Achromatopsia Achromatopsia, or ACHM, is an IRD that specifically prevents cone photoreceptors from functioning. ACHM patients are legally blind from birth and usually suffer from severely reduced visual acuity of 20/200 or worse, a disabling sensitivity to light, or photoaversion, total color blindness and involuntary back and forth eye movements, or nystagmus. ACHM patients suffer significant vision loss due to the complete lack of cone function. ACHM occurs in approximately one in 30,000 people in the United States. The CNGB3 and CNGA3 genes are the two most common genes that have been identified as causing ACHM, together accounting for up to 92% of ACHM cases, with CNGB3 slightly more common than CNGA3 in most geographic territories. There are estimated to be approximately 12,000 patients with ACHM caused by mutations in CNGB3 in the United States, Japan, and the EU5, with about 25% of those patients being under the age of 18 and approximately 125 new cases being diagnosed annually. We believe the availability of a therapeutic option may increase patient identification and the estimated prevalence of ACHM. ACHM is predominantly a stationary disease, which means that ACHM patients’ retinas contain non-functioning cones that survive intact for many decades. This is in contrast to many IRDs in which the entire retina slowly degenerates over a patient’s life. This extended survival of cones with their potential for light sensitivity presents a wide window of opportunity to introduce a normal copy of the mutated gene via a gene therapy product candidate and thereby restore cone function. While the stationary nature of ACHM means that cones remain present for decades, the functional connections between active cones and the visual cortex in the brain are thought to become fixed in teenage years. Therefore, we believe that younger individuals are likely to benefit most from gene therapy treatment for ACHM because of their greater visual plasticity. Another debilitating symptom of ACHM, which lasts throughout life, is photoaversion. A disabling and ubiquitous symptom of ACHM, photoaversion is the avoidance of light due to discomfort in the presence of levels of light equivalent to a normally lit room or daylight. ACHM patients often avoid light and wear dark glasses, which further diminishes their already very poor vision. We believe it is possible that restoration of cone function in adult patients might have an impact on photoaversion even if brain plasticity is limited. We believe that gene therapy treatment for ACHM in which we aim to restore cone function via a gene replacement strategy may offer benefits across a range of ages, which we aim to define in our clinical development programs. 10 Table of Contents We have designed specifically optimized gene therapy viral vector candidates to treat ACHM caused by mutations in each of CNGB3 and CNGA3, with which we aim to address the majority of patients suffering from ACHM. Our product candidates are delivered via subretinal injection covering the central macula region of the eye, where most of the cones in the retina are located. We have an ongoing natural history study in ACHM including over 90 patients that allows us to collect structural and functional data for up to five years on prospectively defined endpoints, including functional tests, retinal imaging and electrophysiological assessments. We believe access to these ACHM patients has enabled us to efficiently enroll the most appropriate patients into our CNGB3 and CNGA3 Phase 1/2 clinical trials. In addition to giving us access to patients and potentially accelerated enrollment in our treatment studies, we believe the prospective natural history data on each treated patient allow us to gather robust data from our Phase 1/2 clinical trials in a condensed timeframe. Clinical Development of AAV-CNGB3 for the Treatment of ACHM Caused by Mutations in the CNGB3 Gene We have developed a product candidate, AAV-CNGB3, to treat ACHM caused by mutations in the CNGB3 gene. Mutations in the CNGB3 gene prevent cone photoreceptors from functioning because CNGB3’s gene product is integral to the formation of a specific membrane channel that enables cones’ electrical response to light. CNGB3 is a gene exclusively expressed in cones and our aim is to replace the absent function of the mutant CNGB3 gene with a normal copy of the gene in cones of IRD patients and thereby restore cone function. In order to drive expression of the functional CNGB3 gene specifically in cones and not in other cells of the retina, we use the cone specific human cone arrestin, or CAR, promoter to drive the expression of a codon optimized CNGB3 cDNA. Codon optimization improves protein expression by increasing translation efficiency. To transfect cone photoreceptors, we use the AAV8 capsid, which enables the efficient delivery of the CNGB3 gene cargo to those photoreceptors. As the vast majority of the cones in the eye are located centrally and concentrated in the macula, we treat this central region of the retina through subretinal injection to deliver the viral vector product candidate to the photoreceptors in which its activity is required. We have completed enrollment and dosing of the Phase 1/2 clinical trial of AAV-CNGB3 in both adult and pediatric patients. In this trial, AAV-CNGB3 was delivered via subretinal injection of up to 0.5mL targeting the central region of the retina, including the macula and fovea, where most of the cones are located. One eye is treated in each patient. The primary endpoint of this open-label, dose-escalation clinical trial is safety. Secondary endpoints include the outcomes of a range of functional and structural assessments. Dosing was completed in this clinical trial in May 2019. In the dose escalation portion of the trial, we treated 11 adults. We also treated 12 children in the pediatric expansion cohorts. Six months following treatment, patients can move onto a long term follow up study in which they are followed for safety and indication of benefit for an additional four and a half years. Our gene therapy product candidate AAV-CNGB3 was granted orphan drug designation by the FDA and the European Commission for the treatment of achromatopsia caused by mutations in the CNGB3 gene, rare pediatric disease designation by the FDA for the treatment of achromatopsia caused by mutations in the CNGB3 gene, and Fast Track designation by the FDA for the treatment of achromatopsia caused by CNGB3 mutations. We were granted PRIME designation by the EMA in October 2018 based on data from the first adult treatment cohort along with preclinical data. Clinical Development of AAV-CNGA3 for the Treatment of ACHM Caused by Mutations in the CNGA3 Gene We are also developing AAV-CNGA3 to treat ACHM caused by mutations in the CNGA3 gene. We have designed a synthetic promoter to drive high levels of CNGA3 expression specifically in cones because we believe a larger amount of CNGA3 protein is required to restore cone function as compared to CNGB3. AAV-CNGA3 utilizes this proprietary pan cone promoter to drive a codon optimized CNGA3 gene sequence. We believe this novel promoter can 11 Table of Contents drive sufficient expression of CNGA3 in cones to restore light sensitivity to these cones in CNGA3 deficient patients. We use the AAV8 capsid to transfect cone photoreceptors in the back of the eye and we target the cones concentrated in the central region of the retina via a subretinal injection that covers the macula. We have completed enrollment and dosing of the open-label, dose-escalation Phase 1/2 clinical trial of AAV- CNGA3 in patients with ACHM due to mutations in the CNGA3 gene. Our gene therapy product candidate AAV-CNGA3 was granted orphan drug designation by the FDA and EMA, rare pediatric disease designation by the FDA, and in January 2021, was granted Fast Track designation by the FDA for the treatment of ACHM caused by CNGA3 mutations. AAV-AIPL1 for the Treatment of LCA4 LCA4 is an IRD that causes complete blindness before age five. AIPL1 is a central protein for the maintenance of photoreceptor structure and function. Deletion of the AIPL1 gene causes the most severe form of early retinal dystrophy, LCA4, in which the retinal structure is destroyed with complete vision loss. LCA4 is rare, representing approximately 8% of all LCA cases. There are currently no approved treatments for LCA4, and we believe an effective intervention will require introducing a normal functional copy of the AIPL1 gene into rod and cone photoreceptors early in a patient’s life while some retinal structure remains in order to activate function and survival of the photoreceptors that are still present. We believe gene therapy has the potential to be the only effective way to address the disease’s root cause. LCA4’s extremely rapid progression, rarity and early age of onset make the standard process of seeking regulatory approval through clinical development challenging because adult safety trials would not yield meaningful data given the early onset of the disease. To address LCA4, we developed a viral vector to replace the AIPL1 gene in all photoreceptors by using the AIPL1 cDNA driven by the rhodopsin kinase promoter, which is active in both rods and cones. We have manufactured and released AAV-AIPL1 for compassionate use under an MHRA specials license in the UK to treat LCA4 patients. A specials license allows physicians to prescribe a treatment of AAV-AIPL1 for LCA4 patients they deem appropriate. We play no role in the physician’s treatment decision. We intend to use any data produced by the compassionate use treatment to inform any potential clinical development plan as well as any interactions with the regulatory agencies that would enable us to make this intervention more widely available to the LCA4 patient population. As the manufacturer of AAV-AIPL1 under a specials license, we have a record retention requirement and a continuing obligation to inform the MHRA of any suspected adverse reaction to our medicinal product which is a serious adverse reaction. The UK’s Human Medicines Regulations 2012 allow for the manufacture and supply of medicinal products not authorized for marketing to patients with special needs at the request of the healthcare professional responsible for the patient’s care (these products are referred to as “specials”). A special may only be supplied in: (i) response to an unsolicited order from a healthcare professional responsible for the care of the patient, (ii) if the product is manufactured and assembled in accordance with the specifications of that healthcare professional to fulfil the special needs of the individual patient that cannot be met by products already authorized for marketing and (iii) if the product is manufactured under a specials license granted by the MHRA. Manufacturing a special also imposes a five year record retention requirement subject to review by the MHRA, including details of any suspected adverse reaction to the product so sold or supplied of which the person is aware or 12 Table of Contents subsequently becomes aware, as well as a continuing obligation to notify the MHRA of any suspected adverse reaction to the medicinal product which is a serious adverse reaction. The FDA and European Commission granted orphan designation to AAV-AIPL1 for treatment of inherited retina dystrophy due to defects in AIPL1 gene. Ophthalmology Preclinical Development Pipeline We also have a preclinical IRD development pipeline focused on diseases caused by mutations in additional genes. In order to expand our gene therapy pipeline for retinal diseases, we are also developing treatments for certain multifactorial eye diseases, which are diseases caused by multiple genetic or environmental factors. AAV-RDH12 for the Treatment of RDH12 Mutation-Associated Retinal Dystrophy Disease-causing sequence variants in RDH12 cause severe retinal dystrophy most often resulting in the clinical diagnosis of Leber congenital amaurosis (LCA) and early onset severe retinal dystrophy (EOSRD); although RDH12 variants have also been associated with a clinical diagnosis of RP. Sequence variants in RDH12 account for 3.4%–10.5% of LCA/EOSRD. Individuals with RDH12 deficiency exhibit widespread retinal degeneration impacting both rods and cones, with early macular involvement. Most people with RDH12–LCA/EOSRD experience marked central visual loss by their late teens to twenties. AAV-RDH12 is an AAV based gene therapy designed to deliver a functional copy of the RDH12 gene to the retina of patients with genetically defined RDH12 deficiency. We received orphan drug designation from the FDA as well as orphan medicinal product designation from the European Commission for AAV-RDH12 for the treatment of RDH12-associated retinal dystrophy. We currently have an ongoing natural history study for patients with RDH12 mutation-associated retinal dystrophy. This will allow us to collect structural and functional data for up to five years on prospectively defined endpoints including functional tests, retinal imaging and electrophysiological assessments. We believe access to these patients and their data will enable us to efficiently enroll the most appropriate patients into a clinical trial for AAV-RDH12. Wet and Dry Neovascular Age Related Macular Degeneration (AMD) We are developing pre-clinical programs relating to neovascular age related macular degeneration, or wet AMD. We use a gene therapy product to deliver an antibody targeting the vascular endothelial growth factor receptor 2, or anti- VEGFR2, with the aim of blocking disease related vascular formation in the eye. Additionally, we are developing a novel approach to treat advanced dry AMD patients who have lost central vision through our innovative “rod-to-cone” technology. By genetically engineering rods with molecules that will improve their speed of response to light, we aim to effectively transform a patch of rod photoreceptors in the outer part of the retina to behave more like cone photoreceptors, thus improving vision. There is no currently approved therapy that impacts disease progression of dry AMD. The best available treatment for patients after they lose central vision and acuity is support and rehabilitation services to help them better utilize the remaining peripheral part of their retina. Our Salivary Gland Programs Our second area of clinical focus is xerostomia, a chronic and debilitating disorder of the salivary glands in which saliva production is impaired. Xerostomia may be caused by a number of different insults to the salivary glands, including radiation therapy for head and neck cancer and certain autoimmune diseases. 13 Table of Contents AAV-hAQP1 for the Treatment of Radiation-Induced Grade 2/3 Xerostomia Radiation-induced xerostomia, or RIX, is a severe and debilitating long-term side effect of radiation treatment for head and neck cancer. Chronic RIX results in severe side effects, including difficulty swallowing, or dysphagia, oral discomfort, malnutrition, oral mucositis, changes in taste, increased oral infections and dental cavities, resulting in a significant negative impact on patient quality of life. Current treatment options for RIX are few and are of limited benefit. The sialogogues pilocarpine (approved for RIX) and cevimeline (used off-label) are minimally effective in patients with grade 2/3 RIX where the gland structure and function have been significantly impaired. No new medications for RIX have been approved in over 20 years. Worldwide, there are approximately 650,000 new cases of head and neck cancer diagnosed each year, with approximately 54,000 cases in the U.S. alone, making it the fifth most common malignancy. Approximately 85% of patients who receive radiation treatment for head and neck cancer experience reduced saliva production during treatment, and approximately 50% of those patients who remain cancer free for two or more years after treatment continue to suffer from grade 2 or 3 RIX. There are approximately 170,000 such patients in the U.S., with approximately 5,000 to 10,000 new cases each year in the U.S. Salivary glands are an attractive target organ for gene therapy treatments because they are self-contained, partially immune protected and easily accessible, allowing for non-invasive delivery of small vector doses. We are developing AAV-hAQP1 to treat RIX by increasing water conduction in the chronically damaged salivary glands by introducing a water conducting channel into the remaining epithelial cells of these damaged glands. Adequate water secretion by surviving epithelial cells has the potential to deliver the protective exocrine proteins produced by remaining gland cells into the mouth. The key to our approach is that, unlike the water conducting acinar cells, the water impermeable duct cells of the glands appear to be resilient to infrared radiation exposure. As a consequence of this relative resilience to radiation treatment, salivary glands damaged by radiation treatment tend to contain mostly water impermeable ductal epithelial cells. To make these duct cells permeable to water, AAV-hAQP1 introduces the gene for the human aquaporin water channel, or hAQP1. We have demonstrated that this has the potential to convey water permeability and causes ductal cells to generate an osmotic gradient, which causes them to secrete fluid into the lumen of the duct. The proof of concept for this mechanism and its ability to increase the volume of saliva secreted by damaged salivary glands was observed in a Phase 1 clinical trial conducted by the NIH in patients with chronic grade 2 or 3 RIX. The trial was designed as a short-term dose escalation trial of a gene therapy using adenovirus as the vector to deliver the hAQP1 to the remaining epithelial cells in the parotid gland of 11 patients suffering from chronic RIX. There were no reported severe adverse events among the patients treated, two out of three patients in each of the first three cohorts in this clinical trial were observed to have objective increases in saliva volume produced by the treated parotid gland, with increases in parotid flow ranging from 60% to 540%, and all but one of these patients showed a decrease in symptoms of dry mouth as measured by subjective visual analog scales, validated in other forms of xerostomia. The results of this study were published in Proceedings of the National Academy of Sciences in 2012. We are currently conducting a Phase 1 dose escalation clinical trial of AAV-hAQP1 at the NIH in patients with grade 2 or 3 RIX who remain cancer free for at least five years after receiving radiation treatment. In this trial we are using AAV2 to deliver the hAQP1 gene, as we believe AAV2 efficiently transfects the salivary gland cells and does not spread beyond the target cells. The aim of the trial is to determine the safety of inserting hAQP1 locally into the salivary glands of RIX patients, as well as to measure changes in salivary flow resulting from the introduction of this channel. This clinical trial is being conducted in conjunction with the National Institute of Dental and Craniofacial Research at the United States National Institutes of Health, or the NIH, Dental Clinic. 14 Table of Contents In the third quarter of 2019, we also initiated an open-label, multi-center Phase 1 dose escalation clinical trial of a single administration of our product candidate AAV-hAQP1 to one or both parotid glands in patients with grade 2 or 3 RIX. In December 2021, we announced preliminary data from this Phase 1 clinical trial. The announcement included data from seven patients treated in cohorts 1, 2 and 3 of the unilateral dose escalation phase of the clinical trial. Six of the seven patients who reached 90 days following treatment reported their symptoms of dry mouth as better following treatment pursuant to a validated patient reported assessment of xerostomia symptoms, constituting clinically meaningful improvement. One patient who reported the maximum response evaluable at 12-months had reached the 24-month time point and reported the same level of response. In March 2022, we completed enrollment of the study. A total of 24 patients received either unilateral (n=12) or bilateral (n=12) treatment in one of eight escalating dose cohorts of three patients each. In December 2022, we announced additional positive clinical data from the Phase 1 dose escalation clinical trial of AAV-hAQP1. As of the cutoff date of November 30, 2022, all 12 unilaterally treated participants had undergone their 12-month assessment, with three having completed their 24-month assessment and one having completed their 36-month assessment in the long-term follow-up study. All 12 bilaterally treated participants had undergone their 6-month assessment. The investigational gene therapy AAV-hAQP1 has been well tolerated with no dose limiting toxicity or treatment-related serious adverse events, and improvements have been seen in validated patient reported assessments of xerostomia symptoms and in whole salivary flow rate. All subjects are to be followed for one year post-treatment in the present study and for an additional four years in the long-term follow-up study, per FDA guidelines. The study’s primary endpoint is safety. Secondary endpoints include change from baseline in patient reported measures of xerostomia symptoms as well as whole salivary flow rates. Based on the safety and efficacy profile of AAV-hAQP1 in the Phase 1 clinical trial and regulatory precedent, we intend to initiate a randomized, double-blind, placebo-controlled Phase 2 study evaluating two active doses of AAV-hAQP1 for the treatment of grade 2 or 3 RIX in the first half of 2023. The FDA granted orphan drug designation to AAV-hAQP1 for the treatment of symptoms of grade 2 and grade 3 late xerostomia from parotid gland hypofunction caused by radiotherapy for cancer of the oral cavity. AAV-hAQP1 for the Treatment of Sjogren’s Syndrome The destruction of salivary tissue resulting in chronic xerostomia may also be caused by chronic autoimmune disease. Sjogren’s syndrome is an autoimmune disease in which a patient’s immune system may target the salivary glands. Chronic inflammation of the salivary glands results in long term damage and chronic xerostomia in many Sjogren’s patients. Data from preclinical studies in animal models of Sjogren’s syndrome and data from explants of minor salivary glands of Sjogren’s patients suggest that Sjogren’s syndrome may also be treatable with our AAV-hAQP1 vector. Supported by data from our preclinical studies and our ongoing RIX clinical trials, we are currently conducting IND- enabling studies of AAV-hAQP1 for xerostomia caused by Sjogren’s syndrome. Our Neurodegenerative Disease Programs Neurodegenerative diseases are our third area of focus. Relying on our expertise in viral vector design, delivery, production and manufacturing, we are aiming to develop and optimize vectors to effectively treat both genetic and sporadic forms of these diseases. AAV-GAD for the Treatment of Parkinson’s Disease Our first target indication is Parkinson’s disease, where we have Phase 2 clinical data from a successful randomized, double-blind, sham-controlled trial. 15 Table of Contents Affecting nearly one million Americans and 10 million worldwide, Parkinson’s disease is the second-most common neurodegenerative disease after Alzheimer’s disease and is the 14th-leading cause of death in the United States. It is associated with a progressive loss of motor control (e.g., shaking or tremor at rest and lack of facial expression), as well as non-motor symptoms (e.g., depression and anxiety). There is no cure for Parkinson’s disease and 60,000 new cases are diagnosed each year in the United States alone. Our product candidate targeting Parkinson’s disease, AAV-GAD, is designed to deliver the glutamic acid decarboxylase, or GAD, gene to the subthalamic nucleus in order to increase production of GABA, the primary inhibitory neurotransmitter in the human brain. GAD is the rate-limiting enzyme in the synthesis of GABA, therefore we believe that increasing subthalamic nucleus GAD expression through gene therapy has the potential to address the dysregulation of motor circuits and improve symptoms in Parkinson’s disease patients without affecting other brain regions, which can be responsible for complications of existing therapies. Clinical Development of AAV-GAD In a blinded Phase 2 clinical trial of AAV-GAD in patients with medically refractory Parkinson’s disease, 45 patients were randomized 1:1 to receive either AAV-GAD gene therapy delivered by injection into the subthalamic nucleus on both sides of the brain or bilateral sham surgery. Subjects were followed for one year and all results remained blinded until the final treated patient reached the 6-month primary endpoint. The trial met the primary endpoint, of six-month change from baseline in double-blind assessment of off-medication motor scores of the Unified Parkinson’s Disease Rating Scale, or UPDRS. At the six-month endpoint, UPDRS score for the AAV-GAD group decreased by 8.1 points (SD 1.7, 23.1%; p<0.0001) and by 4.7 points in the sham group (1.5, 12.7%; p=0.003). The AAV-GAD group showed a significantly greater improvement from baseline in UPDRS scores compared with the sham group over the six-month course of the study (RMANOVA, p=0.04). An improvement in complications of medical therapy as measured by the UPDRS part 4 was observed in the AAV-GAD group at both six and 12 months. A significant decline in duration of disabling dyskinesia was observed only in the AAV-GAD treated patients. AAV-GAD was reported to be well-tolerated, with no significant adverse events related to the therapy and no speech or cognitive complications observed. The results of the trial were published in the March 2011 issue of The Lancet Neurology, the August 2014 issue of the Journal of Clinical Investigation and the April 2017 issue of JCI Insight, building upon publications of the Phase 1 trial data in The Lancet and the Proceedings of the National Academy of Sciences. In addition, in research published in the November 28, 2018 issue of Science Translational Medicine, fifteen patients treated with AAV-GAD gene therapy were observed to have expressed a treatment-related reorganization of functional brain connectivity that was related to disease symptom improvement. These flurodeoxyglucose positron emission tomography analyses provided objective biological evidence of improvements in abnormal brain networks associated with Parkinson’s disease following AAV-GAD gene therapy. These results were observed in patients treated in both Phase 1 and Phase 2 studies. Blinded analyses showed significant improvements in abnormal thalamic metabolism, a key node in the movement circuitry, in the AAV-GAD treated patients. This pattern of brain network activity was not seen in untreated hemispheres or patients in the sham arm. Furthermore, a specific pattern of brain network activity was identified in those subjects with clinical improvements in the sham arm, which was different from the pattern observed in AAV-GAD responders. We filed an Investigational New Drug application (IND) for AAV-GAD in May 2022, and we are now dosing patients in an AAV-GAD Phase 1 study with material that has been manufactured with our in-house proprietary manufacturing process at our cGMP manufacturing facility in London. The objective of the AAV-GAD trial is to evaluate the safety and tolerability of delivery of AAV-GAD into the subthalamic nuclei of participants with Parkinson’s disease. 16 Table of Contents Neurodegenerative Disease Preclinical Development Pipeline In addition to our clinical stage Parkinson’s disease program, we continue to conduct research to develop our preclinical pipeline of gene therapy product candidates for the treatment of other serious diseases of the central nervous system, including AAV-UPF1 to address motor neuron death in ALS, and an Alzheimer’s disease program focused on endosomal trafficking dysfunction. Each of these programs are directed towards the underlying cell biology that may be driving neurogeneration in these diseases. ALS ALS is a devastating, progressive, neurodegenerative disease leading to the loss of motor neurons, which are the neurons that control the ability to move, speak, swallow and ultimately to breathe. The gradual paralysis in ALS invariably leads to death. While 10% of ALS cases are caused by inherited genetic mutations, most ALS occurs sporadically, with no known genetic cause. Mutations in over 20 genes have been identified that cause the inherited ALS cases. Characterization of these disease-causing genes have implicated several cellular pathways in the disease, with a prominent role emerging for genes involved in the cellular control of RNA. Many new regulatory roles are being discovered for RNA, particularly in neurons. We have designed a viral vector product candidate, AAV-UPF1, with the aim of increasing UPF1 expression in the motor neurons of ALS patients. In preclinical studies, we observed that administration of AAV-UPF1 reduced motor neuron death thought to be driven by the toxic effects of several different genetic causes of ALS including, TDP-43, FUS and C9orf72. Improvements in ALS-like symptoms related to limb strength and mobility in rodent models of ALS have also been observed following administration of AAV-UPF1. We believe that gene therapy using AAV-UPF1 may increase UPF1 levels in cells affected by ALS, and we intend to deliver our viral vector product candidate to the central nervous system via intrathecal injection, or injection into the spinal canal. Alzheimer’s Disease With the world population aging, Alzheimer’s disease has emerged as an extremely common and costly disease. While some treatments that have temporary effects on Alzheimer’s disease symptoms are available, there is currently no approved treatment that halts the progression of the disease. Our Alzheimer’s disease program focuses on the endosomal trafficking pathway. In preclinical studies, we observed that increasing levels of key retromer proteins may reverse endosomal trafficking defects. We are identifying suitable retromer targets for gene augmentation in pre-symptomatic Alzheimer’s patients. There are several reasons why gene therapy is, in principle, well suited for Alzheimer’s disease and other neurodegenerative diseases. The first relates to the pathophysiology, time course, and anatomical spread of these disorders. Neurodegenerative diseases generally begin locally in selectively vulnerable regions with “cell sickness” years before rampant cell death and wide-spread anatomical distribution. To be most effective, we believe interventions should be administrated early and will benefit from local delivery. Even then, however, an intervention must maintain its efficacy for years because, unlike other cells in the body, neurons do not typically divide over the course of their life. We believe AAV- delivered gene therapy products may have a durable effect. In the best case scenario, one delivery successfully taken up by targeted neurons would be sufficient for years of efficacy. An important component of our approach is the development and validation of surrogate markers of endosomal dysfunction and predictive markers of Alzheimer’s disease. In particular, several well studied biomarkers linked to Alzheimer’s disease, such as amyloid-beta and tau, have also been shown to be biomarkers of endosomal trafficking dysfunction in neurons. Such biomarkers could potentially be used to identify patients with Alzheimer’s disease, as well 17 Table of Contents as demonstrate potential product efficacy in the absence of Alzheimer’s disease symptoms. By targeting endosomal trafficking dysregulation we aim to address the underlying cause of Alzheimer’s disease as well as other neurodegenerative diseases, such as certain forms of Parkinson’s disease. Our Strengths In addition to our three core therapeutic areas of focus, our six ongoing clinical development programs, and our broad pipeline of preclinical programs, we have core capabilities in viral vector design and optimization, gene therapy manufacturing and a potentially transformative gene regulation platform technology that allows precise, dose responsive control of gene expression by oral small molecules with dynamic range that can exceed 5000-fold. Utilizing the following key strengths, we aim to develop, commercialize and expand our portfolio of product candidates. ● Deep Expertise in Gene Therapy Development: We believe our expertise in viral vector design, optimization and process development allows us to efficiently advance gene therapy products candidates from preclinical development to cGMP manufacturing and clinical development through commercialization. ● Potentially Transformative Gene Regulation Platform Technology: We are developing proprietary technology to enable innovative gene therapy treatments whose expression can be turned on and off with an easily administered small molecule. We believe the capacity for temporal control of gene therapy products has the potential to transform the gene therapy landscape by opening up new treatment possibilities. ● Manufacturing Capabilities and Capacity: We have a flexible and scalable cGMP manufacturing facility and production process in London, which we expect can supply our current clinical and preclinical programs through regulatory approval and, should they be approved, provide sufficient capacity for their commercial production. We have also expanded our manufacturing capabilities with our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland. Coming online in 2022 and stretching over 150,000 square feet, it is the first commercial-scale gene therapy manufacturing site in Ireland and is unique in its scale and integrated capabilities. The site contains three facilities, one built to be flexible and scalable for viral vector production for clinical and commercial supply, in addition, a facility to manufacture plasmid DNA – the critical starting material for producing gene therapy products – and thirdly, a QC hub performing advanced biochemical quality control testing for our clinical and commercial programs. ● Robust and Diverse Clinical and Preclinical Pipeline: Applying our portfolio approach to gene therapy product development, our initial focus is on treatments for ocular disorders, including IRDs and large degenerative ocular diseases, as well as salivary gland disorders and neurodegenerative diseases. We have six programs in clinical development, one program under a compassionate use specials license and a broad preclinical development pipeline. ● Relationships with Leading Institutions: Our longstanding relationships with leading institutions and experts provides us with guidance on development strategy and access to potential patients for our clinical trials. ● Natural History Study Data: We sponsor ongoing prospective long-term natural history studies in IRDs that facilitate our ability to efficiently enroll our treatment studies, potentially reducing clinical trial timelines and providing insight into the appropriate endpoints for regulatory approval. 18 Table of Contents Our Strategy Our goal is to develop and commercialize innovative gene therapy products to treat serious disorders and broaden the scope of indications that may be treatable by our gene therapies. Our strategy to achieve this goal is to: ● successfully complete clinical development, obtain regulatory approval and commercialize our pipeline of gene therapy product candidates; ● continue to advance the development of our preclinical pipeline product candidates; ● utilize our viral vector design and optimization capabilities to identify and develop new gene therapies for serious diseases; ● advance the development of our potentially transformative proprietary technology for regulating the activity of gene therapy products using small molecules and initiate clinical trials of new regulatable product candidates; and ● continue to pursue and evaluate further strategic collaborations with additional biotechnology and pharmaceutical companies to leverage our capabilities, manufacturing capacity and proprietary gene regulation technology. Gene Therapy Overview Gene therapy uses a delivery vehicle, referred to as a vector, to insert a functionally active gene into cells in the body. The gene encodes a therapeutic protein that may block disease pathways or may enhance a deficient pathway. Gene therapy has been studied for over 50 years, with a variety of different viral vectors employed to deliver therapeutic genes. Since the first clinical study of therapeutic gene transfer in humans in 1990, thousands of gene therapy studies covering a broad range of disease targets have been initiated. In recent years, the first gene therapies have received regulatory approval, including approval by the FDA of Luxturna, marketed by Spark Therapeutics, Inc. which was purchased by Roche, for treatment of RPE65-associated retinal dystrophy, and Zolgensma, marketed by AveXis, Inc., a Novartis company, for the treatment of spinal muscular atrophy, resulting in a growing acceptance of gene therapy technology as a potentially safe and effective therapeutic approach. Our current programs use adeno-associated virus, or AAV, as the vector for delivering gene sequences into a patient’s cells. The key components of an AAV vector include: (i) the capsid, or the outer viral protein shell that encloses the target DNA, which is responsible for binding to the cell surface and allowing the therapeutic gene that it is carrying to enter the cell; (ii) the therapeutic gene, or transgene, that encodes the therapeutic protein; and (iii) the promoter, or the DNA sequence that drives the expression of the transgene. AAV is a good vector for gene therapy delivery because of its relative safety and broad applicability. AAV is less immunogenic, or less prone to causing an immune reaction, than previous generations of gene therapy vectors, such as adenoviral vectors and AAV does not readily integrate into the genome of the target cell, reducing the potential for oncogenesis, or the induction of cancer. AAV vectors can transfer a therapeutic gene into, or transduce, numerous cell types. Slight differences in capsid proteins can modulate the efficiency with which different capsids deliver genes to different cells, thus allowing different AAV capsids to be selected to most effectively target particular cell types. The therapeutic gene sequence that enters the targeted cell includes both the protein coding region and an engineered promoter sequence that is used to drive functional gene expression. These engineered promoters may be designed to drive different levels of gene expression or to limit gene expression to specific cell types. Additional aspects of the transgene sequence may be engineered for optimal gene expression, such as codon usage and synthetic introns, which may enhance levels of therapeutic protein expression. 19 Table of Contents Gene therapy can be used to address monogenic diseases, which result in mutations in a single gene in a patient’s genome. In such cases, the viral vector is used to deliver a normal copy of the gene to the cells that are defective due to the lack of the gene function. The normal gene then drives production of the missing protein and offers a therapeutic benefit in patients with the disease. This gene replacement approach underlies all of our IRD programs. In addition to replacing a gene that is defective or missing in a monogenic disease, gene therapy can also provide a therapeutic impact by adding a particular new gene function to cells and thereby change cell behavior and function in other types of diseases. This is the aim of our salivary gland programs, where our treatment is designed to promote water to flow through otherwise impermeable cells in damaged salivary glands and increase saliva flow into the mouth. Additionally, gene therapy may be used to deliver a therapeutic protein that may block a disease pathway or enhance a deficient cellular pathway in multifactorial diseases such as wet AMD and neurodegenerative diseases, including ALS and Alzheimer’s disease. Importantly, AAV vectors enable targeting of therapeutic genes to non-dividing cells, in which they are thought to remain for the rest of the cell’s life. This means that a single treatment may offer patients a durable effect and long-term benefit. The specific cells of the eye, salivary gland and the neurons that we target in our current gene therapy programs are largely non-dividing cells and preclinical evidence has shown that they can be effectively targeted by the specific AAV capsids that we use, enabling us to potentially achieve a durable impact on each of the diseases that we treat. Our Competitive Advantage in IRDs: Vector Engineering, Natural History Studies and Relationships with Leading Institutions IRDs as a class are the most common cause of blindness in the working age population worldwide and a leading cause of impaired vision in children in developed countries. There are approximately 200,000 people in each of the U.S., EU and UK affected by IRDs. However, IRDs may be caused by mutations in over 300 identified genes, and in many cases each genetically defined IRD may be a small patient population. Meaningful clinical trials for these sorts of rare indications are especially challenging because they require access to sufficient patients and baseline data on each patient in order to secure clear indicators of efficacy as a result of intervention. We seek to address this problem by sponsoring prospectively designed natural history studies in each of the indications that we are treating in our Phase ½ trials. For each of the natural history studies, baseline assessments are made upon enrollment, with follow up assessments at later time points. A broad range of assessments are used, including functional tests, retinal imaging and electrophysiological assessments. The same assessments used for each natural history study are used in our corresponding clinical trial targeting the same indication, allowing us to compare the impact of our product candidates on the progression of these diseases on a population, as well as individual patient basis. We expect the natural history studies will enhance our understanding of disease progression for each indication that we are targeting and allow us to identify optimal windows for intervention, provide specific functional and structural parameters to quantify treatment effects and define clinical endpoints. These studies also provide us with a source of potential patients for our treatment studies and have facilitated efficient enrollment of these studies. These patients are not only genotyped, but also have up to five years of detailed functional and structural assessment data prior to enrollment into an appropriate treatment study. We also have longstanding active relationships and clinical site agreements with leading institutions in retinal disorder treatments, including, among others, Moorfields Eye Hospital in London, the University of Michigan Kellogg Eye Center, Massachusetts Eye and Ear, the Medical College of Wisconsin & Froedtert Hospital and the Casey Eye Institute at the Oregon Health & Science University. These institutions and others where we have active relationships are among the premier treatment centers for the indications that we are pursuing and provide us with access to potential patients for our clinical trials and experts in IRDs who offer strategic guidance and expertise for our development 20 Table of Contents strategy. They provide services with respect to our preclinical and clinical studies. Participants enrolled at the University of Michigan Kellogg Eye Center and Massachusetts Eye and Ear Hospital may travel to the Medical College of Wisconsin & Froedtert Hospital for adaptive optic assessments. The Casey Eye Institute at the Oregon Health & Science University provides certain reading center and other clinical services with respect to our clinical trials. Our Gene Regulation Platform We are developing a potentially transformative technology designed to precisely and specifically control gene therapy expression levels via dose-response to orally delivered small molecules. The aim of this gene regulation platform is to transform gene therapy into a generalizable mechanism for the delivery of biologic drugs. The idea is that the gene encoding a particular biologic drug or a therapeutic antibody would be delivered to target cells in the body, but these genes would only be activated in the presence of a specific, proprietary small molecule. The therapeutic protein would be manufactured by the body only in the presence of the small molecule so that intermittent production of the therapeutic protein would be achieved by dosing with the small molecule drug. This temporal regulation of gene therapy products by exogenous small molecules has long been a goal of gene therapy researchers. The ability to regulate transgenes by introducing temporal control has the potential to transform the gene therapy landscape and the biologics industry as a whole. Our approach focuses on riboswitches to regulate gene expression rather than on the modulation of transcription factor activity. Riboswitches are pieces of RNA that fold into alternative shapes depending on the binding of a specific small molecule to that RNA sequence. One RNA shape allows the gene containing the riboswitch to be active, while the alternative shape inactivates the gene. Riboswitches are used extensively by bacteria, but none have been identified in mammalian cells to date. We designed de-novo mammalian riboswitches that we have observed respond to small molecules to switch genes on and off in mammalian cells and in vivo in mice. Our riboswitch contains a stretch of RNA sequence, called an aptamer, that binds to a specific small molecule. The riboswitch is inserted into the therapeutic transgene cDNA. In the absence of the specific small molecule, the unbound riboswitch folds into the shape that drives the destruction of the RNA message and no therapeutic protein is produced in the absence of the small molecule. However, when the small molecule is present and binds to the riboswitch it adopts the alternative RNA shape, causing stable messages to be formed and the therapeutic protein to be produced. One of the features of our mammalian riboswitch is its unprecedented dynamic range of greater than 5,000-fold. We believe this technology is viable for a therapeutic product and is also the first instance of a proprietary system for screening randomized aptamers and small molecules within mammalian cells for functional interactions. Using our proprietary technology, we have demonstrated the ability to regulate multiple genes in vitro and in vivo in multiple tissue types using multiple small molecules. Our Manufacturing Capabilities We own and operate a cGMP manufacturing facility situated in London, United Kingdom. Supporting our global approach to clinical development and market supply, we designed the 29,000 square foot facility to meet multiple regulatory standards, including the MHRA, EMA and FDA standards. We believe our facility can supply our current clinical and preclinical programs through regulatory approval and, should they be approved, provide sufficient capacity, for commercial production. Strategically, we believe our facility will minimize our dependence on third-party CMOs, which we believe provides a significant strategic, clinical and commercial advantage. 21 Table of Contents Our London facility is flexible and scalable, with eleven independent air handling units, two cell culture suites and three separate viral vector production suites, which allows us to produce multiple product candidates in parallel, as well as sequentially at different scales. This allows us to accommodate up to three independent parallel manufacturing streams of viral vector products that are isolated within dedicated production areas. Our London manufacturing facility includes an integrated analytical department and in-house analytical tool kit that allows for in-house release of clinical and commercial manufactured products. It is also equipped with dedicated areas for microbiology, molecular biology, and cell-based analytics. Our analytical department can perform product related assays, allowing us to retain and gain expertise that is normally lost to third parties. The close integration allows for rapid turnaround and flexibility in scheduling of key assays, reducing lead times for product candidate releases. Further, our dedicated product fill and finish suite allows us to manufacture a full range of clinical and commercial products under one roof and in our control. We have more than 205 highly trained multidisciplinary staff on our manufacturing team with backgrounds in a diverse array of manufacturing sciences, technologies, analytics and production working together to expedite delivery of gene therapy products. We have identified and licensed a proprietary HEK-293 cell line that is well characterized and that we have banked in hundreds of vials. The specific cell line, size of the bank, culture media, and cryopreservation agents have been selected to facilitate bridging between process development platforms and targets. Our HEK-293 cells are suitable for both the adherent culture platform and the bioreactor process. We believe the ability to use the same cell line throughout the product and process development lifecycle will allow us to use a bracketed approach to process validation and comparability, which we believe may reduce the time and costs related to their implementation. We have expanded our manufacturing capabilities with our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland. We completed the acquisitions of the buildings and long leasehold interest in January 2021. The campus encompasses 150,000 square feet and contains three facilities, one built to be flexible and scalable for viral vector production for clinical and commercial supply, in addition, a facility to manufacture plasmid DNA – the critical starting material for producing gene therapy products – and thirdly, a QC hub performing advanced biochemical quality control testing for MeiraGTx clinical and commercial programs. We believe that building a second viral vector manufacturing facility and bringing cGMP plasmid and DNA production, as well as QC analytics, in-house provides greater flexibility and efficiency as we advance our product candidates through development, and should they be approved, commercial production. Our significant investment in the development of our internal manufacturing capacity and expertise to allow for better control over our process development timelines, costs, product quality and intellectual property provides us with a key competitive advantage. Competition The biotechnology and pharmaceutical industries are characterized by rapidly changing technologies, significant competition and a strong emphasis on intellectual property. This is true in the field of gene therapy generally, and in the treatments for our key disease areas. While we believe that the strength of our team, gene therapy expertise, scientific knowledge and intellectual property provide us with competitive advantages, we face competition from several sources, including large and small biopharmaceutical companies, academic research institutions, government agencies and public and private research institutions. Not only must we compete with other companies that are focused on gene therapy, but any product candidates that we successfully develop and commercialize will compete with existing therapies and new therapies that may become available in the future. 22 Table of Contents Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, clinical trials, regulatory approvals and product marketing than we do. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials and acquiring technologies complementary to, or necessary for, clinical programs. Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. There are other organizations working to improve existing therapies or to develop new therapies for our initially selected disease indications. Depending on how successful these efforts are, it is possible they may increase the barriers to adoption and success for our product candidates, if approved. These efforts include two product candidates Applied Genetic Technologies Corporation, or AGTC, have in Phase ½ clinical trials to treat ACHM related to CNGB3 and CNGA3, respectively, a product candidate in Phase ½ clinical trials by each of 4D Molecular Therapeutics, Inc. and AGTC to treat XLRP, as well as Luxturna, marketed by Spark Therapeutics, Inc., and has been approved to treat RPE65- associated retinal dystrophy. We are not aware of any other gene therapy product candidates in clinical development targeting xerostomia. We are aware of other ALS gene therapies utilizing different treatment mechanisms to treat different genetically defined subsets of ALS patients, as well as gene therapy product candidates being developed for the treatment of Parkinson’s disease, including those being developed by Voyager Therapeutics, Inc., Prevail Therapeutics, Inc. and Axovant Sciences Ltd. We anticipate that we will face intense and increasing competition as new drugs enter the market and advanced technologies become available. We expect any treatments that we develop and commercialize to compete on the basis of, among other things, efficacy, safety, convenience of administration and delivery, price, the level of generic competition and the availability of reimbursement from government and other third-party payors. Intellectual Property Our success depends in large part upon our ability to secure and maintain proprietary protection for our technologies and products and to operate without infringing the proprietary rights of others. Our policy is to protect our proprietary position by, among other methods, filing or collaborating with our licensors to file U.S. and foreign patent applications related to our proprietary technology, inventions and improvements that are important to the development and implementation of our business. We also use other forms of protection, such as confidential information and trademark protection, particularly where we do not believe patent protection is appropriate or obtainable. Our patent portfolio consists of a combination of issued patents and pending patent applications that are owned or licensed from third parties. As of December 31, 2022, we own, co-own, have an exclusive license, or an exclusive option to license 297 United States and foreign issued or allowed patents and 466 patent applications, pending in the United States and internationally. For any individual patent, the term depends on the applicable law in the country in which the patent is granted. In most countries where we have filed patent applications or in-licensed patents and patent applications, patents have a term of 20 years from the application filing date or earliest claimed non-provisional priority date. In the United States, the patent term is 20 years but may be shortened if a patent is terminally disclaimed over another patent that expires earlier. The term of a U.S. patent may also be lengthened by a patent term adjustment, in order to address administrative delays by the United States Patent and Trademark Office in granting a patent. In the United States, the term of a patent that covers an FDA-approved drug or biologic may be eligible for patent term extension in order to restore the period of a patent term lost during the premarket FDA regulatory review process. The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the natural expiration of the patent. The patent term restoration period is generally equal to the regulatory review period for the approved product which period occurs after the date the patent is issued, subject to certain exceptions. Only one patent may be extended for a regulatory review period for any product, and the application 23 Table of Contents for the extension must be submitted prior to the expiration of the patent. In the future, we may decide to apply for restoration of patent term for one of our currently owned or licensed patents to extend its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant Biologics License Application. Company-Owned Intellectual Property We own eight patent families relating to gene regulation platform technologies developed by us. The first patent family includes 49 issued patents in the United States (two patents), African Regional Intellectual Property Organization, Albania, Australia, Austria, Belgium, Bulgaria, China, Croatia, Cyprus, Czech, Denmark, Estonia, Eurasian Patent Organization, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Luxembourg, Malaysia, Malta, Mexico, Monaco, Netherlands, North Macedonia, Norway, Philippines, Poland, Portugal, Romania, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland/Liechtenstein, Turkey and the United Kingdom and 22 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Intellectual Property Organization, Australia, Brazil, Canada, China, Egypt, Eurasian Patent Organization, Hong Kong, India, Indonesia, Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand (two applications), Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire February 2, 2036, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The second patent family includes two issued patents in the United States and China and 23 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Intellectual Property Organization, Australia, Brazil, Canada, Egypt, Eurasian Patent Organization, Hong Kong, India, Indonesia (two applications), Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand, Philippines (two applications), Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire February 2, 2037, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The third patent family includes two issued patents in Indonesia and Japan and 20 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Intellectual Property Organization, Australia, Brazil, Canada, China, Egypt, Eurasian Patent Organization, Hong Kong, India, Israel, Republic of Korea, Malaysia, Mexico, New Zealand, Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire February 2, 2037, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The fourth patent family includes two issued patents in the United States and Japan and 22 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Industrial Property Organization, Australia, Brazil, Canada, China, Egypt, Eurasian Patent Organization, Hong Kong, India, Indonesia, Israel, Republic of Korea, Malaysia, Mexico, New Zealand (two applications), Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire August 3, 2037, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The fifth patent family includes one issued patent in Japan and 21 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Industrial Property Organization, Australia, Brazil, Canada, China, Eurasian Patent Organization, Egypt, Hong Kong, Indonesia, Israel, India, Republic of Korea, Mexico, Malaysia, New Zealand, Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire on March 2, 2038, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The sixth patent family includes one issued patent in Japan and 21 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Industrial Property 24 Table of Contents Organization, Australia, Brazil, Canada, China, Eurasian Patent Organization, Egypt, Hong Kong, India, Indonesia, Israel, Republic of Korea, Mexico, Malaysia, New Zealand, Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire on February 21, 2038, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The seventh patent family includes 21 pending patent applications with claims directed to compositions of matter and methods of use in the United States, Europe, African Regional Industrial Property Organization, Australia, Brazil, Canada, China, Eurasian Patent Organization, Egypt, India, Indonesia, Israel, Japan, Republic of Korea, Mexico, Malaysia, New Zealand, Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire on March 24, 2041, not including any patent term adjustments that may extend the patent term in certain jurisdictions. The eighth patent family includes one pending Patent Cooperation Treaty patent application with claims directed to compositions of matter and methods of use. Patents issued from this family are expected to expire on December 15, 2042, not including any patent term adjustments that may extend the patent term in certain jurisdictions. Licensed Intellectual Property Certain of our issued patents and pending patent applications are exclusively licensed to us from UCL Business, Plc (“UCLB”), Brandeis University (“Brandeis”) and the National Institute of Dental and Craniofacial Research (“NIDCR”). UCLB The UCLB portfolio includes three licensed patent families relating to our RPE65, CNGA3, and RPGR gene therapy programs and one optioned patent family relating to our dry AMD gene therapy program with a combined 100 United States and foreign issued patents and 53 pending patent applications. The first patent family, with claims directed to compositions of matter and methods of use relating to our RPE65 program, and the AAV-RPE65 product candidate includes 43 issued patents in the United States, Albania, Australia, Austria, Belgium, Bulgaria, China, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Luxembourg, Malta, Mexico, Monaco, Netherlands, North Macedonia, Norway, Philippines, Poland, Portugal, Romania, San Moreno, Serbia, Singapore, Slovakia, Slovenia, Spain, Sweden, Switzerland/Liechtenstein, Turkey and the United Kingdom and 13 pending patent applications in the United States, Europe, Brazil, Canada, Egypt, Hong Kong, Israel, Malaysia, Mexico, New Zealand (two applications), Nigeria and Thailand. Patents issued from this family are expected to expire February 8, 2036, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. The second patent family includes 22 pending patent applications with claims directed to compositions of matter and methods of use relating to our achromatopsia program and the AAV-CNGA3 product candidate in the United States, Europe, African Regional Intellectual Property Organization, Australia, Brazil, Canada, China, Egypt, Eurasian Patent Convention, Hong Kong, India, Indonesia, Israel, Japan, Republic of Korea, Malaysia, Mexico, New Zealand, Philippines, Singapore, South Africa and Vietnam. Patents issued from this family are expected to expire January 14, 2039, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. The third patent family, with claims directed to compositions of matter and methods of use relating to our retinitis pigmentosa program and the botaretigene sparoparvovec product candidate, includes 42 issued patents in the United States (two patents), Albania, Austria, Belgium, Bulgaria, Croatia, Cyprus, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Japan (three patents), Latvia, Lithuania, Luxembourg, Malta, Monaco, Netherlands, North Macedonia, Norway, Poland, Portugal, Romania, San Moreno, Serbia, Slovakia, Slovenia, 25 Table of Contents Spain, Sweden, Switzerland/Liechtenstein, Turkey and the United Kingdom and four pending applications in Europe, Canada, China and Hong Kong. Patents issued from this family are expected to expire July 17, 2035, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. The fourth patent family which we have optioned, with claims directed to compositions of matter and methods of use relating to our dry AMD gene therapy program, includes 11 issued patents in Australia, Canada, Indonesia, Israel, Japan, Republic of Korea, Malaysia, New Zealand, Nigeria, Singapore and South Africa and 14 pending applications in the United States, Europe, African Regional Intellectual Property Organization, Australia, Brazil, China, Eurasian Patent Organization, Hong Kong (two applications), Mexico, Philippines, Singapore, Thailand and Vietnam. Patents issued from this family are expected to expire February 19, 2036, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. Brandeis The licensed Brandeis portfolio includes one patent family with claims directed to compositions of matter and methods of use relating to our ALS gene therapy program and the AAV-UPF1 product candidate. This patent family includes 17 issued patents in the United States (two patents), Austria, Australia, Belgium, Denmark, France, Germany, Hong Kong, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland/Liechtenstein and the United Kingdom and four pending patent applications in the United States, Europe, Canada and Hong Kong. Patents issued from this family are expected to expire October 8, 2033, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. National Institute of Dental and Craniofacial Research The exclusively licensed NIDCR portfolio includes one patent family with claims directed to compositions of matter and methods of use relating to our Sjogren’s Syndrome gene therapy program. This patent family includes 16 issued patents in the United States, Canada, Australia, Austria, Belgium, Denmark, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland and the United Kingdom. Patents issued from this family are expected to expire August 30, 2033, not including any patent term extensions or adjustments that may extend the patent term in certain jurisdictions. License Agreements License Agreements with UCLB We previously entered into several license agreements with UCLB, covering the following inherited retinal disease programs: (a) ACHM caused by mutations in CNGB3; (b) ACHM caused by mutations in CNGA3; (c) XLRP; and (d) RPE65-mediated IRD (together, the “Licensed Gene Therapy Programs”). The terms of these license agreements were set forth in (i) the license agreement, dated February 4, 2015, as amended, between Athena Vision Ltd. and UCLB (the “First UCLB License Agreement”); (ii) the license agreements, dated July 29, 2017, as amended, between MeiraGTx UK II Limited and UCL Business, Plc (the “Second UCLB License Agreement”); and (iii) the license agreement, dated March 15, 2018, among MeiraGTx Limited, MeiraGTx UK II Limited and UCL Business Plc (the “Third UCLB License Agreement” and, collectively, the “prior UCLB license agreements”). In January and February 2019, we amended and restated the prior UCLB license agreements to establish a new standalone license agreement (each, a “Stand-Alone UCLB Agreement”) for each of the Licensed Gene Therapy Programs. We have removed from each of the Stand-Alone UCLB Agreements our obligation to pay UCLB a share of certain sublicensing revenues as was provided under the First UCLB License Agreement and have aligned the material terms of the Stand-Alone UCLB Agreements to track those under the Third UCLB License Agreement as previously disclosed and a summary of which is set forth below as is now reflected in each of the Stand-Alone UCLB Agreements. 26 Table of Contents Under the terms of the Third UCLB License Agreement, we paid an initial upfront payment of £6,994, and issued to UCLB £100,000 of our ordinary shares. Under each of the Stand-Alone UCLB Agreements, UCLB granted us an exclusive, worldwide, and sublicensable license under certain intellectual property rights controlled by UCLB relating to one of the Licensed Gene Therapy Programs to develop and commercialize licensed products in a relevant field of gene therapy. We must use diligent efforts to develop and commercialize the licensed products. Under the terms of each Stand-Alone UCLB Agreement, we are required to pay UCLB sales milestone payments of up to a total of £39.8 million in the aggregate and an annual management fee of £50 thousand until certain royalty payments have been paid. Additionally, pursuant to the Stand-Alone UCLB Agreement related to CNGB3, we paid UCLB an upfront payment of £1.5 million and issued £1.5 million of the Company’s ordinary shares. Commencing on the first commercial sale of licensed products under each Stand-Alone UCLB Agreement, we must make low single-digit percentage royalty payments to UCLB on net sales of such products. Our royalty obligations under each agreement continue on a licensed product-by-licensed product and country-by-country basis until the latest to occur of the expiration of the last valid claim of a patent claiming such licensed product in such country, the expiration of any regulatory exclusivity for all licensed products in such country, or the tenth anniversary of first commercial sale of such licensed product in such country. Each Stand-Alone UCLB Agreement will remain in effect on a country-by-country basis until the expiration of the last payment obligation in such country. Each Stand-Alone UCLB Agreement may be terminated: (a) by either party in the event of the other party’s material breach that remains uncured for 30 days (or for 14 days in the case of breaches related to payment obligations), (b) by either party for the other party’s insolvency, (c) immediately by UCLB if we are in persistent breach of the agreement and the parties fail to agree upon a mechanism to remedy such persistent breach (or we do not comply with such agreed upon mechanism), or (d) immediately by UCLB if we undergo certain change of control events or if we enter into a sublicense with certain prohibited persons, which may adversely affect UCL’s and/or UCLB’s reputation. Each Stand-Alone UCLB Agreement may also be terminated or converted to a non-exclusive license by UCLB upon three months’ notice if we, based on an independent expert determination, fail to use diligent efforts to develop and commercially exploit licensed products and do not cure such failure within a certain cure period. License Agreement between BRI-Alzan Inc. and Brandeis In May 2013, BRI-Alzan Inc., or BRI-Alzan, entered into a license agreement with Brandeis, or the Brandeis Agreement. On December 31, 2015, we entered into an Agreement and Plan of Merger, or the BRI-Alzan Merger Agreement, with BRI-Alzan, and the Brandeis Agreement was assigned to us as a result of such merger. Pursuant to the terms of the BRI-Alzan Merger Agreement, we agreed to make cash payments to the sellers of BRI-Alzan upon the achievement of certain milestones, subject to an aggregate cap of $4,500,000. In addition, we agreed to make low single- digit percentage royalty payments to the sellers of BRI-Alzan on net sales of any product for the therapeutic or prophylactic treatment of ALS that is covered by a valid claim of the patent rights licensed under the Brandeis Agreement. The BRI-Alzan Merger Agreement includes customary confidentiality, indemnification, non-competition and non- solicitation provisions. Pursuant to the Brandeis Agreement, Brandeis granted us an exclusive, worldwide license under certain patent rights with claims directed to compositions of matter and methods of use relating to our ALS gene therapy program and the AAV-UPF1 product candidate to develop and commercialize licensed products. We must use commercially reasonable efforts to develop and commercialize licensed products. We also acquired non-exclusive, worldwide licenses to certain know-how controlled by Brandeis to exploit licensed products. We are required to pay Brandeis developmental and regulatory milestone payments of up to a total of $1.0 million in the aggregate. We are also required to pay Brandeis annual license maintenance fees ranging from $15,000 to $100,000 27 Table of Contents depending on the development stage of the licensed product. Commencing on the first commercial sale of licensed products, we must make low single-digit percentage royalty payments to Brandeis on net sales of such products. In addition, we must pay Brandeis mid-teen percentages of sublicensing revenues. The Brandeis Agreement will remain in effect on a country-by-country basis until the earlier of: (a) 1 year after the date that we, our affiliates or sublicensees last sell any licensed product in such country or (b) until the expiration of the last–to-expire of the licensed patent rights in such country. The Brandeis Agreement may be terminated by Brandeis for our insolvency or for our material breach that remains uncured for 60 days (or for 30 days in the case of breaches related to payment obligations). Such material breach may be cured only once in any 12-month period. Brandeis may also terminate any license granted under the Brandeis Agreement if we fail to timely achieve certain regulatory milestone events. Trade Secrets We also rely on trade secrets, technical know-how and continuing innovation to develop and maintain our competitive advantage. We require inventors who are identified on any company-owned patent applications to assign rights to us. We also rely on confidentiality agreements with our employees, consultants and other advisors to protect our proprietary information. Our policy is to require third parties that receive material confidential information to enter into confidentiality agreements with us. Trademarks Our trademark MeiraGTx has been registered in the U.S., UK and EU. Government Regulation and Product Approval Governmental authorities in the U.S., at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, labeling, packaging, promotion, storage, advertising, distribution, marketing, post-approval monitoring and reporting and export and import of products such as those we are developing. 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 authorities, are extensive and require the expenditure of substantial time and financial resources. FDA Approval Process We expect our product candidates to be regulated as biologics. Biological products, including gene therapy products, are subject to extensive regulation by the FDA under the Federal Food, Drug, and Cosmetic Act, or FDCA, and the Public Health Service Act, or PHSA, and other federal, state, local and foreign statutes and regulations. Both the FDCA and the PHSA and their corresponding regulations govern, among other things, the research, development, safety, testing, packaging, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post- approval monitoring and reporting, sampling, and import and export of biological products. U.S. Biological Products Development Process Our products must be approved by the FDA through the Biologics License Application, or BLA, process before they may be legally marketed in the United States. The process required by the FDA before a biologic may be marketed in the United States generally involves the following: ● completion of extensive nonclinical studies, sometimes referred to as preclinical laboratory tests, and preclinical studies and applicable requirements for the humane use of laboratory animals and formulation studies in accordance with applicable regulations, including good laboratory practices, or GLPs; 28 Table of Contents ● submission to the FDA of an IND which must become effective before clinical trials may begin; ● approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the trial is commenced; ● performance of adequate and well controlled human clinical trials according to the FDA’s regulations commonly referred to as good clinical practices, or GCPs, and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use; ● submission to the FDA of a BLA for marketing approval that includes substantive evidence of safety, purity, potency and efficacy from results of nonclinical testing and clinical trials; ● satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity, strength, quality and purity; ● potential FDA audit of the nonclinical and clinical study sites that generated the data in support of the BLA; and ● FDA review and approval, or licensure, of the BLA. Before testing any biological product candidate, including a gene therapy product, in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements, including GLPs. The clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing and controls, information about product chemistry, analytical data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical testing, such as reproductive toxicity tests and carcinogenicity in animals, may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA, after which human clinical trials may begin unless the FDA places the clinical trial on a clinical hold within that 30-day time period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. The FDA may also impose clinical holds on a biological product candidate at any time before or during clinical trials due to safety concerns or non-compliance. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization and then only under terms authorized by the FDA. In addition to the IND submission process, sponsors of certain human clinical trials of cells containing recombinant or synthetic nucleic acid molecules, including human gene transfer studies, are subject to evaluation and assessment by an institutional biosafety committee, or IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution, pursuant to the National Institutes of Health’s Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, or NIH Guidelines. The IBC assesses the safety of the research and identifies any potential risk to the public health or the environment, and such review may result in some delay before initiation of a clinical trial. While the NIH Guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. Clinical trials involve the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified investigators, generally physicians not employed by or under the study sponsor’s 29 Table of Contents control. Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, the efficacy measurements to be evaluated and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations comprising the GCP requirements, including the requirement that all research subjects provide informed consent. Further, each clinical trial must be reviewed and approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical trial will be conducted. An IRB is charged with protecting the welfare and rights of study participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject or his or her legal representative and must monitor the clinical trial until completed. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: ● Phase 1. The biological product candidate is initially introduced into healthy human subjects and tested for safety. In the case of some products for severe or life-threatening diseases, especially when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often conducted in patients. ● Phase 2. The biological product candidate is evaluated in a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule. ● Phase 3. Clinical trials are undertaken to further evaluate dosage, clinical efficacy, potency, and safety in an expanded patient population at geographically dispersed clinical trial sites. These clinical trials are intended to establish the overall risk/benefit ratio of the product and provide an adequate basis for product labeling. In most cases, the FDA requires two adequate and well controlled Phase 3 clinical trials to demonstrate the safety and efficacy of a biological product. In some instances, a single Phase 3 trial, together with other confirmatory evidence may be sufficient to support a BLA submission. Post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. The FDA recommends that sponsors observe subjects for potential gene therapy-related delayed adverse events for a 15-year period, including a minimum of five years of annual examinations followed by ten years of annual queries, either in person or by questionnaire. During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators. Annual progress reports detailing the results of the clinical trials must be submitted to the FDA. Written IND safety reports must be promptly submitted to the FDA, the NIH and the investigators for serious and unexpected adverse events, any findings from other trials, tests in laboratory animals or in vitro testing that suggest a significant risk for human subjects, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all. The FDA or the sponsor or its data safety monitoring board may suspend or permanently discontinue a clinical trial at any time on various grounds, including a finding that the research subjects or patients are being exposed to an unacceptable health risk or the clinical trial is not being conducted in accordance with FDA regulations. Similarly, an IRB can suspend or terminate approval of a clinical 30 Table of Contents study at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product candidate has been associated with unexpected serious harm to patients. The FDA and the IRB may also halt, terminate or impose other conditions if either believes the patients are subject to unacceptable risk. There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial results to public registries. Sponsors of clinical trials of FDA-regulated products, including biologics, are required to register and disclose certain clinical trial information, which is publicly available at www.clinicaltrials.gov. Information related to the product, patient population, phase of investigation, study sites and investigators, and other aspects of the clinical trial is then made public as part of the registration. Sponsors are also obligated to discuss the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed until the new product or new indication being studied has been approved. Concurrent with clinical trials, companies usually complete additional animal trials and must also develop additional information about the physical characteristics of the biological product candidate as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements. To help reduce the risk of the introduction of adventitious agents with use of biological products, the PHSA emphasizes the importance of manufacturing control for products whose attributes cannot be precisely defined. The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the sponsor must develop methods for testing the identity, strength, quality, potency and purity of the final biological product. Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the biological product candidate does not undergo unacceptable deterioration over its shelf life. U.S. Review and Approval Processes After the completion of clinical trials of a biological product candidate, FDA approval of a BLA must be obtained before commercial marketing and distribution of the biological product. The BLA must include results of product development, laboratory and animal trials, human trials, information on the manufacture, pharmacology, chemistry and controls of the product, proposed labeling and other relevant information. In addition, under the Pediatric Research Equity Act, or PREA, a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the biological product candidate 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. A sponsor who is planning to submit a marketing application for a drug or biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit an initial Pediatric Study Plan, or PSP, within sixty days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. The initial PSP must include, among other things, an outline of the pediatric study or studies that the sponsor plans to conduct, including to the extent practicable study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information, along with any other information specified in FDA regulations. The FDA and the sponsor must reach agreement on the PSP. A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from nonclinical studies, early phase clinical trials, and/or other clinical development programs. The FDA may grant deferrals for submission of data or full or partial waivers. Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted. Under the Prescription Drug User Fee Act, or PDUFA, as amended, each BLA must be accompanied by a user fee. The FDA adjusts the PDUFA user fees on an annual basis. PDUFA also imposes an annual program fee for products. Fee waivers or reductions are available in certain circumstances, including a waiver of the application fee for the first human drug application filed by a small business. Additionally, no user fees are assessed on BLAs for products designated as orphan drugs, unless the product also includes a non-orphan indication. 31 Table of Contents Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the agency accepts it for filing. The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. The resubmitted application is also subject to an initial review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA. The FDA’s goal is to complete the review of standard BLAs within ten months after it accepts an application for filing, or, if the application qualifies for priority review, six months after the FDA accepts the application for filing. In both standard and priority reviews, the review process is often significantly extended by FDA requests for additional information or clarification. The FDA reviews the BLA to determine, among other things, whether the proposed product is safe and potent, or effective, for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP requirements to assure and preserve the product’s identity, safety, strength, quality, potency and purity. The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and 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. During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use of the biological product candidate. If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS; the FDA will not approve the BLA without a REMS, if required. Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the product 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 a BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND study requirements and GCP requirements. To assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production, and quality control. Notwithstanding the submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria for approval and deny approval. If the agency decides not to approve the BLA in its present form, the FDA will issue a complete response letter that usually describes all of the specific deficiencies in the BLA identified by the FDA. The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical trials. Additionally, the complete response letter may include recommended actions that the applicant might take to place the application in a condition for approval. If a complete response letter is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the BLA, the FDA will issue an approval letter. Under the current PDUFA guidelines, the FDA has committed to reviewing such resubmissions in two or six months of receipt depending on the type of information included. If regulatory approval of a product is granted, such approval will be granted for particular indications and may entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a REMS, to ensure the benefits of the product outweigh its potential risks. A REMS is a safety strategy to manage a known or potential serious risk associated with a medicine and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. The requirement for a REMS can materially affect the potential market and profitability of the product. 32 Table of Contents Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace. Changes to some of the conditions established in an approved BLA, including changes in indications, product labeling, manufacturing processes or facilities, require submission and FDA approval of a new BLA or BLA supplement before the change can be implemented. A BLA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing BLA supplements as it does in reviewing BLAs. The FDA may require one or more Phase 4 post-market studies or surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post- marketing studies. Orphan Drug Designation The FDA may grant orphan drug designation to drugs or biologics intended to treat a rare disease or condition that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals in the United States, there is no reasonable expectation that the cost of developing and marketing the drug or biologic for this type of disease or condition will be recovered from its sales in the United States. Orphan drug designation must be requested before submitting a BLA. After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and BLA user-fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has orphan designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application, including a full BLA, to market the same drug or biologic for the same disease or condition for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer with orphan exclusivity is unable to assure sufficient quantities of the approved orphan-designated product. Competitors, however, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block the approval of one of our products for seven years if a competitor obtains approval of the same biological product as defined by the FDA or if our product candidate is determined to be contained within the competitor’s product for the same indication or disease. If a drug or biological product designated as an orphan product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan product exclusivity. In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. Expedited Development and Review Programs The FDA has a Fast Track program that is intended to expedite or facilitate the process for reviewing new biological products that meet certain criteria. Specifically, new biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a new biologic may request that the FDA designate the biologic as a Fast Track product at any time during clinical development of the product. The FDA must determine if the biologic product candidate qualifies for Fast Track designation within 60 days of receipt of the sponsor’s request. Unique to a Fast Track product, the FDA may consider for review sections of the marketing application on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the application, the FDA agrees to accept sections of the application and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the application. In addition, a Fast Track designated product is eligible for more frequent meetings with the FDA to discuss 33 Table of Contents the biologic product’s development plan and ensure collection of appropriate data needed to support approval, and may result in more frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers. In addition, the FDA established a Breakthrough Therapy designation which is intended to expedite the development and review of products that are intended to treat serious or life-threatening diseases or conditions. A Breakthrough Therapy-designated product candidate is defined as a drug or biologic that is intended, alone or in combination with one or more other drugs or biologics, 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 designation includes all of the features of Fast Track designation, as well as more intensive FDA interaction and guidance. Any product submitted to the FDA for marketing, including a product that has received a Fast Track or Breakthrough Therapy designation, may be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. An application seeking marketing approval for a biologic product is eligible for priority review if the biologic has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or there is potential for a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a new biological product designated for priority review in an effort to facilitate the review. Priority review means the FDA’s goal is to take action on an application within six months (compared to 10 months under standard review). Additionally, a product may be eligible for accelerated approval. Biological products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may be eligible for accelerated approval, which means that they may be approved on the basis of adequate and well controlled clinical trials establishing that the product has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments. As a condition of approval, the FDA may require that a sponsor of a biological product subject to accelerated approval perform adequate and well-controlled post-marketing Phase 4 clinical trials. Failure to conduct required post-approval trials, or to confirm a clinical benefit during post-marketing trials, will allow the FDA to withdraw the approved biologic product from the market on an expedited basis. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product. Fast Track designation, priority review and accelerated approval do not change the standards for approval but may expedite the development or approval process. Furthermore, as part of its implementation of the 21st Century Cures Act, the FDA established the Regenerative Medicine Advanced Therapy, or RMAT, designation, to facilitate an efficient development program for, and expedite review of, certain drugs and biological products. A biological product is eligible for RMAT designation if it qualifies as a RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions, and is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the biological product has the potential to address unmet medical needs for such a disease or condition. Like Breakthrough Therapy designation, RMAT designation provides potential benefits that include more frequent meetings with FDA to discuss the development plan for the product candidate, and eligibility for rolling review and priority review. Products granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites. RMAT-designated products that receive accelerated approval may, as appropriate, fulfill their post-approval requirements through the submission of clinical 34 Table of Contents evidence, clinical trials, patient registries, or other sources of real world evidence (such as electronic health records); through the collection of larger confirmatory data sets; or via post-approval monitoring of all patients treated with such therapy prior to approval of the therapy. Fast Track designation, priority review, accelerated approval, Breakthrough Therapy designation and RMAT designation do not change the standards for approval but may expedite the development or approval process. Even if these designations are received, the FDA may later decide that a product candidate no longer meets the conditions for qualification. Post-Approval Requirements Rigorous and extensive FDA regulation of biological products continues after approval, particularly with respect to cGMP requirements. Manufacturers are required to comply with applicable requirements in the cGMP regulations, including quality control and quality assurance and maintenance of records and documentation. Other post-approval requirements applicable to biological products, include reporting of cGMP deviations that may affect the identity, potency, purity and overall safety of a distributed product, record-keeping requirements, reporting of adverse effects, reporting updated safety and efficacy information, and complying with electronic record and signature requirements. After a BLA is approved, the product also may be subject to official lot release. As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot. The FDA also may perform certain confirmatory tests on lots of some products, such as viral vaccines, before releasing the lots for distribution by the manufacturer. In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, potency, and effectiveness of biological products. The FDA may require one or more Phase 4 post-market trials or surveillance to further assess and monitor the product’s safety and effectiveness after commercialization, and may limit further marketing of the product based on the results of these post-marketing studies. We also must comply with the FDA’s advertising and promotion requirements, such as those related to direct-to-consumer advertising, the prohibition on promoting products for uses or in patient populations that are not described in the product’s approved labeling (known as “off-label use”), industry-sponsored scientific and educational activities, and promotional activities involving the Internet. Biologics may be marketed only for the approved indications and in accordance with the provisions of the approved labeling. Discovery of previously unknown problems or the failure to comply with the applicable regulatory requirements may result in restrictions on the marketing of a product or withdrawal of the product from the market as well as possible civil or criminal sanctions. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant or manufacturer to administrative or judicial civil or criminal sanctions and adverse publicity. FDA sanctions could include refusal to approve pending applications, withdrawal of an approval, clinical hold, warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, mandated corrective advertising or communications with doctors, debarment, restitution, disgorgement of profits, or civil or criminal penalties. Biological product manufacturers and other entities involved in the manufacture and distribution of approved biological products are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP requirements and other laws. Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance. Discovery of problems with a product after approval may result in 35 Table of Contents restrictions on a product, manufacturer, or holder of an approved BLA, including withdrawal of the product from the market. In addition, changes to the manufacturing process or facility generally require prior FDA approval before being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval. Biosimilars and Exclusivity The Biologics Price Competition and Innovation Act of 2009, or BPCIA, created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical trial or trials. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. However, complexities associated with the larger, and often more complex, structures of biological products, as well as the processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being worked out by the FDA. Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing the sponsor’s own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of their product. The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an FDA-issued “Written Request” for such a study. Other Healthcare Laws and Compliance Requirements Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business, which may constrain the financial arrangements and relationships through which we conduct our research, as well as, sell, market and distribute any products for which we obtain marketing approval. Such laws include, without limitation, federal and state anti-kickback, fraud and abuse, false claims and transparency laws and regulations regarding drug pricing and payments or other transfers of value made to physicians and other licensed healthcare professionals. If their operations are found to be in violation of any of such laws or any other governmental regulations that apply, they may be subject to penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of operations, exclusion from participation in federal and state healthcare programs, integrity oversight and reporting obligations to resolve allegations of non-compliance and imprisonment. Coverage and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any pharmaceutical or biological product for which we obtain regulatory approval. Sales of any product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state, and foreign government healthcare programs, 36 Table of Contents commercial insurance and managed healthcare organizations, and the level of reimbursement for such product by third- party payors. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan- by-plan basis. For products administered under the supervision of a physician, obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization. In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost- containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Third party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity and reviewing the cost effectiveness of pharmaceutical or biological products, medical devices and medical services, in addition to questioning safety and efficacy. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product. Decreases in third-party reimbursement for any product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand for the product. Healthcare Reform The United States and some foreign jurisdictions are considering or have enacted a number of reform proposals to change the healthcare system. There is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biopharmaceutical products, especially under government-funded health care programs, and increased governmental control of drug pricing. In March 2010, the Patient Protection and Affordable Care Act, or the ACA, was signed into law, which substantially changed the way healthcare is financed by both governmental and private insurers in the United States, and significantly affected the pharmaceutical industry. The ACA contained a number of provisions of particular import to the pharmaceutical and biotechnology industries, including, but not limited to, those governing enrollment in federal healthcare programs, 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, and annual fees based on pharmaceutical companies’ share of sales to federal health care programs. Since its enactment, there have been judicial, Congressional and executive branch challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. Prior to the Supreme Court’s decision, President Biden issued an executive order to initiate a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace from February 15, 2021 through August 15, 2021. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA. Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year, which was temporarily suspended from May 1, 2020 through March 31, 2022, and reduced payments to several types of Medicare providers. Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. At 37 Table of Contents the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical 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. Additionally, on May 30, 2018, the Trickett Wendler, Frank Mongiello, Jordan McLinn, and Matthew Bellina Right to Try Act of 2017, or 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 1 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 pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act. U.S. Data Privacy and Security Laws In the United States, numerous federal and state laws and regulations, including data breach notification laws, health information privacy and security laws, including the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, and regulations promulgated thereunder, or collectively, HIPAA, and federal and state consumer protection laws and regulations (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure, and protection of health- related and other personal information could apply to our operations or the operations of our partners. In addition, certain state laws, such as the California Consumer Privacy Act, or CCPA, and the California Privacy Rights Act, or CPRA, govern the privacy and security of personal information, including health-related information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation. Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to make compliance efforts more challenging, and can result in investigations, proceedings, or actions that lead to significant penalties and restrictions on data processing. U.S. Foreign Corrupt Practices Act The U.S. Foreign Corrupt Practices Act of 1977, or FCPA, prohibits U.S. corporations and individuals from engaging in certain activities to obtain or retain business or secure any improper advantage, or to influence a person working in an official capacity. It is illegal to pay, offer to pay or authorize the payment of anything of value to any employee or official of a foreign government or public international organization, or political party, political party official, or political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity. The scope of the FCPA also includes employees and officials of state-owned or controlled enterprises, which may include healthcare professionals in many countries. Equivalent laws have been adopted in other foreign countries that impose similar obligations. Government Regulation Outside of the United States In addition to regulations in the United States, we may be subject to a variety of regulations in other jurisdictions, for instance in the UK or EU, governing, among other things, clinical trials, marketing authorizations, post-marketing authorization requirements and any commercial sales and distribution of our products. Because biologically sourced raw materials are subject to unique contamination risks, their use may be restricted in some countries. In addition, ethical, social and legal concerns about gene therapy, genetic testing, genetic research and gene-editing technology, could result in additional regulations restricting or prohibiting the processes we may use. 38 Table of Contents Whether or not we obtain FDA approval of a product, we must obtain the requisite approvals from regulatory authorities in foreign countries prior to the commencement of clinical trials or marketing of the product in those countries. The requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country. If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution. Non-Clinical Studies and Clinical Trials Similar to the United States, the various phases of non-clinical and clinical research abroad are subject to significant regulatory controls. Non-clinical studies are performed to demonstrate the health or environmental safety of new chemical or biological substances. Non-clinical studies must be conducted in compliance with the principles of GLP, as set forth in EU Directive 2004/10/EC. In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements. Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization, or ICH, guidelines on GCPs, as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki. Additional GCP guidelines from the European Commission, focusing in particular on traceability, apply to clinical trials of ATMPs. If the sponsor of the clinical trial is not established within the EU, it must appoint an entity within the EU to act as its legal representative. The sponsor must take out a clinical trial insurance policy, and in most EU member states, the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial. The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law. The CTR notably harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System, which contains a centralized EU portal and database. While the EU Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The CTA must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR foresees a three-year transition period. The extent to which ongoing and new clinical trials will be governed by the CTR varies. Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the EU Clinical Trials Directive, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the EU Clinical Trials Directive remain governed by the EU Clinical Trials Directive until 39 Table of Contents January 31, 2025. After this date, all clinical trials (including those which are ongoing) will become subject to the provisions of the CTR. Medicines used in clinical trials must be manufactured in accordance with good manufacturing practices, or GMP. Other national and EU-wide regulatory requirements may also apply. During the development of a medicinal product, the EMA and national regulators within the EU provide the opportunity for dialogue and guidance on the development program. At the EMA level, this is usually done in the form of scientific advice, which is given by the Scientific Advice Working Party of the Committee for Medicinal Products for Human Use, or CHMP. A fee is incurred with each scientific advice procedure. Advice from the EMA is typically provided based on questions concerning, for example, quality (chemistry, manufacturing and controls testing), nonclinical testing and clinical trials, and pharmacovigilance plans and risk-management programs. Advice is not legally binding with regard to any future marketing authorization application of the product concerned. Marketing Authorizations In the EU, medicinal products can only be placed on the market after obtaining a marketing authorization, or MA. To obtain regulatory approval of an investigational chemical or biological product in the EU, we must submit a marketing authorization application, or MAA. The process for doing this depends, among other things, on the nature of the medicinal product. “Centralized MAs” issued by the European Commission, based on the opinion of the EMA, are valid across the entire territory of the EU. The centralized procedure is compulsory for certain types of product candidates, such as: (i) medicinal products derived from biotechnology processes, such as genetic engineering, (ii) medicinal products containing a new active substance indicated for the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) designated orphan medicines and (iv) ATMPs, such as gene therapy, somatic cell therapy or tissue-engineered medicines. The centralized procedure is optional for product candidates containing a new active substance not yet authorized in the EU, or for product candidates that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU. The Committee for Advanced Therapies, or CAT, is responsible in conjunction with the CHMP for the evaluation of advanced therapy medicinal products, or ATMPs. The CAT is primarily responsible for the scientific evaluation of ATMPs and prepares a draft opinion on the quality, safety and efficacy of each ATMP for which an MAA is submitted. The CAT’s opinion is then taken into account by the CHMP when giving its final recommendation regarding the authorization of a product in view of the balance of benefits and risks identified. Although the CAT’s draft opinion is submitted to the CHMP for final approval, the CHMP may depart from the draft opinion, if it provides detailed scientific justification. The CHMP and CAT are also responsible for providing guidelines on ATMPs and have published numerous guidelines, including specific guidelines on gene therapies and cell therapies. These guidelines provide additional guidance on the factors that the EMA will consider in relation to the development and evaluation of ATMPs and include, among other things, the preclinical studies required to characterize ATMPs; the manufacturing and control information that should be submitted in an MAA; and post-approval measures required to monitor patients and evaluate the long term efficacy and potential adverse reactions of ATMPs. Although these guidelines are not legally binding, we believe that our compliance with them is likely necessary to gain and maintain approval for any of our product candidates. Under the centralized procedure, the maximum timeframe for the evaluation of an MAA by the EMA is 210 days. This excludes so-called clock stops, during which additional written or oral information is to be provided by the applicant in response to questions asked by the CHMP. At the end of the review period, the CHMP provides an opinion to the European Commission. If this opinion is favorable, the Commission may then adopt a decision to grant an MA. 40 Table of Contents “National MAs” are issued by the competent authorities of the EU member states, only cover their respective territory, and are available for product candidates not falling within the mandatory scope of the centralized procedure. Where a product has already been authorized for marketing in an EU member state, this national MA can be recognized in another member state through the mutual recognition procedure. If the product has not received a national MA in any member state at the time of application, it can be approved simultaneously in various member states through the decentralized procedure. Under the decentralized procedure an identical dossier is submitted to the competent authorities of each of the member states in which the MA is sought, one of which is selected by the applicant as the reference member state. MAs have an initial duration of five years. After these five years, the authorization may be renewed on the basis of a reevaluation of the risk-benefit balance. Once renewed, the MA is valid for an unlimited period unless the European Commission or the national competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal In exceptional cases, the CHMP might perform an accelerated review of an MAA in no more than 150 days (not including clock stops). Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the PRIME scheme, which provides incentives similar to the Breakthrough Therapy designation in the U.S. PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicines that target unmet medical needs. It is based on increased interaction and early dialogue with companies developing promising medicines, to optimize their product development plans and speed up their evaluation to help them reach patients earlier. Product developers that benefit from PRIME designation can expect to be eligible for accelerated assessment but this is not guaranteed. 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 MAA assessment once a dossier has been submitted. Importantly, a dedicated contact and rapporteur from the CHMP is appointed early in the PRIME scheme facilitating increased understanding of the product at EMA’s committee level. An initial meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies. Moreover, in the EU, the European Commission may grant a so-called “conditional MA” prior to obtaining the comprehensive clinical data required for an application for a full MA. Such conditional MAs may be granted for product candidates (including medicines designated as orphan medicinal products), if (i) the risk-benefit balance of the product candidate is positive, (ii) it is likely that the applicant will be in a position to provide the required comprehensive clinical trial data, (iii) the product fulfills an unmet medical need and (iv) the benefit to public health of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required. A conditional MA may contain specific obligations to be fulfilled by the MA holder, including obligations with respect to the completion of ongoing or new studies, and with respect to the collection of pharmacovigilance data. Conditional MAs are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions and/or specific obligations. The MA can be converted into a standard MA once the MA holder fulfils the obligations that were imposed and the complete data confirm that the medicine’s benefits continue to outweigh its risks. The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional MA. The European Commission may also grant a so-called “marketing authorization under exceptional circumstances”. Such MA is intended for products for which the applicant can demonstrate that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use even after the product has been authorized, because the indications for which the product in question is intended are encountered so rarely that the applicant cannot reasonably be expected to provide comprehensive evidence, or in the present state of scientific knowledge, comprehensive information cannot be provided, or it would be contrary to generally accepted principles of 41 Table of Contents medical ethics to collect such information. Consequently, MAs under exceptional circumstances may be granted subject to certain specific obligations, which may include the following: ● the applicant must complete an identified program of studies within a time period specified by the competent authority, the results of which form the basis of a reassessment of the benefit/risk profile; ● the medicinal product in question may be supplied on medical prescription only and may in certain cases be administered only under strict medical supervision, possibly in a hospital and in the case of a radio- pharmaceutical, by an authorized person; and ● the package leaflet and any medical information must draw the attention of the medical practitioner to the fact that the particulars available concerning the medicinal product in question are as yet inadequate in certain specified respects. An MA under exceptional circumstances is subject to annual review to reassess the risk-benefit balance in an annual reassessment procedure. Continuation of the authorization is linked to the annual reassessment and a negative assessment could potentially result in the MA being suspended or revoked. The renewal of an MA of a medicinal product under exceptional circumstances, however, follows the same rules as a “normal” MA. Thus, an MA under exceptional circumstances is granted for an initial five years, after which the authorization will become valid indefinitely, unless the EMA decides that safety grounds merit one additional five-year renewal. An MA under exceptional circumstances should not be granted when a conditional MA is more appropriate. The EU medicines rules expressly permit the EU member states to adopt national legislation prohibiting or restricting the sale, supply or use of any medicinal product containing, consisting of or derived from a specific type of human or animal cell, such as embryonic stem cells. While the products we have in development do not make use of embryonic stem cells, it is possible that the national laws in certain EU member states may prohibit or restrict us from commercializing our products, even if they have been granted an MA. Data and Marketing Exclusivity The EU also provides opportunities for market exclusivity. Upon receiving MA, reference products generally receive eight years of data exclusivity and an additional two years of market exclusivity. If granted, data exclusivity prevents generic or biosimilar applicants from relying on the preclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar MA in the EU during a period of eight years from the date on which the reference product was first authorized in the EU. The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the EU until ten years have elapsed from the initial MA of the reference product in the EU. The overall ten-year market exclusivity period may be extended to a maximum of eleven years if during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications with significant clinical benefit over existing therapies. However, there is no guarantee that a product will be considered by the EU regulatory authorities to be a new chemical or biological entity, and products may not qualify for data exclusivity. There is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product, for example, because of differences in raw materials or manufacturing processes. For such products, the results of appropriate preclinical or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product. There are no such guidelines for complex biological products, such as gene or cell therapy medicinal products, and so it is unlikely that biosimilars of those products will currently be approved in the EU. However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time. 42 Table of Contents Orphan Medicinal Products The criteria for designating an “orphan medicinal product” in the EU are similar in principle to those in the United States. A medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition. Orphan drug designation entitles a party to incentives such as reduction of fees or fee waivers, protocol assistance, and access to the centralized MA procedure. The application for orphan drug designation must be submitted before the MAA. The applicant will receive a fee reduction for the MAA if the orphan drug designation has been granted, but not if the designation is still pending at the time the MA is submitted. Upon grant of an MA and assuming the requirement for orphan designation are also met at the time the MA is granted, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication, which means that regulatory authorities cannot accept another MA or grant an MA or accept an application to extend an existing MA in respect of a similar medicinal product for the same indication for a period of ten years. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed pediatric investigation plan, or PIP. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the orphan designation threshold. Additionally, an MA may be granted to a similar product for the same indication at any time if (1) the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior, (2) the applicant consents to a second orphan medicinal product application; or (3) the applicant cannot supply enough orphan medicinal product. Pediatric Development In the EU, MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a PIP agreed with the EMA’s Pediatric Committee, or PDCO. The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the drug for which an MA 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 are 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 MA is obtained in all EU member states and study results are included in the product information, even when negative, the product is eligible for a six-months supplementary protection certificate extension (if any is in effect at the time of approval) or, in the case of orphan medicinal products, a two year extension of the orphan market exclusivity is granted. Post-Approval Requirements Similar to the United States, both MA holders and manufacturers of medicinal products are subject to comprehensive regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the member states. The holder of an MA must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance who is responsible for oversight of that system. Key obligations 43 Table of Contents include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs. All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product. The regulatory authorities may also impose specific obligations as a condition of the MA. Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies. The advertising and promotion of medicinal products is also subject to laws concerning promotion of medicinal products, interactions with physicians, misleading and comparative advertising and unfair commercial practices. All advertising and promotional activities for the product must be consistent with the approved summary of product characteristics, and therefore all off-label promotion is prohibited. Direct-to-consumer advertising of prescription medicines is also prohibited in the EU. Although general requirements for advertising and promotion of medicinal products are established under EU directives, the details are governed by regulations in each member state and can differ from one country to another. Failure to comply with EU and member state laws that apply to the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of the MA, manufacturing of pharmaceutical products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the MA, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties. The aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Iceland, Liechtenstein and Norway. Pricing and Reimbursement Even if a medicinal product obtains an MA in the EU, there can be no assurance that reimbursement for such product will be secured on a timely basis or at all. Governments influence the price of medicinal products through their pricing and reimbursement rules and control of national healthcare systems that fund a large part of the cost of those products to consumers. Member states are free to restrict the range of pharmaceutical products for which their national health insurance systems provide reimbursement, and to control the prices and reimbursement levels of pharmaceutical products for human use. Some jurisdictions operate positive and negative list systems under which products may only be marketed once a reimbursement price has been agreed to by the government. Member states may approve a specific price or level of reimbursement for the pharmaceutical product, or alternatively adopt a system of direct or indirect controls on the profitability of the company responsible for placing the pharmaceutical product on the market, including volume-based arrangements, caps and reference pricing mechanisms. To obtain reimbursement or pricing approval, some of these countries may require the completion of clinical trials that compare the cost-effectiveness of a particular product candidate to currently available therapies. Other EU member states allow companies to fix their own prices for medicines, but monitor and control company profits. The downward pressure on healthcare costs in general, particularly prescription medicines, has become very intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in some countries, cross border imports from low-priced markets exert a commercial pressure on pricing within a country. Brexit and the Regulatory Framework in the United Kingdom The UK formally left the EU on January 31, 2020, commonly referred to as “Brexit”. Since the end of the Brexit transition period on January 1, 2021, Great Britain (England, Scotland and Wales) has not been directly subject to 44 Table of Contents EU laws, however under the terms of the Protocol on Ireland and Northern Ireland, EU laws have generally applied to Northern Ireland. On February 27, 2023, the UK Government and the European Commission reached a political agreement on the “Windsor Agreement” which may revise the Protocol on Ireland and Northern Ireland in order to address some of the perceived shortcomings in its operation. Under the proposed changes, Northern Ireland would be reintegrated under the regulatory authority of the MHRA with respect to medicinal products. These proposed changes need to be codified and agreed by the respective parliaments of the UK and EU before taking effect. UK Clinical Trials It is currently unclear to what extent the UK will seek to align its regulations with the EU. The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation), and after Brexit, EU laws on clinical trials (including the CTR) are no longer directly applicable in Great Britain (i.e., the UK excluding Northern Ireland). On January 17, 2022, the MHRA launched an eight-week consultation on reframing the UK legislation for clinical trials. The consultation closed on March 14, 2022 and aims to streamline clinical trials approvals, enable innovation, enhance clinical trials transparency, enable greater risk proportionality, and promote patient and public involvement in clinical trials. The outcome of the consultation is being closely watched and will determine whether the UK chooses to align with the CTR or diverge from it to maintain regulatory flexibility. Under the terms of the Protocol on Ireland and Northern Ireland, provisions of the CTR which relate to the manufacture and import of investigational medicinal products and auxiliary medicinal products currently apply in Northern Ireland. On February 27, 2023, the UK Government and the European Commission reached a political agreement on the “Windsor Agreement” which may revise the Protocol on Ireland and Northern Ireland in order to address some of the perceived shortcomings in its operation. If implemented, this may have further impact on the application of the CTR in Northern Ireland. UK Marketing Authorizations The MHRA is now the UK’s standalone regulator for MAAs. All existing centralized procedure MAs were automatically converted into UK MAs effective in Great Britain and issued with a UK MA number on January 1, 2021 (unless MA holders opted out of this scheme by January 21, 2021). As a result of the implementation of the Protocol on Ireland and Northern Ireland, centralized procedure MAs remain valid for marketing products in Northern Ireland. Pending applications which were submitted to EMA prior to the end of the transition period will either be determined in parallel by the MHRA, or will be put “on hold” until the CHMP issues a positive decision which can be relied upon by the MHRA. Converted EU MAs will be treated as if they were granted on the date the corresponding centralized procedure MA was granted and the renewal date will stay the same. If renewals were submitted and no decision was rendered before January 1, 2021, the MHRA will ensure the renewal process is concluded and processed appropriately, and there will be no need to resubmit the application. From January 1, 2021 the requirements for renewal submissions remain the same as required by the EMA and the MA holders should continue to submit renewal applications to the MHRA nine months before they expire (or six months in relation to conditional MAs). Following January 1, 2021, an applicant for a centralized procedure MA must be established in the EU. After this date, companies established in the UK can no longer use the centralized procedure and instead must follow one of the UK national authorization procedures or one of the remaining post-Brexit international cooperation procedures (such as the Access Consortium) to obtain an MA to market products in the UK. In addition, for a two-year period from January 1, 2021, MHRA may rely on a decision taken by the European Commission on the approval of a new centralized procedure MA when determining an application for a Great Britain MA; or use the MHRA’s decentralized or mutual recognition procedures which enable MAs approved in EU member states (or Iceland, Liechtenstein, Norway) to be granted in Great Britain. Additionally, the ‘Unfettered Access Procedure’ enables MA holders in Northern Ireland to seek recognition in Great Britain. Post Brexit, the MHRA has updated various aspects of the regulatory regime for medicines in the UK, including: introducing the Innovative Licensing and Access Procedure to accelerate the time to market and facilitate patient access for innovative medicines; updates to the UK national approval procedure, 45 Table of Contents introducing a 150-day objective for assessing applications for MAs in the UK, Great Britain and Northern Ireland and a rolling review process for MA applications (rather than a consolidated full dossier submission). UK Orphan Designation Post-Brexit, the UK has retained the EU Regulation which governs the designation of medicinal products as orphan medicinal products and which establishes incentives thereto (Regulation (EC) No. 141/2000) as part of UK law by virtue of the EU (Withdrawal) Act 2018. However under the Retained EU Law (Revocation and Reform) Bill, which is currently before the UK Parliament, unless this legislation is expressly preserved and “assimilated” into domestic law or extended by ministerial regulations (to no later than June 23, 2026) it will automatically expire and be revoked by December 31, 2023. There is therefore uncertainty about the future regulations relating to orphan designation in Great Britain, and any future changes to the legal requirements could lead to greater regulatory complexity and increased costs to our business. The MHRA is responsible for reviewing applications from companies for orphan designation at the time of a MAA. If a medicinal product has been designated orphan in the EU under Regulation (EC) 141/2000, a Great Britain orphan MAA can be made under regulation 50G of the Human Medicines Regulation 2012 (as amended). A UK-wide orphan MAA can only be considered in the absence of an active EU orphan designation. If a UK-wide orphan MA is granted and the medicinal product subsequently receives EU orphan designation, the MA holder would need to submit a variation to change this to a Great Britain orphan MA. UK Specials Regulation The UK’s Human Medicines Regulations 2012 allow for the manufacture and supply of medicinal products not authorized for marketing to patients with special needs at the request of the healthcare professional responsible for the patient’s care (these products are referred to as “specials”). A special may only be supplied: (i) in response to an unsolicited order from a healthcare professional responsible for the care of the patient, (ii) if the product is manufactured and assembled in accordance with the specifications of that healthcare professional to fulfil the special needs of the individual patient which cannot be met by products already authorized for marketing, and (iii) if the product is manufactured under a specials license granted by the UK’s MHRA. Manufacturing a special also imposes a five year record retention requirement subject to review by the MHRA, including details of any suspected adverse reaction to the product so sold or supplied of which the person is aware or subsequently becomes aware, as well as a continuing obligation to notify the MHRA of any suspected adverse reaction to the medicinal product which is a serious adverse reaction. Privacy and Data Protection Laws We are also subject to laws and regulations in non-U.S. countries in which we are established or in which we run clinical trials, as well as countries in which we may sell, market and distribute products for which we obtain marketing approval. These laws and regulations cover data privacy and the protection of health-related and other personal data. Laws and regulations in the EU and other jurisdictions apply broadly to the collection, use, storage, disclosure, processing and security of personal data, and have generally become more stringent over time. For example, the General Data Protection Regulation, or GDPR, imposes strict requirements for processing the personal data of individuals within the EEA. The GDPR allows EU member states to make additional laws and regulations further regulating the processing of genetic, biometric or health data. Failure to comply with the requirements of GDPR and the applicable national data protection laws of the EU member states may result in fines of up to €20 million or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other administrative penalties and may expose us to compensation claims from affected individuals. 46 Table of Contents Further, from January 1, 2021, we are subject to the GDPR and also the UK GDPR, which, together with the amended UK Data Protection Act 2018, retains the GDPR in UK national law. The UK GDPR mirrors the fines under the GDPR, e.g. fines up to the greater of £17.5 million or 4% of the total worldwide annual turnover of the preceding financial year. The European Commission has adopted an adequacy decision in favor of the UK, enabling data transfers from EU member states to the UK without additional safeguards. However, the UK adequacy decision will automatically expire in June 2025 unless the European Commission re-assesses and renews/extends that decision, and it continues to remain under review by the Commission during this period. Employees As of December 31, 2022, we had 358 employees, 343 of which are full-time employees. None of our employees is subject to a collective bargaining agreement or represented by a trade or labor union. We consider our relationship with our employees to be good. Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants. The principal purposes of our equity incentive plans are to attract, retain and reward personnel through the granting of equity-based compensation awards in order to increase shareholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. Corporate Information MeiraGTx Holdings plc was formed on May 1, 2018 under the laws of the Cayman Islands. Our predecessor, MeiraGTx Limited, a limited company under the laws of England and Wales, was formed on March 20, 2015. In connection with our initial public offering (“IPO”), we reorganized whereby MeiraGTx Limited became a wholly owned subsidiary of MeiraGTx Holdings plc. Available Information Our website can be found at http://www.meiragtx.com. From time to time, we may use our website as a channel of distribution of material company information. Financial and other material information is routinely posted and accessible under the Investors and Media section of our website at http://www.meiragtx.com. We file annual, quarterly and current reports, proxy statements and other information with the U.S. Securities and Exchange Commission (“SEC”). Our SEC filings are available to the public over the Internet at the SEC’s website at http://www.sec.gov. Our SEC filings are also available without charge under the Investors and Media section of our website at http://www.meiragtx.com. We make this information available on our website as soon as reasonably practicable after we electronically file such information with, or furnish it to, the SEC. Our website and the information contained on or connected to that site are not incorporated into this Form 10-K. ITEM 1A. RISK FACTORS Investing in our ordinary shares involves a high degree of risk. You should consider carefully the risks described below, together with the other information included or incorporated by reference in this Form 10-K. If any of the following risks occur, our business, financial condition, results of operations and future growth prospects could be materially and adversely affected. In these circumstances, the market price of our ordinary shares could decline. Other events that we do not currently anticipate or that we currently deem immaterial may also affect our business, prospects, financial condition and results of operations, particularly in light of the continually evolving nature of the COVID-19 pandemic, containment measures, vaccine distribution, vaccination rates, new variants and the related impacts to economic and operating conditions. 47 Table of Contents Risks Related to Our Financial Position and Need for Additional Capital We have incurred significant losses since inception and anticipate that we will incur continued losses for the foreseeable future, and may never achieve or maintain profitability. We are a clinical stage company with limited operating history. We were formed and began operations in 2015. We have never been profitable and do not expect to be profitable in the foreseeable future. We have incurred net losses since inception, including net losses of approximately $129.6 million and $79.6 million for the twelve months ended December 31, 2022 and 2021, respectively. As of December 31, 2022, we had an accumulated deficit of approximately $470.2 million. Since our inception, we have devoted substantially all of our resources to developing our technology platform, establishing our viral vector manufacturing facilities and plasmid and DNA production facility, developing manufacturing processes, advancing the product candidates in our ophthalmology, salivary gland and neurodegenerative disease programs, research and development activities, building our intellectual property portfolio, organizing and staffing our company, developing our business plans, raising capital, securing debt financing and providing general and administrative support for these operations. We have not yet demonstrated an ability to successfully complete large-scale, pivotal clinical trials, obtain marketing approval, manufacture product at a commercial scale, or arrange for a third party to do so on our behalf, or conduct sales and marketing activities necessary for successful product commercialization. Given the length of time typically needed to develop a new drug from the time it enters Phase 1 clinical trials to when it is approved for treating patients, predictions about our future success or viability may not be as accurate as they could be if we had a longer operating history or a history of successfully developing and commercializing genetic medicine products. We expect to continue to incur significant expenses and additional operating losses for the foreseeable future as we seek to advance product candidates through preclinical and clinical development, expand our research, development and manufacturing activities, develop new product candidates, build and expand our intellectual product portfolio, complete clinical trials, seek regulatory approval and, if we receive regulatory approval, commercialize our products. Furthermore, the costs of advancing product candidates into each succeeding clinical phase tend to increase substantially over time, including the ongoing Phase 3 Lumeos clinical trial of botaretigene sparoparvovec for the treatment of patients with XLRP, although we believe that certain of these increases will be partially offset by the research funding in connection with the Collaboration Agreement. In addition, we expect to continue incurring increasing research and development costs associated with our clinical activities for AAV-hAQP1 for the treatment of radiation-induced xerostomia and xerostomia associated with Sjogren’s syndrome, as well as for AAV-GAD for the treatment of Parkinson’s disease. The total costs to advance any of our product candidates to marketing approval in even a single jurisdiction would be substantial. Because of the numerous risks and uncertainties associated with gene therapy product development, we are unable to accurately predict the timing or amount of increased expenses or whether we will be able to begin generating revenue from the commercialization of products or achieve or maintain profitability. Our expenses have and will continue to increase substantially as a public company and as we continue to add clinical, scientific, operational, financial, manufacturing, compliance and management information systems and personnel, including personnel to support our product development, manufacturing and planned future commercialization efforts. Before we generate any revenue from product sales, each of our programs and product candidates will require additional preclinical and/or clinical development, potential regulatory approval in multiple jurisdictions, manufacturing, building of a commercial organization, substantial investment and significant marketing efforts. Our expenses could increase beyond expectations if we are required by the FDA, MHRA, EMA, or other regulatory authorities to perform preclinical studies and clinical trials in addition to those that we currently anticipate. These risks are further described under “—Risks Related to Discovery, Development, Clinical Testing, Manufacturing and Regulatory Approval” and “— Risks Related to Commercialization.” As a result, we expect to continue to incur net losses for the foreseeable future. These net losses have had, and will continue to have, an adverse effect on our shareholders’ equity and working capital. As we continue to build our business, we expect our financial condition and operating results may fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of which are beyond our control. Accordingly, you should not rely upon the results of any particular quarterly or annual period as indications of future 48 Table of Contents operating performance. If we are unable to develop and commercialize one or more of our product candidates either alone or with collaborators, or if revenues from any product candidate that receives marketing approval are insufficient, we will not achieve profitability. Even if we do achieve profitability, we may not be able to sustain or increase profitability. If we are unable to achieve and then maintain profitability, the value of our equity securities will be adversely affected. We will require additional capital to fund our operations, which may not be available on acceptable terms, if at all. We expect to spend substantial amounts to complete the development of, seek regulatory approvals for and commercialize our product candidates, as well as continue to expand our manufacturing and supply chain capabilities. This will require additional capital, which we may raise through equity offerings, debt financings, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or other sources. Our ability to raise additional capital when needed has been and may in the future be adversely affected by external factors beyond our control, including changes in the political climate, geopolitical actions, changes in market interest rates, potential reforms and changes to government regulations, the effect of healthcare reform legislation, including those that may limit pricing of pharmaceutical products and drugs, market prices and conditions, prospects for favorable or unfavorable clinical trial results, new product initiatives, the manufacturing and distribution of new products, product safety and efficacy issues, new collaborations, strategic alliances and licensing arrangements, and the COVID-19 outbreak and mitigation measures. Furthermore, we expect to continue to incur costs associated with operating as a public company. Adequate additional financing may not be available to us on acceptable terms, or at all. Our failure to raise capital as and when needed would have a negative effect on our financial condition and our ability to pursue our business strategy. In addition, attempting to secure additional financing has diverted and may in the future divert the time and attention of our management from day- to-day activities and harm our product candidate development efforts. If we are unable to raise capital when needed or on acceptable terms, we would be forced to delay, reduce or eliminate certain of our research and development programs. Our operations have consumed significant amounts of cash since inception. As of December 31, 2022, our cash and cash equivalents were $115.5 million. In addition, we expect to receive $21.3 million in receivables which we expect to collect in the first quarter of 2023 from Janssen in connection with the Collaboration Agreement. Based on our cash and cash equivalents at December 31, 2022 and the research funding and milestone payments we expect to receive under the Collaboration Agreement, we estimate that such funds will be sufficient to enable us to fund our operating expenses and capital expenditure requirements into the fourth quarter of 2024. This estimate is based on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Changing circumstances could cause us to spend more than expected or consume capital significantly faster than we currently anticipate, such as inflation or other factors that may significantly increase our business costs. Because the length of time and activities associated with successful development of our product candidates is uncertain, we are unable to estimate the actual funds we will require for development and any approved marketing and commercialization activities. Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: ● the progress, timing, costs and results of our ongoing clinical development for our X-linked retinitis pigmentosa product candidate, botaretigene sparoparvovec, including the ongoing Phase 3 Lumeos clinical trial of botaretigene sparoparvovec for the treatment of patients with XLRP, for our CNGB3 achromatopsia gene therapy product candidate, AAV-CNGB3, for our CNGA3 achromatopsia gene therapy product candidate, AAV-CNGA3, for our RPE65-associated retinal dystrophy product candidate, AAV-RPE65, and to continue to conduct our ongoing natural history studies for inherited retinal diseases, or IRDs; ● the progress, timing, costs and results of our clinical development for our radiation-induced xerostomia product candidate, AAV-hAQP1, and for our product candidate for the treatment of Parkinson’s disease, AAV-GAD; 49 Table of Contents ● the development of our product candidate for the treatment of ALS, AAV-UPF1, for our product candidate for the treatment of xerostomia associated with Sjogren’s syndrome, AAV-hAQP1, and our product candidate for the treatment of neovascular age related macular degeneration, or wet AMD; ● the development of potentially transformative gene regulation technology designed to precisely and specifically control gene therapy expression levels via dose-response to orally delivered small molecules; ● continuing our current research programs and our preclinical development of product candidates from our current research programs; ● seeking to identify, assess, acquire and/or develop additional research programs and additional product candidates; ● the preclinical testing and clinical trials for any product candidates we identify and develop; ● the outcome, timing and cost of meeting regulatory requirements established by the FDA, MHRA, EMA and other regulatory authorities; ● the cost of expanding and protecting our intellectual property portfolio, including filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights; ● the cost of defending potential intellectual property disputes, including patent infringement actions brought by third parties against us or any of our product candidates; ● the effect of competing technological and market developments; ● the cost of further developing and scaling our manufacturing facilities and processes; ● the cost and timing of completion of commercial-scale manufacturing facilities and activities; ● the cost of making royalty, milestone or other payments under current and any future in-license agreements; ● our ability to establish and maintain strategic collaborations, licensing or other agreements and the financial terms of such agreements; ● the extent to which we in-license or acquire rights to other products, product candidates and technologies; ● the cost of establishing sales, marketing and distribution capabilities for our product candidates in regions where we choose to commercialize our products; and ● the initiation, progress, timing and results of our commercialization of our product candidates, if approved for commercial sale. Raising additional capital through the sale of equity or convertible debt securities will dilute your ownership interest, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a shareholder. For example, in connection with entering into the Financing Agreement (as defined below), we issued 50 Table of Contents warrants to Perceptive (as defined below), to purchase 400,000 ordinary shares at an exercise price of $15.00 per share and 300,000 ordinary shares at an exercise price of $20.00 per share. Additional debt financing or preferred equity financing, if available, may involve agreements that include covenants further limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may be required to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. We may not have sufficient cash flows or cash on hand to satisfy our debt obligations or covenants under our financing arrangements, or we may not be able to effectively manage our business in compliance with such covenants. On August 2, 2022, we, as borrower, and our wholly-owned subsidiaries MeiraGTx UK II Limited and MeiraGTx Ireland DAC, as guarantors (the “Subsidiary Guarantors”), entered into a senior secured financing arrangement (the “Financing Agreement”) by and among us, the Subsidiary Guarantors, the lenders and other parties from time to time party thereto and Perceptive Credit Holdings III, LP, as administrative agent and lender (“Perceptive”). On December 19, 2022, the Financing Agreement was converted to a note purchase agreement (the “Note Purchase Agreement”) between the same parties and under substantially the same terms and conditions as the Financing Agreement, subject to certain customary note constitution terms. The Note Purchase Agreement provides for an initial $75 million notes issuance (the “Tranche 1 Notes”), and we may request an additional $25 million notes issuance to be made at Perceptive’s sole discretion before August 2, 2024 (the “Tranche 2 Notes”, together with the Tranche 1 Notes, the “Notes”). The Notes incur interest, subject to certain provisions therein, at a fluctuating rate per annum equal to 10.00% plus the secured overnight financing rate administered by the Federal Reserve Bank of New York for a one-month tenor, subject to a 1.00% floor. The Note Purchase Agreement matures on August 2, 2026 and is interest-only during the term. The Note Purchase Agreement also contains various restrictions and covenants, including, among other things, covenants regarding the incurrence of additional indebtedness, limitations on liens, limitations on certain investments, limitations on making distributions, dividends and other payments, mergers, consolidations and acquisitions, dispositions of assets, maintenance of at least $3.0 million in a U.S. bank account, transactions with affiliates, changes to governing documents, changes to certain agreements and leases and changes in control. Our obligations under the Note Purchase Agreement are secured by our London, UK and Shannon, Ireland manufacturing facilities, $3.0 million of our cash and the bank accounts of the Subsidiary Guarantors, and the issued and outstanding equity interests of the Subsidiary Guarantors. There can be no assurance that Perceptive will elect to issue the Tranche 2 Notes or that our cash and cash equivalents available under the Note Purchase Agreement and under any future financings, together with any funds generated by our operations, will be sufficient to satisfy our debt payment obligations. Our inability to generate funds, obtain financing sufficient to satisfy our debt payment obligations or remain in compliance with the debt covenants may result in such obligations being accelerated by our lenders, which would likely have a material adverse effect on our business, financial condition and results of operations. The covenants may restrict our current and future operations, particularly our ability to respond to certain changes in our business or industry, or take future actions. Additionally, our ability to comply with these restrictive covenants may be impacted by events beyond our control, such as economic conditions or major central bank policy actions. Our Note Purchase Agreement provides that our breach or failure to satisfy certain covenants constitutes an event of default. Upon the occurrence of an event of default, in addition to an increase in the rate of interest on the Notes of 3% per annum, Perceptive could elect to declare all amounts outstanding thereunder to be immediately due and payable, proceed against the assets we provided as collateral, and, if such debt were accelerated, we may not have sufficient cash on hand or be able to sell sufficient collateral to repay it, which would have an immediate adverse effect on our business and operating results. This could potentially cause us to cease operations and result in a complete loss of your investment in our ordinary shares. 51 Table of Contents We are heavily dependent on the success of our Most Advanced Product Candidates, which are still in development, and if none of them receive regulatory approval or are successfully commercialized, our business may be harmed. Our future success and ability to generate product revenue is substantially dependent on our ability to successfully develop, obtain regulatory approval for and successfully commercialize our product candidates. We currently have no products that are approved for commercial sale and may never be able to develop marketable products. We have invested and expect to continue to invest a meaningful portion of our efforts and expenditures over the next few years in the development of botaretigene sparoparvovec, AAV-GAD, AAV-CNGB3, AAV-CNGA3, AAV-RPE65 and AAV-hAQP1 (the “Most Advanced Product Candidates”), which will require additional clinical development, management of clinical and manufacturing activities, regulatory approval in multiple jurisdictions, manufacturing sufficient supply, building of a commercial organization, substantial investment and significant marketing efforts before we can generate any revenues from any commercial sales. While we have entered into a Collaboration Agreement with Janssen with respect to AAV- CNGB3, AAV-CNGA3 and botaretigene sparoparvovec, pursuant to which we received a $100 million upfront payment and will also receive funding for certain research, manufacturing, clinical development and commercialization costs, potential additional milestone payments upon the achievement of such milestones and royalties on future net sales of products, there can be no assurance that these three product candidates will be successfully developed and commercialized by us and Janssen. We cannot be certain that our Most Advanced Product Candidates will be successful in clinical trials, receive regulatory approval or be successfully commercialized even if we receive regulatory approval. Even if we receive approval to market our Most Advanced Product Candidates from the FDA, MHRA or other regulatory bodies, we cannot be certain that our product candidates will be successfully commercialized by us or our collaborators, widely accepted in the marketplace or more effective than other commercially available alternatives. Additionally, the research, testing, manufacturing, labeling, approval, sale, marketing and distribution of gene therapy products are and will remain subject to extensive and evolving regulation by the FDA, MHRA and other regulatory authorities. We are not permitted to market our Most Advanced Product Candidates in the United States until they receive approval of a biologics license application, or BLA, from the FDA, we cannot market them in the UK or EU until we receive approval for an MA, from the MHRA or European Commission, respectively, and we cannot market them in other countries until we receive any other required regulatory approval in those countries. Because some of our other product candidates are based on similar technology as our Most Advanced Product Candidates, if any of our product candidates show unexpected adverse events or a lack of efficacy in the indications we intend to treat, or if we experience other regulatory or developmental issues, our development plans and business could be significantly harmed. Further, competitors may be developing products with similar technology and may experience problems with their products that could identify problems that would potentially harm our business. We may not be successful in our efforts to identify additional product candidates. Part of our strategy involves identifying novel product candidates. The process by which we identify product candidates may fail to yield product candidates for clinical development for a number of reasons, including those discussed in these risk factors and also: ● we may not be able to assemble sufficient resources to acquire or discover additional product candidates; ● competitors may develop alternatives that render our potential product candidates obsolete or less attractive; ● potential product candidates we develop may nevertheless be covered by third parties’ patents or other exclusive rights; ● potential product candidates may, on further study, be shown to have harmful side effects, toxicities or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance; 52 Table of Contents ● potential product candidates may not be effective in treating their targeted diseases; ● the market for a potential product candidate may change so that the continued development of that product candidate is no longer reasonable; ● a potential product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all; or ● the regulatory pathway for a potential product candidate may be too complex and difficult to navigate successfully or economically. In addition, we may choose to focus our efforts and resources on a potential product candidate that ultimately proves to be unsuccessful. As a result, we may fail to capitalize on viable commercial products or profitable market opportunities, be required to forego or delay pursuit of opportunities with other product candidates or other diseases that may later prove to have greater commercial potential, or relinquish valuable rights to such product candidates through collaboration, licensing or other royalty arrangements in cases in which it would have been advantageous for us to retain sole development and commercialization rights. If we are unable to identify additional suitable product candidates for clinical development, this would adversely impact our business strategy and our financial position and share price and could potentially cause us to cease operations. Risks Related to Discovery, Development, Clinical Testing, Manufacturing and Regulatory Approval COVID-19 has impacted and may continue to impact our business, and any other pandemic, epidemic or outbreak of an infectious disease may materially and adversely impact our business, including our preclinical studies, clinical trials, manufacturing capabilities and regulatory approvals. As a result of the COVID-19 pandemic, we have at times restricted onsite activities and have also experienced some delays in enrolling, treating and monitoring patients in our clinical trials, as well as limited supply chain disruptions. We may experience these or other disruptions from the COVID-19 pandemic or other pandemic, epidemic or outbreak of an infectious disease that could severely impact our business, preclinical studies, clinical trials and laboratory and manufacturing activities, including, for example, delays or difficulties in enrolling patients in our clinical trials, delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff, diversion of healthcare resources away from the conduct of clinical trials, interruption of key clinical trial activities due to limitations on travel imposed or recommended by regulatory authorities or others, interruption or delays in the operations of the FDA, MHRA, EMA or other regulatory authorities, interruption of, or delays in, the manufacturing of our product candidates, interruptions in preclinical studies due to restricted or limited operations at our laboratory facilities, limitations on employee resources that would otherwise be focused on the conduct of our preclinical studies and clinical trials, and interruption or delays to our sourced discovery and clinical activities. The COVID-19 pandemic continues to impact businesses globally. The extent to which the outbreak or any variants may further impact our business, preclinical studies, clinical trials and laboratory and manufacturing activities will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of the pandemic, the timing, distribution and effectiveness of vaccines, vaccination rates, travel restrictions and physical distancing requirements in the countries where we do business, business closures or business disruptions, and the effectiveness of actions taken in the countries where we do business to contain and treat the disease, respond to the reduction in global economic activity and resume normal economic and operating conditions. If we or any of the third parties with whom we engage experience prolonged 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. Furthermore, the magnitude of the economic impact of COVID-19 pandemic and its variants including sustained inflation, supply chain disruptions, and major central bank policy actions continues to be difficult to assess or predict and may continue to result in significant disruption of global financial markets, which could materially affect our performance, financial condition, 53 Table of Contents results of operations, and cash flows, as well as our ability to raise additional capital. Additionally, major central bank policy actions may have a negative impact on our payment obligations under the Note Purchase Agreement. It is difficult to predict the time and cost of product candidate development on our novel gene therapy platform. Very few gene therapies have been approved in the United States or in Europe. We have concentrated a portion of our research and development efforts on our gene therapy platform, which uses both transduction and gene control technology. Our future success depends on the successful development of these novel therapeutic approaches. To date, very few products that utilize gene transfer have been approved in the United States or Europe. Our gene therapy platform is based on a suite of viral vectors which we can deploy with gene therapy constructs, which relies on the ability of AAV to efficiently transmit a therapeutic gene to certain kinds of cells. The mechanism of action by which these vectors target particular tissues is still not completely understood. Therefore, it is difficult for us to determine that our vectors will be able to properly deliver gene transfer constructs to enough tissue cells to reach therapeutic levels. We cannot be certain that animal models will exist for some of the diseases we expect to pursue, that our viral vectors will be able to meet safety and efficacy levels needed to be therapeutic in humans or that they will not cause significant adverse events or toxicities. Furthermore, prior work conducted by a third party in non-human primates suggests that intravenous, or IV, delivery of certain AAV vectors at very high doses may result in severe toxicity. The indications that we target do not use IV administration for viral vector delivery and do not use doses as high as those tested in these publications, and to date we have not observed the severe toxicities described in these publications with the naturally occurring AAV vectors that we use. However, we cannot be certain that we will be able to avoid triggering toxicities in our future preclinical studies or clinical trials. Any such results could impact our ability to develop a product candidate. As a result of these factors, it is more difficult for us to predict the time and cost of product candidate development, and we cannot predict whether the application of our gene therapy platform, or any similar or competitive gene therapy platforms, will result in the identification, development, and regulatory approval of any product candidates, or that other gene therapy technologies will not be considered better or more attractive. There can be no assurance that any development problems we experience in the future related to our gene therapy platform or any of our research programs will not cause significant delays or unanticipated costs, or that such development problems can be solved. Any of these factors may prevent us from completing our preclinical studies or clinical trials or commercializing any product candidates we may develop on a timely or profitable basis, if at all. In addition, because our gene regulation technology is still in the research stage, we have not yet been able to assess safety in humans, and there may be long-term effects from treatment that we cannot predict at this time. Because gene therapy is novel and the regulatory landscape that governs any product candidates we may develop is uncertain and may change, we cannot predict the time and cost of obtaining regulatory approval, if we receive it at all, for any product candidates we may develop. The regulatory requirements that will govern any novel gene therapy product candidates we develop are not entirely clear and may change. Within the broader genetic medicine field, very few therapeutic products have received marketing authorization from the FDA, MHRA and European Commission. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing. Regulatory requirements governing gene therapy products and cell therapy products have changed frequently and will likely continue to change in the future. Moreover, there is substantial, and sometimes uncoordinated, overlap in those responsible for regulation of existing gene therapy products and cell therapy products, which could impact the timing and cost of any regulatory approval. For example, in the United States, the FDA has established the Office of Tissues and Advanced Therapies within its Center for Biologics Evaluation and Research, or CBER, to consolidate the review of gene therapy and related products, and the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its review. Gene therapy clinical trials are also subject to review and oversight by an institutional biosafety committee, or IBC, and/or 54 Table of Contents an institutional review board, or IRB, which are local institutional committees or boards, as applicable, that review, approve and oversee basic and clinical research conducted at the institution participating in the clinical trial. In the EU, the EMA’s Committee for Advanced Therapies, or CAT, is responsible for assessing the quality, safety, and efficacy of ATMPs. ATMPs include gene therapy medicines, somatic-cell therapy medicines and tissue-engineered medicines. The role of the CAT is to prepare a draft opinion on an application for marketing authorization for a gene therapy medicinal candidate that is submitted to the EMA. In the EU, the development and evaluation of a gene therapy product must be considered in the context of the relevant EU guidelines. The EMA may issue new guidelines concerning the development and marketing authorization for gene therapy products and require that we comply with these new guidelines. As a result, the procedures and standards applied to gene therapy products and cell therapy products may be applied to any gene therapy product candidate we may develop, but that remains uncertain at this point. Post Brexit, MAAs for ATMPs in Great Britain are regulated nationally and assessed in accordance with the general provisions in place for the licensing of medicines, taking the specific requirements for this group of medicines into account. In Northern Ireland, ATMPs continue to be authorized according to the EU’s centralized procedure. Definitions for individual classes of ATMPs remain unchanged and classification of ATMPs are undertaken by the MHRA in accordance with EU legislation and current guidance from CAT. Data, traceability, exemptions from licensing, packaging and post-authorization requirements remain in line with EU requirements transposed into UK law. However, if the EMA issues new guidance on ATMPs going forward, there is a risk of regulatory divergence with the MHRA and separate procedures and standards with which we may need to comply. Adverse developments in preclinical studies or clinical trials conducted by others in the field of gene therapy and gene regulation products may cause the FDA, MHRA and other regulatory bodies to revise the requirements for approval of any product candidates we may develop or limit the use of products utilizing gene regulation technologies, either of which could harm our business. In addition, the clinical trial requirements of the FDA, MHRA and other regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate vary substantially according to the type, complexity, novelty, and intended use and market of the potential products. The regulatory approval process for product candidates such as ours can be more expensive and take longer than for other, better known, or more extensively studied pharmaceutical or other product candidates. Further, as we are developing novel treatments for diseases in which there is little clinical experience with new endpoints and methodologies, there is heightened risk that the FDA, MHRA, EMA or other regulatory bodies may not consider the clinical trial endpoints to provide clinically meaningful results, and the resulting clinical data and results may be more difficult to analyze. The prospectively designed natural history studies with the same endpoints as our corresponding clinical trials may not be accepted by the FDA, MHRA, EMA or other regulatory authorities. Regulatory agencies administering existing or future regulations or legislation may not allow production and marketing of products utilizing gene regulation technology in a timely manner or under technically or commercially feasible conditions. In addition, regulatory action or private litigation could result in expenses, delays, or other impediments to our research programs or the commercialization of resulting products. The regulatory review committees and advisory groups described above and the new guidelines they promulgate may lengthen the regulatory review process, require us to perform additional preclinical studies or clinical trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these treatment candidates, or lead to significant post-approval limitations or restrictions. As we advance our research programs and develop future product candidates, we will be required to consult with these regulatory and advisory groups and to comply with applicable guidelines. If we fail to do so, we may be required to delay or discontinue development of any product candidates we identify and develop. Clinical trials are expensive, time-consuming, difficult to design and implement, and involve an uncertain outcome. Further, we may encounter substantial delays in our clinical trials. The clinical trials and manufacturing of our product candidates are, and the manufacturing and marketing of our products, if approved, will be, subject to extensive and rigorous review and regulation by numerous government authorities 55 Table of Contents in the United States and in other countries where we intend to test and market our product candidates. Before obtaining regulatory approvals for the commercial sale of any of our product candidates, we must demonstrate through lengthy, complex and expensive preclinical testing and clinical trials that our product candidates are both safe and effective for use in each target indication. In particular, because our product candidates are subject to regulation as biological drug products, we will need to demonstrate that they are safe, pure, and potent for use in their target indications. Each product candidate must demonstrate an adequate risk versus benefit profile in its intended patient population and for its intended use. Clinical testing is expensive, can take many years to complete and is subject to uncertainty. We cannot guarantee that any clinical trials will be conducted as planned or completed on schedule, if at all. Failure can occur at any time during the clinical trial process. Even if our future clinical trials are completed as planned, we cannot be certain that their results will support the safety and effectiveness of our product candidates for their targeted indications. Our future clinical trial results may not be successful. In addition, even if such trials are successfully completed, we cannot guarantee that the FDA, MHRA, EMA or other regulatory authorities will interpret the results as we do, and more trials could be required before we submit our product candidates for approval. To the extent that the results of the trials are not satisfactory to the FDA, MHRA, EMA or other regulatory authorities for support of an MAA, we may be required to expend significant resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates. To date, we have not completed any clinical development programs required for the approval of any of our product candidates. Although we are currently conducting several clinical development programs, we may experience delays in conducting any clinical trials and we do not know whether our ongoing and future clinical trials will begin on time, need to be redesigned, be able to recruit and enroll patients on time or be completed on schedule, or at all. Events that may prevent successful or timely completion of clinical development include: ● inability to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation of clinical trials; ● delays in sufficiently developing, characterizing or controlling a manufacturing process suitable for advanced clinical trials; ● delays in developing suitable assays for screening patients for eligibility for trials with respect to certain product candidates; ● delays in reaching agreement with the FDA, MHRA or other regulatory authorities as to the design or implementation of our clinical trials and obtaining regulatory approval to commence a clinical trial; ● inability to reach an agreement on acceptable terms with clinical trial sites or prospective contract research organizations, or CROs, the terms of which can be subject to extensive negotiation and may vary significantly among different clinical trial sites; ● our inability to recruit and train clinical trial investigators with the appropriate competencies and experience to conduct the clinical trials, administer our product candidates and oversee clinical trial staff; ● delays in obtaining IRB or ethics committee approval or positive opinion at each site; ● inability to recruit suitable patients to participate in a clinical trial; ● inability to develop and validate the companion diagnostic to be used in a clinical trial, if applicable; 56 Table of Contents ● delays in sufficiently developing, designing and manufacturing equipment or medical devices used in our clinical trials; ● patients not completing a clinical trial or returning for post-treatment follow-up; ● clinical sites, CROs, or other third parties deviating from trial protocol or dropping out of a trial; ● failure to perform in accordance with the FDA’s good clinical practice, or GCP, requirements, or applicable regulatory guidelines in other countries; ● addressing patient safety concerns that arise during the course of a trial, including occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits; ● having an insufficient number of clinical trial sites; or ● inability to manufacture sufficient quantities of our product candidates for use in clinical trials. We may experience numerous unforeseen events during, or as a result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product candidates or significantly increase the cost of such trials, including: ● we may experience changes in regulatory requirements or guidance, or receive feedback from regulatory authorities that requires us to modify the design of our clinical trials; ● 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 or abandon development programs; ● the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials 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 may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; ● we or our investigators might have to suspend or terminate clinical trials of our product candidates for various reasons, including non-compliance with regulatory requirements, a finding that our product candidates have undesirable side effects or other unexpected characteristics, or a finding that the participants are being exposed to unacceptable health risks; ● the cost of clinical trials of our product candidates may be greater than we anticipate, and we may not have funds to cover the costs; ● the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our product candidates may be insufficient or inadequate; ● business interruptions resulting from geopolitical actions, including war and terrorism, or a widespread health emergency, such as the COVID-19 pandemic, or natural disasters including earthquakes, typhoons, floods and fires, or from economic or political instability; and 57 Table of Contents ● any future collaborators that conduct clinical trials may face any of the above issues, and they may conduct clinical trials in ways they view as advantageous to them but that are suboptimal for us. If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may: ● incur unplanned costs; ● be delayed in obtaining marketing approval for our product candidates or not obtain marketing approval at all; ● obtain marketing approval in some countries and not in others; ● obtain marketing approval for indications or patient populations that are not as broad as intended or desired; ● obtain marketing approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings; ● be subject to additional post-marketing testing requirements; or ● have the product removed from the market after obtaining marketing approval. We could encounter delays if a clinical trial is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, or DSMB, for such trial or by the FDA, MHRA or other foreign regulatory authorities. Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA, MHRA or other regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. Our Most Advanced Product Candidates will require extensive clinical testing before we are prepared to submit a BLA or MAA for regulatory approval. We cannot predict with any certainty if or when we might complete the clinical development for our product candidates and submit a BLA or MAA for regulatory approval of any of our product candidates or whether any such BLA or MAA will be approved. We may also seek feedback from the FDA, MHRA, EMA or other regulatory authorities on our clinical development program, and the FDA, MHRA, EMA or such regulatory authorities may not provide such feedback on a timely basis, or such feedback may not be favorable, which could further delay our development programs. If we experience delays in the commencement or completion of our clinical trials, or if we terminate a clinical trial prior to completion, the commercial prospects of our product candidates could be harmed, and our ability to generate revenues from our product candidates may be delayed. In addition, any delays in our clinical trials could increase our costs, slow down the development and approval process and jeopardize our ability to commence product sales and generate revenues. Any of these occurrences may harm our business, financial condition and results of operations. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates. 58 Table of Contents In addition, the FDA’s and other regulatory authorities’ policies with respect to clinical trials may change and additional government regulations may be enacted. For instance, the regulatory landscape related to clinical trials in the EU recently evolved. The CTR adopted in April 2014 became applicable on January 31, 2022 and repeals the EU Clinical Trials Directive. While the EU Clinical Trials Directive required a separate CTA to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, the CTR introduces a centralized process and only requires the submission of a single application for multi-center trials. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed. The CTR foresees a three-year transition period. The extent to which ongoing and new clinical trials will be governed by the CTR varies. Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the EU Clinical Trials Directive, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the EU Clinical Trials Directive remain governed by said EU Clinical Trials Directive until January 31, 2025. After this date, all clinical trials (including those which are ongoing) will become subject to the provisions of the CTR. Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our development plans. It is currently unclear to what extent the UK will seek to align its regulations with the EU. The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation). On January 17, 2022, the MHRA launched an eight-week consultation on reframing the UK legislation for clinical trials. The consultation closed on March 14, 2022 and aims to streamline clinical trials approvals, enable innovation, enhance clinical trials transparency, enable greater risk proportionality, and promote patient and public involvement in clinical trials. The outcome of the consultation is being closely watched and will determine whether the UK chooses to align with the CTR or diverge from it to maintain regulatory flexibility. Under the terms of the Protocol on Ireland and Northern Ireland, provisions of the CTR which relate to the manufacture and import of investigational medicinal products and auxiliary medicinal products currently apply in Northern Ireland. On February 27, 2023, the UK Government and the European Commission reached a political agreement on the “Windsor Agreement” which may revise the Protocol on Ireland and Northern Ireland in order to address some of the perceived shortcomings in its operation. If implemented, this may have further impact on the application of the CTR in Northern Ireland. A decision by the UK not to closely align its regulations with the new approach that will be adopted in the EU may have an effect on the cost of conducting clinical trials in the UK as opposed to other countries. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may also be impacted. The affected populations for our product candidates may be smaller than we or third parties currently project, which may affect the addressable markets for our product candidates. Our projections of the number of people who have the diseases we are seeking to treat, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are estimates based on our knowledge and understanding of these diseases. The total addressable market opportunity for our product candidates will ultimately depend upon a number of factors including the diagnosis and treatment criteria included in the final label, if approved for sale in specified indications, acceptance by the medical community, patient access and product pricing and reimbursement. Incidence and prevalence estimates are frequently based on information and assumptions that are not exact and may not be appropriate, and the methodology is forward-looking and speculative. The process we have used in developing an estimated incidence and prevalence range for the indications we are targeting has involved collating limited data from multiple sources. Accordingly, the incidence and prevalence estimates included, or supporting the information, in our SEC filings and other materials should be viewed with caution. Further, the data and statistical information included, or supporting the information, in our SEC filings and other materials, including estimates derived 59 Table of Contents from them, may differ from information and estimates made by our competitors or from current or future studies conducted by independent sources. The use of such data involves risks and uncertainties and is subject to change based on various factors. Our estimates may prove to be incorrect and new studies may change the estimated incidence or prevalence of the diseases we seek to address. The number of patients with the diseases we are targeting in the United States, the UK, the EU and elsewhere may turn out to be lower than expected or may not be otherwise amenable to treatment with our products, or new patients may become increasingly difficult to identify or access, all of which would harm our results of operations and our business. Negative public opinion of gene therapy and increased regulatory scrutiny of gene therapy and genetic research may adversely impact public perception of our current and future product candidates. Our potential therapeutic products involve introducing genetic material into patients’ cells. The clinical and commercial success of our potential products will depend in part on public acceptance of the use of gene therapy and gene regulation for the prevention or treatment of human diseases. Public attitudes may be influenced by claims that gene therapy and gene regulation are unsafe, unethical, or immoral, and, consequently, our products may not gain the acceptance of the public or the medical community. Public attitudes may adversely impact our ability to enroll clinical trials. Moreover, our success will depend upon physicians prescribing, and their patients being willing to receive, treatments that involve the use of product candidates we may develop in lieu of, or in addition to, existing treatments with which they are already familiar and for which greater clinical data may be available. More restrictive government regulations or negative public opinion would have a negative effect on our business or financial condition and may delay or impair the development and commercialization of our product candidates or demand for any products once approved. For example, in 2003, trials using early versions of murine gamma-retroviral vectors, which integrate with, and thereby alter, the host cell’s DNA, have led to several well-publicized adverse events, including reported cases of leukemia. Although none of our current product candidates utilize murine gamma-retroviral vectors, our product candidates use a viral delivery system. Adverse events in our clinical trials, even if not ultimately attributable to our product candidates, and the resulting publicity could result in increased governmental regulation, unfavorable public perception, potential regulatory delays in the testing or approval of our product candidates or the halting of clinical trials, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidates. The risk of cancer remains a concern for gene therapy and we cannot assure that it will not occur in any of our planned or future clinical trials. In addition, there is the potential risk of delayed adverse events following exposure to gene therapy products due to persistent biological activity of the genetic material or other components of products used to carry the genetic material. If any such adverse events occur, commercialization of our product candidates or further advancement of our clinical trials could be halted or delayed, which would have a negative impact on our business and operations. We may fail to maintain the benefits of certain regulatory designations that we have obtained for our product candidates, and may in the future seek and fail to obtain such designations for other of our current or potential future product candidates. Even if such designations are obtained, they may not lead to faster development or regulatory review or approval, and they do not increase the likelihood that our product candidates will receive marketing approval. A sponsor may seek approval of its product candidate under programs designed to accelerate the FDA’s review and approval of new drugs and biological products that meet certain criteria. For example, the FDA has a Fast Track designation program that is intended to expedite or facilitate the process for reviewing new products that meet certain criteria. Specifically, new drugs and biological products are eligible for Fast Track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs. Fast Track designation applies to the combination of the product and the specific indication for which it is being studied. For product candidates with Fast Track designation, sponsors may be eligible for more frequent meetings with the FDA to discuss the 60 Table of Contents candidate’s development plan and more frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers. In addition, the FDA may consider for review sections of the BlA on a rolling basis before the complete application is submitted if relevant criteria are satisfied, including an agreement with FDA on the proposed schedule for the submission of portions of the BLA, and the payment of applicable user fees before FDA may initiate a review. Even if Fast Track designation is granted, it may be rescinded if the product no longer meets the qualifying criteria. In April 2018, botaretigene sparoparvovec was issued Fast Track designation by the FDA for the treatment of X-linked retinitis pigmentosa owing to defects in RPGR. In August 2018, AAV-CNGB3 was issued Fast Track designation by the FDA for the treatment of achromatopsia caused by CNGB3 mutations. In January 2021, AAV-CNGA3 was issued Fast Track designation by the FDA for the treatment of achromatopsia caused by CNGA3 mutations. Similarly, the EMA has established the PRIME scheme to expedite the development and review of product candidates that show a potential to address to a significant extent an unmet medical need, based on early clinical data. In February 2018, AAV-CNGB3 in the treatment of achromatopsia associated with defects in CNGB3 was admitted to the PRIME scheme of the EMA. In February 2020, botaretigene sparoparvovec for the treatment of X-linked retinitis pigmentosa owing to defects in RPGR was admitted to the PRIME scheme of the EMA. A sponsor may also seek an RMAT designation for its product candidates. In 2017, the FDA established the RMAT designation as part of its implementation of the 21st Century Cures Act. A biological product is eligible for RMAT designation if it qualifies as an RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions, and is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition and for which preliminary clinical evidence indicates that the biological product has the potential to address unmet medical needs for such a disease or condition. In a February 2019 guidance, the FDA also stated that certain gene therapies that lead to a sustained effect on cells or tissues may meet the definition of a regenerative medicine therapy. RMAT designation provides potential benefits that include more frequent meetings with the FDA to discuss the development plan for the product candidate, and eligibility for rolling review and priority review. Products granted RMAT designation may also be eligible for accelerated approval on the basis of a surrogate or intermediate endpoint reasonably likely to predict long-term clinical benefit, or reliance upon data obtained from a meaningful number of sites, including through expansion to additional sites. RMAT- designated products that receive accelerated approval may, as appropriate, fulfill their post-approval requirements through the submission of clinical evidence, clinical trials, patient registries, or other sources of real world evidence (such as electronic health records); through the collection of larger confirmatory data sets; or via post-approval monitoring of all patients treated with such therapy prior to approval of the therapy. Such regulatory designations are within the discretion of the FDA, MHRA, EMA and other regulatory authorities. Accordingly, even if we believe one of our product candidates meets the criteria for such regulatory programs designed to accelerate the review and approval of new drugs and we seek such designations, the FDA, MHRA, EMA or other applicable regulatory authority may disagree and instead determine not to make such designation for such product candidate. We cannot be sure that our evaluation of our product candidates as qualifying for such regulatory designations will meet the regulatory authority’s expectations. In any event, the receipt of such regulatory designations for a product candidate may not result in a faster development process, review, or approval compared to product candidates considered for approval under conventional regulatory procedures and does not assure ultimate approval by the regulatory authorities. In addition, even if additional product candidates are granted such regulatory designations, the regulatory authority may later decide that such product candidates no longer meet the conditions for qualification or decide that the time period for review or approval will not be shortened. We have received orphan drug designation from the FDA and European Commission for AAV-CNGB3, AAV-CNGA3, AAV-RPE65, botaretigene sparoparvovec, AAV-AIPL1, AAV-RDH12 and from the FDA for AAV-hAQP1, and we may seek orphan drug designation for additional product candidates in the future, but any orphan drug designations we have received or may receive in the future may not confer marketing exclusivity or other expected benefits. 61 Table of Contents Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is intended to treat a rare disease or condition, defined as one occurring in a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. In the EU, the European Commission grants orphan designation on the basis of the EMA’s Committee for Orphan Medicinal Products opinion. A medicinal product may be designated as orphan if (1) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in 10,000 persons in the EU when the application is made, or (b) the product, without the benefits derived from orphan status, would not generate sufficient return in the EU to justify investment; and (3) there exists no satisfactory method of diagnosis, prevention or treatment, of such condition authorized for marketing in the EU, or if such a method exists, the product will be of significant benefit to those affected by the condition. In the United States, orphan drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax credits for qualified clinical testing, and user-fee waivers. In addition, if a product receives the first FDA approval of that drug for the indication for which it has orphan designation, the product is entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug for the same disease or condition for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the rare disease or condition. Under the FDA’s regulations, the FDA will deny orphan drug exclusivity to a designated drug upon approval if the FDA has already approved another drug with the same principal molecular structural features, in the case of a biologic, for the same indication, unless the drug is demonstrated to be clinically superior to the previously approved drug. In the EU, orphan designation entitles a party to financial incentives such as reduction of fees or fee waivers, protocol assistance, and access to the centralized MA procedure. Moreover, upon grant of an MA and assuming the requirement for orphan designation are also met at the time the MA is granted, orphan medicinal products are entitled to a ten-year period of market exclusivity for the approved therapeutic indication. The period of market exclusivity is extended by two years for orphan medicinal products that have also complied with an agreed PIP. This period may be reduced to six years if, at the end of the fifth year, the orphan designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity, or where the prevalence of the condition has increased above the orphan designation threshold. In the EU, an MA for an orphan designated product will not be granted if a similar product has been approved in the EU for the same therapeutic indication, unless the applicant can establish that (i) its product, although similar to the orphan medicinal product already authorized is safer, more effective or otherwise clinically superior; (ii) the MA holder for the orphan medicinal product grants its consent; or (iii) if the MA holder of the orphan medicinal product is unable to supply sufficient quantities of product. A similar medicine is a product containing a similar active substance or substances as those contained in an already authorized product. Similar active substance is defined as an identical active substance, or an active substance with the same principal molecular structural features (but not necessarily all of the same molecular features) and which acts via the same mechanism. Post-Brexit, the UK has retained the EU Regulation which governs the designation of medicinal products as orphan medicinal products and which establishes incentives thereto (Regulation (EC) No. 141/2000) as part of UK law by virtue of the EU (Withdrawal) Act 2018. However under the Retained EU Law (Revocation and Reform) Bill, which is currently before the UK Parliament, unless this legislation is expressly preserved and “assimilated” into domestic law or extended by ministerial regulations (to no later than June 23, 2026) it will automatically expire and be revoked by December 31, 2023. There is therefore uncertainty about the future regulations relating to orphan designation in Great Britain, and any future changes to the legal requirements could lead to greater regulatory complexity and increased costs to our business. The MHRA is responsible for reviewing applications from companies for orphan designation at the time of an MAA. If a medicinal product has been designated orphan in the EU under Regulation (EC) 141/2000, a Great Britain orphan MAA can be made under regulation 50G of the Human Medicines Regulation 2012 (as amended). A UK-wide orphan MAA can only be considered in the absence of an active EU orphan designation. If a UK-wide orphan MA is 62 Table of Contents granted and the medicinal product subsequently receives EU orphan designation, the MA holder would need to submit a variation to change this to a Great Britain orphan MA. We have obtained orphan drug designation from the FDA and European Commission for AAV-CNGB3 for the treatment of achromatopsia caused by mutations in the CNGB3 gene, for AAV-CNGA3 for the treatment of achromatopsia due to autosomal-recessive CNGA3 gene mutations, for AAV-RPE65 for the treatment of Leber congenital amaurosis, for botaretigene sparoparvovec for the treatment of X-linked retinitis pigmentosa, for AAV-AIPL1 for the treatment of inherited retinal dystrophy due to defects in AIPL1 gene and for AAV-RDH12 for the treatment of retinol dehydrogenase 12 (RDH12) mutation-associated retinal dystrophy, and we obtained orphan drug designation from the FDA for AAV- hAQP1 for the treatment of grade 2 and grade 3 late xerostomia from parotid gland hypofunction caused by radiotherapy. We may seek orphan drug designation for other current and future product candidates. Even with orphan drug designation, we may not be the first to obtain marketing approval for any particular orphan indication due to the uncertainties associated with developing pharmaceutical products, which could prevent us from marketing our product candidates if another company is able to obtain orphan drug exclusivity before we do. In addition, exclusive marketing rights in the United States and the EU may be unavailable if we seek approval for an indication broader than the orphan-designated indication or may be lost in the United States or EU if the FDA or foreign authorities later determine that the request for designation was materially defective or if we are unable to assure sufficient quantities of the drug to meet the needs of patients with the rare disease or condition following approval. Further, even if we obtain orphan drug exclusivity, that exclusivity may not effectively protect our product candidates from competition because different biologics with different active principal molecular structural features can be approved for the same condition. In addition, the FDA can subsequently approve products with the same principal molecular structural features, in the case of a biologic, for the same condition if the FDA concludes that the later product is safer, more effective, or makes a major contribution to patient care. Likewise, in the EU and Great Britain, the European Commission or MHRA, respectively, can authorize a similar product for the same therapeutic indication, if it concludes that the later product is safer, more effective or clinically superior; if the MA holder for the initial orphan medicinal product grants its consent; or if such MA holder is unable to supply sufficient quantities of the product. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process. In addition, while we intend to seek orphan drug designation for other existing and future product candidates, we may never receive such designations. There have been legal challenges to aspects of the FDA’s regulations and policies concerning the exclusivity provisions of the Orphan Drug Act, and future challenges could lead to changes that affect the protections afforded our product candidates in ways that are difficult to predict. It is uncertain how ongoing and future challenges might affect our business. We and our contract manufacturers for plasmid are subject to significant regulation with respect to manufacturing our products. Our manufacturing facilities and the third-party manufacturing facilities which we rely on may not continue to meet regulatory requirements and have limited capacity. We currently have relationships with a limited number of suppliers for the manufacturing of plasmid, a component of our viral vectors and product candidates. We completed the fit-out of our first cGMP manufacturing facility in early 2018 and we completed the acquisition of the buildings for our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland in January 2021 to expand our manufacturing and supply chain capabilities. However, if we experience slowdowns or problems with our completed facility or the development and completion of our new facilities and are unable to establish or scale our internal manufacturing capabilities, we will need to continue to contract with manufacturers that can produce the preclinical, clinical and commercial supply of our products. Each supplier may require licenses to manufacture such components if such processes are not owned by the supplier or in the public domain and we may be unable to transfer or sublicense the intellectual property rights we may have with respect to such activities. All entities involved in the preparation of therapeutics for clinical trials or commercial sale, including our existing contract manufacturers for components of our product candidates, are subject to extensive regulation. Components of a finished therapeutic product approved for commercial sale or used in late-stage clinical trials must be manufactured in accordance with cGMP. These regulations govern manufacturing processes and procedures (including record keeping) and 63 Table of Contents the implementation and operation of quality systems to control and assure the quality of investigational products and products approved for sale. Poor control of production processes can lead to the introduction of adventitious agents or other contaminants, or to inadvertent changes in the properties or stability of our product candidates that may not be detectable in final product testing. We or our contract manufacturers must supply all necessary documentation in support of a BLA or MAA on a timely basis. Our facilities and quality systems and the facilities and quality systems of some or all of our third- party contractors must pass a pre-approval inspection for compliance with the applicable regulations as a condition of regulatory approval of our product candidates or any of our other potential products. In addition, the regulatory authorities may, at any time, audit or inspect a manufacturing facility involved with the preparation of our product candidates or our other potential products or the associated quality systems for compliance with the regulations applicable to the activities being conducted. If these facilities do not pass a pre-approval plant inspection, FDA, MHRA or other regulatory approval of the products will not be granted. If any such inspection or audit identifies a failure to comply with applicable regulations or if a violation of our product specifications or applicable regulations occurs independent of such an inspection or audit, we or the relevant regulatory authority may require remedial measures that may be costly and/or time-consuming for us or a third party to implement and that may include the temporary or permanent suspension of a clinical trial or commercial sales or the temporary or permanent closure of a facility. Any such remedial measures imposed upon us or third parties with whom we contract could harm our business. If we or any of our third-party manufacturers fail to maintain regulatory compliance, the FDA, MHRA or other regulatory authorities can impose regulatory sanctions including, among other things, refusal to approve a pending application for a new drug product or biologic product, or revocation of a pre-existing approval. As a result, our business, financial condition and results of operations may be harmed. Additionally, if supply from one approved manufacturer is interrupted, there could be a significant disruption in commercial supply. An alternative manufacturer would need to be qualified through a BLA and/or MAA supplement which could result in further delay. The regulatory agencies may also require additional studies if a new manufacturer is relied upon for commercial production. Switching manufacturers may involve substantial costs and is likely to result in a delay in our desired clinical and commercial timelines. These factors could cause the delay of clinical trials, regulatory submissions, required approvals or commercialization of our product candidates, cause us to incur higher costs and prevent us from commercializing our products successfully. Furthermore, if our suppliers fail to meet contractual requirements, and we are unable to secure one or more replacement suppliers capable of production at a substantially equivalent cost, our clinical trials may be delayed, or we could lose potential revenue. Any contamination in our manufacturing process, shortages of raw materials or failure of our plasmid supplier to deliver necessary components, or other issues with the manufacturing process, could result in delays in our clinical development or marketing schedules. Given the nature of biologics manufacturing, there is a risk of contamination. Any contamination could adversely affect our ability to produce product candidates on schedule and could, therefore, harm our results of operations and cause reputational damage. Some of the raw materials required in our manufacturing process are derived from biologic sources. Such raw materials are difficult to procure and may be subject to contamination or recall. In addition, our manufacturing process is complex, and the manufacturing batch cycle period can be several weeks long. Each batch cycle may not yield planned quantities or meet the required standards. A material shortage, contamination, recall or restriction on the use of biologically derived substances in the manufacture of our product candidates, failure of manufacturing equipment or systems or other issues with our manufacturing process, could adversely impact or disrupt the commercial manufacturing or the production of clinical material, which could adversely affect our development timelines and our business, financial condition, results of operations and prospects. 64 Table of Contents Expanding our manufacturing capacity has and will continue to be costly and we may be unsuccessful in doing so in a timely manner, which could delay our current and future clinical development programs, or delay the commercialization of our product candidates. In addition to our existing manufacturing facility in London, United Kingdom, we may lease, operate, purchase, or construct additional facilities to conduct expanded manufacturing or other related activities in the future. In January 2021, we completed the acquisition of our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland. Expanding our manufacturing capacity to produce the preclinical, clinical and commercial supply of our products and their components will require completing our new facilities in Ireland, substantial additional expenditures, time, and various regulatory approvals and permits, all of which may be impacted by the COVID-19 pandemic. Further, we will need to hire and train significant numbers of employees and managerial personnel to staff our expanding manufacturing and supply chain operations, including in our new facilities in Ireland. Start-up costs can be large and may exceed our expectations, and scale-up entails significant risks related to process development and manufacturing yields. In addition, we may face difficulties or delays in developing or acquiring the necessary production equipment and technology to manufacture sufficient quantities of our product candidates for use in clinical trials and, should they be approved, to supply the commercial market at reasonable costs and in compliance with applicable regulatory requirements. We may not successfully expand or establish sufficient manufacturing capabilities or manufacture our products economically or in compliance with cGMP and other regulatory requirements, and we and our collaborators may not be able to build or procure additional capacity in the required timeframe to meet the requirements of our clinical programs or to meet potential commercial demand for our product candidates. This could also delay or require us to discontinue one or more of our clinical development programs or could interfere with our efforts to successfully commercialize our products. As a result, our business, prospects, operating results, and financial condition could be materially harmed. If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. The timely completion of clinical trials in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of patients who remain in the study until its conclusion. The natural history studies may fail to provide us with patients for our clinical trials because patients enrolled in the natural history studies may not be good candidates for our clinical trials or may choose to not enroll in our clinical trials. We may encounter delays in enrolling, or be unable to enroll, a sufficient number of patients to complete any of our clinical trials, and even once enrolled we may be unable to retain a sufficient number of patients to complete any of our trials. This may result in increased costs, program delays or both, which could have a harmful effect on our ability to develop our product candidates, or could render further development impossible. The enrollment of patients depends on many factors, including: ● the size and nature of the patient population; ● the patient eligibility criteria defined in the protocol; ● the size of the patient population required for analysis of the trial’s primary endpoints; ● the proximity of patients to study sites; ● the design of the trial or side effects that may arise in development; ● our ability to recruit clinical trial investigators with the appropriate competencies and experience; 65 Table of Contents ● clinicians’ and patients’ perceptions as to the potential advantages of the product candidate being studied in relation to other available therapies, including any new products that may be approved for the indications we are investigating; ● our ability to obtain and maintain patient consents; ● the risk that patients enrolled in clinical trials will drop out of the trials before completion; and ● business interruptions resulting from geopolitical actions, including war and terrorism, or widespread health emergencies, such as the COVID-19 pandemic, or natural disasters including earthquakes, typhoons, floods and fires, or from economic or political instability. In addition, other clinical trials for product candidates that are in the same therapeutic areas as our product candidates or approved products for the same clinical indications (such as Luxturna marketed by Spark Therapeutics, Inc. for the treatment of RPE65-associated retinal disease) may reduce the number and type of patients available to us. Our product candidates may cause serious adverse events or undesirable side effects or have other properties which may delay or prevent their regulatory approval, limit the commercial profile of an approved label, or, result in significant negative consequences following marketing approval, if any. Serious adverse events or undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA, MHRA or other authorities. Results of our clinical trials could reveal a high and unacceptable severity and prevalence of side effects, toxicities or unexpected characteristics, including death. A risk in any gene therapy product based on viral vectors is the risk of insertional mutagenesis. If unacceptable side effects or deaths arise in the development of our product candidates, we, the FDA, the IRBs at the institutions in which our studies are conducted, DSMB, or other regulatory bodies could suspend or terminate our clinical trials or the FDA, MHRA or other regulatory authorities could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications. Undesirable side effects or deaths in clinical trials with our product candidates may cause the FDA or comparable foreign regulatory authorities to place a clinical hold on the associated clinical trials, to require additional studies, or otherwise to delay or deny approval of our product candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. In addition, these side effects may not be appropriately recognized or managed by the treating medical staff. We expect to have to train medical personnel using our product candidates to understand the side effect profiles for our clinical trials and upon any commercialization of any of our product candidates. Inadequate training in recognizing or managing the potential side effects of our product candidates could result in patient injury or death. Any of these occurrences may harm our business, financial condition and prospects significantly. If any of our product candidates receives marketing approval, and we or others later identify undesirable side effects caused by any such product, including during any long-term follow-up observation period recommended or required for patients who receive treatment using our products, a number of potentially significant negative consequences could result, including: ● regulatory authorities may withdraw approvals of such product; ● we may be required to recall a product or change the way such product is administered to patients; 66 Table of Contents ● additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product; ● regulatory authorities may require additional warnings on the label, such as a “black box” warning or contraindication; ● we may be required to implement a Risk Evaluation and Mitigation Strategy, or REMS, or create a medication guide outlining the risks of such side effects for distribution to patients or similar risk management measures; ● the product could become less competitive; ● 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 market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects. Success in preclinical studies or clinical trials may not be indicative of results in future clinical trials. Results from previous preclinical studies or clinical trials are not necessarily predictive of future clinical trial results, and interim results of a clinical trial are not necessarily indicative of final results. Our product candidates may fail to show the desired safety and efficacy in clinical development despite positive results in preclinical studies or having successfully advanced through initial clinical trials. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will generate the same results or otherwise provide adequate data to demonstrate the efficacy and safety of a product candidate. Frequently, product candidates that have shown promising results in early clinical trials have subsequently suffered significant setbacks in later clinical trials. In addition, the design of a clinical trial can determine whether its results will support approval of a product and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced. We have limited experience designing clinical trials and may be unable to design and execute a clinical trial to support regulatory approval. There is a high failure rate for drugs and biologic products proceeding through clinical trials. Data obtained from preclinical and clinical activities are subject to varying interpretations, which may delay, limit or prevent regulatory approval, which could negatively impact our business, financial condition, results of operations and prospects. The regulatory approval processes of the FDA, MHRA, competent authorities in the EU and other regulatory authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately unable to obtain regulatory approval for our product candidates, our business will be substantially harmed. The time required to obtain approval by the FDA, MHRA, European Commission and other regulatory authorities is unpredictable but typically takes many years following the commencement of clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. In addition, approval policies, 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. For instance, the EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020. The European Commission’s proposal for revision of several legislative instruments related to medicinal products (potentially revising the duration of regulatory exclusivity, eligibility for expedited pathways, etc.) is currently expected during the first quarter of 2023. The proposed revisions, 67 Table of Contents once they are agreed and adopted by the European Parliament and European Council (not expected before the end of 2024 or early 2025) may have a significant impact on the pharmaceutical industry in the long term. We have not obtained regulatory approval for any product candidate and it is possible that none of our product candidates in clinical programs or any other product candidates we may seek to develop in the future will ever obtain regulatory approval. Neither we nor any future collaborator is permitted to market any of our product candidates in the United States, the UK or the EU until we receive regulatory approval of a BLA from the FDA or of an MAA from the MHRA or European Commission, respectively. It is possible that the FDA may refuse to accept for substantive review any BLAs, or the MHRA or EMA any of our MAAs, that we submit for our product candidates or may conclude after review of our data that our application is insufficient to obtain marketing approval of our product candidates. Prior to obtaining approval to commercialize a product candidate in the United States, the UK, the EU or elsewhere, we or our collaborators must demonstrate with substantial evidence from well-controlled clinical trials, and to the satisfaction of the FDA, MHRA, EMA or foreign regulatory agencies, that such product candidates are safe and effective for their intended uses. Results from nonclinical studies and clinical trials can be interpreted in different ways. Even if we believe the nonclinical or clinical data for our product candidates are promising, such data may not be sufficient to support approval by the FDA, MHRA, European Commission or other regulatory authorities. The FDA, MHRA or EMA may also require us to conduct additional preclinical studies or clinical trials for our product candidates either prior to or post-approval, or it may object to elements of our clinical development program. Depending on the extent of these or any other FDA, MHRA or EMA required studies, approval of any regulatory approval applications that we submit may be delayed by several years, or may require us to expend significantly more resources than we have available. Of the large number of potential products in development, only a small percentage successfully complete the FDA, MHRA, or other foreign regulatory approval processes and are commercialized. The lengthy approval process as well as the unpredictability of future clinical trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly harm our business, results of operations and prospects. Even if we and / or our collaboration partners, as applicable, obtain FDA, MHRA or European Commission approval for AAV-GAD, botaretigene sparoparvovec, AAV-CNGB3, AAV-CNGA3, AAV-RPE65, AAV-hAQP1 or our other product candidates in the United States, UK or EU, we may never obtain approval for or commercialize them in any other jurisdiction, which would limit our ability to realize their full market potential. In order to market any products in any particular jurisdiction, we must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval by the FDA in the United States, the MHRA in Great Britain or the competent authorities in the EU does not ensure approval by regulatory authorities in other countries or jurisdictions. However, the failure to obtain approval in one jurisdiction may negatively impact our ability to obtain approval elsewhere. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country. Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Seeking foreign regulatory approval could result in difficulties and increased costs for us and require additional preclinical studies or clinical trials which could be costly and time consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in those countries. We do not have any product candidates approved for sale in any jurisdiction, including in international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of any product we develop will be unrealized. 68 Table of Contents Even if we receive regulatory approval of one or more of our product candidates, we will be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense, and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our product candidates. Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post- approval clinical data, labeling, packaging, distribution, adverse event reporting, storage, recordkeeping, export, import, advertising and promotional activities for such product, among other things, will be subject to extensive and ongoing requirements of and review by the FDA, MHRA and other regulatory authorities. These requirements include submissions of safety and other post-marketing information and reports, establishment registration and drug listing requirements, continued compliance with cGMP and similar requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping and GCP requirements for any clinical trials that we conduct post-approval. The FDA, MHRA and other regulatory authorities closely regulate the post-approval marketing and promotion of genetic therapy medicines to ensure they are marketed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA, MHRA and other regulatory authorities impose stringent restrictions on manufacturers’ communications regarding off-label use and if we market our products for uses beyond their approved indications, we may be subject to enforcement action for off-label marketing. Violations of the U.S. federal Food, Drug, and Cosmetic Act, or FDCA, relating to the promotion of prescription drugs may lead to FDA enforcement actions and investigations alleging violations of federal and state health care fraud and abuse laws, as well as state consumer protection laws. Similar risks apply in foreign jurisdictions. In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, including adverse events of unanticipated severity or frequency, or with our manufacturing processes or third-party manufacturers, or failure to comply with regulatory requirements, may yield various results, including: ● restrictions on manufacturing such products; ● restrictions on the labeling or marketing of a product; ● restrictions on product distribution or use; ● requirements to conduct post-marketing studies or clinical trials; ● warning letters or holds on clinical trials; ● withdrawal of the products from the market; ● refusal to approve pending applications or supplements to approved applications that we submit; ● recall of products; ● fines, restitution or disgorgement of profits or revenues; ● suspension or withdrawal of marketing approvals; ● refusal to permit the import or export of our products; ● product seizure or detention; or 69 Table of Contents ● injunctions or the imposition of civil or criminal penalties. The FDA’s and foreign regulatory authorities’ policies may change and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates. We also cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action, either in the United States or in other countries. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained which would adversely affect our business, prospects and ability to achieve or sustain profitability. Interim, “topline” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data. From time to time, we may publicly disclose preliminary or topline data from our clinical trials, which is based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular study or trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Topline and preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the topline or preliminary data we previously published. As a result, topline and preliminary data should be viewed with caution until the final data are available. From time to time, we may also disclose interim data from our clinical trials. Interim data from these trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as subject enrollment continues and more data become available. Adverse differences between interim data and topline, preliminary, or final data could significantly harm our business prospects. Further, disclosure of interim data by us or by our competitors could result in volatility in the price of our ordinary shares. Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular product candidate or product and our company in general. In addition, the information we choose to publicly disclose regarding a particular clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure. If the interim, topline, or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the conclusions reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could harm our business, operating results, prospects or financial condition. We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on 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 research programs and product candidates that we identify 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. Our resource allocation decisions may cause us to fail to timely 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 70 Table of Contents 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. Changes in funding for, or disruptions caused by global health concerns impacting, the FDA and other government or regulatory agencies could hinder their ability to hire and retain key leadership and other personnel, or otherwise prevent new products and services from being developed, approved or commercialized in a timely manner, which could negatively impact our business. The ability of the FDA and foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, disruptions caused by global health concerns such as the COVID-19 pandemic, ability to hire and retain key personnel, including those with experience relating to novel gene therapy product candidates, acceptance of the payment of user fees, statutory, regulatory, and policy changes and other events that may otherwise affect the FDA’s or foreign regulatory authorities’ ability to perform routine functions. Average review times at the FDA and foreign regulatory authorities have fluctuated in recent years as a result. In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable. Disruptions at the FDA and other government or regulatory agencies such as the EMA, following its relocation to Amsterdam and related reorganization (including staff changes), may also slow the time necessary for new product candidates to be reviewed and/or approved, which would adversely affect our business. For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA employees and stop critical activities. Risks Related to Healthcare Laws and Other Legal Compliance Matters Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates and may affect the prices we may set. In the United States, the UK, the EU and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and regulatory changes and proposed changes to the healthcare system that could affect our future results of operations. In particular, there have been and continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. For example, in March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers. Among the provisions of the ACA, those of greatest importance to the pharmaceutical and biotechnology industries include the following: ● an annual, non-deductible fee payable by any entity that manufactures or imports certain branded prescription drugs and biologic agents (other than those designated as orphan drugs), which is apportioned among these entities according to their market share in certain government healthcare programs; ● 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; ● 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; ● a licensure framework for follow on biologic products; 71 Table of Contents ● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and ● establishment of a Center for Medicare & Medicaid Innovation at the Centers for Medicare & Medicaid Services, or CMS, to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending. Since its enactment, there have been judicial, Congressional and executive branch challenges to certain aspects of the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. Prior to the Supreme Court’s decision, President Biden issued an executive order to initiate a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace from February 15, 2021 through August 15, 2021. The executive order also instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA. In addition, other legislative changes have been proposed and adopted in the United States since the ACA was enacted. In August 2011, the Budget Control Act of 2011, among other things, led to aggregate reductions of Medicare payments to providers of 2% per fiscal year. These reductions went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2030, with the exception of a temporary suspension from May 1, 2020 through March 31, 2022. Under current legislation, the actual reduction in Medicare payment varies from 1% from April 1, 2022 through June 30, 2022, to up to 3% in the final year of this sequester, unless additional action is taken by Congress. In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws or any other similar laws introduced in the future may result in additional reductions in Medicare and other health care funding, which could negatively affect our customers and accordingly, our financial operations. Moreover, payment methodologies may be subject to changes in healthcare legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, such as bundled payment models. In addition, recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S. Congressional inquiries and proposed and enacted federal legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs. We expect that additional U.S. federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that the U.S. federal government will pay for healthcare products and services, which could result in reduced demand for our product candidates or additional pricing pressures. Individual states in the United States have also increasingly passed legislation and implemented 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. Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial condition and prospects. 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. This could reduce the ultimate demand for our product candidates or put pressure on our product pricing. 72 Table of Contents In addition, FDA regulations and guidance may be revised or reinterpreted by the FDA in ways that may significantly affect our business and our products. Any new regulations or guidance, or revisions or reinterpretations of existing regulations or guidance, may impose additional costs or lengthen FDA review times for our product candidates. We cannot determine how changes in regulations, statutes, policies, or interpretations when and if issued, enacted or adopted, may affect our business in the future. Such changes would likely require substantial time and impose significant costs, or could reduce the potential commercial value of our product candidates, and could materially harm our business and our financial results. In addition, delays in receipt of or failure to receive regulatory clearances or approvals for any other products would harm our business, financial condition, and results of operations. In the UK and EU, similar political, economic and regulatory developments may affect our ability to profitably commercialize our product candidates, if approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the UK or the EU or member state level may result in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the UK and the EU, including the establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national law and policy. National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in the UK and in most EU member states have resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever- increasing national regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our product candidates, restrict or regulate post-approval activities and affect our ability to commercialize our product candidates, if approved. In markets outside of the United States, the UK and the EU, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on specific products and therapies. We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action in the United States, the UK the EU or any other jurisdiction. If we or any third parties we may engage are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or such third parties are not able to maintain regulatory compliance, our product candidates may lose any regulatory approval that may have been obtained and we may not achieve or sustain profitability. Our business operations and current and future relationships with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties. Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient organizations and customers, may expose us to broadly applicable fraud and abuse laws and other healthcare laws and regulations. These laws may constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute our product candidates, if approved. Such laws include: ● the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under U.S. federal and state healthcare programs such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; 73 Table of Contents ● the U.S. federal civil and criminal false claims and civil monetary penalties laws, including the civil False Claims Act, which, among other things, impose criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to avoid, decrease or conceal an obligation to pay money to the U.S. federal government. In addition, the government may assert that a claim including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the False Claims Act; ● the U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal statutes which prohibit, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or 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. Similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; ● the FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; ● the U.S. Public Health Service Act, which prohibits, among other things, the introduction into interstate commerce of a biological product unless a biologics license is in effect for that product; ● federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; ● the U.S. Physician Payments Sunshine Act and its implementing regulations, which requires certain manufacturers of drugs, devices, biologics and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the government information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse midwives), and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; ● analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by any third-party payor, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws and regulations that require drug manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws that require the registration of pharmaceutical sales representatives; and ● similar healthcare laws and regulations in the UK, EU and other jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers. 74 Table of Contents Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, agency guidance 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 the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions, integrity oversight and reporting obligations to resolve allegations of non-compliance, disgorgement, individual imprisonment, contractual damages, reputational harm, diminished profits and the curtailment or restructuring of our operations. If any of the physicians or other providers or entities with whom we expect to do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs and imprisonment, which could affect our ability to operate our business. Further, defending against any such actions can be costly, time-consuming and may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our business may be impaired. We are subject to regulation and other legal obligations relating to privacy and data protection. Compliance with these requirements is complex and costly. Failure to comply could materially harm our business. The global data protection landscape is rapidly evolving, and we are or may become subject to numerous state, federal and foreign laws, requirements and regulations governing the collection, use, disclosure, retention and security of personal information. In the U.S., HIPAA imposes privacy, security and breach reporting obligations with respect to individually identifiable health information upon “covered entities” (health plans, health care clearinghouses and certain health care providers), and their respective business associates, individuals or entities that create, receive, maintain or transmit protected health information in connection with providing a service for or on behalf of a covered entity, as well as their covered subcontractors. Most healthcare providers, including research institutions and other vendors from which we may obtain patient health information, are subject to privacy and security regulations promulgated under HIPAA. We do not believe that we are currently acting as a covered entity or business associate under HIPAA and thus are not directly subject to its requirements or penalties. However, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information. In addition, certain state laws govern the privacy and security of health information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts. Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation. Further, we may also be subject to other state laws governing the privacy, processing and protection of personal information. For example, the California Consumer Privacy Act, or CCPA, confers individual privacy rights for California consumers (as such term is defined in the law) and places increased privacy and security obligations on entities handling personal information of consumers or households. The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that has increased the likelihood of, and risks associated with, data breach litigation. Further, the California Privacy Rights Act, or the CPRA, generally went into effect in January 2023, and significantly amends the CCPA and imposes additional data protection obligations on covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data. It also created a new California data protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement. Additional compliance investment and potential business process changes may be required. The CCPA, the CPRA and other domestic privacy and data protection laws and regulations may increase our compliance costs and potential liability. 75 Table of Contents Our operations abroad may also be subject to increased scrutiny or attention from data protection authorities. For example, the GDPR imposes stringent requirements for processing the personal data of individuals within the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Lichtenstein and Iceland. Companies that must comply with the GDPR face increased compliance obligations and risk, including more robust regulatory enforcement of data protection requirements and potential fines for noncompliance of up to €20 million or up to 4% of the total worldwide annual turnover of the relevant undertaking in the preceding financial year, whichever is higher, and other administrative penalties. Among other requirements, the GDPR regulates transfers of personal data subject to the GDPR to third countries that have not been found to provide adequate protection to such personal data, including the U.S. In July 2020, the Court of Justice of the European Union, or CJEU, limited how organizations could lawfully transfer personal data from the EEA to the U.S. by invalidating the Privacy Shield for purposes of international transfers and imposing further restrictions on the use of standard contractual clauses (a standard form of contract approved by the European Commission as an adequate personal data transfer mechanism, and potential alternative to the Privacy Shield), or SCCs. In March 2022, the U.S. and EU announced a new regulatory regime intended to replace the invalidated regulations; however, this new EU-U.S. Data Privacy Framework has not been implemented beyond an executive order signed by President Biden on October 7, 2022 on Enhancing Safeguards for United States Signals Intelligence Activities. European court and regulatory decisions subsequent to the CJEU decision of July 2020 have taken a restrictive approach to international data transfers. As supervisory authorities issue further guidance on personal data export mechanisms, including circumstances where the SCCs cannot be used, and/or start taking enforcement action, we could suffer additional costs, complaints and/or regulatory investigations or fines. If, owing to the restriction or perceived restriction of personal data transfers, we are otherwise unable to transfer personal data between and among countries and regions in which we operate, it could affect the manner in which we provide our services, the geographical location or segregation of our relevant systems and operations, and could adversely affect our financial results. Further, we are subject to the UK data protection regime, which imposes separate but similar obligations to those under the GDPR and comparable penalties, including fines of up to £17.5 million or 4% of a noncompliant company’s global annual revenue for the preceding financial year, whichever is greater. As we continue to expand into other foreign countries and jurisdictions, we may be subject to additional laws and regulations that may affect how we conduct business. Although we work to comply with applicable laws, regulations and standards, as well as our contractual obligations and other legal obligations, relating to data privacy and security, these requirements are evolving and may be modified, interpreted and applied in an inconsistent manner from one jurisdiction and/or organization to another, and may conflict with one another or other legal obligations with which we must comply. Any failure or perceived failure by us or our employees, representatives, contractors, consultants, collaborators, or other third parties to comply with such requirements or adequately address privacy and security concerns, even if unfounded, could result in additional cost and liability to us, damage our reputation, and adversely affect our business and results of operations. We are subject to environmental, health and safety laws and regulations, and we may become exposed to liability and substantial expenses in connection with environmental compliance or remediation activities. Our operations, including our development, testing and manufacturing activities, are subject to numerous environmental, health and safety laws and regulations. These laws and regulations govern, among other things, the controlled use, handling, release and disposal of and the maintenance of a registry for, hazardous materials and biological materials, such as chemical solvents, human cells, carcinogenic compounds, mutagenic compounds and compounds that have a toxic effect on reproduction, laboratory procedures and exposure to blood-borne pathogens. If we fail to comply with such laws and regulations, we could be subject to fines or other sanctions. Additionally, if environmental regulations are enacted that restrict our ability to use one or more of the materials or compounds necessary to manufacture our product candidates, and we are unable to find suitable alternatives or such alternatives require additional testing or will 76 Table of Contents extend the manufacturing timeline, then we may be unable to manufacture our product candidates in a timely manner, or at all. We may be subject to environmental liability inherent in our current and historical activities, including liability relating to releases of or exposure to hazardous or biological materials. Environmental, health and safety laws and regulations are becoming more stringent. We may be required to incur substantial expenses in connection with future environmental compliance or remediation activities, in which case, our production efforts or those of our third-party manufacturers may be interrupted or delayed. Due to our international operations, we are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws governing our operations. If we fail to comply with these laws, we could be subject to civil or criminal penalties, other remedial measures and legal expenses. Our operations are subject to anti-corruption laws, including the UK Bribery Act 2010, or Bribery Act; the U.S. Foreign Corrupt Practices Act, or FCPA; and other anti-corruption laws that apply in countries where we do business and may do business in the future. The Bribery Act, FCPA, and these other laws generally prohibit us, our officers and our employees and intermediaries from bribing, being bribed by, or providing prohibited payments or anything else of value to government officials or other persons to obtain or retain business or gain some other business advantage. We may in the future operate in jurisdictions that pose a high risk of potential Bribery Act or FCPA violations, and we may participate in collaborations and relationships with third parties whose actions could potentially subject us to liability under the Bribery Act, FCPA, or local anti-corruption laws. In addition, we cannot predict the nature, scope, or effect of future regulatory requirements to which any of our international operations might be subject or the manner in which existing laws might be administered or interpreted. We also are subject to other laws and regulations governing any international operations, including regulations administered by the governments of the UK and the U.S., and authorities in the EU, including applicable export control regulations, economic sanctions on countries and persons, customs requirements and currency exchange regulations, or, collectively, the Trade Control laws. There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti- corruption laws, including the Bribery Act, the FCPA, or other legal requirements, including Trade Control laws. If we are not in compliance with the Bribery Act, the FCPA, and other anti-corruption laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement, and other sanctions and remedial measures and legal expenses. Any investigation of any potential violations of the Bribery Act, the FCPA, other anti-corruption laws, or Trade Control laws by UK, U.S., or other authorities, even if it is ultimately determined that we did not violate such laws, could be costly and time-consuming, require significant personnel resources, and harm our reputation. We have established internal controls to detect and prevent violations of applicable anti-corruption laws and to remedy any weaknesses identified. There can be no assurance, however, that the policies and procedures will be followed at all times or effectively detect and prevent violations of the applicable laws by one or more of our employees, consultants, agents, or collaborators and, as a result, we could be subject to fines, penalties, or prosecution. Risks Related to Commercialization We face significant competition in an environment of rapid technological change, and there is a possibility that our competitors may achieve regulatory approval before us or develop therapies that are safer or more advanced or effective than ours, which may harm our financial condition and our ability to successfully market or commercialize any product candidates we may develop. 77 Table of Contents The development and commercialization of new gene therapy products is highly competitive. Moreover, the gene regulation and manufacturing fields are characterized by rapidly changing technologies and a strong emphasis on intellectual property. We may face competition with respect to any product candidates that we may seek to develop or commercialize in the future from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies worldwide. Potential competitors also include academic institutions, government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for research, development, manufacturing, and commercialization. There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of products for the treatment of the disease indications for which we have research programs, including inherited retinal diseases and neurodegenerative diseases. Some of these competitive products and therapies are based on scientific approaches that are similar to our approach, and others are based on entirely different approaches. Differences in the scientific approaches may create confusion or uncertainty among clinical trial investigators or patient populations, which could delay or hinder enrollment or initiation of our clinical trials. Our platform and products focus on the development of gene therapies and gene regulation technology. In 2017, the FDA approved the first gene treatment for RPE65-associated retinal disease, Luxturna, a commercially available product developed by Spark Therapeutics, Inc., which was purchased by Roche. There are a number of other companies developing ocular gene therapy products, including Applied Genetic Technologies Corporation, and 4D Molecular Therapeutics, Inc. There are a number of companies developing gene therapy products for neurodegenerative diseases, including Voyager Therapeutics, Inc., Brain Neurotherapy Bio, Inc., Axovant Gene Therapies Ltd. and Prevail Therapeutics Inc. (which was purchased by Eli Lilly and Company). In addition to competition from other gene therapies, any products we may develop may also face competition from other types of therapies, such as small molecule, antibody, or protein therapies. Many of our current or potential competitors, either alone or with their collaboration partners, have greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical, biotechnology, and gene therapy industries may result in even more resources being concentrated among a smaller number of our competitors. These competitors also compete with us in recruiting and retaining qualified scientific, manufacturing and management personnel and establishing clinical trial sites and patient enrollment in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than any products that we may develop, limiting demand or the price we are able to charge, or that could render any products that we may develop obsolete or non-competitive. Our competitors also may obtain FDA, MHRA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, as a result of the expiration or successful challenge of our patent rights, we could face more litigation with respect to the validity and/or scope of patents relating to our competitors’ products. The successful commercialization of our product candidates will depend in part on the extent to which governmental authorities and health insurers establish coverage, adequate reimbursement levels and pricing policies. Failure to obtain or maintain coverage and adequate reimbursement for our product candidates, if approved, could limit our ability to market those products and decrease our ability to generate revenue. The availability of coverage and adequacy of reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health insurers and other third-party payors are essential for most patients to be able to afford medical services and pharmaceutical products such as our product candidates, assuming FDA approval. Our ability to achieve acceptable levels of coverage and reimbursement for our products or procedures using our products by governmental authorities, private health insurers and other organizations will have an effect on our ability to successfully commercialize our product candidates. Obtaining coverage and adequate reimbursement for our products may be particularly difficult because of the higher prices often associated with drugs administered under the supervision of a 78 Table of Contents physician. Separate reimbursement for the product itself or the treatment or procedure in which our product is used may not be available. A decision by a third-party payor not to cover or separately reimburse for our products or procedures using our products, could reduce physician utilization of our products if approved. Assuming there is such coverage by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find unacceptably high. We cannot be sure that coverage and reimbursement in the United States, the UK, the EU or elsewhere will be available for our product candidates or any product that we may develop, and any reimbursement that may become available may not be adequate or may be decreased or eliminated in the future. Third-party payors increasingly are challenging prices charged for pharmaceutical products and services, and many third-party payors may refuse to provide coverage and reimbursement for particular drugs or biologics when an equivalent generic drug, biosimilar or a less expensive therapy is available. It is possible that a third-party payor may consider our product candidates as substitutable and only offer to reimburse patients for the less expensive product. Even if we show improved efficacy or improved convenience of administration with our product candidates, pricing of existing third-party therapeutics may limit the amount we will be able to charge for our product candidates. These payors may deny or revoke the reimbursement status of a given product or establish prices for new or existing marketed products at levels that are too low to enable us to realize an appropriate return on our investment in our product candidates. If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize our product candidates and may not be able to obtain a satisfactory financial return on our product candidates. There is significant uncertainty related to the insurance coverage and reimbursement of newly-approved products. In the United States, third-party payors, including private and governmental payors, such as the Medicare and Medicaid programs, play an important role in determining the extent to which new drugs and biologics will be covered. The Medicare and Medicaid programs increasingly are used as models in the United States for how private payors and other governmental payors develop their coverage and reimbursement policies for drugs and biologics. Some third-party payors may require pre-approval of coverage for new or innovative devices or drug therapies before they will reimburse healthcare providers who use such therapies. We cannot predict at this time what third-party payors will decide with respect to the coverage and reimbursement for our product candidates. No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States. Therefore, coverage and reimbursement for products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and costly process that will require us to provide scientific and clinical support for the use of our product candidates to each payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Furthermore, rules and regulations regarding reimbursement change frequently, in some cases on short notice. Outside the United States, international operations are generally subject to extensive governmental price controls and other market regulations, and we believe the increasing emphasis on cost-containment initiatives in Europe and other countries have and will continue to put pressure on the pricing and usage of our product candidates. In many countries, the prices of medical products are subject to varying price control mechanisms as part of national health systems. Other countries allow companies to fix their own prices for medical products but monitor and control company profits. Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our product candidates. Accordingly, in markets outside the United States, the reimbursement for our product candidates may be reduced compared with the United States and may be insufficient to generate commercially-reasonable revenue and profits. Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or reduce healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate payment for our product candidates. We expect to experience pricing pressures in connection with the sale of our product candidates due to the trend toward managed health care, the increasing influence of health maintenance organizations and additional legislative changes. The downward pressure on healthcare costs in general, particularly prescription drugs and biologics and surgical 79 Table of Contents procedures and other treatments, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. Even if our product candidates receive marketing approval, they may fail to achieve market acceptance by physicians, patients, third-party payors or others in the medical community necessary for commercial success. If our product candidates receive marketing approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. If they do not achieve an adequate level of acceptance, we may not generate significant product revenues or become profitable. The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including but not limited to: ● the efficacy and potential advantages compared to alternative treatments; ● effectiveness of sales and marketing efforts; ● the cost of treatment in relation to alternative treatments, including any similar generic treatments; ● our ability to offer our product candidates for sale at competitive prices; ● the convenience and ease of administration; ● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support, and publicity concerning our products or competing products and treatments; ● the timing of market introduction of competitive products; ● the availability of third-party coverage and adequate reimbursement; ● product labeling or product insert requirements of the FDA, MHRA, EMA or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; ● the prevalence and severity of any side effects; and ● any restrictions on the use of our product together with other medications. Because we expect sales of our product candidates, if approved, to generate substantially all of our product revenues for a substantial period, the failure of these product candidates to find market acceptance would harm our business and could require us to seek additional financing. If we are unable to establish sales, marketing and distribution capabilities either on our own or in collaboration with third parties, we may not be successful in commercializing our product candidates or realizing the synergies in the target indications of our programs, even if they are approved. We do not have any infrastructure for the sales, marketing or distribution of our products, and the cost of establishing and maintaining such an organization may exceed the cost-effectiveness of doing so or we may seek collaborative arrangements or external funding to commercialize our product candidates. For example, Janssen will be solely responsible for the commercialization of botaretigene sparoparvovec, AAV-CNGB3 and AAV-CNGA3 pursuant 80 Table of Contents to our Collaboration Agreement with them. There are significant expenses and risks involved with establishing our own sales, marketing and distribution capabilities, including our ability to hire, retain and appropriately incentivize qualified individuals, generate sufficient sales leads, provide adequate training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. Any failure or delay in the development of such capabilities could delay any product launch, which would adversely impact the commercialization of our product candidates. Additionally, if any commercial launch is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel. We may not have the resources in the foreseeable future to allocate to the sales and marketing of our product candidates in certain markets. Therefore, our future sales in these markets will largely depend on our ability to enter into and maintain collaborative relationships for such capabilities, the collaborator’s strategic interest in the product and such collaborator’s ability to successfully market and sell the product. We may pursue collaborative arrangements regarding the sale and marketing of AAV-GAD, AAV-RPE65, AAV-hAQP1 or other future gene therapy programs, if approved, for the United States and/or certain markets overseas; however, there can be no assurance that we will be able to establish or maintain such collaborative arrangements, or if able to do so, that they will have effective sales forces. If we are unable to build our own sales force or negotiate or maintain a collaborative relationship for the commercialization of our product candidates, we may be forced to delay potential commercialization or reduce the scope of our sales or marketing activities. If we elect to increase our expenditures to fund commercialization activities internationally, we will need to obtain additional capital, which may not be available to us on acceptable terms, or at all. We could enter into arrangements with collaborative partners at an earlier stage than otherwise would be ideal and we may be required to relinquish rights or otherwise agree to terms unfavorable to us, any of which may have an adverse effect on our business, operating results and prospects. Some indications targeted by our ophthalmology programs are rare, but we anticipate realizing synergies in commercializing our IRD product candidates, should they be approved. Failure to realize synergies in our sales, marketing and distribution efforts may harm our commercialization efforts. If we or our collaborators are unable to establish or maintain adequate sales, marketing and distribution capabilities, we will not be successful in commercializing our product candidates and may not become profitable and may incur significant additional losses. We will be competing with many companies that currently have extensive and well- funded marketing and sales operations. Without an internal team or the support of a third party to perform marketing and sales functions, we may be unable to compete successfully against these more established companies. If any of our products are commercialized outside of the United States, the UK or the EU, a variety of risks associated with international operations could adversely affect our business. If any of our products are approved for commercialization, we have entered into, and intend to enter into, agreements with third parties to market them in certain jurisdictions outside the United States, the UK and the EU, such as under our Collaboration Agreement with Janssen. We expect that we and our third-party collaborators will be subject to additional risks related to international pharmaceutical operations, including: ● different regulatory requirements for drug and biologic approvals and rules governing drug and biologic commercialization in foreign countries; ● tighter restrictions on privacy and the collection and use of patient data; ● reduced or loss of protection for intellectual property rights; ● foreign reimbursement, pricing and insurance regimes; 81 Table of Contents ● unexpected changes in tariffs, trade barriers and regulatory requirements; ● economic weakness, including inflation, or political instability in particular foreign economies and markets; ● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country; ● business interruptions resulting from geopolitical actions, including war and terrorism, or widespread health emergencies, such as the COVID-19 pandemic, or natural disasters including earthquakes, typhoons, floods and fires, or from economic or political instability; ● greater difficulty with enforcing our contracts; ● potential noncompliance with the FCPA, the Bribery Act and similar anti-bribery and anticorruption laws in other jurisdictions; ● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and ● workforce uncertainty in countries where labor unrest is more common than in the United States and compliance with tax, employment, immigration and labor laws for employees living or traveling abroad. We have no prior experience in these areas and we may rely on other third parties to help us establish our international commercialization operations. In addition, there are complex regulatory, tax, labor and other legal requirements imposed by individual countries in Europe with which we and our third-party collaborators will need to comply. If we are unable to successfully manage the challenges of international expansion and operations, our business and operating results could be harmed. Any product candidates for which we intend to seek approval as biologic products may face competition sooner than anticipated. The ACA includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA- licensed reference biological product. Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date on which the reference product was first licensed by the FDA. During this 12-year period of exclusivity, another company may still market a competing version of the reference product if the FDA approves a full BLA for the competing product containing the sponsor’s own pre-clinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity and potency of the other company’s product. We believe that any of our product candidates approved as a biological product under a BLA should qualify for the 12-year period of exclusivity. However, there is a risk that any of our product candidates approved as a biological product under a BLA would not qualify for the 12-year period of exclusivity or that this exclusivity could be shortened due to Congressional action or otherwise, or that the FDA will not consider our product candidates to be reference products for competing products, potentially creating the opportunity for generic competition sooner than anticipated. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have also been the subject of recent litigation. Jurisdictions outside the United States have established abbreviated pathways for regulatory approval 82 Table of Contents of biological products that are biosimilar to earlier approved reference products. For example, the EU has had an established regulatory pathway for biosimilars since 2006. Moreover, the extent to which a biosimilar, once licensed, will be substituted for any one of our reference products in a way that is similar to traditional generic substitution for non- biological products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still developing. If competitors are able to obtain marketing approval for biosimilars referencing our products, our products may become subject to competition from such biosimilars, with the attendant competitive pressure and consequences. Risks Related to Our Dependence on Third Parties If our cGMP and GMP manufacturing facilities are unable to supply our product candidates for all of our current preclinical, clinical and potential commercial needs, we will be forced to seek out third-party manufacturers. We currently contract with third parties for the manufacture of plasmid used in producing our product candidates. Relying on third parties increases the risk that we will not have sufficient quantities of such materials, product candidates, or any medicines that we may develop and commercialize, or that such supply will not be available to us at an acceptable cost, which could delay, prevent, or impair our development or commercialization efforts. We produce our product candidates in our cGMP viral vector manufacturing facility completed in early 2018 and we completed the acquisition of our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland in January 2021 to expand our manufacturing and supply chain capabilities. However, if our current facility is damaged, suffers any form of delay or regulatory challenges, we experience slowdowns or problems with the development and completion of our new facilities or we are unable to scale our internal manufacturing capabilities to meet demand for our product candidates, we will need to contract with third- party manufacturers to produce our product candidates. While we now have our own plasmid manufacturing capabilities in our Shannon, Ireland facilities, we may also rely on third-party manufacturers from time to time for the manufacture of plasmid used in the production of some of our product candidates. We do not have a long-term supply agreement with any of the third-party manufacturers, and we purchase our required supply on a purchase order basis. We and our third-party manufacturers may also encounter difficulties or delays in manufacturing of our product candidates or the plasmid used in the production of our product candidates. Geopolitical actions, natural disaster or a widespread health emergency, such as the COVID-19 pandemic, could impact our supply chain. To the extent that we or our third-party manufacturers are located in geographies affected by these matters, it may result in the temporary closing of manufacturing facilities and may increase the costs associated with manufacturing our product candidates. We may be unable to establish any agreements with third-party manufacturers or to do so on acceptable terms. Even if we are able to establish agreements with third-party manufacturers, reliance on third-party manufacturers entails additional risks, including: ● the possible breach of the manufacturing agreement by the third party, including failure to provide appropriate quantities in a timely manner; ● the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us; and ● reliance on the third party for regulatory compliance, quality assurance, safety, and pharmacovigilance and related reporting. We and our third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements that might be required by the FDA, MHRA or EMA. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines, 83 Table of Contents injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocations, seizures or recalls of product candidates or medicines, operating restrictions, and criminal prosecutions, any of which could adversely affect supplies of our candidates and harm our business, financial condition, results of operations, and prospects. Any therapies that we may develop may compete with other product candidates and products for access to manufacturing facilities. There are a limited number of manufacturers that operate under cGMP or similar regulations and that might be capable of manufacturing for us. Any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval. Our current and anticipated future dependence upon others for the manufacture of any product candidates we may develop or any components required for the manufacture of our product candidates may adversely affect our future profit margins and our ability to commercialize any product candidates that receive marketing approval on a timely and competitive basis. We have in the past, and may in the future, collaborate with third parties for the development, manufacture and commercialization of our product candidates. We may not succeed in establishing and maintaining collaborative relationships, which may significantly limit our ability to develop and commercialize our product candidates successfully, if at all. We have entered into collaboration agreements with third parties for the development and commercialization of our product candidates, including our Collaboration Agreement with Janssen for the development and commercialization of AAV-CNGB3, AAV-CNGA3 and botaretigene sparoparvovec. We have also entered into a manufacturing research collaboration agreement with Janssen to further develop processes for manufacturing AAV viral vectors. We may seek additional collaborative relationships in the future. Failure to obtain a collaborative relationship for our product candidates may significantly impair their commercial potential. We also may need to enter into collaborative relationships to provide funding to support our other research and development programs. The process of establishing and maintaining collaborative relationships is difficult, time-consuming and involves significant uncertainty, such as: ● a collaboration partner may shift its priorities and resources away from our product candidates due to a change in business strategies, or a merger, acquisition, sale or downsizing; ● a collaboration partner may seek to renegotiate or terminate their relationships with us due to unsatisfactory clinical results, manufacturing issues, a change in business strategy, a change of control or other reasons; ● a collaboration partner may cease development in therapeutic areas which are the subject of our strategic collaboration; ● a collaboration partner may not devote sufficient capital or resources towards our product candidates; ● a collaboration partner may change the success criteria for a product candidate thereby delaying or ceasing development of such candidate; ● a significant delay in initiation of certain development activities by a collaboration partner will also delay payment of milestones tied to such activities, thereby impacting our ability to fund our own activities; ● a collaboration partner could develop a product that competes, either directly or indirectly, with our product candidate; 84 Table of Contents ● a collaboration partner with commercialization obligations may not commit sufficient financial or human resources to the marketing, distribution or sale of a product; ● a collaboration partner with manufacturing responsibilities may encounter regulatory, resource or quality issues and be unable to meet demand requirements; ● a collaboration partner may terminate a strategic alliance; ● a dispute may arise between us and a partner concerning the research, development or commercialization of a product candidate resulting in a delay in milestones, royalty payments or termination of an alliance and possibly resulting in costly litigation or arbitration which may divert management attention and resources; and ● a partner may use our products or technology in such a way as to make us subject to litigation with a third party. If any collaborator fails to fulfill its responsibilities in a timely manner, or at all, our research, clinical development, manufacturing or commercialization efforts related to that collaboration could be delayed or terminated, or it may be necessary for us to assume responsibility for expenses or activities that would otherwise have been the responsibility of our collaborator. If we are unable to establish and maintain collaborative relationships on acceptable terms or to successfully transition terminated collaborative agreements, we may have to delay or discontinue further development of one or more of our product candidates, undertake development and commercialization activities at our own expense or find alternative sources of capital. We have relied, and we expect to continue to rely, on third parties to conduct, supervise and monitor our preclinical studies and clinical trials, and if these third parties perform in an unsatisfactory manner, our business could be harmed. We expect to rely on CROs, clinical trial sites, and other vendors to ensure our preclinical studies and clinical trials are conducted properly and on time. We may also engage third parties such as clinical data management organizations, medical institutions and clinical investigators to conduct or assist in our clinical trials or other preclinical and clinical research and development work. While we will have agreements governing their activities, we will have limited influence over their actual performance. We will control only certain aspects of our third-party service providers’ activities. Nevertheless, we will be responsible for ensuring that each of our preclinical studies and clinical trials is conducted in accordance with the applicable protocol, legal, quality, regulatory and scientific standards. Our reliance on these third parties does not relieve us of our regulatory responsibilities. For example, we are conducting the Phase 3 Lumeos clinical trial of botaretigene sparoparvovec for the treatment of patients with XLRP caused by mutations in the RPGR gene at multiple clinical trial sites in North America and Europe. If any locations terminate the clinical trial, we may be required to find another party to conduct any new trials. We may be unable to find a new party to conduct new trials of our product candidates or obtain clinical supply of our product candidates or AAV vectors for such trials. If we elect to internalize some or all activities related to the conduct of our preclinical studies or clinical trials that are currently performed by our third-party service providers, or if we are required to do so due to a service provider’s termination of our relationship, then we may be required to source additional technology and personnel in order to perform the relevant activities. We may be unsuccessful in our efforts to internalize some or all relevant activities, either on the desired timeline or at all. Our third-party service providers are not our employees, and we are therefore unable to directly monitor whether or not they devote sufficient time, attention, expertise and resources to our clinical and nonclinical programs. These third- party service providers may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other drug development activities that could harm our competitive position. If our third-party service providers do not successfully carry out their contractual duties or obligations or fail to meet 85 Table of Contents expected deadlines, or if the quality or accuracy of the preclinical or clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements, or for any other reasons, our preclinical studies or clinical trials may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize our product candidates. As a result, our financial results and the commercial prospects for our product candidates could be harmed, our costs could increase, and our ability to generate revenues could be delayed. If our relationship with any CROs terminate, we may not be able to enter into arrangements with alternative CROs or do so on commercially reasonable terms. Switching or adding additional CROs involves substantial cost and requires management time and focus. In addition, there is a natural transition period when a new CRO commences work. As a result, delays occur, which can materially impact our ability to meet our desired clinical development timelines. Though we intend to carefully manage our relationships with our CROs, there can be no assurance that we will not encounter challenges or delays in the future or that these delays or challenges will not have an adverse impact on our business, financial condition and prospects. Risks Related to Intellectual Property We depend on proprietary technology licensed from others. If we lose our existing licenses or are unable to acquire or license additional proprietary rights from third parties, we may not be able to continue developing our product candidates. We currently in-license certain intellectual property from research institutions, universities and other third parties. We may also enter into additional agreements, including license agreements, with other parties in the future that impose diligence, development and commercialization timelines, milestone payments, royalties, insurance and other obligations on us. If we fail to comply with our obligations to any of our current or future collaborators, our counterparties may have the right to terminate these agreements, in which event we might not be able to develop, manufacture or market any product candidate that is covered by these agreements, which could adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology. We may rely on other third parties from whom we license proprietary technology to file and prosecute patent applications and maintain patents and otherwise protect the intellectual property we license from them. We may have limited control over these activities or any other intellectual property that may be related to our in-licensed intellectual property. For example, we cannot be certain that such activities by these licensors will be conducted in compliance with applicable laws and regulations or will result in valid and enforceable patents and other intellectual property rights. We may have limited control over the manner in which our licensors initiate an infringement proceeding against a third-party infringer of the intellectual property rights, or defend certain of the intellectual property that may be licensed to us. It is possible that the licensors’ infringement proceedings or defense activities may be less vigorous than if we conduct them ourselves. The licensing and acquisition of third-party intellectual property rights is a competitive practice, and companies that may be more established, or have greater resources than we do, may also be pursuing strategies to license or acquire third-party intellectual property rights that we may consider necessary or attractive in order to commercialize our product candidates. More established companies may have a competitive advantage over us due to their larger size and cash resources or greater clinical development and commercialization capabilities. There can be no assurance that we will be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional product candidates that we may seek to acquire. If we are unable to obtain and maintain patent protection for our technology and product candidates or if the scope of the patent protection obtained is not sufficiently broad, we may not be able to compete effectively in our markets. 86 Table of Contents If we are unable to obtain and maintain patent protection for our technology and product candidates or if the scope of the patent protection obtained is not sufficiently broad, we may not be able to compete effectively in our markets. We rely upon a combination of patents, trade secret protection and confidentiality agreements to protect the intellectual property related to our proprietary technologies, product candidate development programs and product candidates. Our success depends in part on our ability to secure and maintain patent protection in the United States and other countries with respect to our current product candidates and any future product candidates we may develop. We seek to protect our proprietary position by filing or collaborating with our licensors to file patent applications in the United States and abroad related to our proprietary technologies, development programs and product candidates. The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. Moreover, the issuance, scope, validity, enforceability and commercial value of our patent rights are uncertain. It is also possible that we might fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. We may not have the right to control the preparation, filing, and prosecution of patent applications, or to maintain the rights to patents licensed to third parties. Therefore, these patents and patent applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. The patent applications that we own or in-license may fail to result in issued patents with claims that cover our proprietary products and technology, including current product candidates, any future product candidates we may develop, and our gene regulation technology in the United States or in other countries, in whole or in part. Alternately, our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from using our technology or from developing competing products and technologies. There is no assurance that all potentially relevant prior art relating to our patents and patent applications has been found, which can prevent a patent from issuing from a pending patent application or later invalidate or narrow the scope of an issued patent. For example, 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 published until 18 months after filing or, in some cases, not at all. Therefore, 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. In addition, 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. Even if patents do successfully issue and even if such patents cover our current product candidates, any future product candidates we may develop and our gene regulation technology, third parties may challenge their validity, enforceability or scope thereof, which may result in such patents being narrowed, invalidated, or held unenforceable. Any successful challenge to these patents or any other patents owned by or licensed to us could deprive us of rights necessary for the successful commercialization of any of our product candidates or gene regulation technology. Our competitors may be able to circumvent our patents by developing similar or alternative product candidates in a non-infringing manner. Further, if we encounter delays in regulatory approvals, the period of time during which we could market a product candidate and our gene regulation technology under patent protection could be reduced. If the patent applications we hold or have in-licensed with respect to our development programs and product candidates fail to issue, if their validity, breadth or strength of protection is threatened, or if they fail to provide meaningful exclusivity for any of our current or future product candidates or technology, it could dissuade companies from collaborating with us to develop product candidates, encourage competitors to develop competing products or technologies and threaten our ability to commercialize future product candidates. Any such outcome could harm our business. The patent position of biotechnology and pharmaceutical companies is uncertain, involves complex legal and factual questions, and is characterized by the existence of large numbers of patents and frequent litigation based on allegations of patent or other intellectual property infringement or violation. In addition, the laws of jurisdictions outside 87 Table of Contents the United States may not protect our rights to the same extent as the laws of the United States. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or narrow the scope of our patent protection. 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 in the courts or patent offices in the United States and abroad. Such challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products. Thus, even if our patent applications issue as patents, they may not issue in a form that will provide us with meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. Moreover, patents have a limited lifespan. In the United States, the natural expiration of a patent is generally 20 years after it is filed. Various extensions may be available; however, the life of a patent, and the protection it affords, is limited. Without patent protection for our current or future product candidates, we may be open to competition from generic versions of such products. Given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. Third parties may assert claims against us alleging infringement of their patents and proprietary rights, or we may need to become involved in lawsuits to defend or enforce our patents, either of which could result in substantial costs or loss of productivity, delay or prevent the development and commercialization of our product candidates, prohibit our use of proprietary technology or sale of products or put our patents and other proprietary rights at risk. Our commercial success depends, in part, upon our ability to develop, manufacture, market and sell our product candidates without alleged or actual infringement, misappropriation or other violation of the patents and proprietary rights of third parties. However, our research, development and commercialization activities may be subject to claims that we infringe or otherwise violate patents or other intellectual property rights owned or controlled by third parties. Litigation relating to infringement or misappropriation of patent and other intellectual property rights in the pharmaceutical and biotechnology industries is common, including patent infringement lawsuits, interferences, oppositions and inter partes reviews, and reexamination proceedings before the U.S. Patent and Trademark Office, or USPTO, and corresponding foreign patent offices. In addition, many companies in intellectual property-dependent industries, including the biotechnology and pharmaceutical industries, have employed intellectual property litigation as a means to gain an advantage over their competitors. Numerous U.S., EU and foreign issued patents and pending patent applications, which are owned by third parties, exist in the fields in which we are developing product candidates, and as the biotechnology and pharmaceutical industries expand and more patents are issued, the risk increases that our product candidates may be subject to claims of infringement of the intellectual property rights of third parties. Some claimants may have substantially greater resources than we do and may be able to sustain the costs of complex intellectual property litigation to a greater degree and for longer periods of time than we could. In addition, patent holding companies that focus solely on extracting royalties and settlements by enforcing patent rights may target us. We may be subject to third-party claims including infringement, interference or derivation proceedings, post-grant review and inter partes review before the USPTO or similar adversarial proceedings or litigation in other jurisdictions. Even if such claims are without merit, a court of competent jurisdiction could hold that these third-party patents are valid, enforceable and infringed, and the holders of any such patents may be able to block our ability to commercialize the applicable product candidate unless we obtained a license under the applicable patents, or until such patents expire or are finally determined to be invalid or unenforceable. In addition, third parties may obtain patents in the future and claim that use of our technologies infringes upon these patents, and the holders of any such patents may be able to prohibit our use of those compositions, formulations, methods of treatment, prevention or use or other technologies, effectively blocking our ability to develop and commercialize the applicable product candidate until such patent expires or is finally determined to be invalid or unenforceable or unless we obtained a license. 88 Table of Contents In addition, defending such claims would cause us to incur substantial expenses and, if we are not successful in defending such claims, it could cause us to pay substantial damages if we are found to be infringing a third party’s patent rights. These damages potentially include increased damages (possibly treble damages) and attorneys’ fees if we are found to have infringed such rights willfully. Further, if a patent infringement suit is brought against us or our third-party service providers, our development, manufacturing or sales activities relating to the product or product candidate that is the subject of the suit may be delayed or terminated. As a result of patent infringement claims, or in order to avoid potential infringement claims, we may choose to seek, or be required to seek, a license from the third party, which may require payment of substantial royalties or fees, or require us to grant a cross-license under our intellectual property rights. These licenses may not be available on reasonable terms or at all. Even if a license can be obtained on reasonable terms, the rights may be nonexclusive, which would give our competitors access to the same intellectual property rights. If we are unable to enter into a license on acceptable terms, we could be prevented from commercializing one or more of our product candidates, or forced to modify such product candidates, or to cease some aspect of our business operations, which could harm our business significantly. We might also be forced to redesign or modify our product candidates so that we no longer infringe the third-party intellectual property rights, which may result in significant cost or delay to us, or which redesign or modification could be impossible or technically infeasible. Even if we were ultimately to prevail, any of these events could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business. Competitors may infringe our patents or other intellectual property. If we or one of our licensors were to initiate legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that our patent is invalid or unenforceable. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. Such litigation or proceedings could substantially increase our operating losses and reduce our resources available for development activities. We may not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their substantially greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have an adverse effect on our ability to compete in the marketplace. We may not identify relevant third-party patents or may incorrectly interpret the relevance, scope or expiration of a third-party patent, which might adversely affect our ability to develop, manufacture and market our product candidates. We cannot guarantee that any of our or our licensors’ patent searches or analyses, including but not limited to the identification of relevant patents, analysis of the scope of relevant patent claims or determination of the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending application in the United States, the UK, the EU and elsewhere that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction. For example, in the United States, applications filed before November 29, 2000 and certain applications filed after that date that will not be filed outside the United States remain confidential until patents issue. Patent applications in the United States, the UK, the EU and elsewhere are published approximately 18 months after the earliest filing for which priority is claimed, with such earliest filing date being commonly referred to as the priority date. Therefore, patent applications covering our product candidates could be filed by others without our knowledge. Additionally, pending patent applications that have been published can, subject to certain limitations, be later amended in a manner that could cover our product candidates or the use of our product candidates. After issuance, the scope of patent claims remains subject to construction as determined by an interpretation 89 Table of Contents of the law, the written disclosure in a patent and the patent’s prosecution history. Our interpretation of the relevance or the scope of a patent or a pending application may be incorrect, which may negatively impact our ability to market our product candidates. We may incorrectly determine that our product candidates are not covered by a third-party patent or may incorrectly predict whether a third party’s pending application will issue with claims of relevant scope. Our determination of the expiration date of any patent in the United States, the UK, the EU or elsewhere that we consider relevant may be incorrect, which may negatively impact our ability to develop and market our product candidates. Our failure to identify and correctly interpret relevant patents may negatively impact our ability to develop and market our product candidates. If we fail to correctly identify or interpret relevant patents, we may be subject to infringement claims. We cannot guarantee that we will be able to successfully settle or otherwise resolve such infringement claims. If we fail in any such dispute, in addition to being forced to pay monetary damages, we may be temporarily or permanently prohibited from commercializing our product candidates. We might, if possible, also be forced to redesign our product candidates in a manner that no longer infringes third-party intellectual property rights. Any of these events, even if we were ultimately to prevail, could require us to divert substantial financial and management resources that we would otherwise be able to devote to our business. Changes in patent laws or patent jurisprudence could diminish the value of patents in general, thereby impairing our ability to protect our product candidates. Obtaining and enforcing patents in the biotechnology and genetic medicine industries involve both technological complexity and legal complexity. In addition, the Leahy-Smith America Invents Act, or the AIA, which was passed in September 2011, resulted in significant changes to the U.S. patent system. An important change introduced by the AIA is that, as of March 16, 2013, the United States transitioned from a “first-to-invent” to a “first-to-file” system for deciding which party should be granted a patent when two or more patent applications are filed by different parties claiming the same invention. Under a “first-to-file” system, assuming the other requirements for patentability are met, the first inventor to file a patent application generally will be entitled to a patent on the invention regardless of whether another inventor had made the invention earlier. A third party that files a patent application in the USPTO after that date but before us could therefore be awarded a patent covering an invention of ours even if we made the invention before it was made by the third party. This will require us to be cognizant of the time from invention to filing of a patent application and diligent in filing patent applications, but circumstances could prevent us from promptly filing patent applications on our inventions. In addition, a third party may attempt to use the USPTO procedures to invalidate our patent claims that would not have been invalidated if first challenged by the third party as a defendant in a district court action because of a lower evidentiary standard in USPTO proceedings compared to the evidentiary standard in U.S. federal courts necessary to invalidate a patent claim. An adverse determination in any such proceeding could reduce the scope of, or invalidate, our owned or in-licensed patent rights, allow third parties to commercialize our technology or products and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third-party patent rights. Additionally, the U.S. Supreme Court has ruled on several patent cases in recent years either narrowing the scope of patent protection available in certain circumstances or weakening the rights of patent owners in certain situations, and there are other open questions under patent law that courts have yet to decisively address. In addition to increasing uncertainty with regard to our ability to obtain patents in the future, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on decisions by Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways and could weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future. In addition, the European patent system is relatively stringent in the type of amendments that are allowed during prosecution, but, the 90 Table of Contents complexity and uncertainty of European patent laws has also increased in recent years. Complying with these laws and regulations could limit our ability to obtain new patents that may be important for our business. We enjoy only limited geographical protection with respect to certain patents and we may not be able to protect our intellectual property rights throughout the world. Filing, prosecuting and defending patents covering our product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less extensive than those in the United States. In-licensing patents covering our product candidates in all countries throughout the world may similarly be prohibitively expensive, if such opportunities are available at all. And in- licensing or filing, prosecuting and defending patents even in only those jurisdictions in which we develop or commercialize our product candidates may be prohibitively expensive or impractical. Competitors may use our and our licensors’ technologies in jurisdictions where we have not obtained patent protection or licensed patents to develop their own products and, further, may export otherwise infringing products to territories where we and our licensors have patent protection, but enforcement is not as strong as that in the United States, the UK or the EU. These products may compete with our product candidates, and our or our licensors’ patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. The laws of some jurisdictions do not protect intellectual property rights to the same extent as the laws or regulations in the United States, the UK and the EU, and many companies have encountered significant difficulties in protecting and defending proprietary rights in such jurisdictions. Moreover, the legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets or other forms of intellectual property, which could make it difficult for us to prevent competitors in some jurisdictions from marketing competing products in violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions, whether or not successful, are likely to result in substantial costs and divert our efforts and attention from other aspects of our business, and additionally could put at risk our or our licensors’ patents of being invalidated or interpreted narrowly, could increase the risk of our or our licensors’ patent applications not issuing, or could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, while damages or other remedies may be awarded to the adverse party, which may be commercially significant. If we prevail, damages or other remedies awarded to us, if any, may not be commercially meaningful. Accordingly, our efforts, or the efforts of our licensors or collaborators, to enforce intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. Patent terms may be inadequate to protect our competitive position on our product candidates for an adequate amount of time. The term of any individual patent depends on applicable law in the country where the patent is granted. In the United States, provided all maintenance fees are timely paid, a patent generally has a term of 20 years from its application filing date or earliest claimed non-provisional filing date. Extensions may be available under certain circumstances, but the life of a patent and, correspondingly, the protection it affords is limited. Even if we or our licensors obtain patents covering our product candidates, when the terms of all patents covering a product expire, our business may become subject to competition from competitive medications, including generic medications. Given the amount of time required for the development, testing and regulatory review and approval of new product candidates, patents protecting such candidates may expire before or shortly after such candidates are commercialized. As a result, our owned and licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. 91 Table of Contents If we do not obtain patent term extension in the United States under the Hatch-Waxman Act and in foreign countries under similar legislation, thereby potentially extending the term of marketing exclusivity for our product candidates, our business may be harmed. In the United States, a patent that covers an FDA-approved drug or biologic may be eligible for a term extension designed to restore the period of the patent term that is lost during the premarket regulatory review process conducted by the FDA. Depending upon the timing, duration and conditions of FDA marketing approval of our product candidates, one or more of our U.S. patents may be eligible for limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, which permits a patent term extension of up to five years for a patent covering an approved product as compensation for effective patent term lost during product development and the FDA regulatory review process. In the UK and the EU, our product candidates may be eligible for term extensions based on similar legislation. In each of these jurisdictions, however, we may not receive an extension if we fail to apply within applicable deadlines, fail to apply prior to expiration of relevant patents or otherwise fail to satisfy applicable requirements. Even if we are granted such extension, the duration of such extension may be less than our request. If we are unable to obtain a patent term extension, or if the term of any such extension is less than our request, the period during which we can enforce our patent rights for that product will be essentially shortened and our competitors may obtain approval to market competing products sooner. The resulting reduction in revenue from applicable products could be substantial. Our proprietary rights may not adequately protect our technologies and product candidates, and do not necessarily address all potential threats to our competitive advantage. The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, or permit us to maintain our competitive advantage. The following examples are illustrative: ● others may be able to make products that are the same as or similar to our product candidates but that are not covered by the claims of the patents that we own or have exclusively licensed; ● others, including inventors or developers of our owned or in-licensed patented technologies who may become involved with competitors, may independently develop similar technologies that function as alternatives or replacements for any of our technologies without infringing our intellectual property rights; ● we or our licensors or our other collaboration partners might not have been the first to conceive and reduce to practice the inventions covered by the patents or patent applications that we own, license or will own or license; ● we or our licensors or our other collaboration partners might not have been the first to file patent applications covering certain of the patents or patent applications that we or they own or have obtained a license, or will own or will have obtained a license; ● we or our licensors may fail to meet obligations to the U.S. government with respect to in-licensed patents and patent applications funded by U.S. government grants, leading to the loss of patent rights; ● issued patents that we own or exclusively license may not provide us with any competitive advantage, or may be held invalid or unenforceable, as a result of legal challenges by our competitors; and ● our competitors might conduct research and development activities in countries where we do not have patent rights, or in countries where research and development safe harbor laws exist, and then use the 92 Table of Contents information learned from such activities to develop competitive products for sale in our major commercial markets. Our reliance on third parties may require us to share our trade secrets, which increases the possibility that our trade secrets will be misappropriated or disclosed, and confidentiality agreements with employees and third parties may not adequately prevent disclosure of trade secrets and protect other proprietary information. We consider proprietary trade secrets, confidential know-how and unpatented know-how to be important to our business. We may rely on trade secrets and confidential know-how to protect our technology, especially where patent protection is believed by us to be of limited value. However, trade secrets and confidential know-how are difficult to protect, and we have limited control over the protection of trade secrets and confidential know-how used by our licensors, collaborators and suppliers. Because we have relied in the past on third parties to manufacture our product candidates, because we may continue to do so in the future, and because we expect to collaborate with third parties on the development of our current product candidates and any future product candidates we develop, we may, at times, share trade secrets with them. We also conduct joint research and development programs that may require us to share trade secrets under the terms of our research and development partnerships or similar agreements. Under such circumstances, trade secrets and confidential know-how can be difficult to maintain as confidential. To protect this type of information against disclosure or appropriation by competitors, our policy is to require our employees, consultants, contractors and advisors to enter into confidentiality agreements and, if applicable, material transfer agreements, consulting agreements or other similar agreements with us 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. However, current or former employees, consultants, contractors and advisers may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. We may also be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of their former employers or other third parties. The need to share trade secrets and other confidential information increases the risk that such trade secrets become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements. Given that our competitive 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 an adverse effect on our business and results of operations. Enforcing a claim that a third party obtained illegally and is using trade secrets and/or confidential know-how is expensive, time consuming and unpredictable, and the enforceability of confidentiality agreements may vary from jurisdiction to jurisdiction. Courts outside the United States are sometimes less willing to protect proprietary information, technology and know-how. If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected. If our trademarks and trade names are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected. Our trademark MeiraGTx has been registered in the EU, UK and United States. We may not be able to protect our rights to these trademarks and trade names, which we need to build name recognition among potential partners or customers in our markets of interest. At times, competitors may adopt trade names or trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion. In addition, there could be potential trade name or trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our unregistered trademarks or trade names. Over the long term, if we are unable to successfully register our trademarks and trade names and establish name recognition based on our trademarks and trade names, then we may not be able to compete effectively and our business may be adversely affected. Our efforts to enforce or protect our proprietary rights related to trademarks, trade secrets, domain names, copyrights or other intellectual property may be ineffective and could 93 Table of Contents result in substantial costs and diversion of resources and could adversely impact our financial condition or results of operations. We may need to license or acquire additional intellectual property from third parties, and such intellectual property may not be available or may not be available on commercially reasonable terms. The growth of our business may depend in part on our ability to acquire or in-license additional proprietary rights. For example, our programs may involve product candidates or equipment that may require the use of additional proprietary rights held by third parties. Our product candidates may also require specific formulations to work effectively and efficiently. These formulations may be covered by intellectual property rights held by others. We may develop products containing our compositions and pre-existing pharmaceutical compositions. These pharmaceutical products may be covered by intellectual property rights held by others. We may be required by the FDA, MHRA, EMA or other foreign regulatory authorities to provide a companion diagnostic test or tests with our product candidates. These diagnostic test or tests may be covered by intellectual property rights held by others. We may be unable to acquire or in-license any relevant third-party intellectual property rights that we identify as necessary or important to our business operations. We may fail to obtain any of these licenses at a reasonable cost or on reasonable terms, if at all, which would harm our business. We may need to cease use of the compositions or methods covered by such third-party intellectual property rights, and may need to seek to develop alternative approaches that do not infringe on such intellectual property rights which may entail additional costs and development delays, even if we were able to develop such alternatives, which may not be feasible. Even if we are able to obtain a license under such intellectual property rights, any such license may be non-exclusive, which may allow our competitors access to the same technologies licensed to us. Risks Related to Employee Matters and Managing Growth We may need to expand our organization, and we may experience difficulties in managing this growth, which could disrupt our operations. As of December 31, 2022, we had 358 employees. We expect to continue to expand our organization, including hiring and training employees and managerial personnel to staff our expanding manufacturing and supply chain operations in our new facilities in Ireland. We may have difficulty identifying, hiring and integrating new personnel. Future growth would impose significant additional responsibilities on our management, including the need to identify, recruit, maintain, motivate and integrate additional employees, consultants and contractors. Also, our management may need 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. We may not be able to effectively manage the expansion of our operations, which may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees and reduced productivity among remaining employees. Our expected growth could require significant capital expenditures and may divert financial resources from other projects, such as the development of product candidates. If our management is unable to effectively manage our growth, our expenses may increase more than expected, our ability to generate and/or grow revenues could be reduced, and we may not be able to implement our business strategy. Our future financial performance and our ability to commercialize our product candidates and compete effectively will depend, in part, on our ability to effectively manage any future growth. Our expected growth could require significant capital expenditures and may divert financial resources from other projects, such as the development of additional product candidates. If our management is unable to effectively manage our expected growth, our expenses may increase more than expected, our potential ability to generate revenue could be reduced and we may not be able to implement our business strategy. Many of the biotechnology companies that we compete against for qualified personnel and consultants have greater financial and other resources, different risk profiles and a longer history in the industry than we do. If we are unable to continue to attract and retain high-quality personnel and consultants, the rate and success at which we can discover and develop product candidates and operate our business will be limited. 94 Table of Contents Our future success depends on our ability to retain our key personnel and to attract, retain and motivate qualified personnel. Our industry has experienced a high rate of turnover of management personnel in recent years. We are highly dependent on the development, regulatory, commercialization and business development expertise of Alexandria Forbes, Ph.D., our President and Chief Executive Officer, Rich Giroux, our Chief Operating Officer and Chief Financial Officer and Stuart Naylor, Ph.D., our Chief Development Officer, as well as the other principal members of our management, scientific and clinical teams. Although we have formal employment agreements with certain of our executive officers, these agreements do not prevent them from terminating their employment with us at any time and, for certain of our executive officers, entitle them to receive severance payments in connection with their voluntary resignation of employment. If we lose one or more of our executive officers or key employees, our ability to implement our business strategy successfully could be seriously harmed. Furthermore, replacing executive officers and 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 develop, gain regulatory approval of and commercialize product candidates successfully. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these additional key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development and commercialization strategy. Our consultants and advisors may be engaged by entities other than us and may have commitments under consulting or advisory contracts 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 develop and commercialize product candidates will be limited. Potential product liability lawsuits against us could cause us to incur substantial liabilities and limit commercialization of any products that we may develop. The use of our product candidates in clinical trials and the sale of any products for which we obtain marketing approval exposes us to the risk of product liability claims. Product liability claims might be brought against us by consumers, health care providers, pharmaceutical companies or others selling or otherwise coming into contact with our products. On occasion, large judgments have been awarded in class action lawsuits based on products that had unanticipated adverse effects. If we cannot successfully defend against product liability claims, we could incur substantial liability and costs. In addition, regardless of merit or eventual outcome, product liability claims may result in: ● impairment of our business reputation and significant negative media attention; ● withdrawal of participants from our clinical trials; ● significant time, costs and diversion of management resources to defend the related litigation; ● substantial monetary awards to patients or other claimants; ● inability to commercialize our product candidates; ● product recalls, withdrawals or labeling, marketing or promotional restrictions; ● decreased demand for our product candidates, if approved for commercial sale; and ● loss of revenue. 95 Table of Contents Our insurance policies are expensive and protect us only from some business risks, which leaves us exposed to significant uninsured liabilities. We do not carry insurance for all categories of risk that our business may encounter. Some of the policies we currently maintain include general liability, clinical trial liability, employment practices liability, property, auto, workers’ compensation, umbrella, cyber and directors’ and officers’ insurance. Any additional product liability insurance coverage we acquire in the future, may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive and restrictive, and in the future we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. If we obtain marketing approval for our product candidates, we intend to acquire insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. A successful product liability claim or series of claims brought against us could cause our share price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business, including preventing or limiting the commercialization of any product candidates we develop. We do not carry specific biological or hazardous waste insurance coverage, and our property, casualty and general liability insurance policies specifically exclude coverage for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended. Operating as a public company may make it more difficult and more expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. As a result, it may be more difficult for us to attract and retain qualified people to serve on our board of directors, our board committees or as executive officers. If we are unable to maintain existing insurance with adequate levels of coverage, any significant uninsured liability may require us to pay substantial amounts, which would adversely affect our cash position and results of operations. Our employees and independent contractors, including consultants, vendors, and any third parties we may engage in connection with development and commercialization may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could harm our business. Misconduct by our employees and independent contractors, including consultants, vendors, and any third parties we may engage in connection with development and commercialization, could include intentional, reckless or negligent conduct or unauthorized activities that violate: (i) applicable laws and regulations of the FDA, MHRA, EMA and other regulatory or governmental authorities, including those laws that require the reporting of true, complete and accurate information to such authorities; (ii) manufacturing standards; (iii) data privacy, security, fraud and abuse and other healthcare laws and regulations; or (iv) laws that require the reporting of true, complete and accurate financial information and data. Specifically, sales, marketing and business arrangements in the healthcare industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Activities subject to these laws could also involve the improper use or misrepresentation of information obtained in the course of clinical trials, creation of fraudulent data in preclinical studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other 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 comply with such laws or regulations. Additionally, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business and results of operations, including the imposition of significant civil, criminal and administrative penalties, damages, monetary fines, disgorgements, possible exclusion from participation in Medicare, Medicaid, other U.S. federal healthcare programs or healthcare programs in other jurisdictions, integrity oversight and 96 Table of Contents reporting obligations to resolve allegations of non-compliance, individual imprisonment, other sanctions, contractual damages, reputational harm, diminished profits and future earnings, and curtailment of our operations. Our business and operations may suffer in the event of system failures and our systems and those of our business partners and service providers may be vulnerable to cybersecurity risks. Our information technology systems, including manufacturing systems, as well as those of our business partners and service providers, are vulnerable to damage from computer viruses, unauthorized access, hardware and software failures, natural disasters, terrorism, war and telecommunication and electrical failures. If such an event were to occur, it could result in a material disruption of our product candidate development programs or manufacturing operations. For example, the loss of preclinical study or clinical trial data from completed, ongoing or planned trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. A significant interruption to our manufacturing operations could delay the completion of clinical trials and increase the costs of those trials. To the extent that any disruption or security breach were to result in a loss of or damage to our data or applications, or inappropriate disclosure of personal, confidential or proprietary information, we could incur liability and the further development of our product candidates could be delayed. In the ordinary course of our business, we, our business partners and our service providers collect, process and store sensitive data, including intellectual property, clinical trial data, proprietary business information, personal data and personally identifiable information of our clinical trial subjects and employees. The secure processing, maintenance and transmission of this information is critical to our operations. Increased cybersecurity threats pose a risk to this information, in addition to our and our business partners’ and service providers’ systems and networks. Attacks upon information technology systems are increasing in their frequency, levels of persistence, sophistication and intensity, and are being conducted by sophisticated and organized groups, governments and individuals with a wide range of motives and expertise. We may also face increased cybersecurity risks due to our reliance on internet technology and the number of our employees who are working remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities. Furthermore, because the techniques used to obtain unauthorized access to, or to sabotage, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures. We may also experience security breaches that may remain undetected for an extended period. Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using tools and techniques that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence. Despite our security measures, our information technology and infrastructure may be vulnerable to cyber-attacks by hackers or internal bad actors, or breached due to employee error, a technical vulnerability, malfeasance or other disruptions that could have a negative impact, including loss or destruction of data (including confidential or critical business information). Although, to our knowledge, we have not experienced any such material security breach to date, we may experience cybersecurity incidents such as malware infections, ransomware, phishing attempts, thefts of personal, confidential, proprietary or other critical business information and other attempts at compromising our information technology that are typical for a company of our size in our market. Any security breach could compromise our networks and the information stored there could be accessed, publicly disclosed, lost or stolen. Any such access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the privacy of personal information, significant regulatory penalties, and such an event could disrupt our operations, damage our reputation, result in significant expenses in implementing future security measures and cause a loss of confidence in us and our ability to conduct clinical trials, which could adversely affect our reputation and financial results, and delay clinical development of our product candidates. 97 Table of Contents The UK’s withdrawal from the EU has resulted in changes to regulatory requirements and has had and may continue to have a negative effect on global economic conditions, financial markets and our business, which could reduce the price of our shares. Following a national referendum and enactment of legislation by the government of the UK, the UK formally withdrew from the EU on January 31, 2020, commonly referred to as “Brexit”. Since the end of the Brexit transition period on January 1, 2021, Great Britain (England, Scotland and Wales) has not been directly subject to EU laws, however under the terms of the Protocol on Ireland and Northern Ireland, EU laws have generally applied to Northern Ireland. On February 27, 2023, the UK Government and the European Commission reached a political agreement on the “Windsor Agreement” which may revise the Protocol on Ireland and Northern Ireland in order to address some of the perceived shortcomings in its operation. Under the proposed changes, Northern Ireland would be reintegrated under the regulatory authority of the MHRA with respect to medicinal products. These proposed changes need to be codified and agreed by the respective parliaments of the UK and EU before taking effect. There could be additional uncertainty and risk around what these changes will mean to our business. More generally, it is currently unclear to what extent the UK Government will seek to align its regulations with the EU. The EU laws that have been transposed into UK law through secondary legislation remain applicable in Great Britain. However, under the Retained EU Law (Revocation and Reform) Bill 2022, which is currently before the UK parliament, any retained EU law not expressly preserved and “assimilated” into domestic law or extended by ministerial regulations (to no later than June 23, 2026) will automatically expire and be revoked by December 31, 2023. In addition, new legislation such as the CTR is not applicable in Great Britain. Whilst the EU-UK Trade and Cooperation Agreement, or TCA, includes the mutual recognition of Good Manufacturing Practice, or GMP inspections of manufacturing facilities for medicinal products and GMP documents issued, it does not contain wholesale mutual recognition of UK and EU pharmaceutical regulations and product standards. There may be divergent local requirements in Great Britain from the EU in the future, which may impact clinical and development activities that occur in the UK in the future. Similarly, clinical trial submissions in the UK will not be able to be bundled with those of EU member states within the EMA Clinical Trial Information System, or CTIS, adding further complexity, cost and potential risk to future clinical and development activity in the UK. Significant political and economic uncertainty remains about how much the relationship between the UK and EU will differ as a result of the UK’s withdrawal. These developments, or the perception that any related developments could occur, have had and may continue to have a material adverse effect on global economic conditions and the stability of global financial markets, and may significantly reduce global market liquidity and restrict the ability of key market participants to operate in certain financial markets. Any of these factors could depress economic activity and restrict our access to capital, which could have a material adverse effect on our business, financial condition and results of operations and reduce the price of our ordinary shares. Companies established in Great Britain cannot use the centralized procedure and instead must follow one of the UK national authorization procedures or one of the remaining post-Brexit international cooperation procedures (such as the Access Consortium) to obtain an MA to market products in Great Britain. The MHRA may rely on a decision taken by the European Commission on the approval of a new (centralized procedure) MA when determining an application for a Great Britain MA; or use the MHRA’s decentralized or mutual recognition procedures which enable MAs approved in EU member states (or Iceland, Liechtenstein, Norway) to be granted in Great Britain. Additionally, the ‘Unfettered Access Procedure’ enables an MA holder in Northern Ireland to seek recognition in Great Britain. The full impact of these new arrangements and requirements, both on our existing processes and our ability to adjust our business and operations to operate successfully in the UK and EU, as well as more broadly on UK-EU cross- border trade and the economy, are expected to become clearer in the coming years. In particular, it remains to be seen whether the initial implementation of, and adjustment of UK-EU trading processes for, the TCA could disrupt or otherwise negatively impact our business and operations. These negative impacts could include amongst others a decrease in foreign direct investment in the UK, an increase of our costs, disruption of our supply chains, restrictions on 98 Table of Contents our ability to access capital and depression on economic activity or economic instability, which could in turn lead to a reduction in asset valuations, currency exchange rates and credit ratings. In addition, the TCA has imposed additional restrictions on the free movement of people between the UK and the EU, which could have a material adverse effect on us, since we compete in these jurisdictions for well qualified employees in all aspects of our business. Any impact on our ability to attract new employees and to retain existing employees in their current jurisdictions could decrease our competitiveness. Any of these factors could have an adverse effect on our business, financial condition, results of operations, and prospects. Risks Related to Our Ordinary Shares The market price of our ordinary shares may be volatile and fluctuate substantially, which could result in substantial losses for purchasers of our ordinary shares. Our share price is likely to be volatile. The stock market in general and the market for smaller biopharmaceutical companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, you may not be able to sell your ordinary shares at or above your purchase price. The market price for our ordinary shares may be influenced by many factors, including: ● the success of competitive products or technologies; ● actual or expected changes in our growth rate relative to our competitors; ● results of clinical trials of our product candidates or those of our competitors; ● developments related to our existing or any future collaborations; ● regulatory or legal developments in the United States and other countries; ● development of new product candidates that may address our markets and make our product candidates less attractive; ● changes in physician, hospital or healthcare provider practices that may make our product candidates less useful; ● announcements by us, our partners or our competitors of significant acquisitions, strategic partnerships, joint ventures, collaborations or capital commitments; ● 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 any of our product candidates or clinical development programs; ● failure to meet or exceed financial estimates and projections of the investment community or that we provide to the public; ● the results of our efforts to discover, develop, acquire or in-license additional product candidates or products; 99 Table of Contents ● actual or expected changes in estimates as to financial results, development timelines, recommendations by securities analysts or shifting investor perceptions; ● 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; ● changes in accounting principles; and ● the other factors described in this “Item 1A. Risk Factors” section and elsewhere in this Form 10-K. In addition, the stock market in general, and Nasdaq and biopharmaceutical companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. In the past, when the market price of a security has been volatile, holders of that security have sometimes instituted securities class action litigation against the issuer. This risk is especially relevant for us because biopharmaceutical companies have experienced significant stock price volatility in recent years and during the COVID-19 pandemic. If any of the holders of our ordinary shares were to bring such a lawsuit against us, we could incur substantial costs defending the lawsuit and the attention of our senior management would be diverted from the operation of our business. Any adverse determination in litigation could also subject us to significant liabilities. Broad market and industry factors may negatively affect the market price of our ordinary shares, as well as general economic, political and market conditions such as recessions, interest rate changes or international currency fluctuations, regardless of our actual operating performance. Further, a decline in the financial markets and related factors beyond our control may cause the price of our ordinary shares to decline rapidly and unexpectedly. If the market price of our ordinary shares does not exceed your purchase price, you may not realize any return on your investment in us and may lose some or all of your investment. Our executive officers, directors and principal shareholders, if they choose to act together, have the ability to significantly influence all matters submitted to shareholders for approval. As of December 31, 2022, our executive officers, directors and shareholders who owned more than 5% of our outstanding ordinary shares and their respective affiliates, in the aggregate, hold ordinary shares representing approximately 40.0% of our outstanding ordinary shares. In addition, in connection with entering into the Financing Agreement, we issued to an affiliate of Perceptive Advisors, LLC, our largest shareholder that employs a director serving on our board, warrants to purchase an aggregate of 700,000 of our ordinary shares. As a result, if these shareholders choose to act together, they would be able to significantly influence all matters submitted to our shareholders for approval, as well as our management and affairs. For example, these persons, if they choose to act together, would significantly influence the election of directors, the composition of our management and approval of any merger, consolidation, sale of all or substantially all of our assets or other business combination that other shareholders may desire. Any of these actions could adversely affect the market price of our ordinary shares. We are an “emerging growth company” and a “smaller reporting company,” and the reduced disclosure requirements applicable to emerging growth companies and smaller reporting companies may make our ordinary shares less attractive to investors. We are an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act of 2012 (“JOBS Act”), and may remain an emerging growth company until the last day of the fiscal year December 31, 2023, which represents the fifth year anniversary of our IPO. However, if certain events occur prior to the end of such five-year period, 100 Table of Contents including if we become a “large accelerated filer,” our annual gross revenues exceed $1.07 billion or we issue more than $1.0 billion of non-convertible debt in any three-year period, we will cease to be an emerging growth company prior to the end of such five-year period. For so long as we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies that are not emerging growth companies. These exemptions include: ● reduced disclosure obligations relating to the presentation of financial statements in the “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure in our periodic reports filed with the SEC; ● not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting; ● not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements; ● reduced disclosure obligations regarding executive compensation; and ● exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not previously approved. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies. We have elected to take advantage of this extended transition period. We are also a smaller reporting company, and we will remain a smaller reporting company until the fiscal year following the determination that our voting and non-voting ordinary shares held by non-affiliates is more than $250 million measured on the last business day of our second fiscal quarter, or our annual revenues are more than $100 million during the most recently completed fiscal year and our voting and non-voting ordinary shares held by non-affiliates is more than $700 million measured on the last business day of our second fiscal quarter. Similar to emerging growth companies, smaller reporting companies are able to provide simplified executive compensation disclosure, are exempt from the auditor attestation requirements of Section 404, and have certain other reduced disclosure obligations, including, among other things, not being required to provide selected financial data, supplemental financial information or risk factors. We may choose to take advantage of some, but not all, of the available exemptions for emerging growth companies and smaller reporting companies. We cannot predict whether investors will find our ordinary shares less attractive if we rely on these exemptions. If some investors find our ordinary shares less attractive as a result, there may be a less active trading market for our ordinary shares and our share price may be more volatile. Anti-takeover provisions in our organizational documents and Cayman Islands law may discourage or prevent a change of control, even if an acquisition would be beneficial to our shareholders, which could depress the price of our ordinary shares and prevent attempts by our shareholders to replace or remove our current management. Our memorandum and articles of association contain provisions that may discourage unsolicited takeover proposals that shareholders may consider to be in their best interests. Our board of directors is divided into three classes with staggered, three-year terms. Our board of directors has the ability to designate the terms of and issue preferred shares without shareholder approval. We are also subject to certain provisions under Cayman Islands law that could delay or prevent a change of control. Together these provisions may make more difficult the removal of management and may 101 Table of Contents discourage transactions that otherwise could involve payment of a premium over prevailing market prices for our ordinary shares. There may be difficulties in enforcing foreign judgments against our management or us. Certain of our directors and management reside outside the United States. A significant portion of our assets and such persons’ assets are located outside the United States. As a result, it may be difficult or impossible for investors to effect service of process upon us within the United States or other jurisdictions, including judgments predicated upon the civil liability provisions of the federal securities laws of the United States. In particular, investors should be aware that there is uncertainty as to whether the courts of the Cayman Islands or any other applicable jurisdictions would recognize and enforce judgments of U.S. courts obtained against us or our directors or management predicated upon the civil liability provisions of the securities laws of the United States or any state in the United States or entertain original actions brought in the Cayman Islands or any other applicable jurisdiction’s courts against us or our directors or officers predicated upon the securities laws of the United States or any state in the United States. The rights of our shareholders differ from the rights typically offered to shareholders of a U.S. corporation. Our corporate affairs and the rights of holders of ordinary shares are governed by Cayman Islands law, including the provisions of the Cayman Islands Companies Act (as amended), or the Companies Act, the common law of the Cayman Islands and by our memorandum and articles of association. We are also subject to the federal securities laws of the United States. The rights of shareholders to take action against the directors, actions by minority shareholders and the fiduciary responsibilities of our directors to us under Cayman Islands law are to a large extent governed by the common law of the Cayman Islands. The common law of the Cayman Islands is derived in part from comparatively limited judicial precedent in the Cayman Islands as well as from English common law, the decisions of whose courts are of persuasive authority, but are not binding on a court in the Cayman Islands. The rights of our shareholders and the fiduciary responsibilities of our directors under Cayman Islands law are different from what they would be under statutes or judicial precedent in some jurisdictions in the United States. In particular, the Cayman Islands has a different body of securities laws as compared to the United States, and certain states, such as Delaware, may have more fully developed and judicially interpreted bodies of corporate law. In addition, Cayman Islands companies may not have standing to initiate a shareholders derivative action in a Federal court of the United States. As a result of all of the above, public shareholders may have more difficulty in protecting their interests in the face of actions taken by management, members of the board of directors or controlling shareholders than they would as public shareholders of a United States company. We expect to be treated as resident in the UK for tax purposes, but may be treated as a dual resident company for UK tax purposes. Our board of directors conducts our affairs so that the central management and control of the company is exercised in the UK. As a result, we expect to be treated as resident in the UK for UK tax purposes. Accordingly, we expect to be subject to UK taxation on our income and gains, except where an exemption applies. However, we may be treated as a dual resident company for UK tax purposes. As a result, our right to claim certain reliefs from UK tax may be restricted, and changes in law or practice in the UK could result in the imposition of further restrictions on our right to claim UK tax reliefs. 102 Table of Contents We may be classified as a passive foreign investment company, or PFIC, for U.S. federal income tax purposes, which could result in adverse U.S. federal income tax consequences to U.S. investors in our ordinary shares. Based on the current and anticipated value of our assets, including goodwill, and the current and anticipated composition of our income, assets and operations, we do not believe we were a PFIC for the taxable year ended on December 31, 2022, and do not expect to be a PFIC for the current taxable year. However, the application of the PFIC rules is subject to uncertainty in several respects, and we cannot assure you that the U.S. Internal Revenue Service, or the IRS, will not take a contrary position. Furthermore, a separate determination must be made after the close of each taxable year as to whether we are a PFIC for that year. Accordingly, we cannot assure you that we were not a PFIC for our taxable year ended on December 31, 2022 or that we will not be a PFIC for our current taxable year or any future taxable year. A non-U.S. company will be considered a PFIC for any taxable year if (i) at least 75% of its gross income is passive income (including interest income), or (ii) at least 50% of the value of its assets (based on an average of the quarterly values of the assets during a taxable year) is attributable to assets that produce or are held for the production of passive income. The value of our assets generally is determined by reference to the market price of our ordinary shares, which may fluctuate considerably. In addition, the composition of our income and assets is affected by how, and how quickly, we spend any cash we raise. If we were to be classified as a PFIC for any taxable year during which a U.S. holder holds our ordinary shares, certain materially adverse U.S. federal income tax consequences could apply to such U.S. holder. If a United States person is treated as owning at least 10% of our ordinary shares, such holder may be subject to adverse U.S. federal income tax consequences. If a U.S. holder of our ordinary shares is treated as owning (directly, indirectly or constructively) at least 10% of the value or voting power of our ordinary shares, such U.S. holder may be treated as a “United States shareholder” with respect to each “controlled foreign corporation” in our group (if any). If our group includes one or more U.S. subsidiaries, certain of our non-U.S. subsidiaries could be treated as controlled foreign corporations (regardless of whether we are treated as a controlled foreign corporation). A United States shareholder of a controlled foreign corporation may be required to report annually and include in its U.S. taxable income its pro rata share of “Subpart F income,” “global intangible low-taxed income” and investments in U.S. property by controlled foreign corporations, regardless of whether we make any distributions. An individual that is a United States shareholder with respect to a controlled foreign corporation generally would not be allowed certain tax deductions or foreign tax credits that would be allowed to a United States shareholder that is a U.S. corporation. Failure to comply with these reporting obligations may subject you to significant monetary penalties and may prevent the statute of limitations from starting with respect to your U.S. federal income tax return for the year for which reporting was due. We cannot provide any assurances that we will assist investors in determining whether any of our non-U.S. subsidiaries is treated as a controlled foreign corporation or whether such investor is treated as a United States shareholder with respect to any of such controlled foreign corporations. Further, we cannot provide any assurances that we will furnish to any United States shareholders information that may be necessary to comply with the aforementioned reporting and tax payment obligations. U.S. holders of our ordinary shares should consult their tax advisors regarding the potential application of these rules to their investment in our ordinary shares. Changes in tax laws or challenges to our tax position could adversely affect our results of operations and financial condition. We are subject to complex tax laws that are subject to change or differing interpretations, including on a retroactive basis. Any such changes in tax laws, regulations and treaties, or the interpretation thereof, tax policy initiatives and reforms under consideration and the practices of tax authorities in jurisdictions in which we operate could adversely affect our tax position, including our effective tax rate or tax payments. 103 Table of Contents We have significant U.S. federal and state net operating losses, or NOLs, and UK carryforward tax losses which we may not be able to realize or which may be restricted under applicable law. We also benefit from certain tax incentive regimes, such as research and development tax credits. Any adverse change to these regimes, the application thereof or challenges to the tax position we have adopted under these rules could adversely affect our results of operations and financial condition. As of December 31, 2022, we had federal and state NOL carryforwards in the United States of $63.8 million and $64.4 million, respectively, and cumulative carryforward tax losses in the UK of $187.9 million, which we expect to be available to reduce future taxable income subject to any relevant restrictions (including those in the U.S. and UK that limit the percentage of taxable income that can be reduced by NOLs and carried forward losses). The U.S. federal and state NOLs incurred prior to January 1, 2018 in the amount of approximately $1.0 million and $0.8 million, respectively, will begin to expire in 2036. U.S. federal NOLs generated after December 31, 2017 are not subject to expiration but such NOLs may only offset 80% of taxable income for taxable years beginning after December 31, 2020. As of December 31, 2022, we also had orphan drug and research and development credits in the U.S. in the amount of $9.4 million and research and development credits in the UK of $2.4 million. The UK carryforward tax losses will continue indefinitely, subject to relevant restrictions, under current UK legislation. The NOLs and carryforward tax losses are subject to review and possible adjustment by the applicable tax authorities. Additionally, NOLs and UK carryforward tax losses, and research and development tax credits, may become subject to limitations in the event of certain cumulative changes in the ownership interest of significant shareholders, as determined under Sections 382 of the United States Internal Revenue Code, as well as the Corporation Tax Act 2010 Part 14 under the UK tax rules. This could limit the amount of NOLs or carryforward tax losses that we can utilize annually to offset future taxable income or tax liabilities. We have conducted a review of changes in the ownership interest of significant shareholders and determined that as of December 31, 2021, there were no limitations in the UK. However, for U.S. federal tax purposes, we have determined that ownership changes occurred in August 2016 and June 2018. We are still in the process of determining the annual limitation on NOLs as a result of such ownership changes. Subsequent ownership changes and changes to the U.S. federal or state or UK tax rules in respect of the utilization of NOLs and carryforward tax losses may further affect the limitation in future years. General Risk Factors We may engage in acquisitions that could disrupt our business, cause dilution to our shareholders or reduce our financial resources. We have, and may in the future, enter into transactions to acquire other businesses, products or technologies. If we do identify suitable candidates, we may not be able to make such acquisitions on favorable terms, or at all. Any acquisitions we make may not strengthen our competitive position, and these transactions may be viewed negatively by customers or investors. We may decide to incur debt in connection with an acquisition or issue our ordinary shares or other equity securities to the shareholders of the acquired company, which would reduce the percentage ownership of our existing shareholders. We could incur losses resulting from undiscovered liabilities of the acquired business that are not covered by the indemnification we may obtain from the seller. In addition, we may not be able to successfully integrate the acquired personnel, technologies and operations into our existing business in an effective, timely and nondisruptive manner. Acquisitions may also divert management attention from day-to-day responsibilities, increase our expenses and reduce our cash available for operations and other uses. We cannot predict the number, timing or size of future acquisitions or the effect that any such transactions might have on our operating results. Exchange rate fluctuations may adversely affect our results of operations and financial condition. Owing to the international scope of our operations, fluctuations in exchange rates may adversely affect us, particularly between the U.S. dollar on the one hand, and the pound sterling and euro on the other hand. As a result, our business and the market price of our securities may be affected by such fluctuations, which may have a significant impact 104 Table of Contents on our results of operations and cash flows from period to period. Currently, we do not have any exchange rate hedging arrangements in place. Our management team has broad discretion as to the use of the net proceeds from public and private equity or debt financings and the investment of these proceeds may not yield a favorable return. We may invest the proceeds in ways with which our shareholders disagree. We have broad discretion in the application of any net proceeds we have received in the past or may receive in the future pursuant to existing or future equity and debt financings. Shareholders may not agree with our decisions, and our use of the proceeds and our existing cash and cash equivalents may not improve our results of operation or enhance the value of our ordinary shares. Our ability to apply certain proceeds may be restricted. For example, the proceeds provided under our Note Purchase Agreement may be used for working capital and general corporate purposes. Our failure to apply any such funds effectively could have a material adverse effect on our business, delay the development of our product candidates and cause the market price of our ordinary shares to decline. In addition, until the net proceeds are used, they may be placed in investments that do not produce significant income or that may lose value. Additionally, our existing cash and cash equivalents are subject to general credit, liquidity, market and interest rate risks, which have been and may, in the future, be exacerbated by a U.S. and/or global financial crises. We may realize losses in the fair value of certain of our investments or a complete loss of these investments if the credit markets tighten, which would have an adverse effect on our results of operations, liquidity and financial condition. We incur substantial costs as a result of operating as a public company, and our management is required to devote substantial time to new compliance initiatives and corporate governance practices. As a public company, and particularly if we no longer qualify as an emerging growth company and smaller reporting company in the future, we incur and will continue to incur significant legal, accounting and other expenses that we did not incur as a private company. The Sarbanes-Oxley Act of 2002, the Dodd-Frank Wall Street Reform and Consumer Protection Act, The Nasdaq Global Select listing requirements 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 need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations increase our legal and financial compliance costs. Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish a report by our management on our internal control over financial reporting. However, while we remain an emerging growth company, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404, we engage in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, potentially engage outside consultants, adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing whether such 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, or our independent registered public accounting firm if we no longer qualify as an emerging growth company, will not be able to conclude that our internal control over financial reporting is effective as required by Section 404. In addition, any testing by us conducted in connection with Section 404, or any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls 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. If we identify one or more material weaknesses or determine we have inadequate internal controls, it could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements. 105 Table of Contents If securities or industry analysts cease to publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our ordinary shares, our share price and trading volume could decline. The trading market for our ordinary shares relies in part on the research and reports that industry or securities analysts publish about us or our business. We do not control these analysts. Furthermore, if any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our share performance, or if any of our preclinical studies or clinical trials and operating results fail to meet the expectations of analysts, our share price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our share price or trading volume to decline. Expectations relating to environmental, social and governance factors may impose additional costs and expose us to new risks. There is an increasing focus from the SEC, stock exchanges, certain investors and other stakeholders concerning corporate responsibility, specifically related to environmental, social and governance factors. The SEC is considering and in some cases has proposed rules regarding new disclosure requirements relating to environmental, social and governance factors, and the SEC approved in 2021 new Nasdaq listing and disclosure requirements relating to board diversity that are applicable to us. Some investors may use these factors to guide their investment strategies and, in some cases, may choose not to invest in us if they believe our policies and disclosures relating to corporate responsibility are inadequate. Third-party providers of corporate responsibility ratings and reports on companies have varied and in some cases inconsistent standards. In addition, the criteria by which companies’ corporate responsibility practices are assessed are evolving, which could result in greater expectations of us and cause us to undertake costly initiatives to satisfy such new criteria. Alternatively, if we elect not to or are unable to satisfy such new criteria or do not meet the criteria of a specific third-party provider, some investors may conclude that our policies with respect to corporate responsibility are insufficient. We may face reputational damage in the event that our corporate responsibility procedures or standards do not meet the standards set by various constituencies. Furthermore, if our competitors’ corporate responsibility performance is perceived to be greater than ours, potential or current investors may elect to invest with our competitors instead. In addition, in the event that we communicate or disclose certain initiatives and goals regarding environmental, social and governance matters, we could fail, or be perceived to fail, in our achievement of such initiatives or goals, or we could be criticized for the scope of such initiatives or goals or be subject to litigation for such failures. If we fail to satisfy the expectations of investors and other stakeholders or our initiatives are not executed as planned, our reputation and financial results could be adversely affected. Because we do not anticipate paying any cash dividends on our ordinary shares in the foreseeable future, capital appreciation, if any, would be your sole source of gain. Under Cayman Islands law, we may only make distributions by way of dividend out of profits, or out of our share premium account (provided that immediately following the date that the dividend is proposed to be paid we are able to pay our debts as they fall due in the ordinary course of business). We have never declared or paid any cash dividends on our ordinary shares. We currently anticipate that we will retain future earnings for the development, operation and expansion of our business and do not anticipate declaring or paying any cash dividends for the foreseeable future. In addition, the Note Purchase Agreement prohibits us from paying dividends during its term and the terms of existing and future financing agreements may also preclude us from paying dividends. As a result, capital appreciation, if any, of our ordinary shares would be your sole source of gain on an investment in our ordinary shares for the foreseeable future. See the “Dividend Policy” section of this Form 10-K for the year ended December 31, 2022 for additional information. ITEM 1B. UNRESOLVED STAFF COMMENTS Not applicable. 106 Table of Contents ITEM 2. PROPERTIES Our principal office is located at 450 East 29th Street, New York, New York, USA, where we lease 22,721 square feet of office and laboratory space. We lease this office space under a lease that terminates on October 31, 2026. We also own a long leasehold interest in the ground rights where our 29,000 square foot manufacturing facility is located, at 92 Britannia Walk, London, United Kingdom. The long leasehold interest expires in 2126, and there is no facility rent due. Additionally, we lease an 11,306 square foot office facility located at 34-38 Provost Street, London, United Kingdom and 6,679 square feet of laboratory facilities at 15 Ebenezer Street, London, United Kingdom. The office space lease terminates on September 8, 2029 and the laboratory leases terminate on May 24, 2027. We also lease 10,126 square feet of office, laboratory and storage facilities at Paalbergweg 2-4, Amsterdam, Netherlands. The lease terminates on March 30, 2031. In January 2021, we completed the acquisition of the buildings for our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility located in Buildings 2 and 3, Block K, Airport Avenue, Shannon Free Zone, Shannon, Ireland. The campus encompasses an aggregate of 150,000 square feet. We also entered into a lease for each property providing for a long leasehold interest that expires in 2211. ITEM 3. LEGAL PROCEEDINGS We are not subject to any material legal proceedings. ITEM 4. MINE SAFETY DISCLOSURES Not applicable. 107 Table of Contents PART II ITEM 5. AND ISSUER PURCHASES OF EQUITY SECURITIES MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS Market Information Our ordinary shares trade on the Nasdaq Global Select Market under the symbol “MGTX.” Holders of Record As of March 8, 2023, there were 55 holders of record. The actual number of shareholders of our ordinary shares is greater than this number of record holders and includes shareholders who are beneficial owners but whose ordinary shares are held in street name by brokers and other nominees. This number of holders of record also does not include shareholders whose ordinary shares may be held in trust by other entities. Dividend Policy We have never declared or paid any cash dividends on our ordinary shares. We intend to retain future earnings, if any, to finance the operation and expansion of our business and do not anticipate paying any cash dividends in the foreseeable future. In addition, the Note Purchase Agreement prohibits us from paying dividends during its term and the terms of existing and future financing agreements may also preclude us from paying dividends. However, if we do pay a cash dividend on our ordinary shares in the future, we will only pay such dividend out of our profits or share premium (subject to solvency requirements) as permitted under Cayman Islands law. Recent Sales of Unregistered Securities On November 9, 2022, we entered into a securities purchase agreement with Johnson and Johnson Innovation – JJDC, Inc., the investment arm of Johnson and Johnson (“JJDC”), pursuant to which we, in a private placement, agreed to issue and sell to JJDC an aggregate of 3,742,514 ordinary shares at a purchase price of $6.68 per share for gross proceeds of approximately $25.0 million. The ordinary shares were issued in reliance on the exemption from registration provided by Section 4(a)(2) of the Securities Act of 1933, as amended. ITEM 6. RESERVED ITEM 7. RESULTS OF OPERATIONS MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND You should read the following discussion and analysis of financial condition and operating results together with our financial statements and the related notes appearing in this Form 10-K. Some of the information contained in this discussion and analysis or set forth elsewhere in this Form 10-K, including information with respect to our plans and strategy for our business and related financing, includes forward-looking statements that involve risks and uncertainties. As a result of many important factors, including those set forth in the section of this Form 10-K captioned “Item 1A. Risk Factors” and elsewhere in this 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. For convenience of presentation some of the numbers have been rounded in the text below. 108 Table of Contents Overview We are a vertically integrated, clinical stage gene therapy company with six programs in clinical development and a broad pipeline of preclinical and research programs. We have core capabilities in viral vector design and optimization and gene therapy manufacturing, as well as a potentially transformative gene regulation platform technology that allows precise, dose responsive control of gene expression by oral small molecules with dynamic range that can exceed 5000-fold. Led by an experienced management team, we have taken a portfolio approach by licensing, acquiring and developing technologies that give us depth across both product candidates and indications. Our initial focus is on three distinct areas of unmet medical need: ocular diseases, including both inherited retinal diseases as well as large degenerative ocular diseases, neurodegenerative diseases, and severe forms of xerostomia. Though initially focusing on the eye, central nervous system and salivary gland, we intend to expand our focus in the future to develop additional gene therapy treatments for patients suffering from a range of serious diseases. We are an exempted company incorporated under the laws of the Cayman Islands in 2018, and prior to that, we commenced operations as MeiraGTx Limited, a private limited company incorporated under the laws of England and Wales in 2015. Our discussion of our financial condition and results of operations is based upon our financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States (“GAAP”). Since our formation, we have devoted substantially all of our resources to developing our technology platform, establishing our viral vector manufacturing facilities and our cGMP plasmid and DNA production facility and developing manufacturing processes, advancing the product candidates in our ophthalmology, salivary gland and neurodegenerative disease programs, building our intellectual property portfolio, organizing and staffing our company, developing our business plan, raising capital, and providing general and administrative support for these operations. To date, we have financed our operations primarily with cash on hand and proceeds from the sales of our Series A ordinary shares, Convertible Preferred C Shares and ordinary shares. Through December 31, 2022, we received gross proceeds of approximately $471.0 million from sales of our ordinary shares, Series A ordinary shares and convertible preferred C shares, gross proceeds of approximately $75.0 million from issuance of debt and $130.0 million from the collaboration, option and license agreement with Janssen Pharmaceuticals, Inc. (“Janssen”), one of the Janssen Pharmaceuticals Companies of Johnson & Johnson (the “Collaboration Agreement”). As of December 31, 2022, we had cash and cash equivalents of $115.5 million, as well as $21.3 million we expect to receive from Janssen in the first quarter of 2023 in connection with the Collaboration Agreement. We are a clinical stage company and have not generated any product revenues to date. We have six clinical programs and a pipeline of preclinical programs. Since inception, we have incurred significant operating losses. Our net losses for the years ended December 31, 2022 and 2021 were $129.6 million and $79.6 million, respectively. As of December 31, 2022, we had an accumulated deficit of $470.2 million. We do not expect to generate revenue from sales of products for several years, if at all. Under the Collaboration Agreement, we received an upfront payment in the amount of $100.0 million in March 2019 and a milestone payment in the amount of $30.0 million in December 2021. Additionally, pursuant to the Collaboration Agreement, we are eligible to receive research and development funding and additional potential milestone payments and royalties. Our total operating expenses were $132.3 million and $110.5 million for the years ended December 31, 2022 and 2021, respectively. While we expect our operating expenses to continue to increase in connection with our ongoing development activities related to our product candidates, including the ongoing Phase 3 Lumeos clinical trial of botaretigene sparoparvovec for the treatment of patients with XLRP, we believe that certain of these increases will be partially offset by the research funding in connection with the Collaboration Agreement. In addition, we expect to continue incurring increasing costs associated with our clinical activities for AAV-hAQP1 for the treatment of radiation-induced xerostomia and xerostomia associated with Sjogren’s syndrome, as well as for AAV-GAD for the treatment of Parkinson’s disease. We also incurred expenses during the year ended December 31, 2022 and expect to continue to incur expenses related to research activities in additional therapeutic areas to expand our pipeline, developing our potentially transformative gene regulation technology, hiring additional personnel as needed in manufacturing, research, clinical operations, quality and other functional areas, and associated cash and share-based compensation expense, as 109 Table of Contents well as the further development of internal manufacturing capabilities and capacity and other associated costs including the management of our intellectual property portfolio. On August 2, 2022 we, as borrower, and the Subsidiary Guarantors, entered into the Financing Agreement by and among the Company, the Subsidiary Guarantors, the lenders and other parties from time to time party thereto and Perceptive, as administrative agent and lender. On December 19, 2022, the Financing Agreement was converted to a Note Purchase Agreement between the same parties and under substantially the same terms and conditions as the Financing Agreement, subject to certain customary note constitution terms. The Note Purchase Agreement provides for the issuance of the Tranche 1 Notes in an initial amount of $75.0 million, and we may request the issuance of the Tranche 2 Notes in an additional amount of $25.0 million to be made available at Perceptive’s sole discretion before August 2, 2024. The Note Purchase Agreement matures on August 2, 2026 and is interest-only during the term. We have the option to redeem outstanding principal notes at any time along with an applicable early redemption fee. Outstanding amounts under the Note Purchase Agreement bear interest at a fluctuating rate per annum equal to 10.00% plus the secured overnight financing rate administered by the Federal Reserve Bank of New York for a one-month tenor, subject to a 1.00% floor. On November 9, 2022, we entered into a securities purchase agreement with JJDC, pursuant to which we, in a private placement, agreed to issue and sell to JJDC an aggregate of 3,742,514 ordinary shares at a purchase price of $6.68 per share for gross proceeds of approximately $25.0 million. We will require additional capital in the future, which we may raise through equity offerings, debt financings, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or other sources to enable us to complete the development and potential commercialization of our product candidates. Furthermore, we expect to continue incurring costs associated with being a public company. Adequate additional financing may not be available to us on acceptable terms, or at all. Our failure to raise capital as and when needed would have a negative effect on our financial condition and our ability to pursue our business strategy. In addition, attempting to secure additional financing may divert the time and attention of our management from day-to-day activities and harm our product candidate development efforts. If we are unable to raise capital when needed or on acceptable terms, we would be forced to delay, reduce or eliminate certain of our research and development programs. Based on our cash and cash equivalents at December 31, 2022 and the research funding and milestone payments we expect to receive under the Collaboration Agreement, we estimate that such funds will be sufficient to enable us to fund our operating expenses and capital expenditure requirements through the fourth quarter of 2024. We have based these estimates on assumptions that may prove to be wrong, and we may use our available capital resources sooner than we currently expect. See “Liquidity and Capital Resources.” Because of the numerous risks and uncertainties associated with the development of our product candidates, any future product candidates, our platform and technology and because the extent to which we may enter into collaborations with third parties for development of any of our product candidates is unknown, we are unable to estimate the amounts of increased capital outlays and operating expenses associated with completing the research and development of our product candidates. Adequate additional funds may not be available to us on acceptable terms, or at all. To the extent that we raise additional capital through the sale of equity or convertible securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a shareholder. Any future debt financing or preferred equity or other financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends and may require the issuance of warrants, which could potentially dilute your ownership interests. If we raise additional funds through collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or 110 Table of Contents product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development programs or any future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves. Because of the numerous risks and uncertainties associated with drug development, we are unable to predict the timing or amount of increased expenses or when or if we will be able to achieve or maintain profitability. Even if we are able to generate revenue from product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations. Highlights and Recent Developments Recent Development Highlights and Anticipated 2023 Milestones Botaretigene Sparoparvovec for the Treatment of XLRP: ● On October 1, 2022, clinical data from a Phase 1/2 MGT009 clinical trial (NCT03252847) were presented in a late-breaking oral presentation at the Retina Subspecialty Day program of the AAO 2022 Annual Meeting; treatment with botaretigene sparoparvovec was found to have an acceptable safety profile and efficacy assessments in this study and demonstrated improvements in retinal sensitivity, visual function and functional vision.1 ● Further sensitivity analysis was conducted on study participants by applying the Phase 3 Lumeos (NCT04671433) study eligibility criteria that corroborated the endpoints selected for the Phase 3 study.1 ● We, in collaboration with Janssen, are dosing patients in the pivotal Phase 3 Lumeos clinical trial of botaretigene sparoparvovec and remain on track for a BLA submission in 2024. 1 Michaelides, M et al. Ph1/2 AAV5-RPGR (Botaretigene Sparoparvovec) Gene Therapy Trial in RPGR-associated X- linked Retinitis Pigmentosa (XLRP). Abstract #30071754. Presented at the 2022 American Academy of Ophthalmology Annual Meeting. AAV-hAQP1 for the Treatment of Grade 2/3 Radiation-Induced Xerostomia: ● We reported positive clinical data from the AQUAx Phase 1 clinical trial in December 2022. o Clinically meaningful improvements in xerostomia symptoms and disease burden in two validated Patient-Reported Outcome (PRO) measures in both unilateral and bilateral treated cohorts were demonstrated. ◾ 18/24, or 75% achieved clinically meaningful symptom improvement using the Global Rate of Change (GRCQ) PRO. ◾ Using the Xerostomia Questionnaire (XQ), 71% (17/24) reported an improvement of >8 points (clinically meaningful), and 67% (16/24) had an improvement of ≥10 (considered transformative by KOLs). o Meaningful increases in whole saliva flow rates were observed post-treatment, providing objective evidence of the biological activity of AAV-hAQP1 treatment. o Early long-term follow-up data suggest durability of improvement 2+ years post-treatment. o AAV-hAQP1 appears safe and well-tolerated at each dose tested. ● All participants are followed for 1 year post-treatment and then enter a long-term follow-up study for another 4 years. ● We intend to present the final 12 month data from the bilateral treated cohorts from the AQUAx Phase 1 study in the second quarter of 2023. ● Based on the favorable safety and efficacy profile of AAV-hAQP1 in the AQUAx Phase 1 study, we intend to initiate a randomized, double-blind, placebo-controlled, Phase 2 study evaluating the bilateral administration of two active doses of AAV-hAQP1 in the second quarter of 2023. 111 Table of Contents AAV-GAD for the Treatment of Parkinson’s Disease: ● We are now dosing patients in the AAV-GAD clinical trial under a new IND using material manufactured in our cGMP facility in London, United Kingdom using our proprietary production process. ● The AAV-GAD trial is a three-arm randomized Phase 1 clinical bridging study with subjects randomized to one of two doses of AAV-GAD or sham control. ● The objective of the AAV-GAD trial (NCT05603312) is to evaluate the safety and tolerability of AAV-mediated delivery of glutamic acid decarboxylase (GAD) gene transfer into the subthalamic nuclei (STN) of participants with Parkinson's disease. ● Completion of enrollment is anticipated by the third quarter of 2023. Riboswitch Gene Regulation Platform & Vector Engineering: ● We exhibited 15 poster presentations at the European Society of Gene and Cell Therapy 2022 Annual Congress, which included data from our novel gene regulation platform, including the first data demonstrating the potential to regulate cell therapies including CAR-T, as well as data from our promoter platforms and several new, optimized pre-clinical programs addressing severe unmet needs for indications such as amyotrophic lateral sclerosis (ALS) and Wilson’s disease. In addition, we made several presentations on our proprietary viral vector manufacturing technology and potency assay development. ● Our next-generation riboswitch-based gene regulation platform can be used to precisely control the expression of any gene delivered in any context with an unprecedented dynamic range using novel, synthetic, orally delivered small molecules. ● We now have over 30 novel orally available small molecules with high specificity and potency to our riboswitch aptamers moving through PK, biodistribution and toxicology studies, with the first GMP material for IND currently being manufactured. Gene Therapy Manufacturing: ● Our wholly-owned facilities have now produced GMP clinical trial material for 6 different indications, using multiple AAV serotypes, including administration into the eye, salivary gland and central nervous system. ● We believe that our proprietary platform production process has produced one of the highest yields and full ratios in the industry. ● We believe that bringing all aspects of testing and vector production in-house reduces regulatory risk, ensures the highest quality of products, lowers costs and helps avoid bottlenecks in clinical development. ● In addition to our 30,000-square-foot facility in London, we now have a 150,000-square-foot plant in Shannon, Ireland which contains three facilities: one built to be flexible and scalable for viral vector production, another to manufacture plasmid DNA – the critical starting material for producing gene therapy products – and third, a Quality Control (QC) hub performing advanced biochemical quality control testing appropriate for commercialization. Components of Our Results of Operations License Revenue Our license revenue consisted of the amortization of the upfront and milestone payments we received in connection with the Collaboration Agreement. Operating Expenses Our operating expenses since inception have consisted primarily of general and administrative costs and research and development costs. 112 Table of Contents General and Administrative Expenses General and administrative expenses consist primarily of salaries and other related costs, including share-based compensation, for personnel in our executive, finance, legal, business development and administrative functions. General and administrative expenses also include legal fees relating to intellectual property and corporate matters; professional fees for accounting, auditing, tax and consulting services; insurance costs; travel expenses; and office facility-related expenses, which include direct depreciation costs. We expect that our general and administrative expenses will increase in the future as we increase our personnel headcount to support increased research and development activities. We have also incurred and expect to continue to incur increased expenses associated with being a public company, including costs of accounting, audit, legal, regulatory and tax- related services associated with maintaining compliance with Nasdaq and SEC requirements; director and officer insurance costs; and investor and public relations costs. Research and Development Expenses Research and development expenses consist primarily of costs incurred for our research activities, including our discovery efforts, and the development of our product candidates, and include: ● employee-related expenses, including salaries, benefits and travel of our research and development personnel; ● expenses incurred in connection with third-party vendors that conduct clinical and preclinical studies and manufacture the drug product for the clinical trials and preclinical activities; ● acquisition of in process research and development; ● costs associated with clinical and preclinical activities including costs related to facilities, supplies, rent, insurance, certain legal fees, share-based compensation, and depreciation; and ● expenses incurred with the development and operation of our manufacturing facilities. We expense research and development costs as incurred. Research and development activities are central to our business model. We expect that our research and development expenses will continue to increase substantially for the foreseeable future as we initiate additional preclinical and clinical trials of our existing product candidates, including the ongoing Phase 3 Lumeos trial of botaretigene sparoparvovec for the treatment of patients with XLRP, and continue to discover and develop additional product candidates. Certain of these increases in research and development costs will be partially offset by the research funding provided in connection with the Collaboration Agreement we entered into in January 2019. In addition, we expect to continue incurring increasing research and development costs associated with our clinical activities for AAV-hAQP1 for the treatment of radiation-induced xerostomia and xerostomia associated with Sjogren’s syndrome, as well as for AAV- GAD for the treatment of Parkinson’s disease. We cannot determine with certainty the duration and costs of future clinical trials of our product candidates or any other product candidate we may develop or if, when, or to what extent we will generate revenue from the commercialization and sale of any product candidate for which we obtain marketing approval. We may never succeed in obtaining marketing approval for any product candidate. The duration, costs and timing of clinical trials and development of our existing product candidates or any other product candidate we may develop will depend on a variety of factors, including: 113 Table of Contents ● the scope, rate of progress, expense and results of clinical trials of our existing product candidates, as well as of any future clinical trials of other product candidates and other research and development activities that we may conduct; ● uncertainties in clinical trial design and patient enrollment rates; ● the actual probability of success for our product candidates, including the safety and efficacy, early clinical data, competition, manufacturing capability and commercial viability; ● significant and changing government regulation and regulatory guidance; ● the timing and receipt of any marketing approvals; and ● the expense of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights. 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 or another U.S. or foreign regulatory authority were to require us to conduct clinical trials beyond those that we anticipate will be required for the completion of clinical development of a product candidate, or if we experience significant delays in our clinical trials due to patient enrollment or other reasons, we would be required to expend significant additional financial resources and time on the completion of clinical development. Other non-operating income (expense) Other non-operating income (expense) includes the following: Foreign currency (loss) gain Our consolidated financial statements are presented in U.S. dollars, which is our reporting currency. The financial position and results of operations of our subsidiaries MeiraGTx UK II Limited, MeiraGTx Ireland DAC, MeiraGTx Netherlands B.V., MeiraGTx B.V. and MeiraGTx Belgium are measured using the foreign subsidiaries’ local currency as the functional currency. These entities’ cash accounts holding U.S. dollars and intercompany payables and receivables are remeasured based upon the exchange rate at the date of remeasurement with the resulting gain or loss included in the consolidated statement of operations and comprehensive loss. Other comprehensive income Other comprehensive income includes the following: Foreign currency translation gain Expenses of subsidiaries have been translated into U.S. dollars at average exchange rates prevailing during the period. Assets and liabilities have been translated at the rates of exchange on the consolidated balance sheet date. The resulting translation gain adjustments are recorded directly as a separate component of shareholders’ equity and as other comprehensive loss on the consolidated statements of operations and comprehensive loss. 114 Table of Contents Critical Accounting Policies and Use of Estimates Management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with GAAP. The preparation of these consolidated financial statements requires us to make estimates and judgements that affect the reporting 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 judgements, including those related to license and collaboration revenue, share-based compensation and accrued expenses. We base our estimates on historical experience, known trends and events and various other factors that we believe to be reasonable under the circumstances, the results of which form the basis for making judgements about the carrying value of assets and liabilities that are not readily apparent from our sources. Actual results may differ from these estimates under different assumptions. While our significant accounting policies are described in more detail in the notes to our financial statements appearing in this Form 10-K, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our financial statements. Collaboration Arrangements We evaluate our collaborative arrangements pursuant to Accounting Standards Codification (“ASC”) 808, Collaborative Arrangements (“ASC 808”) and ASC 606, Revenue from Contracts with Customers (“ASC 606”). We consider the nature and contractual terms of collaborative arrangements and assess whether the arrangement involves a joint operating activity pursuant to which we are an active participant and are exposed to significant risks and rewards with respect to the arrangement. If we are an active participant and exposed to significant risks and rewards with respect to the arrangement, we account for the arrangement as a collaboration under ASC 808. To date, we have entered into two separate collaboration agreements, both of which are with Janssen, which were determined to be within the scope of ASC 808. ASC 808 does not address recognition or measurement matters related to collaborative arrangements. Payments between participants pursuant to a collaborative arrangement that are within the scope of other authoritative accounting literature on income statement classification are accounted for using the relevant provisions of that literature. If the payments are not within the scope of other authoritative accounting literature, the income statement classification for the payments is based on an analogy to authoritative accounting literature or if there is no appropriate analogy, a reasonable, rational and consistently applied accounting policy election. Payments received from a collaboration partner to which this policy applies may include upfront payments in respect of a license of intellectual property, development and commercialization-based milestones, and royalties. Revenue Recognition Arrangements with collaborators may include licenses to intellectual property, research and development services, manufacturing services for clinical and commercial supply, and participation on joint steering committees. We evaluate the promised goods or services to determine which promises, or group of promises, represent performance obligations. In contemplation of whether a promised good or service meets the criteria required of a performance obligation, we consider the stage of development of the underlying intellectual property, the capabilities and expertise of the customer relative to the underlying intellectual property, and whether the promised goods or services are integral to or dependent on other promises in the contract. When accounting for an arrangement that contains multiple performance obligations, we must develop judgmental assumptions, which may include market conditions, reimbursement rates for personnel costs, development timelines and probabilities of regulatory success to determine the stand-alone selling price for each performance obligation identified in the contract. 115 Table of Contents When we conclude that a contract should be accounted for as a combined performance obligation and recognized over time, we must then determine the period over which revenue should be recognized and the method by which to measure revenue. We generally recognize revenue using a cost-based input method. The Collaboration Agreement is accounted for under ASC 808, however, as ASC 808 does not address recognition or measurement matters such as determining the appropriate unit of accounting or when the recognition criteria are met, we account for the consideration received from Janssen in accordance with ASC 606. In accordance with ASC 606, we recognize revenue when the customer or collaborator obtains control of promised goods or services, in an amount that reflects the consideration which we expect 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; ii. identify the performance obligations in the contract; iii. determine the transaction price; iv. allocate the transaction price to the performance obligations within 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 we determine that it is probable we 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 by analogy within the scope of ASC 606, we assess the goods or services promised within the contract to determine whether each promised good or service is a performance obligation. The promised goods or services for our arrangements typically consist of a license to our intellectual property and research, development and manufacturing services. We may provide options to additional items in such arrangements, which are accounted for as separate contracts when the customer elects to exercise such options, unless the option provides a material right to the customer. Performance obligations are promises in a contract to transfer a distinct good or service to the customer that (i) the customer can benefit from on its own or together with other readily available resources, and (ii) is separately identifiable from other promises in the contract. Goods or services that are not individually distinct performance obligations are combined with other promised goods or services until such combined group of promises meet the requirements of a performance obligation. We determine transaction prices based on the amount of consideration we expect to receive for transferring the promised goods or services in the contract. Consideration may be fixed, variable, or a combination of both. At contract inception for arrangements that include variable consideration, we estimate the probability and extent of consideration we expect to receive under the contract utilizing either the most likely amount method or expected amount method, whichever best estimates the amount expected to be received. We then consider any constraints on the variable consideration and include in the transaction price variable consideration to the extent it is deemed probable that a significant reversal in the amount of cumulative revenue recognized will not occur when the uncertainty associated with the variable consideration is subsequently resolved. We then allocate the transaction price to each performance obligation based on the relative standalone selling price and recognize as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) control is transferred to the customer and the performance obligation is satisfied. For performance obligations which consist of licenses and 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 116 Table of Contents a point in time and, if over time, the appropriate method of measuring progress. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. We record amounts as accounts receivable when the right to consideration is deemed unconditional. When consideration is received, or such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer under the terms of a contract, a contract liability is recorded as deferred revenue. Amounts received prior to satisfying the revenue recognition criteria are recognized as deferred revenue in our consolidated balance sheet. Amounts expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue – related party, current. Amounts not expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue – related party. Income Taxes Since we have recurring losses and a valuation allowance against deferred tax assets, there was no tax expense (benefit) for the years ended December 31, 2022 and 2021. Research and Development Research and development costs are charged to expense as incurred. These costs include, but are not limited to, employee-related expenses, including salaries, benefits and travel of our research and development personnel; expenses incurred under agreements with contract research organizations and investigative sites that conduct clinical and preclinical studies and manufacture the drug product for the clinical studies and preclinical activities; acquisition of in-process research and development; facilities; supplies; rent, insurance, certain legal fees, stock-based compensation, depreciation and other costs associated with clinical and preclinical activities and regulatory operations. Research funding under collaboration agreements and refundable research and development credits / tax credits received are recorded as an offset to these costs. Costs for certain development activities, such as outside research programs funded by us, are recognized based on an evaluation of the progress to completion of specific tasks with respect to their actual costs incurred. Payments for these activities are based on the terms of the individual arrangements, which may differ from the pattern of costs incurred, and are reflected in the financial statements as prepaid or accrued research and development expense, as the case may be. Share-Based Compensation Options We grant share options to employees, non-employee members of our board of directors and non-employee consultants as compensation for services performed. Employee and non-employee members of the board of directors’ awards of share-based compensation are accounted for in accordance with ASC 718, Compensation—Stock Compensation, or ASC 718. ASC 718 requires all share-based payments to employees and non-employee directors, including grants of share options, to be recognized in the statement of operations and comprehensive loss based on their grant date fair values. The grant date fair value of share options is estimated using the Black-Scholes option valuation model. Using this model, fair value is calculated based on assumptions with respect to (i) the fair value of our ordinary shares on the grant date; (ii) expected volatility of our ordinary share price, (iii) the periods of time over which employees and members of our board of directors are expected to hold their options prior to exercise (expected term), (iv) expected dividend yield on our ordinary shares, and (v) risk-free interest rates. 117 Table of Contents Our ordinary shares were not traded on a public exchange prior to our IPO in June 2018. Therefore, we believe that our future volatility will differ materially during the expected term from the volatility that would be calculated from our historical share prices to date. Consequently, expected volatility is based on an analysis of guideline companies in accordance with ASC 718. The expected dividend yield is zero as we have never paid dividends and do not currently anticipate paying any in the foreseeable future. Risk-free interest rates are based on quoted U.S. Treasury rates for securities with maturities approximating the option’s expected term. Restricted Share Units The Company grants restricted share units (“RSUs”) to employees, non-employee members of our board of directors and non-employee consultants as compensation for services performed. Awards of RSUs are accounted for in accordance with ASC 718, Compensation - Stock Compensation, or ASC 718. ASC 718 requires all share-based payments to employees and non-employee directors, including grants of RSUs, to be recognized in the consolidated statement of operations and comprehensive loss based on their grant date fair values. The grant date fair value of RSUs is determined using the closing market price of the Company’s ordinary shares on the date of grant. Results of Operations Comparison of the Years Ended December 31, 2022 and 2021 License revenue - related party Operating expenses: General and administrative Research and development Total operating expenses Loss from operations Other non-operating income (expense) Foreign currency loss Interest income Interest expense Fair value adjustments Net loss Other comprehensive income: Foreign currency translation gain Comprehensive loss License Revenue 2022 $ 15,920 2021 (in thousands) 37,701 $ Change $ (21,781) 46,550 85,725 132,275 (116,355) (9,452) 777 (4,946) 361 (129,615) 43,765 66,694 110,459 (72,758) (6,293) 212 (288) (434) (79,561) 2,785 19,031 21,816 (43,597) (3,159) 565 (4,658) 795 (50,054) 8,718 $ (120,897) $ 2,226 (77,335) $ 6,492 (43,562) License revenue was $15.9 million for the year ended December 31, 2022, compared to $37.7 million for the year ended December 31, 2021. This decrease is a result of the Company receiving a $30.0 million milestone payment in connection with the Collaboration Agreement during the year ended December 31, 2021. General and Administrative Expenses General and administrative expenses were $46.6 million for the year ended December 31, 2022, compared to $43.8 million for the year ended December 31, 2021. The increase of $2.8 million was primarily due to an increase of $3.4 million in share-based compensation, $2.0 million in legal and accounting fees, $1.3 million in consulting fees and $0.4 million in depreciation. These increases were partially offset by a decrease of $1.7 million in payroll and payroll- 118 Table of Contents related costs, $1.2 million in insurance, $0.8 million in rent and facilities costs and $0.6 million in other general and administrative costs. Research and Development Expenses Research and development expenses for the years ended December 31, 2022 and 2021 were as follows (in millions): Gross research and development expenses Janssen reimbursements Tax incentive reimbursement Research and development expenses 2022 165.8 $ (73.3) (6.8) 85.7 $ 2021 141.1 $ (69.0) (5.4) 66.7 $ $ $ Change 24.7 (4.3) (1.4) 19.0 Gross research and development expenses for the year ended December 31, 2022 increased $24.7 million as compared to the prior year primarily due to an increase of $8.9 million in costs related to the manufacturing of our clinical trial materials, $6.5 million in payroll and payroll-related costs, $4.6 million in costs related to our pre-clinical research and clinical trials, $4.5 million in share-based compensation, $2.7 million in rent and facility costs, $0.5 million in depreciation and $1.1 million in other research costs. These increases were partially offset by a decrease of $2.6 million in license fees and $1.5 million in acquired research and development costs. Reimbursements under the Collaboration Agreement for the year ended December 31, 2022 increased $4.3 million as compared to the prior year primarily due to an increase in activity in the programs licensed under the Collaboration Agreement. Tax incentive reimbursement for the year ended December 31, 2022 increased $1.4 million as compared to the prior year primarily due to the increase in allowable research and development costs. Foreign Currency Loss Foreign currency loss was $9.5 million for the year ended December 31, 2022 compared to a loss of $6.3 million for the year ended December 31, 2021. The increase in the loss of $3.2 million was primarily due to an unrealized loss on the valuation of the Company’s intercompany payables and receivables due to the strengthening of the U.S. dollar against the pound sterling and euro during the year ended December 31, 2022. Interest Income Interest income was $0.8 million for the year ended December 31, 2022 compared to $0.2 million for the year ended December 31, 2021. The increase was due to a higher interest rate during 2022. Interest Expense Interest expense was $4.9 million for the year ended December 31, 2022 compared to $0.3 million for the year ended December 31, 2021. The increase was primarily due to the interest on the Financing Agreement entered into in August 2022, which was later converted to a Note Purchase Agreement in December 2022. 119 Table of Contents Other Comprehensive Income – Foreign Currency Translation Gain Foreign currency translation adjustments resulted in a translation gain of $8.7 million for the year ended December 31, 2022 compared to a translation gain of $2.2 million for the year ended December 31, 2021. The change in the amount of $6.5 million was primarily due to a strengthening of the U.S. dollar against the pound sterling and euro during the year ended December 31, 2022. Liquidity and Capital Resources Since our inception, we have incurred significant operating losses. For the year ended December 31, 2022, we used $73.1 million in cash flows from operations. We did not generate positive cash flows from operations during the year and there are no assurances that we will generate positive cash flows in the future. Additionally, there are no assurances that we will be successful in obtaining an adequate level of financing for the development and commercialization of our product candidates. We expect to incur significant expenses and operating losses for the foreseeable future as we advance the preclinical and clinical development of our product candidates. We expect that our research and development and general and administrative costs will increase in connection with conducting preclinical studies and clinical trials for our product candidates, building out internal capacity to have products manufactured to support preclinical studies and clinical trials, expanding our intellectual property portfolio, and providing general and administrative support for our operations. In addition, on August 4, 2020 we entered into agreements to acquire the buildings for our second, large scale cGMP viral vector manufacturing facility and our first cGMP plasmid and DNA production facility in Shannon, Ireland to expand our manufacturing and supply chain capabilities. We closed on the acquisition of the first building in August 2020 and closed on the second building in January 2021. As a result of these incurred and expected expenses we will need additional capital to fund our operations, which we may obtain from additional equity or debt financings, collaborations, licensing arrangements, or other sources. We do not currently have any approved products and have never generated any revenue from product sales. We have historically financed our operations primarily through cash on hand and proceeds from the sale of our ordinary shares, series A ordinary shares and convertible preferred C shares. In March 2019 and December 2021, we received a $100.0 million upfront payment and a $30.0 million milestone payment, respectively, in connection with the Collaboration Agreement, which also provides us with research funding, and we are eligible to receive additional potential milestone payments and royalties. Additionally, on August 2, 2022, we, as borrower, and our Subsidiary Guarantors, entered into a Financing Agreement by and among us, the Subsidiary Guarantors, the lenders and other parties from time to time party thereto and Perceptive, as administrative agent and lender. On December 19, 2022, the Financing Agreement was converted to a Note Purchase Agreement between the same parties and under substantially the same terms and conditions as the Financing Agreement, subject to certain customary note constitution terms. The Note Purchase Agreement provides for the issuance of the Tranche 1 Notes in an initial amount of $75.0 million, and we may request the issuance of the Tranche 2 Notes in an additional amount of $25.0 million to be made available at Perceptive’s sole discretion before August 2, 2024. The Note Purchase Agreement matures on August 2, 2026 and is interest-only during the term. We have the option to redeem outstanding principal notes at any time along with an applicable early redemption fee. Outstanding amounts under the Note Purchase Agreement bear interest at a fluctuating rate per annum equal to 10.00% plus the secured overnight financing rate administered by the Federal Reserve Bank of New York for a one-month tenor, subject to a 1.00% floor. Our obligations under the Note Purchase Agreement are secured by our London, UK and Shannon, Ireland manufacturing facilities, $3.0 million of our cash and the bank accounts of the Subsidiary Guarantors, and the issued and outstanding equity interests of the Subsidiary Guarantors. 120 Table of Contents The Note Purchase Agreement imposes covenants that include, among other things, enrolling in a Phase III trial for AAV-RPGR on or before June 30, 2023, and ensuring the Company’s Shannon manufacturing facility meets or satisfies all applicable good manufacturing practice requirements on or before December 31, 2023, as well as various restrictions on us and the Subsidiary Guarantors, including restrictions pertaining to: (i) the incurrence of additional indebtedness, (ii) limitations on liens, (iii) limitations on certain investments, (iv) making distributions, dividends and other payments, (v) mergers, consolidations and acquisitions, (vi) dispositions of assets, (vii) our maintenance of at least $3 million in a U.S. bank account, (viii) transactions with affiliates, (ix) changes to governing documents, (x) changes to certain agreements and leases and (xi) changes in control; however, certain of these restrictions contain exceptions which allow us to license, sell and monetize assets in our AAV-hAQP1 program in development to treat radiation-induced xerostomia, our AAV-GAD program in development to treat Parkinson’s disease and our gene regulation platform technologies. In connection with entering into the Financing Agreement, we granted warrants (the “Warrants”) to Perceptive to purchase up to (i) 400,000 ordinary shares of the Company at an exercise price of $15.00 per share and (ii) 300,000 ordinary shares of the Company at an exercise price of $20.00 per share. The Warrants will expire on August 2, 2027. Based on our current cash, cash equivalents and accounts receivable – related party at December 31, 2022 and the research funding and milestone payments we expect to receive under the Collaboration Agreement, we estimate that we will be able to fund our operating expenses and capital expenditure requirements through the fourth quarter of 2024. We have based these estimates on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect. Cash Flows We had $115.5 million and $137.7 million of cash and cash equivalents as of December 31, 2022 and 2021, respectively. The following table summarizes our sources and uses of cash for the period presented: Net cash used in operating activities Net cash used in investing activities Net cash provided by financing activities Net decrease in cash and cash equivalents Operating Activities For the Years Ended December 31, 2022 2021 (in thousands) $ $ (73,098) $ (44,963) 95,200 (22,861) $ (10,530) (61,717) 1,708 (70,539) During the year ended December 31, 2022, our cash used in operating activities of $73.1 million was primarily due to our net loss of $129.6 million as we incurred expenses associated with research activities on our clinical programs, manufacturing of our clinical trial materials, preclinical research programs and general and administrative expenses. The net loss included non-cash charges of $46.9 million, which consisted of $28.6 million of share-based compensation, $9.5 million of a foreign currency loss, $8.7 million of depreciation and amortization, $0.4 million of a fair value downward adjustment, $0.2 million of negative net change in right-of-use assets and liabilities, $0.2 million of amortization of interest on asset retirement obligations and $0.4 million of amortization of the debt discount. Additionally, operating assets, consisting of accounts receivable-related party, prepaid expenses, tax incentive receivable, other current assets and other assets, decreased by $5.2 million and operating liabilities, consisting of accounts payable, accrued expenses, and deferred revenue-related party, decreased by $4.4 million. 121 Table of Contents During the year ended December 31, 2021, our cash used in operating activities of $10.5 million was primarily due to our net loss of $79.6 million as we incurred expenses associated with research activities on our clinical programs, manufacturing of our clinical trial materials, preclinical research programs and general and administrative expenses. The net loss included non-cash charges of $37.8 million, which consisted of $20.8 million of share-based compensation, $6.3 million of a foreign currency loss, $7.9 million of depreciation and amortization, $1.0 million of shares issued in connection with a license agreement, $1.0 million of shares issued in connection with an asset acquisition, $0.4 million of a fair value adjustment, $0.2 million of net change in right-of-use assets and liabilities, $0.1 million of amortization of interest on asset retirement obligations and $0.1 million of loss on disposal of equipment, furniture and fixtures. Additionally, operating assets, consisting of accounts receivable-related party, prepaid expenses, tax incentive receivable, other current assets and other assets, decreased by $17.3 million and operating liabilities, consisting of accounts payable, accrued expenses, and deferred revenue-related party, increased by $14.0 million. Investing Activities Net cash used in investing activities for the year ended December 31, 2022 of $45.0 million consisted of purchases of property and equipment for our manufacturing, laboratory and process development facilities and buildout costs of our new facilities in Ireland. Net cash used in investing activities for the year ended December 31, 2021 of $61.7 million consisted primarily of $8.9 million in payments for the acquisition of the second building and long-term lease of our manufacturing facility in Ireland, $6.5 million in connection with equity method and other investments and $46.3 million for purchases of property and equipment for our manufacturing, laboratory and process development facilities and buildout costs of our new facilities in Ireland. Financing Activities Net cash provided by financing activities was $95.2 million for the year ended December 31, 2022, which consisted primarily of $75.0 million from issuance of the Tranche 1 Notes, $25.0 million from the issuance of ordinary shares and $0.2 million in exercise of share options, which was offset by $2.8 million of payments for withholdings of shares for income taxes, and financing fees of $2.2 million. Net cash provided by financing activities was $1.7 million for the year ended December 31, 2021, which is primarily from the exercise of share options. Off-Balance Sheet Arrangements We have not entered into any off-balance sheet arrangements under applicable SEC rules and do not have any holdings in variable interest entities. Emerging Growth Company Status The Jumpstart Our Business Startups Act of 2012, (the “JOBS Act”), permits an “emerging growth company,” which we are, to take advantage of an extended transition period to comply with new or revised accounting standards applicable to public companies until those standards would otherwise apply to private companies. We have elected to take advantage of this extended transition period through December 31, 2023. 122 Table of Contents ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK. We are exposed to market risks in the ordinary course of our business. These risks primarily include foreign currency exchange rate sensitivities and interest rate risk. Foreign Currency Exchange Risk We currently operate in the United States, the United Kingdom, the Netherlands, Ireland and Belgium. Our activities in these jurisdictions expose us to currency exchange rate fluctuations primarily between the U.S. Dollar and the British pound sterling and euro. When the U.S. Dollar strengthens against these currencies, the U.S. Dollar value of non- U.S. Dollar based losses increases. To the extent that our international activities recorded in local currencies increase in the future, our exposure to fluctuations in currency exchange rates will correspondingly increase. With respect to our foreign currency exposures as of December 31, 2022, we estimate a 10% unfavorable movement in foreign currency exchange rates would have the effect of creating an additional foreign currency loss of approximately $28.1 million within other non- operating income (expense) for the year ended December 31, 2022. Interest Rate Risk We are exposed to market risk as a result of changes in interest rates applicable to borrowings under our Note Purchase Agreement. Borrowings under the Note Purchase Agreement bear interest at a fluctuating rate per annum equal to 10.00% plus the secured overnight financing rate (“SOFR”) administered by the Federal Reserve Bank of New York for a one-month tenor, subject to a 1.00% floor. See Note 14 to our consolidated financial statements included elsewhere in this Form 10-K. We may use interest rate cap derivatives, interest rate swaps or other interest rate hedging instruments to economically hedge and manage interest rate risk with respect to our variable floating rate debt. As of December 31, 2022, the annual interest rate was 13.02% and the outstanding balance of the Tranche 1 Notes was $75.0 million. Assuming no change in the outstanding borrowings under the Note Purchase Agreement, we estimate that a hypothetical 1% increase in the SOFR would increase our annual interest expense by approximately $0.8 million as of December 31, 2022. 123 Table of Contents ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES FOR THE YEARS ENDED DECEMBER 31, 2022 AND 2021 INDEX TO CONSOLIDATED FINANCIAL STATEMENTS Report of Independent Registered Public Accounting Firm (PCAOB ID 42) Consolidated: Balance Sheets Statements of Operations and Comprehensive Loss Statements of Shareholders' Equity Statements of Cash Flows Notes to Consolidated Financial Statements F-1 F-2 F-3 F-4 F-5 F-6 F-7 Table of Contents Report of Independent Registered Public Accounting Firm To the Shareholders and the Board of Directors of MeiraGTx Holdings plc and Subsidiaries Opinion on the Financial Statements We have audited the accompanying consolidated balance sheets of MeiraGTx Holdings plc and Subsidiaries (the “Company”) as of December 31, 2022 and 2021, the related consolidated statements of operations and comprehensive loss, shareholders' equity and cash flows for each of the two years in the period ended December 31, 2022, 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, 2022 and 2021, and the results of its operations and its cash flows for each of the two years in the period ended December 31, 2022, in conformity with U.S. generally accepted accounting principles. 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 Public Company Accounting Oversight Board (United States) (“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. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company's internal control over financial reporting. Accordingly, we express no such opinion. 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 2016. Jericho, New York March 14, 2023 F-2 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES CONSOLIDATED BALANCE SHEETS (in thousands, except share and per share amounts) December 31, 2022 December 31, 2021 ASSETS CURRENT ASSETS: Cash and cash equivalents Accounts receivable - related party Prepaid expenses Tax incentive receivable Other current assets Total Current Assets Property, plant and equipment, net Intangible assets, net In-process research and development Other assets Equity method and other investments Right-of-use assets - operating leases, net Right-of-use assets - finance leases, net TOTAL ASSETS LIABILITIES AND SHAREHOLDERS' EQUITY CURRENT LIABILITIES: Accounts payable Accrued expenses Lease obligations, current Deferred revenue - related party, current Other current liabilities Total Current Liabilities Deferred revenue - related party Lease obligations Asset retirement obligations Deferred income tax liability Note payable, net Other long-term liabilities TOTAL LIABILITIES COMMITMENTS AND CONTINGENCIES (Note 15) SHAREHOLDERS' EQUITY: Ordinary Shares, $0.00003881 par value, 1,288,327,750 authorized, 48,477,209 and 44,548,925 shares issued and outstanding at December 31, 2022 and 2021, respectively Capital in excess of par value Accumulated other comprehensive income (loss) Accumulated deficit Total Shareholders' Equity TOTAL LIABILITIES AND SHAREHOLDERS' EQUITY $ $ $ $ 115,516 21,334 8,133 7,689 1,667 154,339 109,266 1,335 742 1,402 6,326 20,109 24,718 318,237 16,616 39,818 3,884 15,123 6,631 82,072 27,436 17,331 2,179 186 71,033 262 200,499 2 581,893 6,047 (470,204) 117,738 318,237 $ $ $ $ 137,703 22,384 8,102 12,634 2,420 183,243 75,860 1,791 783 1,404 6,656 22,782 27,645 320,164 15,348 27,586 3,374 21,820 — 68,128 43,046 20,359 2,081 196 — 953 134,763 2 528,659 (2,671) (340,589) 185,401 320,164 See Notes to Consolidated Financial Statements F-3 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except share and per share amounts) For the Years Ended December 31, 2021 2022 License revenue - related party $ 15,920 $ 37,701 Operating expenses: General and administrative Research and development Total operating expenses Loss from operations Other non-operating income (expense): Foreign currency loss Interest income Interest expense Fair value adjustments Net loss Other comprehensive income: Foreign currency translation gain Comprehensive loss Net loss Basic and diluted net loss per ordinary share Weighted-average number of ordinary shares outstanding 46,550 85,725 132,275 (116,355) (9,452) 777 (4,946) 361 (129,615) 8,718 (120,897) (129,615) (2.87) 45,177,857 $ $ $ $ $ $ 43,765 66,694 110,459 (72,758) (6,293) 212 (288) (434) (79,561) 2,226 (77,335) (79,561) (1.80) 44,139,655 See Notes to Consolidated Financial Statements F-4 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF SHAREHOLDERS' EQUITY FOR THE YEARS ENDED DECEMBER 31, 2022 AND 2021 (in thousands, except share amounts) Ordinary Shares Amount Capital in Excess of Par Value Accumulated Other Comprehensive Loss Accumulated Deficit Total Shareholders' Equity Balance at December 31, 2020 Share-based compensation activity Issuance of shares in connection with equity method and other investments Issuance of shares in connection with asset acquisitions Other comprehensive income Net loss for the year ended December 31, 2021 Balance at January 1, 2022 Share-based compensation activity Warrants issued in connection with note payable Issuance of shares in connection with private placement, net of issuance costs of $119 Other comprehensive income Net loss for the period ended December 31, 2022 Balance at December 31, 2022 44,189,150 186,638 $ 75,000 98,137 — — 44,548,925 185,770 — 3,742,514 — — $ 48,477,209 $ 2 — — — — — 2 — — — — — $ 2 504,482 22,493 $ (4,897) — $ (261,028) — $ 238,559 22,493 1,165 519 — — 528,659 26,080 2,273 24,881 — — $ 581,893 — — 2,226 — (2,671) — — — — — (79,561) (340,589) — — — 8,718 6,047 — — — (129,615) $ (470,204) $ 1,165 519 2,226 (79,561) 185,401 26,080 2,273 24,881 8,718 (129,615) 117,738 See Notes to Consolidated Financial Statements F-5 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES CONSOLIDATED STATEMENTS OF CASH FLOWS (in thousands) Cash flows from operating activities: Net loss Adjustments to reconcile net loss to net cash used in operating activities: Share-based compensation expense Foreign currency loss Depreciation and amortization Net change in right-of-use assets and liabilities (Gain) loss on disposal of equipment, furniture and fixtures Loss on equity method investment Amortization of interest on asset retirement obligations Amortization of debt discount Issuance of shares in connection with license agreement Issuance of shares in connection with asset acquisition Fair value adjustments (Increase) decrease in operating assets: Accounts receivable - related party Prepaid expenses Tax incentive receivable Other current assets Other assets Increase (decrease) in operating liabilities: Accounts payable Accrued expenses Other current liabilities Deferred revenue - related party Net cash used in operating activities Cash flows from investing activities: Purchase of property, plant and equipment Payment for right-of-use asset Equity method and other investments Net cash used in investing activities Cash flows from financing activities: Exercise of share options Payments of withholdings on shares withheld for income taxes Payments on lease obligations - financing leases Proceeds from the issuance of ordinary shares Proceeds from issuance of note payable Payment of financing fees Net cash provided by financing activities Net decrease in cash and cash equivalents Effect of exchange rate changes on cash Cash and cash equivalents at beginning of the year Cash and cash equivalents at end of the year Supplemental disclosure of non-cash transactions: Issuance of shares in connection with equity method and other investments Fixed asset acquisition included in accounts payable and accrued expenses Right-of-use assets obtained in exchange for lease liabilities Asset retirement obligations incurred in connection with leases Warrants issued in connection with note payable Issuance of shares in connection with asset acquisition Supplemental disclosure of cash flow information: Cash paid for interest $ $ $ $ $ $ $ $ See Notes to Consolidated Financial Statements F-6 For the Years Ended December 31, 2021 2022 $ (129,615) $ (79,561) 28,623 9,452 8,723 (153) — — 168 444 — — (361) 1,032 (329) 4,139 519 (173) 3,737 12,610 4,006 (15,920) (73,098) (44,963) — — (44,963) 231 (2,774) — 25,000 75,000 (2,257) 95,200 (22,861) 674 137,703 115,516 $ 7,106 1,793 9 2,273 — $ $ $ $ $ — $ 329 $ 20,784 6,293 7,873 161 56 9 148 — 976 1,020 434 16,391 (1,083) 310 2,161 (457) 13,347 8,118 (23) (7,487) (10,530) (46,351) (8,866) (6,500) (61,717) 1,709 — (1) — — — 1,708 (70,539) (1,278) 209,520 137,703 1,165 7,178 4,424 120 — 519 139 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 1. Principal Business Activity The Company MeiraGTx Holdings plc and subsidiaries (the “Company” or “Meira Holdings”), an exempted company incorporated under the laws of the Cayman Islands, is a vertically integrated, clinical stage gene therapy company with six programs in clinical development and a broad pipeline of preclinical and research programs. The Company has core capabilities in viral vector design and optimization and gene therapy manufacturing, as well as a potentially transformative gene regulation platform technology that allows precise, dose responsive control of gene expression by oral small molecules with dynamic range that can exceed 5000-fold. Led by an experienced management team, the Company has taken a portfolio approach by licensing, acquiring and developing technologies that give depth across both product candidates and indications. The Company’s initial focus is on three distinct areas of unmet medical need: ocular diseases, including inherited retinal diseases as well as large degenerative ocular diseases, neurodegenerative diseases and severe forms of xerostomia. Though initially focusing on the eye, central nervous system and salivary gland, the Company intends to expand its focus in the future to develop additional gene therapy treatments for patients suffering from a range of serious diseases. The Company also owns and operates a current good manufacturing practices, or cGMP, multi-product, multi-viral vector manufacturing facility in London, United Kingdom (“UK”), which includes fill and finish capabilities and can supply the Company’s clinical and potential commercial material. Additionally, the Company expanded its manufacturing and supply chain capabilities by acquiring a second, large scale cGMP viral vector manufacturing facility and its first cGMP plasmid and DNA production facility in Shannon, Ireland. The Company completed the acquisition of these facilities in January 2021. Acquisition On October 4, 2021, the Company acquired Bullseye Therapeutics, Inc. (“Bullseye”), a company engaged in developing mechanisms to deliver retinal drugs and gene therapies to the eye. Bullseye was renamed MeiraGTx Therapeutics, Inc. This acquisition is part of the Company’s continuing efforts to expand its focus to develop additional gene therapy treatments for patients suffering from a range of serious diseases. (See Note 3 for additional information). Basis of Presentation The accompanying consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“GAAP”). Any reference in these notes to applicable guidance is meant to refer to the authoritative United States generally accepted accounting principles as found in the Accounting Standards Codification (“ASC”) and Accounting Standards Update (“ASU”) of the Financial Accounting Standards Board (“FASB”). Liquidity The Company has not yet achieved profitable operations. There is no assurance that profitable operations, if ever achieved, could be sustained on a continuing basis. In addition, development activities, clinical and preclinical testing, and commercialization of the Company’s product candidates will require significant additional financing. The Company’s accumulated deficit at December 31, 2022 totaled $470.2 million, and management expects to incur substantial losses in future periods. The success of the Company is subject to certain risks and uncertainties, including among others, uncertainty of product development; competition in the Company’s field of use; uncertainty of capital availability; uncertainty in the Company’s ability to enter into agreements with collaborative partners; expanding and protecting the Company’s intellectual property portfolio; dependence on third parties; dependence on key personnel; the COVID-19 pandemic and mitigation measures. For the year ended December 31, 2022, the Company used $73.1 million in cash flows from operations and there are no assurances that the Company will F-7 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS generate positive cash flows in the future. Additionally, there are no assurances that the Company will be successful in obtaining an adequate level of financing for the development and commercialization of its product candidates. As of December 31, 2022, the Company had cash and cash equivalents in the amount of $115.5 million, which consisted of depository and money market accounts held at large international banks. On January 30, 2019, the Company entered into a collaboration, option and license agreement with Janssen Pharmaceuticals, Inc. (“Janssen”), one of the Janssen Pharmaceuticals Companies of Johnson & Johnson (the “Collaboration Agreement”), for the research, development and commercialization of gene therapies for the treatment of inherited retinal diseases (“IRD”). Under the terms of the Collaboration Agreement, the Company received an upfront payment of $100.0 million in March 2019 and a $30.0 million milestone payment in December 2021. The Company also receives funding for certain research, manufacturing, clinical development and commercialization costs, potential additional milestone payments upon the achievement of such milestones and royalties on future net sales of products. The Company estimates that its cash and cash equivalents on hand and accounts receivable – related party at December 31, 2022 will be sufficient to cover its expenses for at least the next twelve months from the date of issuance of these consolidated financial statements. Risks and Uncertainties The Company operates in an industry that is subject to intense competition, government regulation and rapid technological change. The Company’s operations are subject to significant risk and uncertainties including financial, operational, technological, regulatory and other risks, including the potential risk of business failure. There are also many uncertainties regarding the pandemic caused by the novel coronavirus, or COVID-19, and the Company continues to monitor the impact of the pandemic on all aspects of its business, including how the pandemic will impact its financial condition, liquidity, operations, clinical studies, employees, vendors, and industry. While the pandemic did not materially affect the Company's financial results and business operations in the year ended December 31, 2022 and 2021, the Company is unable to predict the impact that COVID-19 will have on its financial position and operating results in future periods due to numerous uncertainties. The Company will continue to assess the evolving impact of the COVID-19 pandemic and will make adjustments to its operations as necessary. The Company’s capital resources and operations to date have been funded primarily with the proceeds from the Collaboration Agreement and private and public equity offerings, as well as the proceeds from the debt financing described in Note 14. In the future, the Company may seek to raise additional capital through equity offerings, debt financings, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or other sources to enable it to complete the development and potential commercialization of its product candidates. The COVID-19 outbreak and mitigation measures also have had, and may continue to have, an adverse impact on global economic conditions, which could have an adverse effect on the Company’s ability to raise capital when needed. 2. Summary of Significant Accounting Policies Consolidation The accompanying consolidated financial statements include the accounts of Meira Holdings and its wholly owned subsidiaries: MeiraGTx Limited, a limited company incorporated under the laws of England and Wales; MeiraGTx, LLC, a Delaware limited liability company (“Meira LLC”); MeiraGTx UK II Limited, a limited company incorporated under the laws of England and Wales (“Meira UK II”); F-8 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS MeiraGTx Ireland DAC, a designated activity company incorporated under the laws of Ireland (“Meira Ireland”); MeiraGTx Netherlands B.V., a private company with limited liability incorporated under the laws of the Netherlands (“Meira Netherlands”); MeiraGTx Belgium, a private company with limited liability incorporated under the laws of Belgium (“Meira Belgium”); BRI-Alzan, Inc., a Delaware corporation (“BRI-Alzan”); MeiraGTx Bio Inc., a Delaware corporation (“Meira Bio”); MeiraGTx B.V., a private company with limited liability incorporated under the laws of the Netherlands (“Meira B.V.”); MeiraGTx Neurosciences, Inc., a Delaware corporation (“Meira Neuro”); MeiraGTx Therapeutics, Inc., a Delaware corporation (“Meira Therapeutics”); and MeiraGTx UK Limited, a limited company incorporated under the laws of England and Wales (“Meira UK”). All intercompany balances and transactions between the consolidated companies have been eliminated in consolidation. Use of 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 consolidated 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. This process may result in actual results differing materially from those estimated amounts used in the preparation of the financial statements if these results differ from historical experience, or other assumptions do not turn out to be substantially accurate, even if such assumptions are reasonable when made. In preparing these consolidated financial statements, management used significant estimates in the following areas, among others: collaboration revenue, the accounting for research and development costs, share-based compensation, leases, asset retirement obligations, fair value of financial instruments and tax incentive receivable. Additionally, the Company has made estimates of the impact of the COVID-19 pandemic within the consolidated financial statements and there may be changes to those estimates in future periods. Actual results may differ from these estimates. Cash and Cash Equivalents The Company considers all highly liquid instruments with an original maturity of 90 days or less at the time of purchase to be cash equivalents. Cash and cash equivalents consist of checking and money market accounts held at large international banks that are readily convertible into cash. Financial Instruments The carrying value of accounts receivable-related party, tax incentive receivable, other current assets, and accounts payable reported in the consolidated balance sheets equal or approximate fair value due to their short maturities. F-9 Table of Contents Tax Incentive Receivable MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS Meira UK II is eligible to participate in a UK research and development tax incentive programs under which it is eligible to receive a cash refund from His Majesty’s Revenue & Customs (“HMRC”) for a percentage of the qualified research and development costs expended by Meira UK II under the small and medium sized enterprises (“SME”) program and the research and development expenditures credit (“RDEC”) program. The SME cash refund is available to companies with less than 500 employees and annual aggregate revenue of less than 100.0 million euros or total aggregate assets less than 86.0 million euros during the reimbursable period. The Company’s estimate of the amount of cash refund it expects to receive related to the SME and RDEC programs is included in tax incentive receivable in the accompanying consolidated balance sheets and such amounts are recorded as a reduction of research and development expense in the statements of operations. During the years ended December 31, 2022 and 2021, the Company recorded reductions to research and development expenses of $6.8 million and $5.4 million, respectively. In addition, the Company incurs Value Added Tax (“VAT”) on services provided by UK and EU vendors, which it is entitled to reclaim. The Company’s estimate of the amount of cash refund it expects to receive related to VAT was $1.1 million and $1.9 million as of December 31, 2022 and 2021, respectively, which is included in other current assets in the accompanying consolidated balance sheets. Fair Value Measurements Fair value is defined as the price that would be received upon sale of an asset or paid upon transfer of a liability in an orderly transaction between market participants at the measurement date and in the principal or most advantageous market for that asset or liability. The fair value should be calculated based on assumptions that market participants would use in pricing the asset or liability, not on assumptions specific to the entity. In addition, the fair value of liabilities should include consideration of non-performance risk including the Company’s own credit risk. The Company follows ASC Topic 820, Fair Value Measurements and Disclosures, or ASC 820, for application to financial assets and liabilities. In addition to defining fair value, the standard expands the disclosure requirements around fair value and establishes a fair value hierarchy for valuation inputs. The hierarchy prioritizes the inputs into three levels based on the extent to which inputs used in measuring fair value are observable in the market. Each fair value measurement is reported in one of the three levels which are determined by the lowest level input that is significant to the fair value measurement in its entirety. These levels are: ● Level 1: Observable inputs such as quoted prices in active markets for identical assets the reporting entity has the ability to access as of the measurement date; ● Level 2: Inputs, other than the quoted prices in active markets, that are observable either directly or indirectly; and ● Level 3: Unobservable inputs in which there is little or no market data, which require the reporting entity to develop its own assumptions. F-10 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The table below represents the values of the Company's financial assets and liabilities that are required to be measured at fair value on a recurring basis (in thousands): Description Cash equivalents Other long-term liabilities Description Cash equivalents Other long-term liabilities December 31, 2022 Fair Value Measurement Using: Significant Observable Inputs (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable (Level 3) 57,336 262 $ $ 57,336 262 $ $ — $ — $ — — December 31, 2021 Fair Value Measurement Using: Significant Observable Inputs (Level 1) Significant Other Observable Inputs (Level 2) Significant Unobservable (Level 3) 66,585 953 $ $ 66,585 953 $ $ — $ — $ — — $ $ $ $ Equity Method and Other Investments The Company accounts for equity investments under the equity method of accounting when the requirements for consolidation are not met, and the Company has significant influence over the operations of the investee. Equity method investments are initially recorded at cost and subsequently adjusted for the Company’s share of net income or loss and cash contributions and distributions and are included in equity method and other investments in the accompanying consolidated balance sheets. Equity investments that do not result in consolidation and are not accounted for under the equity method are measured at fair value, with any changes in fair value recognized in net income (loss). For any such investments that do not have readily determinable fair values, the Company elects the measurement alternative to measure the investments at cost minus impairment, if any, plus or minus changes resulting from observable price changes in orderly transactions for the identical or a similar investment of the same issuer. Equity method investments are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount may not be recoverable. If it is determined that a loss in value of the equity method investment is other than temporary, an impairment loss is measured based on the excess of the carrying amount of an investment over its estimated fair value. Impairment analyses are based on current plans, intended holding periods, and available information at the time the analysis is prepared. Concentrations of Credit Risk The Company maintains its cash and cash equivalents primarily in depository and money market accounts within two large financial institutions in the United States and one large financial institution in the United Kingdom and Ireland. Cash balances deposited at these major financial banking institutions exceed the insured limit. The Company has not experienced any losses on its bank deposits and believes these deposits do not expose the Company to any significant credit risk. Intangible Assets Intangible assets consist of purchased rights to licensed technology as it relates to the Company’s manufacturing processes and has future alternative use in the Company’s operations. The licensed technology is being amortized on a straight-line basis over 7 years, which represents the estimated periods of benefit and the expected pattern of consumption (see Note 7). F-11 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS Property, Plant and Equipment, Net Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation is calculated using the straight-line method over the estimated useful lives of the respective assets. Leasehold improvements are depreciated over the lesser of their useful lives or the term of the lease (see Note 6). The estimated useful lives of the asset categories are as follows: Asset Category Computer and office equipment Laboratory equipment Manufacturing equipment Furniture and fixtures Leasehold improvements Useful Lives 3 years 5 years 7 years 5 years lesser of useful life or remaining term of lease Expenditures for leasehold improvements are capitalized, and expenditures for maintenance and repairs are expensed to operations as incurred. ASC Topic 360, Property, Plant and Equipment, addresses the financial accounting and reporting for impairment or disposal of long-lived assets. The Company reviews the recorded values of long-lived assets for impairment whenever events or changes in business circumstances indicate that the carrying amount of an asset or group of assets may not be fully recoverable. The Company did not record any material impairment charges in 2022 or 2021. Leases The Company accounts for leases in accordance with ASC 842. The Company determines if an arrangement is a lease at contract inception. A lease exists when a contract conveys the right to control the use of identified property, plant, or equipment for a period of time in exchange for consideration. The definition of a lease embodies two conditions: (1) there is an identified asset in the contract that is land or a depreciable asset (i.e., property, plant, and equipment), and (2) the Company has the right to control the use of the identified asset. The Company accounts for the lease and non-lease components as a single lease component. From time to time the Company enters into direct financing lease arrangements that include a lessee obligation to purchase the leased asset at the end of the lease term, a bargain purchase option, or provides for minimum lease payments with a present value of 90% or more of the fair value of the leased asset at the date of lease inception. Operating leases where the Company is the lessee are included in right-of-use (“ROU”) assets – operating leases and lease obligations are included on the Company’s consolidated balance sheets. The lease obligations are initially and subsequently measured at the present value of the unpaid lease payments at the lease commencement date and subsequent reporting periods. Finance leases where the Company is the lessee are included in ROU assets – finance leases, net and lease obligations on the Company’s consolidated balance sheets. The lease obligations are initially measured in the same manner as for operating leases and are subsequently measured at amortized cost using the effective interest method. Key estimates and judgments include how the Company determined (1) the discount rate used to discount the unpaid lease payments to present value, (2) lease term and (3) lease payments. ASC 842 requires a lessee to discount its unpaid lease payments using the interest rate implicit in the lease or, if that rate cannot be readily determined, its incremental borrowing rate. As most of the Company’s leases where it is the F-12 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS lessee do not provide an implicit rate, the Company uses its incremental borrowing rate based on the information available at commencement date in determining the present value of lease payments. The Company’s incremental borrowing rate for a lease is the rate of interest it would have to pay on a collateralized basis to borrow an amount equal to the lease payments under similar terms. The Company uses the implicit rate when readily determinable. The lease term for all of the Company’s leases includes the non-cancellable period of the lease plus any additional periods covered by either a lessee option to extend (or not to terminate) the lease that is reasonably certain to be exercised, or an option to extend (or not to terminate) the lease controlled by the lessor. The ROU asset is initially measured at cost, which comprises the initial amount of the lease liability adjusted for lease payments made at or before the lease commencement date less any lease incentives received. For operating leases, the ROU asset is subsequently measured throughout the lease term at the carrying amount of the lease liability, minus any accrued lease payments, less the unamortized balance of lease incentives received. Lease expense for lease payments is recognized on a straight-line basis over the lease term. For finance leases, the ROU asset is subsequently amortized using the straight-line method from the lease commencement date to the earlier of the end of its useful life or the end of the lease term unless the lease transfers ownership of the underlying asset, or the Company is reasonably certain to exercise an option to purchase the underlying asset. In those cases, the ROU asset is amortized over the useful life of the underlying asset. Amortization of the ROU asset is recognized and presented separately from interest expense on the lease liability. The Company has elected not to recognize ROU assets and lease liabilities for all short-term leases that have a lease term of 12 months or less at lease commencement. Lease payments associated with short-term leases are recognized as an expense on a straight-line basis over the lease term. Asset Retirement Obligations Accounting for asset retirement obligations requires legal obligations associated with the retirement of long-lived assets to be recognized at fair value when incurred and capitalized as part of the related long-lived asset. In the absence of quoted market prices, the Company estimates the fair value of its asset retirement obligations using Level 3 present value techniques, in which estimates of future cash flows associated with retirement activities are discounted using a credit-adjusted risk-free rate. Asset retirement obligations currently reported on the Company’s consolidated balance sheets were measured during a period of historically low interest rates. The impact on measurements of new asset retirement obligations using different rates in the future may be significant. The Company uses estimates to determine the asset retirement obligations at the end of the lease term and discounts such asset retirement obligations using an estimated discount rate. Interest on the discounted asset retirement obligation is amortized over the term of the lease using the effective interest method and is recorded as interest expense in the consolidated statements of operations and comprehensive loss. F-13 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The change in asset retirement obligations is as follows (in thousands): Balance at beginning of period Additional asset retirement obligations during the period Amortization of interest Effects of exchange rate changes Balance at end of period $ $ 2,081 $ 9 168 (79) 2,179 $ 1,814 120 148 (1) 2,081 For the Years Ended December 31, 2022 2021 Share-Based Compensation Expense Options The Company grants share options to employees, non-employee members of the Company’s board of directors and non-employee consultants as compensation for services performed. Employee and non-employee members of the board of directors’ awards of share-based compensation are accounted for in accordance with ASC 718, Compensation – Stock Compensation, or ASC 718. ASC 718 requires all share-based payments to employees and non-employee directors, including grants of share options, to be recognized in the consolidated statement of operations and comprehensive loss based on their grant date fair values. The grant date fair value of share options is estimated using the Black-Scholes option valuation model. Using this model, fair value is calculated based on assumptions with respect to (i) the fair value of the Company’s ordinary shares on the grant date; (ii) expected volatility of the Company’s ordinary share price, (iii) the periods of time over which the optionees are expected to hold their options prior to exercise (expected term), (iv) expected dividend yield on the Company’s ordinary shares, and (v) risk-free interest rates. The assumptions underlying these valuations represented management’s best estimate, which involved inherent uncertainties and the application of management’s judgment. As a result, if the Company had used different assumptions or estimates, the fair value of its ordinary shares and its share-based compensation expense could have been materially different. The fair value of ordinary shares after the Company’s IPO was determined based upon the closing share price on the date of grant. Since the Company’s ordinary shares had not been traded on a public exchange prior to the Company’s IPO and have only been traded on a public exchange for a short period of time since the Company’s IPO, the Company believes that it does not have sufficient company-specific information available to determine the expected term based on its historical data. As a result, the expected term of share options granted to the optionees is determined using the average of the vesting period and contractual life of the option, an accepted method for the Company’s option grants under the Securities and Exchange Commission’s (“SEC”) Staff Accounting Bulletin No. 107 and No. 110, Share-Based Payment. Similarly, the Company believes that its future volatility could differ materially during the expected term from the volatility that would be calculated from its historical share prices to date. Consequently, expected volatility is based on an analysis of guideline companies and the Company’s own volatility in accordance with ASC 718. The expected dividend yield is zero as the Company has never paid dividends and does not currently anticipate paying any in the foreseeable future. Risk-free interest rates are based on quoted U.S. Treasury rates for securities with maturities approximating the option’s expected term. F-14 Table of Contents Restricted Share Units MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The Company grants restricted share units (“RSUs”) to employees, non-employee members of the Company’s board of directors and non-employee consultants as compensation for services performed. Awards of RSUs are accounted for in accordance with ASC 718, Compensation – Stock Compensation, or ASC 718. ASC 718 requires all share-based payments to employees, non-employee members of the Company’s board of directors and non-employee consultants, including grants of RSUs, to be recognized in the consolidated statement of operations and comprehensive loss based on their grant date fair values. The grant date fair value of RSUs is determined using the closing market price of the Company’s ordinary shares on the date of grant. Collaboration Arrangements The Company evaluates its collaborative arrangements pursuant to ASC 808, Collaborative Arrangements (“ASC 808”) and ASC 606, Revenue from Contracts with Customers (“ASC 606”). The Company considers the nature and contractual terms of collaborative arrangements and assesses whether the arrangement involves a joint operating activity pursuant to which the Company is an active participant and is exposed to significant risks and rewards with respect to the arrangement. If the Company is an active participant and is exposed to significant risks and rewards with respect to the arrangement, the Company accounts for the arrangement as a collaboration under ASC 808. To date, the Company has entered into two separate collaboration agreements, both of which are with Janssen, which were determined to be within the scope of ASC 808. ASC 808 does not address recognition or measurement matters related to collaborative arrangements. Payments between participants pursuant to a collaborative arrangement that are within the scope of other authoritative accounting literature on income statement classification are accounted for using the relevant provisions of that literature. If the payments are not within the scope of other authoritative accounting literature, the income statement classification for the payments is based on an analogy to authoritative accounting literature or if there is no appropriate analogy, a reasonable, rational and consistently applied accounting policy election. Payments received from a collaboration partner to which this policy applies may include upfront payments in respect of a license of intellectual property, development and commercialization-based milestones, and royalties. Refer to the discussion in Note 12 for further information related to the accounting for the Collaboration Agreement. Revenue Recognition Arrangements with collaborators may include licenses to intellectual property, research and development services, manufacturing services for clinical and commercial supply, and participation on joint steering committees. The Company evaluates the promised goods or services to determine which promises, or group of promises, represent performance obligations. In contemplation of whether a promised good or service meets the criteria required of a performance obligation, the Company considers the stage of development of the underlying intellectual property, the capabilities and expertise of the customer relative to the underlying intellectual property, and whether the promised goods or services are integral to or dependent on other promises in the contract. When accounting for an arrangement that contains multiple performance obligations, the Company must develop judgmental assumptions, which may include market conditions, reimbursement rates for personnel costs, development timelines and probabilities of regulatory success to determine the stand-alone selling price for each performance obligation identified in the contract. When the Company concludes that a contract should be accounted for as a combined performance obligation and recognized over time, the Company must then determine the period over which revenue should be recognized and the method by which to measure revenue. The Company generally recognizes revenue using a cost-based input method. F-15 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The Collaboration Agreement with Janssen is accounted for under ASC 808, however, as ASC 808 does not address recognition or measurement matters such as determining the appropriate unit of accounting or when the recognition criteria are met, the Company accounts for the consideration received from Janssen in accordance with ASC 606. In accordance with ASC 606, the Company recognizes revenue when its customer or collaborator obtains control of promised goods or services, in an amount that reflects the consideration which the Company 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. v. allocate the transaction price to the performance obligations within the contract; and recognize revenue when (or as) the entity satisfies a performance obligation. The Company only applies the five-step model to contracts when it determines that it is probable it 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 by analogy within the scope of ASC 606, the Company assesses the goods or services promised within the contract to determine whether each promised good or service is a performance obligation. The promised goods or services in the Company’s arrangements typically consist of a license to the Company’s intellectual property and research, development and manufacturing services. The Company may provide options to additional items in such arrangements, which are accounted for as separate contracts when the customer elects to exercise such options, unless the option provides a material right to the customer. Performance obligations are promises in a contract to transfer a distinct good or service to the customer that (i) the customer can benefit from on its own or together with other readily available resources, and (ii) is separately identifiable from other promises in the contract. Goods or services that are not individually distinct performance obligations are combined with other promised goods or services until such combined group of promises meet the requirements of a performance obligation. The Company determines transaction price based on the amount of consideration the Company expects to receive for transferring the promised goods or services in the contract. Consideration may be fixed, variable, or a combination of both. At contract inception for arrangements that include variable consideration, the Company estimates the probability and extent of consideration it expects to receive under the contract utilizing either the most likely amount method or expected amount method, whichever best estimates the amount expected to be received. The Company then considers any constraints on the variable consideration and includes in the transaction price variable consideration to the extent it is deemed probable that a significant reversal in the amount of cumulative revenue recognized will not occur when the uncertainty associated with the variable consideration is subsequently resolved. The Company then allocates the transaction price to each performance obligation based on the relative standalone selling price and recognizes as revenue the amount of the transaction price that is allocated to the respective performance obligation when (or as) control is transferred to the customer and the performance obligation is satisfied. For performance obligations which consist of licenses and 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. The Company evaluates the measure of progress each reporting period and, if necessary, adjusts the measure of performance and related revenue recognition. F-16 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The Company records amounts as accounts receivable when the right to consideration is deemed unconditional. When consideration is received, or such consideration is unconditionally due, from a customer prior to transferring goods or services to the customer under the terms of a contract, a contract liability is recorded as deferred revenue. Amounts received prior to satisfying the revenue recognition criteria are recognized as deferred revenue in the Company’s consolidated balance sheet. Amounts expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue – related party, current. Amounts not expected to be recognized as revenue within the 12 months following the balance sheet date are classified as deferred revenue – related party. The Company’s collaboration revenue arrangements include the following: Up-front License Fees: If a license is determined to be distinct from the other performance obligations identified in the arrangement, the Company recognizes revenues from nonrefundable, up-front fees allocated to the license when the license is transferred to the licensee and the licensee 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, adjusts the measure of performance and related revenue recognition. Milestone Payments: At the inception of an agreement that includes research and development milestone payments, the Company evaluates each milestone to determine when and how much of the milestone to include in the transaction price. The Company first estimates the amount of the milestone payment that the Company could receive using either the expected value or the most likely amount approach. The Company primarily uses the most likely amount approach as that approach is generally most predictive for milestone payments with a binary outcome. Then, the Company considers whether any portion of that estimated amount is subject to the variable consideration constraint (that is, whether it is probable that a significant reversal of cumulative revenue would not occur upon resolution of the uncertainty.) The Company updates the estimate of variable consideration included in the transaction price at each reporting date which includes updating the assessment of the likely amount of consideration and the application of the constraint to reflect current facts and circumstances. Royalties: For arrangements that include sales-based royalties, including milestone payments based on a level of sales, and the license is deemed to be the predominant item to which the royalties relate, the Company will recognize revenue 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). To date, the Company has not recognized any revenue related to sales-based royalties or milestone payments based on the level of sales. Research and Development Services: The Company is incurring research and development costs, with Janssen responsible for up to 100% of the costs, depending on the type of research and development services being performed. The Company records costs associated with the development activities as research and development expenses in the consolidated statement of operations and comprehensive loss consistent with ASC 730, Research and Development. The reimbursement of the research and development costs by Janssen is representative of the joint risk sharing nature of the arrangement. The Company considered the guidance in ASC 808 and recognizes the payments received from Janssen as a reduction to research and development expense when the related costs are incurred. Research and Development Research and development costs are charged to expense as incurred. These costs include, but are not limited to, employee-related expenses, including salaries, benefits and travel of the Company’s research and development F-17 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS personnel; expenses incurred under agreements with contract research organizations and investigative sites that conduct clinical and preclinical studies and for the drug product for the clinical studies and preclinical activities; facilities; supplies; rent, insurance, certain legal fees, share-based compensation, depreciation, other costs associated with clinical and preclinical activities and regulatory operations and acquisition of in process research and development write-offs. Research funding under collaboration agreements and refundable research and development credits / tax credits are recorded as an offset to these costs. Costs for certain development activities, such as Company funded outside research programs, are recognized based on an evaluation of the progress to completion of specific tasks with respect to their actual costs incurred. Payments for these activities are based on the terms of the individual arrangements, which may differ from the pattern of costs incurred, and are reflected in the consolidated financial statements as prepaid or accrued research and development expenses, as the case may be. Foreign Currencies The Company’s consolidated financial statements are presented in U.S. dollars, the reporting currency of the Company. The financial position and results of operations of Meira UK II, Meira Ireland, Meira Netherlands, Meira Belgium and Meira B.V. are measured using the foreign subsidiaries’ local currency as the functional currency. These entities’ cash accounts holding U.S. dollars are remeasured based upon the exchange rate at the date of remeasurement with the resulting gain or loss included in the consolidated statements of operations and comprehensive loss. Expenses of such subsidiaries have been translated into U.S. dollars at average exchange rates prevailing during the period. Assets and liabilities have been translated at the rates of exchange on the consolidated balance sheet dates. The resulting translation gain and loss adjustments are recorded directly as a separate component of shareholders' equity and as other comprehensive loss on the consolidated statements of operations and comprehensive loss. Income Taxes Income taxes are recorded in accordance with ASC 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. Realization of net deferred tax assets is dependent on future taxable income. 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. Realization of net deferred tax assets is dependent on future taxable income (see Note 11). 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, 2022 and 2021, the Company recorded unrecognized tax positions of $0.9 and $0.7 million, respectively. No interest and penalties have been accrued relative to the unrecognized tax positions. The Company is required to estimate income taxes in each of the jurisdictions in which it operates. Net Loss per Ordinary Share Basic net loss per ordinary share is computed by dividing net loss by the weighted average number of shares of the Company’s ordinary shares outstanding during the period of computation. Diluted net loss per ordinary share is F-18 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS computed similar to basic net loss per share except that the denominator is increased to include the number of additional ordinary shares that would have been outstanding if the ordinary share equivalents had been issued at the beginning of the year and if the additional ordinary shares were dilutive (treasury stock method) or the two-class method, whichever is more dilutive. For all periods presented, basic and diluted net loss per ordinary share are the same as any additional ordinary share equivalents would be anti-dilutive. The following securities are considered to be ordinary share equivalents, but were not included in the computation of diluted net loss per ordinary share because to do so would have been anti-dilutive: Share options Restricted share units Warrants Restricted ordinary shares subject to forfeiture Other Comprehensive Loss December 31, December 31, 2022 6,858,409 2,182,500 700,000 14,049 9,754,958 2021 5,924,690 1,415,000 — 173,097 7,512,787 Other comprehensive loss is defined as the change in equity of a business enterprise during a period from transactions and other events and circumstances from non-owner sources. The only component of other comprehensive loss impacting the Company is foreign currency translation. Segment Information Management has concluded it has a single reporting segment for purposes of reporting financial condition and results of operations. The Company’s license revenue, research funding and deferred revenue from its Collaboration Agreement are generated in the United Kingdom. The following table summarizes long-lived assets by geographical area (in thousands): United States United Kingdom European Union December 31, 2022 December 31, 2021 20,809 37,778 105,311 163,898 $ $ 23,636 43,349 69,936 136,921 $ $ Recent 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 adds a new Topic 326 to the Codification and removes the thresholds that companies apply to measure credit losses on financial instruments measured at amortized cost, such as loans, receivables, and held-to-maturity debt securities. Under current GAAP, companies generally recognize credit losses when it is probable that the loss has been incurred. The revised guidance will remove all recognition thresholds and will require companies to recognize an allowance for credit losses for the difference between the amortized cost basis of a financial instrument and the amount of amortized cost that the company expects to collect over the instrument’s contractual life. ASU 2016-13 also amends the credit loss measurement guidance for available-for-sale debt securities and beneficial interests in securitized financial assets. The guidance is applicable for fiscal years beginning after December 15, 2019 and interim periods within those years, however, the FASB extended the F-19 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS effective date for smaller reporting companies to fiscal years beginning after December 15, 2022. The Company does not believe that the adoption of this standard will have a significant impact on its related disclosures. 3. Acquisition Bullseye Therapeutics, Inc. On October 4, 2021 (the “Bullseye Closing Date”), the Company acquired the stock of Bullseye, a company engaged in developing mechanisms to deliver retinal drugs and gene therapies to the eye. As a result, Bullseye is a wholly- owned subsidiary of the Company and was renamed MeiraGTx Therapeutics, Inc. In connection with the acquisition of Bullseye, the consideration to Bullseye’s selling stockholders consisted of an aggregate of 80,276 of the Company’s ordinary shares of which (i) 12,040 ordinary shares were issued on the Bullseye Closing Date, (ii) 28,097 restricted ordinary shares were issued on the Bullseye Closing Date, with 50% of such restricted ordinary shares scheduled to vest on each of the first and second anniversaries of the Bullseye Closing Date, and (iii) 40,139 ordinary shares will be issued 18 months following the Bullseye Closing Date, provided that the shares described in clauses (ii) and (iii) are subject to certain indemnification claims under the Bullseye Merger Agreement. The Company also assumed $0.5 million of Bullseye’s liabilities (“Assumed Liabilities”). Total consideration of $1.5 million was based on the closing price of the Company’s ordinary shares of $13.31 per share on October 1, 2021, plus the Assumed Liabilities. The Company determined this transaction represented an asset acquisition as substantially all of the value was in the intellectual property as defined by ASC 805, Business Combinations (“ASC 805”). The asset acquisition of in-process research and development was recorded at a fair value of $1.5 million as of October 4, 2021. The acquired in process research and development was immediately charged to research and development expense in the consolidated statement of operations and comprehensive loss as of the acquisition date since the Company determined that there was no alternative future use for these assets. The 40,139 ordinary shares that are to be issued 18 months following the Bullseye Closing Date were recorded as a liability at a fair value of $0.5 million on the Bullseye Closing Date. At December 31, 2022 and 2021, the liability was revalued to $0.3 million and $1.0 million, respectively, based upon the closing price of the Company’s ordinary shares of $6.52 and $23.74 per share on December 31, 2022 and 2021, respectively. The $0.7 million and $0.5 million change in fair value was recorded as a fair value adjustment for the years ended December 31, 2022 and 2021, respectively. The change in fair value was included as part of research and development expenses in the prior year, but for comparative purposes it has been presented as a fair value adjustment in the consolidated statements of operations and comprehensive loss. 4. Equity Method and Other Investments The Company’s investments consist of the following (in thousands): Investee Visiogene LLC Other Total equity method and other investments Investment Type Equity Method Investment Equity Investment December 31, 2022 Ownership Percentage Carrying Value Cost Basis 5,156 $ 5,165 1,500 1,170 25 % $ 1.6 % $ 6,326 $ 6,665 F-20 Table of Contents Visiogene LLC MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS On January 4, 2021, the Company and Visiogene LLC (“Visiogene”) entered into a License and Investment Agreement (“Visiogene License Agreement”) for an exclusive, worldwide license to certain of Visiogene’s intellectual property relating to ocular gene therapy. Concurrently, the Company and Visiogene entered into a Preferred Unit Purchase Agreement (“Visiogene Unit Agreement”) pursuant to which the Company purchased 3,000,000 Visiogene preferred units. In connection with the two Visiogene agreements, the Company paid $5.0 million in cash and issued to Visiogene 75,000 ordinary shares of the Company with a fair market value of $1.2 million based on the closing price of the Company’s ordinary shares on the date of closing. The Company accounted for the payments under the Visiogene License Agreement and Visiogene Unit Agreement as a basket transaction and allocated $1.0 million to the Visiogene License Agreement and the remaining $5.2 million was allocated to the Visiogene preferred units. The $1.0 million allocated to the Visiogene License Agreement was expensed as acquired in-process research and development as the Company determined there was no alternative future use. The Company accounts for this investment using the equity method of accounting. During the years ended December 31, 2022 and 2021, the Company recorded de minimis research and development expenses related to the Company’s share of Visiogene’s losses. Other Equity Investment During the year ended December 31, 2022, the Company recognized a $0.3 million impairment due to the dilution of the Company’s ownership percentage of the investment. The $0.3 million impairment was recorded as a fair value adjustment for the year ended December 31, 2022. 5. Prepaid Expenses Prepaid expenses at December 31, 2022 and 2021 consist of the following (in thousands): Clinical trial costs Research and development Insurance Dues and license fees Facilities costs Manufacturing costs Other December 31, 2022 December 31, 2021 3,411 1,220 1,485 909 539 347 222 8,133 $ $ 2,322 991 2,122 1,185 455 624 403 8,102 $ $ F-21 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS 6. Property, Plant and Equipment, net Property, plant and equipment, net at December 31, 2022 and 2021 consist of the following (in thousands): Leasehold improvements Manufacturing equipment Laboratory equipment Computer and office equipment Furniture and fixtures Less: Accumulated depreciation December 31, 2022 December 31, 2021 91,053 17,373 13,804 6,787 642 129,659 (20,393) 109,266 $ $ 60,878 12,156 10,868 5,750 687 90,339 (14,479) 75,860 $ $ In connection with certain operating leases, the Company has determined that it has asset retirement obligations in the aggregate amount of $3.9 million at the end of those leases. The Company discounted the asset retirement obligations using an 8% discount rate and recorded an asset retirement obligation in the aggregate amount of $1.8 million, which is included in leasehold improvements and is being amortized over the term of the respective leases. Depreciation and amortization expense related to property, plant and equipment was $7.3 million and $6.3 million for the years ended December 31, 2022 and 2021, respectively. 7. Intangible Assets In November 2020, the Company entered into a non-exclusive, royalty-free technology license agreement that required the Company to pay an upfront payment to the licensor of $2.1 million. The Company accounted for the transaction as an asset acquisition and recorded an intangible asset as it was determined to have alternative future uses in connection with the Company’s manufacturing capabilities. The following table presents the details of the Company’s intangible assets as of December 31, 2022 and 2021 (in thousands): Licensed Technology Less: Accumulated amortization December 31, 2022 December 31, 2021 $ $ 1,900 (565) 1,335 $ $ 2,119 (328) 1,791 The intangible asset is being amortized over a period of seven years. Amortization expense of $0.2 million and $0.3 million was recorded as a component of research and development expenses for the years ended December 31, 2022 and 2021, respectively. F-22 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS As of December 31, 2022, the expected amortization expense for the next five years and thereafter is as follows (in thousands): 2023 2024 2025 2026 2027 Thereafter Total amortization 8. Accrued Expenses Amortization Expense $ $ 272 272 272 272 247 — 1,335 Accrued expenses at December 31, 2022 and 2021 were comprised of the following (in thousands): Clinical trial costs Compensation and benefits Research and development Manufacturing costs Fixed assets Professional fees Consulting Other 9. Share-Based Compensation Equity Incentive Plans December 31, 2022 December 31, 2021 $ $ 13,041 9,600 7,400 4,326 3,093 732 694 932 39,818 $ $ 12,524 6,029 1,735 2,889 2,077 1,018 858 456 27,586 The Company’s 2018 Incentive Award Plan and 2016 Equity Incentive Plan (collectively, the “Plans”), were adopted by the Company’s board of directors and shareholders. Under the Plans, the Company has granted share options and restricted share units (“RSUs”) to selected officers, employees, non-employee members of the Company’s board of directors and non-employee consultants. The Company’s board of directors or a committee thereof administers the Plans. Upon the adoption of the 2018 Incentive Award Plan, the Company ceased issuing awards under the 2016 Equity Incentive Plan. The number of shares available for issuance under the 2018 Incentive Award Plan are increased on January 1 of each calendar year beginning in 2019 and ending in and including 2028, by an amount equal to the lesser of (A) 4% of the ordinary shares outstanding on the final day of the immediately preceding calendar year and (B) a smaller number of shares determined by the Company's board of directors. Under the 2018 Incentive Award Plan the Company initially reserved up to 3,054,996 shares for issuance, which has been increased to 9,171,660 as of December 31, 2022. As of December 31, 2022, 843,802 shares remain available for future issuance. In January 2023, the number of shares available for issuance under the 2018 Incentive Award Plan increased by 1,939,088 shares. Also, in February 2023, the Company’s board of directors approved up to 2,250,000 options and restricted share units to be granted to certain executives, employees and consultants, in each case, under the 2018 Incentive Award Plan. F-23 Table of Contents Options MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS A summary of the Company’s share option activity related to employees, non-employee members of the board of directors and non-employee consultants as of and for the years ended December 31, 2022 and 2021 is as follows (in thousands, except share and per share amounts): Weighted- Average Exercise Price Weighted- Average Remaining Contractual Term (years) Number of Options Outstanding at December 31, 2020 Granted Exercised Forfeited Outstanding at December 31, 2021 Granted Exercised Forfeited Outstanding at December 31, 2022 Options exercisable at December 31, 2022 Aggregate intrinsic value of options outstanding as of December 31, 2022 Aggregate intrinsic value of options exercisable as of December 31, 2022 5,924,690 1,492,400 4,824,771 1,667,700 $ $ (186,638) $ (381,143) $ $ $ (27,081) $ (531,600) $ $ $ 6,858,409 4,547,271 $ $ 1,819 1,810 11.85 15.53 9.16 12.22 13.16 18.54 8.53 17.52 14.03 12.18 7.40 years 6.86 years 6.00 years Options granted under the Plans have a maximum contractual term of ten years. Options granted generally vest 25% on the first anniversary of the date of grant and the balance ratably over the next 36 months. Options granted to directors when they join the board generally vest in 36 equal monthly installments following the date of grant, and annual options granted to directors generally vest on the earlier of the first anniversary of the date of grant or the day before the Company’s next annual meeting of shareholders after the date of grant. The total share-based compensation expense recorded in connection with the options was $16.1 million and $14.8 million, of which $5.7 million and $6.2 million was recorded as general and administrative expense and $10.4 million and $8.6 million was recorded as research and development expense during the years ended December 31, 2022 and 2021, respectively. The total fair value of options vested during the years ended December 31, 2022 and 2021 was $16.2 million and $14.4 million, respectively. The weighted average grant date fair value of options granted during the years ended December 31, 2022 and 2021 was $12.81 and $11.44, respectively. The grant date fair values of the share options granted were estimated using the Black-Scholes option valuation model with the following ranges of assumptions (see Note 2): Risk-free interest rate Expected volatility Expected dividend yield Expected term (in years) 2022 2021 1.56 - 4.23% 0.62 - 1.39% 80% 0% 5.5 - 6.1 90% 0% 5.5 - 6.1 F-24 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS As of December 31, 2022, the total compensation expense relating to unvested options granted that had not yet been recognized was $24.7 million, which is expected to be recognized over a period of 4.0 years. The Company will issue shares upon exercise of options from ordinary shares reserved under the Plans. Restricted Share Units A summary of the Company’s RSU activity related to employees, non-employee members of the board of directors and non-employee consultants for the years ended December 31, 2022 and 2021 is as follows: Outstanding at December 31, 2020 Granted Vested Forfeited Outstanding at December 31, 2021 Granted Vested Forfeited Outstanding at December 31, 2022 Weighted- Average Grant Date Fair Value Number of Restricted Share Units 545,000 870,000 $ $ — $ — $ $ $ $ $ $ 1,415,000 1,180,000 (397,500) (15,000) 2,182,500 20.02 15.36 — — 17.16 20.12 18.40 8.25 18.59 RSUs granted generally vest 50% on the second anniversary of the date of grant and 25% on the third and fourth anniversaries of the date of grant. Annual RSUs granted to directors generally vest in a single installment on the earliest to occur of the first anniversary of the grant date or the day immediately prior to the date of the next annual meeting of the Company’s shareholders occurring after the date of grant. The RSUs granted to the directors in June 2021 will be paid on or within 30 days after the date a director ceases to serve on the board. For RSUs granted in future years, the directors may elect whether to defer the payment of their annual RSU awards under the Deferred Compensation Plan for Non-Employee Directors, which was adopted by the board on December 17, 2021. The related share-based compensation expense, which is recognized ratably over the requisite service period, is included in general and administrative and research and development expenses, as applicable, in the consolidated statements of operations and comprehensive loss. Total share-based compensation expense recorded in connection with the RSUs was $12.5 million and $6.0 million, of which $8.8 million and $4.9 million was recorded as general and administrative expense and $3.7 million and $1.1 million was recorded as research and development expense during the years ended December 31, 2022 and 2021, respectively. As of December 31, 2022, the total compensation expense relating to unvested RSUs granted that had not yet been recognized was $26.9 million, which is expected to be recognized over a period of 3.0 years. During the years ended December 31, 2022 and 2021 the Company recognized total share-based compensation expense in the accompanying consolidated statements of operations and comprehensive loss as follows (in thousands): Research and development General and administrative Total share-based compensation Years Ended December 31, 2021 2022 $ $ 14,165 14,458 28,623 $ $ 9,685 11,099 20,784 F-25 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The Company does not expect to realize any tax benefits from its share option activity or the recognition of share- based compensation expense because the Company currently has net operating losses and has a full valuation allowance against its deferred tax assets. Accordingly, no amounts related to excess tax benefits have been reported in cash flows from operations or cash flows from financing activities for the years ended December 31, 2022 and 2021. 10. Ordinary Shares 2022 Private Placement On November 9, 2022, the Company entered into a securities purchase agreement with Johnson & Johnson Innovation – JJDC, Inc. (“JJDC”), the investment arm of Johnson & Johnson, pursuant to which the Company, in a private placement, agreed to issue and sell to JJDC an aggregate of 3,742,514 ordinary shares at a purchase price of $6.68 per share, for gross proceeds of approximately $25.0 million. 2021 Equity Method and Other Investments As discussed in Note 3, on January 4, 2021, the Company issued 75,000 ordinary shares in connection with the Visiogene transaction in the amount of $1.2 million. Acquisitions As discussed in Note 3, on October 4, 2021 the Company issued 12,040 ordinary shares as well as 28,097 ordinary shares which are subject to vesting in connection with the Bullseye acquisition. On October 9, 2021, the Company issued 58,000 holdback ordinary shares in connection with a previous acquisition. 11. Income Taxes For the years ended December 31, 2022 and 2021, the Company recognized a tax benefit of $0. As of December 31, 2022, the Company had U.S. federal and state net operating losses (“NOLs”) and foreign carryforward tax losses which are available to reduce future taxable income of (in thousands): United Kingdom United States Other Federal $ 187,939 63,829 $ 22,274 $ State/City $ — 64,405 $ — $ The U.S. federal and state NOLs incurred prior to January 1, 2018 in the amount of approximately $1.0 million and $0.8 million, respectively, will begin to expire in 2036. The U.S. NOLs incurred after December 31, 2017 and the UK carryforward tax losses will be indefinitely carried forward. Also, as of December 31, 2022, the Company had orphan drug and research and development credits in the U.S. in the amount of $9.4 million which will begin to expire in 2036 and research and development credits of $2.4 million in the UK which can be carried forward indefinitely. The U.S. NOLs and UK carryforward tax losses may become subject to an annual limitation in the F-26 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS event of certain cumulative changes in the ownership interest of significant shareholders, as defined under Section 382 of the Internal Revenue Code, as well as UK tax rules. This could limit the amount of NOLs and carryforward tax losses that the Company can utilize annually to offset future taxable income or tax liabilities. As of December 31, 2021, the Company had performed such an analysis and determined that there were no limitations in the UK. However, for U.S. purposes, the Company determined that a change of ownership occurred in April 2016 and again in June 2018. The Company is still in the process of determining the annual limitation on losses that occurred prior to June 2018. The Company’s pre-tax loss is as follows (in thousands): United Kingdom United States Other F-27 $ December 31, 2022 December 31, 2021 (17,056) (49,223) (13,282) (79,561) (54,636) $ (54,513) (20,467) (129,616) $ $ Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS The Company is subject to the corporate tax rate in the UK as a limited UK corporation. The following table summarizes a reconciliation of income tax benefit compared with the amounts at the UK statutory income tax rate (in thousands): Statutory rate Permanent differences - other RTP and other adjustment State and local rate, net of federal tax U.K. tax credit U.S. tax credit Foreign tax rate differential UK rate change (25% & 19% at expected DTA turn) US state rate change Section 162(m) deferred adjustment Change in valuation allowance Actual income tax benefit effective tax rate December 31, 2022 December 31, 2021 (24,627) 2,323 1,244 19.00 % (1.79)% (0.96)% (15,117) 934 (2,735) 19.00 % (1.17)% 3.44 % (5,660) 2,296 (2,436) 195 4.37 % (1.77)% 1.88 % (0.15)% (1,973) (3) 1,386 27,255 1.52 % 0.00 % (1.07)% (21.03)% (5,850) (1,464) (1,491) (540) 7.35 % 1.84 % 1.87 % 0.68 % (10,247) (447) — 36,957 12.88 % 0.56 % 0.00 % (46.45)% — 0.00 % — 0.00 % The Expense/(Benefit) for income taxes from continuing operations consists of the following (in thousands): Current Tax Expense/(Benefit) United Kingdom United States Other Total Current Deferred Tax Expense/(Benefit) United Kingdom United States Other Total Deferred Change in Valuation Allowance Total Income Tax Expense/(Benefit) December 31, 2022 December 31, 2021 — — — — (8,708) (17,466) 219 (25,955) 25,955 — — — — — (16,079) (17,369) (3,509) (36,957) 36,957 — F-28 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS Deferred Tax Assets/(Liabilities) (in thousands): Deferred Tax Assets: Net operating loss carryforwards Capitalized research and development Share-based compensation R&D credit Lease liability Other Deferred tax assets Deferred Tax Liabilities: Indefinite-lived intangibles and fixed assets Depreciation Right of use assets Less: valuation allowance Net deferred tax liability $ $ December 31, 2022 December 31, 2021 74,350 16,288 13,684 10,837 6,461 3,745 125,365 (186) (2,935) (6,207) (116,223) (186) $ $ 74,007 — 10,314 7,498 7,040 1,481 100,340 (196) (3,339) (6,733) (90,268) (196) ASC 740 requires a valuation allowance to reduce the deferred tax assets reported if, based on the weight of available evidence, it is more likely than not that some portion or all of the deferred tax assets will not be realized. After consideration of all the evidence, both positive and negative, the Company has recorded a full valuation allowance, after consideration of the reversal of the deferred tax liabilities for the ROU assets and fixed assets, against its deferred tax assets at December 31, 2022 and 2021 because the Company's management has determined that is it more likely than not that these assets will not be fully realized. Changes to the UK corporation tax rates have been announced which will impact future accounting periods. Finance Act 2021 increases the UK corporation tax rate from 19% to 25% effective April 1, 2023 for companies with profits in excess of GBP 250,000. As the Company does not expect to be able to utilize its carryforward tax losses in the UK until after April 2023, the deferred tax has been calculated using a tax rate of 25%. As of December 31, 2022 and 2021, the Company recorded unrecognized tax positions of $0.9 million and $0.7 million, respectively. The unrecognized tax positions are netted with deferred tax assets above with full valuation allowance. The changes to unrecognized tax positions for 2022 and 2021 were as follows (in thousands): Unrecognized tax benefits as of January 1 Gross increases/(decreases) related to current year Gross increases/(decreases) related to prior years Foreign currency translation Unrecognized tax positions as of December 31 December 31, 2022 December 31, 2021 513 666 $ $ 165 279 (12) (8) — — 666 937 $ $ The Company will recognize interest and penalties related to uncertain tax positions in income tax expense. As of December 31, 2022 and 2021, the Company had no accrued interest or penalties related to uncertain tax positions and no amounts have been recognized in the Company's statements of operations and comprehensive loss. The Company files income tax returns in the United States, UK, various foreign jurisdictions and various U.S. state jurisdictions. In the U.S., all years remain subject to examination. The earliest year subject to examination in the UK is 2020. F-29 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS MeiraGTx Holdings plc is a UK tax resident with no earnings in its foreign subsidiaries and the Company does not expect any temporary basis difference in its investment in these subsidiaries to reverse in the foreseeable future. Therefore, the Company has not recorded deferred taxes on the outside basis difference in its foreign subsidiaries. It is not probable to compute the amounts, if any. 12. Related Party Transactions Collaboration and License Agreements Janssen Pharmaceuticals, Inc. On January 30, 2019, the Company entered into a Collaboration Agreement with Janssen for the research, development and commercialization of gene therapies for the treatment of IRD. Under the agreement, Janssen paid the Company a non-refundable upfront fee of $100.0 million. Janssen and the Company will collaborate to develop the Company’s current clinical programs in retinitis pigmentosa and two genetic forms of achromatopsia and Janssen has the exclusive right to commercialize these three product candidates (“Clinical IRD Product Candidates”) globally. Pursuant to the Collaboration Agreement, the Company and Janssen also agreed on a research collaboration to develop a pipeline of preclinical inherited retinal disease gene therapy candidates (“Research IRD Product Candidates”). The parties will select and prioritize the Research IRD Product Candidates and Janssen has the right to opt-in for a fee for each of the specified targets (each an “Option Target”) to obtain certain development, manufacturing and commercialization rights for the Research IRD Product Candidates. Unless terminated earlier under certain termination clauses, the Collaboration Agreement will continue in effect, on a product-by-product and country-by-country basis, until such time as the royalty terms expire in such country. The Company has determined enforceable rights exist in the Collaboration Agreement as the termination clauses are substantive termination penalties by way of the non-refundable upfront fee and the reversion of any licensed intellectual property granted to Janssen upon the termination of the agreement. On February 27, 2019, in connection with a private placement, the Company issued 2,898,550 ordinary shares to JJDC, the investment arm of Johnson & Johnson and owner of Janssen, on the same terms and conditions as the other investors in the offering. After the offering, JJDC became a related party. On November 9, 2022, the Company entered into a securities purchase agreement with JJDC, pursuant to which the Company, in a private placement, agreed to issue and sell to JJDC an aggregate of 3,742,514 ordinary shares at a purchase price of $6.68 per share, for gross proceeds of approximately $25.0 million. Clinical IRD Product Candidates Under the Collaboration Agreement, the Company and Janssen will jointly develop Clinical IRD Product Candidates to permit Janssen to commercialize such Clinical IRD Product Candidates under an exclusive license from the Company. In general, the Company will have the primary responsibility to develop each Clinical IRD Product Candidate in accordance with the development plan for each Clinical IRD Product Candidate, including where applicable, conducting any necessary research in order to submit the applicable regulatory filings to regulatory authorities. The Company will manufacture these products in its cGMP manufacturing facilities for both clinical and commercial supply. Janssen will pay 100% of the clinical and commercialization costs of the products and the Company is eligible to receive untiered 20% royalties on net sales of products and additional development and commercialization milestones up to $340.0 million. The Company received its first milestone payment of $30.0 million in December 2021. F-30 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS Research IRD Product Candidates Under the Collaboration Agreement, the Company and Janssen will collaborate to develop Research IRD Product Candidates, with Janssen paying for the majority of the research costs. Janssen has the right to exclusively license any product coming out of the collaboration at the time of an investigational new drug application for an additional fee for each Research IRD Product Candidate. Janssen will then pay 100% of the clinical and commercialization costs for these Research IRD Product Candidates and the Company will receive an untiered royalty on net sales in the high teens as well as development milestones for each Research IRD Product Candidate. Revenue Recognition under the Collaboration Agreement The Collaboration Agreement is accounted for under ASC 808, however, ASC 808 does not address recognition or measurement matters. Therefore, the Company will account for the recognition and measurement of consideration under ASC 606. In determining the appropriate amount of revenue to be recognized under ASC 606, the Company performed the following steps: (i) identified the promised goods or services in the contract; (ii) determined whether the promised goods or services are performance obligations including whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of revenue when (or as) the Company satisfies each performance obligation. The Company evaluated the potential performance obligations in the contract, which included the exclusive license to Clinical IRD Product Candidates, the research, development and manufacturing services (“the services”), and the participation in various joint committees and determined that none of the performance obligations by themselves were distinct. Goods and services that are not distinct are bundled with other goods or services in the contract until a bundle of goods or services that is distinct is created. The services, when combined with the licenses, represent a bundle and should be accounted for as a single performance obligation due to the relevance of the services to the value of the early-stage license and the potential for the intellectual property to be significantly modified during the services period. The Company also evaluated whether or not the right to purchase exclusive option rights for specified Research IRD Product Candidates represents future performance obligations and concluded that these represent a separate buyer decision at market rates, rather than a material right performance obligation. As such, these options have been excluded from the initial allocation of transaction price and the Company will account for these options as separate contracts when and if Janssen elects to exercise the options. Under ASC 606, the Company recognized collaboration revenue using the cost-to-cost input method, which it believes best depicts the transfer of control to the customer. Under the cost-to-cost input method, the extent of progress towards completion is measured based on the ratio of actual costs incurred to the total estimated costs expected upon satisfying the combined performance obligation by the potential product candidate. Under this method, revenue is being recorded as a percentage of the estimated transaction price based on the extent of progress towards completion. Under ASC 606, the estimated transaction price includes variable consideration subject to constraints. The Company does not include variable consideration to the extent that it is probable that a significant reversal in the amount of cumulative revenue recognized will occur when any uncertainty associated with the variable consideration is resolved. The estimate of the Company’s measure of progress and estimate of variable consideration to be included in the transaction price will be updated at each reporting date as a change in estimate. The amount related to the unsatisfied portion will be recognized as that portion is satisfied over time. Under ASC 606 the Company accounts for (i) the licenses it conveyed with respect to the Clinical IRD Product Candidates and (ii) its obligations to perform services as a single performance obligation under the Collaboration Agreement with Janssen on a product candidate basis. Janssen’s right to purchase exclusive options to obtain certain development, manufacturing and commercialization rights are accounted for separately as they do not represent material rights, based on the criteria of ASC 606. Upon the exercise of any purchased option by Janssen, the contract promises associated with an Option Target would use a separate cost-to-cost model for purposes of revenue recognition under ASC 606. F-31 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS During the year ended December 31, 2019, the Company received a $100.0 million non-refundable upfront fee from Janssen and during the year ended December 31, 2021, the Company received a $30.0 million milestone payment. The Company allocated these amounts plus other variable consideration not subject to constraint to each identified performance obligation using a combination of methods allowable under ASC 606. The Company applies the practical expedient in Topic 606 and does not include disclosures regarding amounts for variable consideration allocated to wholly-unsatisfied performance obligations or wholly-unsatisfied distinct goods that form part of a single performance obligation, if any. This variable consideration includes expected reimbursement of research and development costs. During the years ended December 31, 2022 and 2021, the Company recognized $15.9 million and $37.7 million, respectively, of the deferred revenue – related party as license revenue. The Company also recognized $73.3 million and $69.0 million during the years ended December 31, 2022 and 2021, respectively, related to the reimbursement of research and development expenses. As of December 31, 2022, the Company expects to recognize the remaining $42.6 million in deferred revenue associated with the non-refundable upfront fee and milestone payment over the estimated research and development period using the cost-to-cost input method over an estimated period of approximately 2.9 years. A summary of the deferred revenue recognition is as follows (in thousands): Deferred revenue at December 31, 2020 Milestone payment from Janssen Deferred revenue recognized as license revenue during the year ended December 31, 2021 Effects of exchange rate changes Deferred revenue at December 31, 2021 Deferred revenue recognized as license revenue during the year ended December 31, 2022 Effects of exchange rate changes Deferred revenue at December 31, 2022 $ $ 72,842 30,000 (37,701) (275) 64,866 (15,920) (6,387) 42,559 Debt Financing On August 2, 2022 the Company, as borrower, and Meira UK II and Meira Ireland, as guarantors (the “Subsidiary Guarantors”), entered into a senior secured financing arrangement (the “Financing Agreement”) by and among the Company, the Subsidiary Guarantors, the lenders and other parties from time to time party thereto and Perceptive Credit Holdings III, LP, as administrative agent and lender (“Perceptive”). On December 19, 2022, the Financing Agreement was converted to a note purchase agreement (the “Note Purchase Agreement”) between the same parties and under substantially the same terms and conditions as the Financing Agreement, subject to certain customary note constitution terms. Perceptive Advisors, LLC, an affiliate of Perceptive, is a 15.6% holder of the ordinary shares of the Company. Additionally, Ellen Hukkelhoven, Ph.D., a director of the Company, is an employee of Perceptive Advisors, LLC. Refer to the discussion in Note 14 for further information related to the accounting for the debt financing. Leases ARE Vivarium Lease Effective May 1, 2019, the Company entered into an operating lease for vivarium space with ARE East River Science Park, LLC (“ARE”), which was subsequently amended to add additional space within the vivarium. ARE is under common control of an entity that is a minority shareholder of the Company and whose executive chairman F-32 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS and founder served as a director of the Company through June 2022. The initial lease had a term of twelve months which automatically renews on an annual basis. The rent expense under this operating lease was $0.15 million and $0.09 million for the years ended December 31, 2022 and 2021, respectively, which are included in loss from operations. The Company made cash payments to ARE in connection with this operating lease in the amount of $0.14 million and $0.09 million during the years ended December 31, 2022 and 2021, respectively. There were no amounts due to ARE under this operating lease at December 31, 2022 and 2021. As of December 31, 2022, the Company’s lease commitment is approximately $0.16 million. 13. Leases The Company has commitments under operating leases for laboratory, warehouse, clinical trial sites and office space. The Company also has finance leases for manufacturing space and office equipment. The Company’s leases have initial lease terms ranging from 3 years to 191 years. Certain lease agreements contain provisions for future rent increases. Payments due under the lease contracts include fixed payments. Total rent expense recorded under these leases was $5.3 million and $5.0 million for the years ended December 31, 2022 and 2021, respectively. As of December 31, 2022, the Company has short term lease commitments amounting to approximately $0.2 million on a monthly basis for one lease for vivarium space that is on a one-year lease. On August 4, 2020, Meira Ireland entered into two agreements (the “Agreements”) with Shannon Commercial Enterprises DAC trading as Shannon Commercial Properties, to acquire two properties in the Shannon Free Zone in Shannon, Ireland for an aggregate price of €18 million, or approximately $21.2 million. These properties will serve as the Company’s second, large scale cGMP viral vector manufacturing facility and its first cGMP plasmid and DNA production facility. The closing for the first building occurred in August 2020 and the closing for the second building occurred in January 2021. The total cost of the first and second buildings, including taxes and legal fees, was €11.9 million and €7.5 million, or approximately $13.8 million and $8.9 million, respectively, and have been recorded as right of use assets in the consolidated balance sheets as of December 31, 2021. There is no corresponding lease liability as the Company paid the full cost on the date of the closings. At the closings, Meira Ireland entered into a lease for each property providing for a long leasehold interest of approximately 191 years. The leases also include customary terms and conditions, with a nominal annual lease cost and annual maintenance fees of approximately €0.3 million, or approximately $0.4 million, in the aggregate, which amount is subject to change depending on the annual maintenance costs within the Shannon Free Zone development. During the year ended December 31, 2022, the Company recognized three operating leases for locations in connection with its clinical trials for its IRD product candidates and office and warehouse space, with initial lease terms between 3 years and 9 years. Payments due under the lease contracts include fixed payments. In conjunction with these operating leases, the Company recognized initial operating lease right-of-use assets in the amount of $1.8 million and corresponding lease liabilities in the amount of $1.8 million which are included in the right-of-use assets and lease obligations in the consolidated balance sheets as of December 31, 2022. F-33 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS During the year ended December 31, 2021, the Company recognized seven operating leases for locations in connection with its clinical trials for its IRD product candidates with initial lease terms between 5 years and 6 years. Certain lease agreements contain provisions for tenant allowances and future rent increases. Payments due under the lease contracts include fixed payments. In conjunction with these operating leases, the Company recognized initial operating lease right-of-use assets in the amount of $2.2 million and corresponding lease liabilities in the amount of $2.3 million which are included in the right-of-use assets and lease obligations in the consolidated balance sheets as of December 31, 2021. The components of lease cost for the years ended December 31, 2022 and 2021 are as follows (in thousands): Finance lease cost Amortization of right-of-use assets Interest on lease liabilities Total finance lease cost Operating lease cost Short-term lease cost Total lease cost 2022 2021 $ $ 1,103 1 1,104 5,307 154 6,565 $ $ 1,227 2 1,229 5,002 751 6,982 Amounts reported in the consolidated balance sheets for leases where the Company is the lessee as of December 31, 2022 and 2021 were as follows (in thousands): Operating leases Right-of-use asset Capitalized lease obligations Finance leases Right-of-use asset Capitalized lease obligations Weighted-average remaining lease term Operating leases Finance leases Weighted-average discount rate Operating leases Finance leases December 31, 2022 December 31, 2021 $ $ $ $ 20,109 21,215 24,718 — $ $ $ $ 22,782 23,721 27,645 12 5.3 years 175.8 years 8.8 % 8.0 % 6.5 years 176.7 years 8.5 % 8.0 % Other information related to leases as of the years ended December 31, 2022 and 2021 are as follows (in thousands): Cash paid for amounts included in the measurement of lease liabilities Operating cash flows from finance leases Operating cash flows from operating leases Financing cash flows from finance leases $ $ $ Right-of-use assets obtained in exchange for lease liabilities $ Operating leases $ Finance leases 2022 2021 52 5,384 $ $ — $ 1,793 $ — $ 16 4,969 2 4,424 — F-34 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS Future minimum lease payments under non-cancellable leases as of December 31, 2022 are as follows (in thousands): 2023 2024 2025 2026 2027 Thereafter Total undiscounted lease payments Less: Imputed interest Total lease liabilities 14. Debt Financing $ Operating Leases 5,513 5,379 5,338 5,067 1,794 2,872 25,963 (4,748) 21,215 $ $ On August 2, 2022 the Company, and the Subsidiary Guarantors, entered into the Financing Agreement with Perceptive. On December 19, 2022, the Financing Agreement was converted to a Note Purchase Agreement between the same parties and under substantially the same terms and conditions as the Financing Agreement, subject to certain customary note constitution terms. The Note Purchase Agreement provides for an initial $75.0 million notes issuance (the “Tranche 1 Notes”), and the Company may request an additional $25.0 million notes issuance to be made available at Perceptive’s sole discretion before August 2, 2024 (the “Tranche 2 Notes”, together with the Tranche 1 Notes, the “Notes”). The Note Purchase Agreement matures on August 2, 2026 and is interest-only during the term. The Company has the option to redeem outstanding principal notes at any time along with an applicable early redemption fee. Outstanding amounts under the Note Purchase Agreement bear interest at a fluctuating rate per annum equal to 10.00% plus the secured overnight financing rate administered by the Federal Reserve Bank of New York for a one-month tenor, subject to a 1.00% floor. The annual interest rate was 13.02% at December 31, 2022. As of December 31, 2022, the outstanding balance of the Tranche 1 Notes was $75.0 million plus accrued interest of $4.0 million. During the year ended December 31, 2022, the Company recorded interest expense of $4.0 million. The Company’s obligations under the Note Purchase Agreement are secured by the Company’s London, UK and Shannon, Ireland manufacturing facilities, $3.0 million of the Company’s cash and the bank accounts of the Subsidiary Guarantors, and the issued and outstanding equity interests of the Subsidiary Guarantors. The Note Purchase Agreement imposes covenants that include, among other things, enrolling in a Phase III trial for AAV-RPGR on or before June 30, 2023, and ensuring the Company’s Shannon manufacturing facility meets or satisfies all applicable good manufacturing practice requirements on or before December 31, 2023, as well as various restrictions on the Company and the Subsidiary Guarantors, including restrictions pertaining to: (i) the incurrence of additional indebtedness, (ii) limitations on liens, (iii) limitations on certain investments, (iv) making distributions, dividends and other payments, (v) mergers, consolidations and acquisitions, (vi) dispositions of assets, (vii) the Company’s maintenance of at least $3.0 million in a U.S. bank account, (viii) transactions with affiliates, (ix) changes to governing documents, (x) changes to certain agreements and leases and (xi) changes in control; however, certain of these restrictions contain exceptions which allow the Company to license, sell and monetize assets in its AAV-hAQP1 program in development to treat radiation-induced xerostomia, its AAV-GAD program in development to treat Parkinson’s disease and its gene regulation platform technologies. In connection with entering into the Financing Agreement, the Company granted warrants to Perceptive to purchase up to (i) 400,000 ordinary shares of the Company at an exercise price of $15.00 per share and (ii) 300,000 ordinary F-35 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS shares of the Company at an exercise price of $20.00 per share. The warrants are exercisable immediately and expire on August 2, 2027. The Company recorded a debt discount of $2.3 million for the allocated fair value of the warrants. The Company also capitalized certain lender and legal costs associated with the Note Purchase Agreement totaling $2.2 million, which were recorded as a discount to the loan. The aggregate discount of $4.4 million is being amortized to interest expense over the term of the Note Purchase Agreement. The Company amortized $0.4 million of the discount to interest expense during the year ended December 31, 2022. At December 31, 2022, the remaining unamortized discount was $4.0 million. 15. Commitments and Contingencies There were no new material commitments or contingencies entered into during the year ended December 31, 2022. 16. Employee Benefit Plans United States On January 1, 2017, Meira LLC adopted a defined contribution retirement plan that complies with Section 401(k) of the Internal Revenue Code. All Meira LLC employees over the age of 21 are eligible to participate in the plan after three consecutive months of service. Employees are able to defer a portion of their pay into the plan on the first day of the month or after the day all age and service requirements have been met. The plan provides for a Company matching contribution. All eligible employees receive an employer matching contribution equal to the lesser of the amount the employee contributes to the plan or 6% of their salary up to the annual IRS limit. United Kingdom On August 1, 2016, Meira UK II adopted a defined contribution group personal pension plan that complies with HMRC for tax relief. All Meira UK II employees are eligible to participate in the plan upon joining the company and providing the required services. All eligible employees, if they elect to join the pension scheme, receive an employer pension contribution equal to 7.5% to 10.0% of their pensionable earnings. Currently, employees are required to contribute 0.5%, to meet minimum legal pension funding levels of 8%, but may make optional contributions up to the annual allowance HMRC limits. Netherlands Meira Netherlands operates a defined contribution pension. All of its employees participate in the plan. All eligible employees receive an employer pension contribution and are also required to contribute. Ireland On November 20, 2020, MeiraGTx Ireland adopted a defined contribution pension plan. All MeiraGTx Ireland employees are eligible to participate in the plan upon joining the Company. All eligible employees, if they elect to F-36 Table of Contents MEIRAGTX HOLDINGS PLC AND SUBSIDIARIES NOTES TO CONSOLIDATED FINANCIAL STATEMENTS join the pension scheme, receive an employer pension contribution. The Company’s current contribution, exclusive of an employee match, is 4.5%, which exceeds Revenue Ireland requirements. Belgium Meira Belgium operates a defined contribution pension plan. All eligible employees receive an employer pension contribution of 8% of their annual salary. Employees do not make contributions to the plan. During the years ended December 31, 2022 and 2021, employer contributions to all plans were $2.0 million and $1.8 million, respectively. F-37 Table of Contents ITEM 9. FINANCIAL DISCLOSURE CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND Not Applicable. ITEM 9A. CONTROLS AND PROCEDURES Limitations on Effectiveness of Controls and Procedures In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to their costs. Evaluation of Disclosure Controls and Procedures Our management, with the participation of our Chief Executive Officer (principal executive officer) and Chief Financial Officer (principal financial officer), evaluated, as of the end of the period covered by this Form 10-K, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)). Based on that evaluation, our Chief Executive Officer (principal executive officer) and Chief Financial Officer (principal financial officer) concluded that our disclosure controls and procedures were effective at the reasonable assurance level at the end of the period covered by this Form 10-K. Management’s Report on Internal Control Over Financial Reporting Management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in Exchange Act Rule 13a-15(f). Our internal control over financial reporting is a process designed under the supervision of our Chief Executive Officer and Chief Financial Officer, and affected by our board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of our financial statements for external reporting purposes in accordance with U.S. GAAP and includes policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of our assets, (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with U.S. GAAP, and that our receipts and expenditures are being made only in accordance with authorizations of our management and directors and (iii) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of our 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 the 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 and procedures may deteriorate. Management assessed the effectiveness of our internal control over financial reporting as of December 31, 2022. In making this assessment, management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control—Integrated Framework (2013). Based on its assessment and those criteria, management has concluded that we maintained effective internal control over financial reporting as of December 31, 2022. 124 Table of Contents Exemption from Attestation Report of the Registered Public Accounting Firm on Internal Control Over Financial Reporting This Form 10-K does not include an attestation report on our internal control over financial reporting from our independent registered public accounting firm since we qualify as an “emerging growth company” as defined under the JOBS Act. Changes in Internal Control Over Financial Reporting There were no changes in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d- 15(f) under the Exchange Act) during the quarter ended December 31, 2022 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. ITEM 9B. OTHER INFORMATION Not applicable. ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS Not applicable. 125 Table of Contents PART III ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE The information required by this Item is incorporated by reference to our definitive proxy statement for our 2023 annual shareholder meeting to be filed with the SEC within 120 days of the fiscal year ended December 31, 2022. ITEM 11. EXECUTIVE COMPENSATION The information required by this Item is incorporated by reference to our definitive proxy statement for our 2023 annual shareholder meeting to be filed with the SEC within 120 days of the fiscal year ended December 31, 2022. ITEM 12. RELATED STOCKHOLDER MATTERS SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND Securities Authorized for Issuance Under Equity Compensation Plans (as of December 31, 2022) The following table provides information as of December 31, 2022, regarding our ordinary shares that may be issued under the MeiraGTx Holdings plc 2016 Equity Incentive Plan, as amended (the “2016 Plan”), the MeiraGTx Holdings plc 2018 Incentive Award Plan (the “2018 Plan”) and the MeiraGTx Holdings plc 2018 Employee Stock Purchase Plan (the “2018 ESPP”). Plan category: Equity compensation plans approved by shareholders (a) Number of Securities to be Issued Upon Exercise of Outstanding Options, Warrants, and Rights Weighted-Average Exercise Price of Outstanding Options, Warrants, and Rights (b) Number of Securities Available for Future Issuance Under Equity Compensation Plans (excludes securities reflected in column(a)) (c) 2016 Plan(1) 2018 Plan (2) (3) 2018 ESPP (4) Equity compensation plans not approved by shareholders Total 1,161,766 7,879,143 $ $ — — $ 9,040,909 5.27 15.82 — — 14.03 — 843,802 2,038,331 — 2,882,133 (1) In connection with our IPO, we assumed the 2016 Plan. As the 2016 Plan was previously approved by our shareholders and, as we will not make future grants or awards under these plans, it is listed as “approved by shareholders.” As such, the securities remaining available under the 2016 Plan have been excluded from the table above. (2) Pursuant to the terms of the 2018 Plan, the number of ordinary shares available for issuance under the 2018 Plan automatically increases on each January 1, until and including January 1, 2028, by an amount equal to the lesser of: (a) 4% of the aggregate number of ordinary shares outstanding on the final day of the immediately preceding calendar year and (b) such smaller number of ordinary shares as is determined by our board of directors. (3) The weighted average exercise price of outstanding awards does not take into account the shares issuable upon vesting of outstanding restricted share units which have no exercise price. At December 31, 2022 there were a total of 2,182,500 shares subject to restricted share units included in the Number of Securities to be Issued Upon Exercise of Outstanding Options, Warrants and Rights. (4) Pursuant to the terms of the 2018 ESPP, the number of ordinary shares available for issuance under the 2018 ESPP automatically increases on each January 1, until and including January 1, 2028, by an amount equal to the lesser of: (a) 1% of the aggregate number of ordinary shares outstanding on the final day of the immediately preceding calendar year and (b) such smaller number of ordinary shares as is determined by our board of directors, subject to the limit set forth in the 2018 ESPP. 126 Table of Contents Other The remaining information required by this Item is incorporated by reference to our definitive proxy statement for our 2023 annual shareholder meeting to be filed with the SEC within 120 days of the fiscal year ended December 31, 2022. ITEM 13. INDEPENDENCE CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR The information required by this Item is incorporated by reference to our definitive proxy statement for our 2023 annual shareholder meeting to be filed with the SEC within 120 days of the fiscal year ended December 31, 2022. ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES The information required by this Item is incorporated by reference to our definitive proxy statement for our 2023 annual shareholder meeting to be filed with the SEC within 120 days of the fiscal year ended December 31, 2022. 127 Table of Contents ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES EXHIBIT INDEX PART IV Exhibit Number Exhibit Description Incorporated by Reference Form File No. Exhibit Filing Date Filed/ Furnished Herewith 3.1 4.1 4.2 4.3 4.4 10.1# 10.2# 10.3# 10.4# 10.5 10.6 10.7# 10.8# 10.9# 10.10† Amended and Restated Memorandum and Articles of Association of the Registrant. Specimen Share Certificate evidencing the ordinary shares of the Registrant. Shareholder Agreement. Description of Securities. Form of Warrant Agreement, dated August 2, 2022, issued by MeiraGTx Holdings plc to certain warrant holders. 2016 Equity Incentive Plan, as amended, and form of option agreements thereunder. 10-Q 001-38520 3.1 8/7/19 S-1 333-224914 10-K 001-38520 10-K 001-38520 4.1 4.2 4.3 5/29/18 3/11/20 3/11/20 10-Q 001-38520 4.1 11/10/22 S-1/A 333-224914 10.1 5/29/18 2018 Incentive Award Plan and forms of award agreements thereunder. S-1/A 333-224914 Non-Employee Director Compensation Program. 10-Q 001-38520 10.2 10.1 5/29/18 08/11/21 Form of Indemnification Agreement for Directors and Officers. S-1/A 333-224914 10.4 5/29/18 License and Sub-Lease Agreement, dated May 31, 2019, between MeiraGTx LLC and Imclone Systems, LLC. Lease Agreement, effective February 2, 2016, among MeiraGTx Limited, Moorfields Eye Hospital NHS, Foundation Trust and Kadmon Corporation LLC. Employment Agreement, dated February 15, 2016, between MeiraGTx Limited and Alexandria Forbes, Ph.D., as amended. Employment Agreement, dated February 15, 2016 between MeiraGTx Limited and Richard Giroux, as amended. Employment Agreement, dated April 27, 2015, between MeiraGTx Limited and Stuart Naylor, Ph.D., as amended. Agreement and Plan of Merger, dated December 31, 2015, among MeiraGTx Acquisition Corporation, BRI-Alzan, Inc., F- Prime Inc., Gregory Petsko, Dagmar Ringe, Brandeis University and MeiraGTx Limited. 10-Q 001-38520 10.2 8/7/19 S-1 333-224914 10.6 5/14/18 S-1/A 333-224914 10.7 5/29/18 S-1/A 333-224914 10.8 5/29/18 S-1/A 333-224914 10.9 5/29/18 S-1/A 333-224914 10.14 5/29/18 10.11# 2018 Employee Share Purchase Plan. S-1/A 333-224914 10.15 5/29/18 128 Table of Contents Exhibit Number Exhibit Description Incorporated by Reference 10.12# 10.13# 10.14# 10.15 10.16 10.17 10.18 10.19† 10. 20† 10. 21† 10. 22† Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10-K 001-38520 10.12 3/26/19 UK Sub-Plan Under the 2018 Incentive Award Plan. Form of Option Grant Notice and Option Agreement Under the UK Sub-Plan to the 2018 Incentive Award Plan. Form of Change in Control Agreement. 10-K 001-38520 10-K 001-38520 10.13 10.14 3/26/19 3/11/21 Lease agreement by and between Moorfields Eye Hospital NHS Foundation Trust and MeiraGTx UK II Limited, dated July 30, 2018. Lease agreement by and between Moorfields Eye Hospital NHS Foundation Trust and MeiraGTx UK II Limited, dated July 30, 2018. Transfer of Title, dated December 14, 2018, and Lease, dated October 12, 2001, relating to the Pharmacy Manufacturing Unit, Britannia Walk, London, England. Overage Deed, dated December 14, 2018, between Moorfields Eye Hospital NHS Foundation Trust and MeiraGTx UK II Limited relating to the Pharmacy Manufacturing Unit, Britannia Walk, London, England. Consulting Agreement, dated October 5, 2018, between MeiraGTx Holdings plc, Vector Consulting LLC, Michael G. Kaplitt, Matthew During, and Stephen B. Kaplitt. License Agreement (RPE65), dated January 29, 2019, as amended and restated by and among UCL Business PLC, MeiraGTx UK II Limited and MeiraGTx Limited. License Agreement (CNGB3), dated January 29, 2019, as amended and restated by and among UCL Business PLC, MeiraGTx Holdings plc, MeiraGTx UK II Limited and MeiraGTx Limited. License Agreement (CNGA3), dated January 29, 2019, as amended and restated by and among UCL Business PLC, MeiraGTx UK II Limited and MeiraGTx Limited. 129 10-Q 001-38520 10.4 8/8/18 10-Q 001-38520 10.5 8/8/18 8-K 001-38520 10.1 12/14/18 8-K 001-38520 10.2 12/14/18 10-K 001-38520 10.19 3/26/19 10-K 001-38520 10.20 3/26/19 10-K 001-38520 10.21 3/26/19 10-K 001-38520 10.22 3/26/19 Table of Contents Exhibit Number Exhibit Description Incorporated by Reference Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10. 23† 10. 24† 10. 25† 10.26†† 10. 27 10.28 10.29# 10.30# 10.31 10.32 License Agreement (RPGR), dated February 5, 2019, as amended and restated by and among UCL Business PLC, MeiraGTx UK II Limited and MeiraGTx Limited. Amendment No. 4 to Exclusive License Agreement, dated January 29, 2019, between UCLB and MeiraGTx Limited. Collaboration, Option and License Agreement, dated January 30, 2019, by and among Janssen Pharmaceuticals, Inc., MeiraGTx UK II Limited and MeiraGTx Holdings plc. First Amendment to Collaboration, Option and License Agreement, dated December 16, 2021. Registration Rights Agreement, dated February 26, 2019, by and among MeiraGTx Holdings plc and the investors named therein. Agreement for Lease with Landlord’s Refurbishment Works, dated May 29, 2019, between MeiraGTx UK II Limited and Provost 1 Limited and Provost 2 Limited, including agreed form of Lease between MeiraGTx UK II Limited and Provost 1 Limited and Provost 2 Limited. Form of Restricted Share Unit Grant Notice and Restricted Share Unit Agreement Under the 2018 Incentive Award Plan. Form of Restricted Share Unit Grant Notice and Restricted Share Unit Agreement Under the UK Sub-Plan to the 2018 Incentive Award Plan. Particulars and Conditions of Sale of Building 2, Block K, Shannon Free Zone, Shannon, County Clare, Ireland, dated as of August 4, 2020, by and between Shannon Commercial Enterprises DAC trading as Shannon Commercial Properties and MeiraGTx Ireland DAC, including agreed form of Lease between Shannon Commercial Enterprises DAC and MeiraGTx Ireland DAC. Particulars and Conditions of Sale of Building 3, Block K, Shannon Free Zone, Shannon, County Clare, Ireland, dated as of August 4, 2020, by and between Shannon Commercial Enterprises DAC trading as Shannon Commercial Properties and MeiraGTx Ireland DAC, including agreed form of Lease between Shannon Commercial Enterprises DAC and MeiraGTx Ireland DAC. 10-K 001-38520 10.23 3/26/19 10-K 001-38520 10.24 3/26/19 10-K 001-38520 10.25 3/26/19 10-K 001-3852 10.26 3/10/22 8-K 001-38520 10.2 2/26/19 10-Q 001-38520 10.3 8/7/19 10-K 001-38520 10.30 3/11/20 10-K 001-38520 10.31 3/11/20 10-Q 001-38520 10.1 11/5/20 10-Q 001-38520 10.2 11/5/20 10.33# Deferred Compensation Plan for Non-Employee Directors. 10-K 001-38520 10.35 3/10/22 130 Table of Contents Exhibit Number Exhibit Description Incorporated by Reference 10.34# 10.35†† 10.36 10.37†† 10.38 10.39 10.40 21 23.1 31.1 31.2 32.1 Form of Restricted Share Unit Grant Notice and Restricted Share Unit Agreement for Non- Employee Directors Under the 2018 Incentive Award Plan. Credit Agreement and Guaranty, dated August 2, 2022, by and among MeiraGTx Holdings plc, as borrower, MeiraGTx UK II Limited and MeiraGTx Ireland DAC, as guarantors, the lenders and other parties from time to time party thereto and Perceptive Credit Holdings III, LP, as administrative agent and lender. Amendment No. 1 to Credit Agreement and Guaranty, dated December 19, 2022, by and among MeiraGTx Holdings plc, as borrower, certain subsidiary guarantors and lenders party thereto, and Perceptive Credit Holdings III, LP, as administrative agent. Amended and Restated Note Purchase Agreement and Guaranty, dated December 19, 2022, by and among MeiraGTx Holdings plc, as issuer, the subsidiary guarantors and noteholders from time to time party thereto, and Perceptive Credit Holdings III, LP, as administrative agent. Tranche 1 Note, dated December 19, 2022, by and among MeiraGTx Holdings plc, as issuer, the subsidiaries guarantors and noteholders from time to time party thereto, and Perceptive Credit Holdings III, LP, as administrative agent. Securities Purchase Agreement, dated November 9, 2022, by and among MeiraGTx Holdings plc and Johnson & Johnson Innovation – JJDC, Inc. Registration Rights Agreement, dated November 15, 2022, by and among MeiraGTx Holdings plc and Johnson & Johnson Innovation – JJDC, Inc. List of Subsidiaries. Consent of Ernst & Young LLP. Certification of Chief Executive Officer pursuant to Rules 13a-14(a)/15d-14(a) under the Securities Exchange Act of 1934, as amended. Certification of Chief Financial Officer pursuant to Rules 13a-14(a)/15d-14(a) under the Securities Exchange Act of 1934, as amended. Certification of Chief Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002. 131 Form File No. Exhibit Filing Date Filed/ Furnished Herewith 10-K 001-38520 10.36 3/10/22 10-Q 001-38520 10.1 11/10/22 * * * * * * * * * ** Table of Contents Exhibit Number Exhibit Description Incorporated by Reference Form File No. Exhibit Filing Date Filed/ Furnished Herewith 32.2 101.INS 101.SCH 101.CAL 101.DEF 101.LAB 101.PRE 104 Certification of Chief Financial Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002. Inline XBRL Instance Document. Inline XBRL Taxonomy Extension Schema Document. Inline XBRL Taxonomy Extension Calculation Linkbase Document. Inline XBRL Taxonomy Definition Linkbase Document. Inline XBRL Taxonomy Label Linkbase Document. Inline XBRL Taxonomy Extension Presentation Linkbase Document. Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101). ** * * * * * * * * Filed herewith ** Furnished herewith # Management contract or compensation plan or arrangement † Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment pursuant to Rule 406 under the Securities Act of 1933, as amended †† Portions of this exhibit (indicated by asterisks) have been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K Certain agreements filed as exhibits to this Form 10-K contain representations and warranties that the parties thereto made to each other. These representations and warranties have been made solely for the benefit of the other parties to such agreements and may have been qualified by certain information that has been disclosed to the other parties to such agreements and that may not be reflected in such agreements. In addition, these representations and warranties may be intended as a way of allocating risks among parties if the statements contained therein prove to be incorrect, rather than as actual statements of fact. Accordingly, there can be no reliance on any such representations and warranties as characterizations of the actual state of facts. Moreover, information concerning the subject matter of any such representations and warranties may have changed since the date of such agreements. ITEM 16. FORM 10-K SUMMARY None. 132 Table of Contents Pursuant to the requirements of Section 13 or 15(d) 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 14, 2023 MeiraGTx Holdings plc (Registrant) By: /s/ Alexandria Forbes Alexandria Forbes President and Chief Executive Officer and Director (Principal Executive Officer) 133 Table of Contents SIGNATURES Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of Registrant and in the capacities and on the dates indicated. Signature Title /s/ Alexandria Forbes, Ph.D. President and Chief Executive Officer and Director (Principal Executive Officer) Alexandria Forbes, Ph.D. /s/ Richard Giroux Richard Giroux Chief Financial Officer (Principal Financial and Accounting Officer) Date March 14, 2023 March 14, 2023 /s/ Keith R. Harris, Ph.D. Chairman of the Board and Director March 14, 2023 Keith R. Harris, Ph.D. /s/ Ellen Hukkelhoven, Ph.D. Director Ellen Hukkelhoven, Ph.D. /s/ Martin Indyk, Ph.D. Director Martin Indyk, Ph.D. /s/ Arnold J. Levine, Ph.D. Director Arnold J. Levine, Ph.D. /s/ Lord Mendoza Director Lord Mendoza /s/ Nicole Seligman Director Nicole Seligman /s/ Thomas E. Shenk, Ph.D. Director Thomas E. Shenk, Ph.D. /s/ Debra Yu, M.D. Director Debra Yu, M.D. 134 March 14, 2023 March 14, 2023 March 14, 2023 March 14, 2023 March 14, 2023 March 14, 2023 March 14, 2023 Exhibit 10.36 AMENDMENT NO. 1 TO CREDIT AGREEMENT AND GUARANTY This AMENDMENT NO. 1 TO CREDIT AGREEMENT AND GUARANTY, dated as of December 19, 2022 (this “Amendment”), is by and among MEIRAGTX HOLDINGS PLC, an exempted company with limited liability incorporated under the laws of the Cayman Islands with registration number 336306 (the “Borrower”), certain Subsidiaries of the Borrower party hereto (the “Subsidiary Guarantors”), the Lenders party hereto, and PERCEPTIVE CREDIT HOLDINGS III, LP, as administrative agent for the Lenders (in such capacity, together with its successors and assigns, the “Administrative Agent”). WITNESSETH: WHEREAS, the Borrower, the Subsidiary Guarantors, the lenders from time to time party thereto (the “Lenders”) and the Administrative Agent are parties to that certain Credit Agreement and Guaranty, dated as of August 2, 2022 (as amended, restated, supplemented or otherwise modified from time to time, the “Credit Agreement”). Capitalized terms used herein without definition shall have the same meanings as set forth in the Credit Agreement as amended hereby; and WHEREAS, subject to the terms and conditions set forth herein the Borrower, the Subsidiary Guarantors, the Lenders and the Administrative Agent desire to amend and restate the Credit Agreement as provided herein. NOW, THEREFORE, the parties hereto hereby agree as follows: ARTICLE I AMENDMENTS TO CREDIT AGREEMENT SECTION 1.01. Amendments to the Credit Agreement. As of, and subject to the occurrence of, the Restatement Effective Date (as defined below), the Credit Agreement is hereby amended and restated in its entirety to read as set forth in Schedule 1 hereto (the Credit Agreement, as so amended and restated, the “Amended and Restated Note Purchase Agreement”). ARTICLE II ACKNOWLEDGEMENT, AGREEMENT AND CONSENT AND REPRESENTATIONS AND WARRANTIES SECTION 2.01. Each Obligor confirms and agrees that, notwithstanding the effectiveness of this Amendment, the Obligations of such Obligor under each Note Document to which such Obligor is a party shall not be impaired and each Note Document to which such Obligor is a party is, and shall continue to be, in full force and effect and is hereby confirmed and ratified in all respects, except that upon the Restatement Effective Date, the terms, conditions, rights and remedies with respect to such Obligations of the Obligors shall be governed by the Amended and Restated Note Purchase Agreement and the Note Documents as in effect on and after the Restatement Effective Date. Each Obligor hereby consents to the modifications made to the Credit Agreement pursuant to this Amendment and the Amended and Restated Note Purchase Agreement and hereby agrees that, upon the occurrence of the Restatement Effective Date, and except as otherwise expressly set forth herein or in the Amended and Restated Note Purchase Agreement, each Note Document to which it is a party is and shall continue to be in full force and effect and the same are hereby ratified in all respects. SECTION 2.02. Each Obligor hereby acknowledges and agrees that the Guaranteed Obligations will include all Obligations under, and as defined in, the Amended and Restated Note Purchase Agreement. Each Obligor hereby ratifies, confirms and reaffirms all terms and conditions of all security and other collateral granted to the Administrative Agent, and confirms that the indebtedness secured thereby includes, without limitation, the Obligations. SECTION 2.03. To induce the Administrative Agent and the Lender party hereto to execute and deliver this Amendment, each Obligor party hereto represents and warrants to the Administrative Agent and the Lender party hereto that as of the date hereof, each of the following statements are true and correct: (a) The representations and warranties made by each Obligor party hereto herein, in the Amended and Restated Note Purchase Agreement and each other Note Document are true and correct in all material respects as if made on and as of such date (or in the case of any representation or warranty qualified by materiality, Material Adverse Effect or similar qualification, true and correct in all respects) unless stated to relate solely to an earlier date, in which case such representations or warranties shall be true and correct in all material respects as of such earlier date. (b) The execution, delivery and performance of this Amendment by each Obligor party hereto, and the resulting amendment and restatement of the Credit Agreement, have been duly authorized by all necessary corporate or other organizational action on the part of such Obligor, and this Amendment and the Amended and Restated Note Purchase Agreement each constitutes a legal, valid and binding agreement of such Obligor, enforceable against such Obligor in accordance with its respective terms, except as enforcement may be limited by (i) bankruptcy, insolvency, reorganization, moratorium or similar laws of general applicability affecting the enforcement of creditors’ rights generally; (ii) general principles of equity (regardless of whether such enforceability is considered in a proceeding in equity or at law); and (iii) solely in respect of the English Guarantor and the Irish Subsidiary Guarantor, the Legal Reservations and the Perfection Requirements. (c) The execution, delivery and performance of this Amendment by any Obligor party hereto, and the resulting amendment and restatement of the Credit Agreement, does not (i) violate or conflict with any Law, (ii) result in the creation or imposition of any Lien (other than Permitted Liens) on any asset of such Obligor or any of its Subsidiaries or (iii) violate, or result in a default under, any Material Agreement binding upon such Obligor or any of its Subsidiaries that, in the case of clause (i) and (iii) above, individually or in the aggregate, could reasonably be expected to result in a Material Adverse Effect. (d) No authorization or approval or other action by, and no notice or filing with, any Governmental Authority or any other Person (other than those that have been duly obtained or made and which are in full force and effect) is required for the due execution, delivery and 2 performance by any Obligor party to this Amendment or the amendment and restatement of the Credit Agreement. (e) Immediately before and after giving effect to this Amendment, no event has occurred and is continuing that constitutes an Event of Default. ARTICLE III CONDITIONS PRECEDENT SECTION 3.01. Conditions to Effectiveness of this Amendment. This Amendment shall become effective only upon, and shall be subject to, the prior or simultaneous satisfaction or waiver of each of the following conditions precedent in a manner reasonably satisfactory to the Administrative Agent (the date satisfaction of such conditions being referred to as the “Restatement Effective Date”): (a) Counterparts. The Administrative Agent shall have received counterparts of (i) this Amendment, and (ii) the Amended and Restated Note Purchase Agreement, in each case executed by each party thereto. (b) Notes Certificate. The Administrative Agent shall have received a Notes Certificate in respect of the Tranche 1 Notes duly executed and delivered by the Borrower. (c) [Reserved] (d) Representations and Warranties. The statements, representations and warranties contained in Section 2 above shall each be true and correct, both immediately before and after giving effect to this Amendment, and the Administrative Agent shall have received a certificate executed by a Responsible Officer of the Borrower, in form and substance reasonably satisfactory to the Administrative Agent, addressed to it and the Lenders and certifying as to the foregoing. (e) Costs and Expenses, Etc. The Administrative Agent shall have received for its account and the account of each Lender all reasonable and documented fees, costs and expenses due and payable to them pursuant to Section 14.03 of the Amended and Restated Note Purchase Agreement and Section 4.09 (including, in each case, the Administrative Agent’s and each Lender’s reasonable and documented legal fees and out-of-pocket expenses) to the extent invoiced at least two (2) Business Days prior to the Restatement Effective Date. ARTICLE IV MISCELLANEOUS SECTION 4.01. Governing Law; Jurisdiction; Jury Trial. This Amendment and the rights and obligations of the parties hereunder shall be governed by, and construed in accordance with the law of the State of New York, without regard to principal of conflicts of law that would result in the application of the laws of any other jurisdiction; provided that Section 5-1401 of the New York General Obligations Law shall apply. The jurisdiction and waiver of jury trial provisions set forth in Sections 14.10 and 14.11 of the Amended and Restated Note Purchase Agreement, respectively, are incorporated herein by reference mutatis mutandis. 3 SECTION 4.02. Effect of Amendment and Restatement. (a) On and after the Restatement Effective Date, each reference in any Note Document (other than this Amendment) to (i) the “Credit Agreement” shall mean and be a reference to the Amended and Restated Note Purchase Agreement and (ii) a “Loan Document” shall mean and be a reference to a Note Document as defined in the Amended and Restated Note Purchase Agreement. (b) This Amendment shall constitute a Note Document for all purposes of the Amended and Restated Note Purchase Agreement. Except as expressly amended hereby, and subject in all events to Section 2.01, the Obligors party hereto agree that all of the representations, warranties, terms, covenants, conditions and other provisions of the Credit Agreement and other Note Documents shall remain unchanged and shall continue to be, and shall remain, in full force and effect in accordance with their respective terms. This Amendment is not and shall not be deemed to be a waiver of any Default or Event of Default or non-compliance with any term or condition contained in the Amended and Restated Note Purchase Agreement and the other Note Documents. (c) The execution, delivery and effectiveness of this Amendment shall not, except as expressly provided herein, operate as a waiver of any right, power or remedy of the Administrative Agent or any Lender under any Note Document or applicable Law, nor constitute a waiver of any provision of the Amended and Restated Note Purchase Agreement except as expressly set forth herein. SECTION 4.03. No Novation. This Amendment is not intended by the parties to be, and shall not be construed to be, a novation of the Credit Agreement or other Note Documents. SECTION 4.04. Counterparts; Electronic Signatures. This Amendment may be executed in any number of counterparts, all of which taken together shall constitute one and the same instrument and any of the parties hereto may execute this Amendment by signing any such counterpart. Delivery of an executed signature page of this Amendment by facsimile transmission or electronic transmission (in PDF format) shall be effective as delivery of a manually executed counterpart hereof. Any signature (including, without limitation, (x) any electronic symbol or process attached to, or associated with, a contract or other record and adopted by a person with the intent to sign, authenticate or accept such contract or record and (y) any facsimile transmission or PDF format signature) hereto or to any other certificate, agreement or document related to this transaction, and any contract formation or record-keeping, in each case, through electronic means, shall have the same legal validity and enforceability as a manually executed signature or use of a paper-based record-keeping system to the fullest extent permitted by applicable law, including the Federal Electronic Signatures in Global and National Commerce Act, the New York State Electronic Signatures and Records Act, or any similar state law based on the Uniform Electronic Transactions Act, and the parties hereto hereby waive any objection to the contrary. SECTION 4.05. Binding Nature. The provisions of this Amendment shall be binding upon and shall inure to the benefit of the parties hereto and their respective successors and permitted assigns; provided that no Obligor may assign or otherwise transfer any of its rights or obligations hereunder without the prior written consent of the Administrative Agent. 4 SECTION 4.06. Captions. The captions and section headings appearing herein are included solely for convenience of reference and are not intended to affect the interpretation of any provision of this Amendment. SECTION 4.07. Severability. If any provision hereof is found by a court to be invalid or unenforceable, to the fullest extent permitted by any applicable Law the parties agree that such invalidity or unenforceability shall not impair the validity or enforceability of any other provision hereof. SECTION 4.08. Integration. This Amendment, together with the other Note Documents, constitutes the entire agreement among the parties with respect to the subject matter hereof and supersedes any and all previous agreements and understanding, oral or written, relating to the subject matter hereof. SECTION 4.09. Costs and Expenses. Each Obligor party hereto agrees to pay or reimburse the Administrative Agent and the Lenders for all of their reasonable and documented out-of-pocket costs of and in connection with the negotiation, preparation, execution and delivery of this Amendment, including, without limitation, the reasonable and documented fees and out-of-pocket fees and expenses of outside counsel for the Administrative Agent and the Lenders. SECTION 4.10.Waiver and Release. (a) EFFECTIVE AS OF THE DATE HEREOF, TO INDUCE THE ADMINISTRATIVE AGENT AND THE LENDER PARTY HERETO TO AGREE TO THE TERMS OF THIS AMENDMENT, THE BORROWER REPRESENTS AND WARRANTS THAT, AS OF THE DATE HEREOF, THERE ARE NO CLAIMS OR OFFSETS AGAINST, OR RIGHTS OF RECOUPMENT WITH RESPECT TO, OR DISPUTES OF, OR DEFENSES OR COUNTERCLAIMS TO, ITS OBLIGATIONS UNDER THIS AMENDMENT OR THE OTHER NOTE DOCUMENTS, AND IN ACCORDANCE THEREWITH, TO THE EXTENT PERMITTED BY APPLICABLE LAW, THE BORROWER: (i) WAIVES ANY AND ALL SUCH CLAIMS, OFFSETS, RIGHTS OF RECOUPMENT, DISPUTES, DEFENSES AND COUNTERCLAIMS, WHETHER KNOWN OR UNKNOWN, ARISING PRIOR TO THE DATE HEREOF; AND (ii) FOREVER RELEASES, RELIEVES, AND DISCHARGES THE ADMINISTRATIVE AGENT AND EACH LENDER AND THEIR RESPECTIVE OFFICERS, DIRECTORS, SHAREHOLDERS, MEMBERS, PARTNERS, PREDECESSORS, SUCCESSORS, ASSIGNS, ATTORNEYS, ACCOUNTANTS, AGENTS, EMPLOYEES, AND REPRESENTATIVES (COLLECTIVELY, THE “RELEASED PARTIES”), AND EACH OF THEM, FROM ANY AND ALL CLAIMS, LIABILITIES, DEMANDS, CAUSES OF ACTION, DEBTS, OBLIGATIONS, PROMISES, ACTS, AGREEMENTS, AND DAMAGES, OF WHATEVER KIND OR NATURE, WHETHER KNOWN OR UNKNOWN, SUSPECTED OR UNSUSPECTED, CONTINGENT OR FIXED, LIQUIDATED OR UNLIQUIDATED, MATURED OR UNMATURED, WHETHER ARISING AT LAW OR IN EQUITY, WHICH THE BORROWER EVER HAD, NOW HAVE, OR MAY, SHALL, OR CAN HEREAFTER 5 HAVE, DIRECTLY OR INDIRECTLY ARISING OUT OF OR IN ANY WAY BASED UPON, CONNECTED WITH, OR RELATED TO MATTERS, THINGS, ACTS, CONDUCT, AND/OR OMISSIONS AT ANY TIME FROM THE LATER OF THE CLOSING DATE OR THE DATE THAT WAS NINETY (90) DAYS PRIOR TO THE DATE HEREOF THROUGH AND INCLUDING THE DATE HEREOF, INCLUDING WITHOUT LIMITATION ANY AND ALL CLAIMS AGAINST THE RELEASED PARTIES ARISING UNDER OR RELATED TO ANY OF THE NOTE DOCUMENTS OR ANY OF THE TRANSACTIONS CONTEMPLATED THEREBY. (b) IN CONNECTION WITH THE RELEASE CONTAINED HEREIN, THE BORROWER ACKNOWLEDGES THAT IT IS AWARE THAT IT MAY HEREAFTER DISCOVER CLAIMS PRESENTLY UNKNOWN OR UNSUSPECTED, OR FACTS IN ADDITION TO OR DIFFERENT FROM THOSE WHICH IT KNOWS OR BELIEVES TO BE TRUE, WITH RESPECT TO THE MATTERS RELEASED HEREIN. NEVERTHELESS, IT IS THE INTENTION OF THE BORROWER, THROUGH THIS AMENDMENT AND WITH ADVICE OF COUNSEL, FULLY, FINALLY, AND FOREVER TO RELEASE ALL SUCH MATTERS, AND ALL CLAIMS RELATED THERETO, WHICH DO NOW EXIST, OR HERETOFORE HAVE EXISTED. IN FURTHERANCE OF SUCH INTENTION, THE RELEASES HEREIN GIVEN SHALL BE AND REMAIN IN EFFECT AS A FULL AND COMPLETE RELEASE OF SUCH MATTERS NOTWITHSTANDING THE DISCOVERY OR EXISTENCE OF ANY SUCH ADDITIONAL OR DIFFERENT CLAIMS OR FACTS RELATED THERETO. (c) THE BORROWER COVENANTS AND AGREES NOT TO BRING ANY CLAIM, ACTION, SUIT, OR PROCEEDING AGAINST THE RELEASED PARTIES, DIRECTLY OR INDIRECTLY, REGARDING OR RELATED IN ANY MANNER TO THE MATTERS RELEASED HEREBY, AND FURTHER COVENANTS AND AGREES THAT THIS AMENDMENT IS A BAR TO ANY SUCH CLAIM, ACTION, SUIT, OR PROCEEDING. (d) THE BORROWER REPRESENTS AND WARRANTS TO THE RELEASED PARTIES THAT IT HAS NOT HERETOFORE ASSIGNED OR TRANSFERRED, OR PURPORTED TO ASSIGN OR TRANSFER, TO ANY PERSON OR ENTITY ANY CLAIMS OR OTHER MATTERS HEREIN RELEASED. (e) THE BORROWER ACKNOWLEDGES THAT IT HAS HAD THE BENEFIT OF INDEPENDENT LEGAL ADVICE WITH RESPECT TO THE ADVISABILITY OF ENTERING INTO THIS RELEASE AND HEREBY KNOWINGLY, AND UPON SUCH ADVICE OF COUNSEL, WAIVE ANY AND ALL APPLICABLE RIGHTS AND BENEFITS UNDER, AND PROTECTIONS OF, CALIFORNIA CIVIL CODE SECTION 1542, AND ANY AND ALL STATUTES AND PRINCIPLES OF COMMON LAW THAT HAVE SIMILAR EFFECT. [Signature pages to follow] 6 IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be duly executed and delivered as of the date hereof. BORROWER: MEIRAGTX HOLDINGS PLC By /s/ Rich Giroux Name: Rich Giroux Title: CFO and COO SUBSIDIARY GUARANTORS: MEIRAGTX UK II LIMITED By /s/ Rich Giroux Name: Rich Giroux Title: CFO and COO MEIRAGTX IRELAND DAC By /s/ Rich Giroux Name: Rich Giroux Title: CFO and COO PERCEPTIVE CREDIT HOLDINGS III, LP, as the Administrative Agent and Lender By: PERCEPTIVE CREDIT OPPORTUNITIES GP, LLC, its general partner By /s/ Sandeep Dixit Name: Sandeep Dixit Title: Chief Credit Officer By /s/ Sam Chawla Name: Sam Chawla Title: Portfolio Manager Certain information marked as [***] has been excluded from this exhibit because it is both not material and is the type that the registrant treats as private or confidential. Exhibit 10.37 AMENDED AND RESTATED NOTES PURCHASE AGREEMENT AND GUARANTY dated as of August 2, 2022 as amended and restated as of December 19, 2022 by and among MEIRAGTX HOLDINGS PLC, as the Issuer THE SUBSIDIARY GUARANTORS FROM TIME TO TIME PARTY HERETO as the Subsidiary Guarantors THE NOTEHOLDERS FROM TIME TO TIME PARTY HERETO, as the Noteholders; and PERCEPTIVE CREDIT HOLDINGS III, LP as the Administrative Agent U.S. $100,000,000 TABLE OF CONTENTS SECTION 1 DEFINITIONS 1.01 Certain Defined Terms 1.02 Accounting Terms and Principles 1.03 Interpretation 1.04 Divisions 1.05 Reference Rate Replacement 1.06 Times of Day; Times of Performance 1.07 Rates 1.08 Miscellaneous. SECTION 2 THE COMMITMENTS AND THE NOTES 2.01 Issuance of Notes 2.02 [Reserved] 2.03 Noteholder Representations. 2.04 Use of Proceeds 2.05 Constitution of the Notes 2.06 Signing and authenticating Notes Certificates 2.07 Status of Notes Certificate 2.08 Stocks of blank Notes Certificates 2.09 Delivery of replacements 2.10 Replacement Notes Certificates 2.11 Replacements to be numbered 2.12 Cancellation and destruction 2.13 Notification 2.14 Legend SECTION 3 PAYMENTS, REDEMPTION AND INTEREST 3.01 Payments and Redemption Generally; Application 3.02 Interest 3.03 Early Redemption; Early Redemption Premium 3.04 Facility Fees -i- Page 1 1 35 35 37 37 37 37 38 38 38 38 38 39 39 39 39 39 39 40 40 40 40 40 40 40 41 42 44 TABLE OF CONTENTS (continued) SECTION 4 PAYMENTS, ETC. 4.01 Payments 4.02 Computations 4.03 Set-Off SECTION 5 YIELD PROTECTION, ETC. 5.01 Additional Costs 5.02 Illegality 5.03 Taxes SECTION 6 CONDITIONS PRECEDENT 6.01 Conditions to the issuance and subscription of the Tranche 1 Notes 6.02 Conditions to the issuance and sale of the Tranche 2 Notes SECTION 7 REPRESENTATIONS AND WARRANTIES 7.01 Power and Authority 7.02 Authorization; Enforceability 7.03 Governmental and Other Approvals for Execution and Delivery of the Notes Document, etc.; No Conflicts 7.04 Financial Statements; Material Adverse Change 7.05 Properties 7.06 No Actions or Proceedings 7.07 Compliance with Laws and Agreements 7.08 Taxes 7.09 Full Disclosure 7.10 Investment Company Act and Margin Stock Regulation 7.11 Solvency 7.12 Equity Holders, Subsidiaries and Other Investments 7.13 Continuing Secured Indebtedness 7.14 Material Agreements 7.15 Restrictive Agreements 7.16 Real Property 7.17 Pension Matters -ii- Page 45 45 45 45 46 46 48 48 54 54 59 59 60 60 60 61 61 64 65 65 65 66 66 66 66 66 66 67 67 TABLE OF CONTENTS (continued) 7.18 Priority of Obligations; Collateral; Security Interest 7.19 Governmental Approvals in Respect of Ordinary Course Activities, Etc. 7.20 Transactions with Affiliates 7.21 Sanctions 7.22 Anti-Corruption 7.23 Deposit and Disbursement Accounts and Investment Accounts 7.24 Centre of Main Interests SECTION 8 AFFIRMATIVE COVENANTS 8.01 Financial Statements and Other Information 8.02 Notices of Material Events 8.03 Existence; Conduct of Business 8.04 Payment of Obligations 8.05 Insurance 8.06 Books and Records; Inspection Rights 8.07 Compliance with Laws and Material Agreements 8.08 Maintenance of Properties, Etc. 8.09 Governmental Approvals, Etc. 8.10 Action under Environmental Laws 8.11 Use of Proceeds 8.12 Certain Obligations Respecting Subsidiaries; Further Assurances 8.13 Termination of Non-Permitted Liens 8.14 Maintenance of the Governmental Approvals and Intellectual Property 8.15 ERISA and Foreign Pension Plan Compliance 8.16 Cash Management 8.17 Title, Headleases, Power to Remedy 8.18 Register of Mortgages and Charges 8.19 Post-Closing Covenants 8.20 Undertaking to list SECTION 9 NEGATIVE COVENANTS 9.01 Indebtedness -iii- Page 67 67 67 67 68 68 68 68 68 70 72 72 72 73 73 73 74 74 74 74 75 75 76 76 77 77 77 78 78 78 TABLE OF CONTENTS (continued) 9.02 Liens 9.03 Fundamental Changes, Acquisitions, Etc. 9.04 Lines of Business 9.05 Investments 9.06 Restricted Payments 9.07 Payments of Indebtedness 9.08 Change in Fiscal Year 9.09 Sales of Assets, Etc. 9.10 Transactions with Affiliates 9.11 Restrictive Agreements 9.12 Modifications of Organic Documents; Termination of Material Agreements 9.13 Sales and Leasebacks 9.14 Hazardous Material 9.15 Accounting Changes 9.16 Compliance with ERISA 9.17 [Reserved] 9.18 Sanctions; Anti-Corruption Use of Proceeds 9.19 Inbound and Outbound Licenses 9.20 Title, Headleases, Development SECTION 10 FINANCIAL COVENANTS 10.01 Minimum Liquidity 10.02 Phase III Trial 10.03 Shannon Manufacturing Facility SECTION 11 EVENTS OF DEFAULT 11.01 Events of Default 11.02 Remedies 11.03 Additional Remedies SECTION 12 THE ADMINISTRATIVE AGENT 12.01 Appointment and Duties -iv- Page 80 82 83 83 85 86 87 87 88 89 90 90 90 90 91 91 91 91 92 92 92 92 92 92 92 96 96 96 96 TABLE OF CONTENTS (continued) 12.02 Binding Effect 12.03 Use of Discretion 12.04 Delegation of Rights and Duties 12.05 Reliance and Liability 12.06 Administrative Agent Individually 12.07 Noteholder Credit Decision 12.08 Expenses; Indemnities 12.09 Resignation of the Administrative Agent 12.10 Release of Collateral 12.11 Additional Secured Parties SECTION 13 GUARANTEE 13.01 The Guarantee 13.02 Obligations Unconditional 13.03 Reinstatement 13.04 Subrogation 13.05 Remedies 13.06 Instrument for the Payment of Money 13.07 Continuing Guarantee 13.08 General Limitation on Guarantee Obligations SECTION 14 MISCELLANEOUS 14.01 No Waiver 14.02 Notices 14.03 Expenses, Indemnification, Etc. 14.04 Amendments, Etc. 14.05 Successors and Assigns 14.06 Survival 14.07 Captions 14.08 Counterparts; Electronic Signatures 14.09 Governing Law 14.10 Jurisdiction, Service of Process and Venue -v- Page 98 98 98 98 99 100 100 100 101 102 102 102 103 103 104 104 104 104 104 105 105 105 105 106 107 110 110 110 110 110 TABLE OF CONTENTS (continued) 14.11 Waiver of Jury Trial 14.12 Waiver of Immunity 14.13 Entire Agreement 14.14 Severability 14.15 No Fiduciary Relationship 14.16 Confidentiality 14.17 Interest Rate Limitation 14.18 Early Redemption Fee 14.19 Judgment Currency 14.20 USA PATRIOT Act 14.21 Acknowledgement and Consent to Bail-In of Affected Financial Institutions Page 111 111 111 112 112 112 112 113 113 114 114 -vi- SCHEDULES AND EXHIBITS TABLE OF CONTENTS (continued) Schedule A Schedule B Schedule 1 Schedule 7.05(b) Schedule 7.06(a) Schedule 7.06(c) Schedule 7.08 Schedule 7.12(a) Schedule 7.12(b) Schedule 7.13 Schedule 7.14 Schedule 7.15 Schedule 7.16 Schedule 7.20 Schedule 7.23 Schedule 9.02 Schedule 9.05 Schedule 9.12(b) Schedule 9.13 Exhibit A Exhibit B Exhibit C Exhibit E Exhibit F Exhibit G Exhibit H Exhibit I Exhibit J - - - - - - - - - - Competitors Specified Assets Commitments Intellectual Property Certain Litigation Labor Matters Taxes Subsidiaries of the Issuer Other Equity Interests owned or held by the Issuer or its Subsidiaries Existing Indebtedness of the Issuer and each of its Subsidiaries - - - - - - - - - - - Material Agreements of Obligors - - - - - - Restrictive Agreements Real Property Owned or Leased by the Issuer or any Subsidiary Transactions with Affiliates Deposit, Disbursement and Investment Accounts Closing Date Liens Closing Date Investments Excluded Agreements Permitted Sales and Leasebacks Form of Note Form of Notes Subscription Request Form of Guarantee Assumption Agreement Form of Compliance Certificate Form of Assignment and Assumption Form of Information Certificate Form of Intercompany Subordination Agreement Form of Solvency Certificate Form of Warrant Certificate -vii- AMENDED AND RESTATED NOTES PURCHASE AGREEMENT AND GUARANTY AMENDED AND RESTATED NOTES PURCHASE AGREEMENT AND GUARANTY, dated as of August 2, 2022, as amended and restated as of December 19, 2022 (this “Agreement”), by and among MeiraGTx Holdings plc, an exempted company with limited liability incorporated under the laws of the Cayman Islands with registration number 336306 (the “Issuer”), certain Subsidiaries of the Issuer required to provide Guarantees from time to time hereunder, Perceptive Credit Holdings III, LP (the “Original Noteholder”) and each other noteholder that may from time to time become a party hereto (each, together with their permitted successors and assigns, a “Noteholder” and collectively, the “Noteholders”), and Perceptive Credit Holdings III, LP, as administrative agent for the Noteholders (in such capacity, together with its permitted successors and assigns, the “Administrative Agent”). WITNESSETH: WHEREAS, the Issuer has requested that the Noteholders provide a senior secured notes issuance facility to the Issuer in an aggregate principal amount of $100,000,000, with (i) $75,000,000 in aggregate principal amount of Notes made available on the Closing Date (the “Tranche 1 Notes”) and (ii) $25,000,000 in aggregate principal amount of Notes (the “Tranche 2 Notes”) to be available after the Closing Date but prior to August 2, 2024 (the “Tranche 2 Notes Draw Period”), in each case subject to the terms and conditions set forth herein, including the applicable terms and conditions set forth in Section 6 hereof and, with respect to the Tranche 2 Notes, at the sole discretion of the Majority Noteholders; and WHEREAS, the Noteholders are willing, on the terms and subject to the conditions set forth herein, to provide such senior secured notes issuance facility; and WHEREAS this Agreement, prior to its amendment and restatement as of the Amendment and Restatement Date, provided for the borrowing of certain loans, and loans (in the aggregate principal amount of $75,000,000) were borrowed by the Issuer and, immediately following such amendment and restatement, remain outstanding under this Agreement as the Tranche 1 Notes. NOW, THEREFORE, the parties hereto agree as follows: SECTION 1 DEFINITIONS 1.01 Certain Defined Terms. As used herein (including the preamble and recitals), the following terms have the following respective meanings: “Account Pledge Agreement” means the Account Pledge Agreement, dated as of the date hereof, by and between the Issuer and the Administrative Agent. “Acquisition” means any transaction, or any series of related transactions, by which any Person directly or indirectly, by means of an amalgamation, consolidation, merger, tender offer, purchase of Equity Interests or other assets or properties, or similar transaction having the same effect as any of the foregoing, (i) acquires all or substantially all of the assets of another Person including substantially all of a business line, business unit or business division of any other Person, (ii) acquires control of Equity Interests of another Person representing more than fifty percent (50%) of the ordinary voting power (as determined on a fully-diluted, as-if-converted or exercised basis) for the election of directors or other governing body if the business affairs of such Person are managed by a Board of directors, or (iii) acquires control of more than fifty percent (50%) of the Equity Interests (as determined on a fully-diluted, as- if-converted or exercised basis) of another Person engaged in any business that is not managed by a Board. “Administrative Agent” has the meaning set forth in the preamble hereto. “Affected Financial Institution” means (a) any EEA Financial Institution, or (b) any UK Financial Institution. “Affiliate” means, with respect to a specified Person, another Person that directly, or indirectly through one or more intermediaries, Controls or is Controlled by or is under common Control with the Person specified; provided that with respect to any Noteholder, an Affiliate of such Noteholder shall include, without limitation, all of such Noteholder’s Related Funds so long as such entities are Controlled by such Noteholder. “Agreement” has the meaning set forth in the preamble hereto. “Amendment and Restatement Date” means December 19, 2022. “Applicable Margin” means ten percent (10.00%), as such percentage may be increased pursuant to Section 3.02(b). “Asset Sale” has the meaning set forth in Section 9.09. “Assignment and Assumption” means an assignment and assumption entered into by a Noteholder and an assignee of such Noteholder in substantially the form of Exhibit F. “Authorisation” means an authorisation, consent, approval, resolution, licence, exemption, filing, notarisation, certificate or registration. “Bail-In Action” means the exercise of any Write-Down and Conversion Powers by the applicable Resolution Authority in respect of any liability of an Affected Financial Institution. “Bail-In Legislation” means (a) with respect to any EEA Member Country implementing Article 55 of Directive 2014/59/EU of the European Parliament and of the Council of the European Union, the implementing law, regulation, rule or requirement for such EEA Member Country from time to time which is described in the EU Bail-In Legislation Schedule, and (b) with respect to the United Kingdom, Part I of the United Kingdom Banking Act 2009 (as amended from time to time) and any other law, regulation or rule applicable in the United Kingdom relating to the resolution of unsound or failing banks, investment firms or other financial institutions or their affiliates (other than through liquidation, administration or other insolvency proceedings). “Bank Levy” means (i) any amount payable by any Recipient or any of its Affiliates on the basis of, or in relation to, its balance sheet or capital base or any part of that person’s liabilities or minimum regulatory capital or any combination thereof (including, without limitation, the UK 2 bank levy as set out in the Finance Act 2011) and any other levy or tax in any jurisdiction levied on a similar basis or for a similar purpose, (ii) any financial activities taxes (or other taxes) of a kind contemplated in the European Commission consultation paper on financial sector taxation dated 22 February 2011), and (iii) any bank surcharge or banking corporation tax surcharge as set out in United Kingdom Finance (No. 2) Act 2015 and any other surcharge or tax of a similar nature implemented in any other jurisdiction, in each case, as amended from time to time. “Bankruptcy Code” means Title 11 of the United States Code entitled “Bankruptcy.” “Benefit Plan” means any employee benefit plan as defined in Section 3(3) of ERISA (whether governed by the laws of the United States or otherwise) to which any Obligor or Subsidiary thereof incurs or otherwise has any obligation or liability, contingent or otherwise. “Board” means, with respect to any Person, the board of directors (or equivalent management or oversight body) of such Person or any committee thereof duly authorized to act on behalf of such board or equivalent body. “Business Day” means a day (other than a Saturday, Sunday or other day that is a legal holiday under the laws of the State of New York, or under the laws of England) on which commercial banks are not authorized or required by Law to close in New York, New York and in London, England; provided that if such day relates to any document governed by the laws of Ireland or the performance of any obligations under the Notes Documents by any Obligor incorporated under the laws of Ireland, the term “Business Day” shall exclude any day on which commercial banks are authorized to close under the laws of, or are in fact closed in, Ireland. “Capital Lease Obligations” means, as to any Person, the obligations of such Person to pay rent or other amounts under a lease of (or other agreement conveying the right to use) real and/or personal property which obligations are required to be classified and accounted for as a capital lease on a balance sheet of such Person under GAAP and, for purposes of this Agreement, the amount of such obligations shall be the capitalized amount thereof without giving effect to any change in accounting for leases pursuant to GAAP, including, without limitation, resulting from changes to (x) Accounting Standards Codification Topic 840, Leases, or the implementation of (y) Accounting Standards Codification Topic 842, Leases). “Casualty Event” means the damage, destruction or condemnation, as the case may be, of any property of any Person. “Certificate of Title” means a certificate of or report on title in respect of the London Manufacturing Facility and Shannon Manufacturing Facility (as applicable) prepared by the Issuer’s solicitors and supplied to the Administrative Agent in accordance with Section 8.17 dated as at the date of this Agreement. “cGMP” means (i) the FDA’s current good manufacturing practice, (ii) any similar or functionally equivalent guidelines or requirements applicable to, or required by, any non-U.S. jurisdiction or Governmental Authority and (iii) all supplements, amendments, or regulatory filings related to any of the foregoing. 3 “Change of Control” means (i) any transaction, or any series of related transactions, by which any Person directly or indirectly, by means of a tender offer, amalgamation, consolidation, merger, purchase of assets, or similar transaction having the same effect as any of the foregoing, acquires ownership, directly or indirectly, beneficially or of record, by any Person or group of Persons acting jointly or otherwise in concert of Equity Interests of the Issuer having more than thirty-five percent (35%) of the aggregate ordinary voting power, determined on a fully diluted, as-if converted or exercised, basis, (ii) the Issuer shall cease to own, directly or indirectly, beneficially and of record, one hundred percent (100%) of the issued and outstanding Equity Interests of each of the Subsidiary Guarantors or (iii) the sale of all or substantially all of the property of the business of the Issuer and its Subsidiaries, taken as a whole. “Change of Law” means any change after the date of this Agreement or, if later, after the date on which the relevant Noteholder became a Noteholder under this Agreement (as applicable) in any law, regulation or Treaty (or in the published interpretation, administration or application of any law, regulation or Treaty) or any published practice or published concession of any relevant tax authority, other than any change that occurs pursuant to, or in connection with, the adoption, ratification, approval or acceptance of, the Multilateral Convention to Implement Tax Treaty Related Measures to Prevent Base Erosion and Profit Shifting of 24 November 2016 in or by any jurisdiction. “Claim” means any claim, demand, complaint, grievance, action, application, suit, cause of action, order, charge, indictment, prosecution, final judgment or other similar process, assessment or reassessment, whether made, converted or assessed in connection with a debt, liability, dispute, breach, failure or otherwise. “Closing Date” means August 2, 2022. “Code” means the U.S. Internal Revenue Code of 1986. “Collateral” means any asset or property in which a Lien is purported to be granted under any Security Documents. “Commitment” means, with respect to each Noteholder the commitments in the amounts set forth opposite such Noteholder’s name on Schedule 1 hereto, as such Schedule may be amended from time to time pursuant to an Assignment and Assumption or otherwise; provided that with respect to the Tranche 1 Facility, the aggregate Commitments of all Noteholders on the Closing Date was equal to $75,000,000. “Commodity Account” means any commodity account, as such term is defined in Section 9-102 of the NY UCC. “Competitor” means any Person that is (i) listed as a competitor in the Issuer’s most recent public filings made with the SEC as may be supplemented from time to time with the SEC or (ii) listed on Schedule A. “Compliance Certificate” has the meaning set forth in Section 8.01(c). 4 “Conforming Changes” means, with respect to either the use or administration of One-Month Term SOFR, any technical, administrative or operational changes (including changes to the definition of “Business Day,” the definition of “U.S. Government Securities Business Day,” the definition of “Interest Period” or any similar or analogous definition (or the addition of a concept of “interest period”), with respect to the timing and frequency of determining rates and making payments of interest, the timing of subscription requests or redemptions, conversion or continuation notices, the applicability and length of lookback periods, the applicability of Section 3.02(e) and other technical, administrative or operational matters) that the Administrative Agent reasonably decides may be appropriate to reflect the adoption and implementation of any such rate or to permit the use and administration thereof by the Administrative Agent in a manner substantially consistent with market practice (or, if the Administrative Agent decides that adoption of any portion of such market practice is not administratively feasible or if the Administrative Agent determines that no market practice for the administration of any such rate exists, in such other manner of administration as the Administrative Agent decides is reasonably necessary in connection with the administration of this Agreement and the other Notes Documents). “Connection Income Taxes” means Other Connection Taxes that are imposed on or measured by net income (however denominated) or that are franchise Taxes or branch profits Taxes. “Contingent Acquisition Obligations” has the meaning set forth in clause (v) of the definition of “Indebtedness”. “Contract” means any contract, license, lease, agreement, obligation, promise, undertaking, understanding, arrangement, document, commitment, entitlement, indenture, instrument, or engagement under which a Person has, or will have, any liability or contingent liability (in each case, whether written or oral, express or implied, and whether in respect of monetary or payment obligations, performance obligations or otherwise). “Control” means, in respect of a particular Person, the possession, by one or more other Persons, directly or indirectly, of the power to direct or cause the direction of the management or policies of such particular Person, whether through the ability to exercise voting power, by contract or otherwise. “Controlling” and “Controlled” (and similar derivatives) have meanings correlative thereto. “Controlled Account” has the meaning set forth in Section 8.16(a). “Copyright” means all copyrights, copyright registrations and applications for copyright registrations, including all renewals and extensions thereof, all rights to recover for past, present or future infringements thereof, and all other rights whatsoever accruing thereunder or pertaining thereto. “Default” means any Event of Default and any event that, upon the giving of notice, the lapse of time or both, would constitute an Event of Default. “Default Rate” has the meaning set forth in Section 3.02(b). 5 “Deposit Account” means any deposit account, as such term is defined in Section 9-102 of the NY UCC. “Designated Jurisdiction” means any country or territory that is itself the target of comprehensive Sanctions (as of the date of this Agreement, Cuba, Iran, North Korea, Syria, the Crimea region of Ukraine, the so- called Donetsk People’s Republic, and the so-called Luhansk People’s Republic). “Disqualified Equity Interests” means, with respect to any Person, any Equity Interest of such Person that, by its terms (or by the terms of any security or other Equity Interest into which it is convertible or for which it is exchangeable upon exercise or otherwise), or upon the happening of any event or condition (i) matures or is mandatorily redeemable (other than solely for Qualified Equity Interests), including pursuant to a sinking fund obligation or otherwise, (ii) is redeemable at the option of the holder thereof (other than solely for Qualified Equity Interests), in whole or in part, (iii) provides for the scheduled payments of dividends or other distributions in cash or other securities that would constitute Disqualified Equity Interests, or (iv) is or becomes convertible into or exchangeable for Indebtedness or any other Equity Interests that would constitute Disqualified Equity Interests, in each case, prior to the date that is ninety-one (91) days after the scheduled Maturity Date; provided that, if such Equity Interests are issued pursuant to any plan for the benefit of directors, officers, employees or consultants of such Person or by any such plan to such directors, officers, employees or consultants, such Equity Interests shall not constitute Disqualified Equity Interests solely because they may be required to be repurchased by such Person upon the death, disability, retirement or termination of employment or service of such director, officer, employee or consultant. “Disqualified Institution” means (i) those Persons that are Competitors, (ii) those Persons separately identified by name by the Issuer to the Administrative Agent in writing on or before the Closing Date, or (iii) in the case of clauses (i) or (ii), any of their respective Affiliates (other than Affiliates that are bona fide debt funds engaged in, or that advise funds or other investment vehicles that are engaged in, making, purchasing, holding or otherwise investing in commercial loans, notes, bonds or similar extensions of credit or securities in the ordinary course of its business except such funds that primarily invest in distressed debt or other distressed financial assets) that are (x) clearly identifiable as Affiliates solely on the basis of their name (provided that the Administrative Agent shall not have any obligation to carry out due diligence in order to identify such Affiliates) or (y) identified by name by the Issuer to the Administrative Agent in writing from time to time; provided that the foregoing shall not apply retroactively to disqualify any Person that previously acquired an assignment or participation interest to the extent such Person was not a Disqualified Institution at the time of the applicable assignment or participation, as the case may be. “Dollars” and “$” means lawful money of the United States of America. “Early Redemption Fee” means, with respect to any redemption of all or any portion of the outstanding principal amount of the Notes on any Early Redemption Date, whether pursuant to clause (a) or (b) of Section 3.03 or otherwise, occurring (i) on or prior to the first anniversary of the Closing Date, an amount equal to the sum of five percent (5.0%) of the aggregate outstanding principal amount of the Notes being prepaid; (ii) at any time after the first anniversary of the 6 Closing Date and on or prior to the second anniversary of the Closing Date, an amount equal to four percent (4.0%) of the aggregate outstanding principal amount of the Notes being redeemed; (iii) at any time after the second anniversary of the Closing Date and on or prior to the third anniversary of the Closing Date, an amount equal to one percent (1.0%) of the aggregate outstanding principal amount of the Notes being redeemed and (iv) thereafter, zero percent (0%) of the aggregate outstanding principal amount of the Notes being redeemed. “Early Redemption Date” has the meaning set forth in Section 3.03(a)(i). “Early Redemption Price” has the meaning set forth in Section 3.0(a)(i). “EEA Financial Institution” means (i) any credit institution or investment firm established in any EEA Member Country which is subject to the supervision of an EEA Resolution Authority, (ii) any entity established in an EEA Member Country which is a parent of an institution described in clause (i) of this definition, or (iii) any financial institution established in an EEA Member Country which is a subsidiary of an institution described in clauses (i) or (ii) of this definition and is subject to consolidated supervision with its parent. “EEA Member Country” means any of the member states of the European Union, Iceland, Liechtenstein, and Norway. “EEA Resolution Authority” means any public administrative authority or any person entrusted with public administrative authority of any EEA Member Country (including any delegee) having responsibility for the resolution of any EEA Financial Institution. “Eligible Transferee” means and includes (i) any commercial bank, (ii) any insurance company, (iii) any finance company, (iv) any financial institution, (v) any investment fund that invests in loans, notes or other obligations for borrowed money, (vi) with respect to any Noteholder, any of its Affiliates, and (vii) any other “accredited investor” (as defined in Regulation D of the Securities Act) that is principally in the business of managing investments or holding assets for investment purposes; provided that, in each case, “Eligible Transferee” shall not include any Disqualified Institution. “English Guarantor” means MeiraGTx UK II Limited incorporated in England and Wales with company registration number 09348737. “English Law Security Agreement” means the English law governed security agreement dated on or about the date of this Agreement and made between the English Guarantor and the Irish Subsidiary Guarantor as chargor and the Administrative Agent as security trustee. “English Law Share Charge” means the English law governed share charge in respect of the shares MeiraGTx Limited owns in the English Guarantor dated on or about the date of this Agreement and made between the Issuer as chargor and the Administrative Agent as security trustee. “English Obligor” means any Obligor incorporated in England and Wales. 7  “Environmental Law” means any Law or Governmental Approval relating to pollution or protection of the environment or the treatment, storage, disposal, release, threatened release or handling of hazardous materials, and all local laws and regulations, whether U.S. or non-U.S., related to environmental matters and any specific agreements entered into with any competent authorities which include commitments related to environmental matters. “Equity Interests” means, with respect to any Person (for purposes of this defined term, an “issuer”), all shares of, interests or participations in, or other equivalents in respect of such issuer’s capital stock, including all membership interests, partnership interests or equivalent, and all debt or other securities (including warrants, options and similar rights) directly or indirectly exchangeable, exercisable or otherwise convertible into, such issuer’s capital stock, whether now outstanding or issued after the Closing Date, and in each case, however classified or designated and whether voting or non-voting. “Equivalent Amount” means, with respect to an amount denominated in a single currency, the amount in another currency that could be purchased by the amount in the former currency determined by reference to the Exchange Rate at the time of determination. “ERISA” means the United States Employee Retirement Income Security Act of 1974, as amended. “ERISA Affiliate” means, collectively, any Obligor, Subsidiary thereof, and any Person under common control, or treated as a single employer, with any Obligor or Subsidiary thereof, within the meaning of Section 414(b), (c), (m) or (o) of the Code. “ERISA Event” means (i) a reportable event as defined in Section 4043 of ERISA with respect to a Title IV Plan, excluding, however, such events as to which the PBGC by regulation has waived the requirement of Section 4043(a) of ERISA that it be notified within thirty (30) days of the occurrence of such event; (ii) a withdrawal by any Obligor or any ERISA Affiliate thereof from a Title IV Plan or the termination of any Title IV Plan resulting in liability under Sections 4063 or 4064 of ERISA; (iii) the withdrawal of any Obligor or any ERISA Affiliate thereof in a complete or partial withdrawal (within the meaning of Section 4203 and 4205 of ERISA) of any ERISA Affiliate from any Multiemployer Plan if there is any potential liability therefor, or the receipt by any Obligor or any ERISA Affiliate thereof of notice from any Multiemployer Plan that it is insolvent pursuant to Section 4245 of ERISA; (iv) the filing of a notice of intent to terminate, the treatment of a plan amendment as a termination under Section 4041 or 4041A of ERISA, or the commencement of proceedings by the PBGC to terminate a Title IV Plan or Multiemployer Plan; (v) the imposition of liability on any Obligor or any ERISA Affiliate thereof pursuant to Sections 4062(e) or 4069 of ERISA or by reason of the application of Section 4212(c) of ERISA; (vi) the failure by any Obligor or any ERISA Affiliate thereof to make any required contribution to a Plan, or the failure to meet the minimum funding standard of Section 412 of the Code with respect to any Title IV Plan (whether or not waived in accordance with Section 412(c) of the Code) or the failure to make by its due date a required installment under Section 430 of the Code with respect to any Title IV Plan or the failure to make any required contribution to a Multiemployer Plan; (vii) the determination that any Title IV Plan is considered an at-risk plan or a plan in endangered to critical status within the meaning of Sections 430, 431 and 432 of the Code or Sections 303, 304 and 305 of ERISA; (viii) an event or condition which could reasonably be 8 expected to constitute grounds under Section 4042 of ERISA for the termination of, or the appointment of a trustee to administer, any Title IV Plan or Multiemployer Plan; (ix) the imposition of any liability under Title I or Title IV of ERISA, other than PBGC premiums due but not delinquent under Section 4007 of ERISA, upon any Obligor or any ERISA Affiliate thereof; (x) an application for a funding waiver under Section 303 of ERISA or an extension of any amortization period pursuant to Section 412 of the Code with respect to any Title IV Plan; (xi) the occurrence of a non-exempt prohibited transaction under Sections 406 or 407 of ERISA for which any Obligor or any Subsidiary thereof may be directly or indirectly materially liable; (xii) receipt from the IRS of notice of the failure of any Qualified Plan to qualify under Section 401(a) of the Code, or the failure of any trust forming part of any Qualified Plan to fail to qualify for exemption from taxation under Section 501(a) of the Code; (xiii) the imposition of any Lien (or the fulfillment of the conditions for the imposition of any Lien) on any of the rights, properties or assets of any Obligor or any ERISA Affiliate thereof, in either case pursuant to Title I or Title IV of ERISA, including Section 302(f) or 303(k) of ERISA or to Section 401(a)(29) or 430(k) of the Code; or (xiv) any Foreign Benefit Event. “ERISA Funding Rules” means the rules regarding minimum required contributions (including any installment payment thereof) to Title IV Plans, as set forth in Sections 412, 430, 431, 432 and 436 of the Code and Sections 302, 303, 304 and 305 of ERISA. “EU Bail-In Legislation Schedule” means the EU Bail-In Legislation Schedule published by the Loan Market Association (or any successor Person), as in effect from time to time. “Euros” or “€” means the single currency of the member states of the European Union that have the euro as their lawful currency in accordance with legislation of the European Union relating to the Economic and Monetary Union. “Event of Default” has the meaning set forth in Section 11.01. “Exchange Rate” means, as of any date of determination, the rate at which any currency may be exchanged into another currency, as set forth on the relevant Reuters screen at or about 11:00 a.m. (New York City time) on such date. In the event that such rate does not appear on the Reuters screen, the “Exchange Rate” shall be determined by reference to such other publicly available service for displaying exchange rates as may be reasonably agreed upon by the Issuer and the Administrative Agent (each acting in good faith) or, in the absence of such agreement within two (2) Business Days, such Exchange Rate shall instead be reasonably designated by the Administrative Agent. “Excluded Taxes” means any of the following Taxes imposed on or with respect to a Recipient or required to be withheld or deducted from a payment to a Recipient: (i) Taxes imposed on or measured by net income (however denominated), franchise Taxes and branch profits Taxes, in each case, (x) imposed as a result of such Recipient being organized under the laws of, or having its principal office or, in the case of any Noteholder, its applicable booking office located in, the jurisdiction imposing such Tax (or any political subdivisions thereof) or (y) that are Other Connection Taxes, (ii) any withholding Taxes imposed under FATCA, or (iii) any UK Tax Deduction that qualifies as a UK Excluded Tax, provided that once the Notes are listed on a 9 Recognised Stock Exchange pursuant to Section 3.02(f), no UK Tax Deduction shall be treated as a UK Excluded Tax. “Exchange Act” means the Securities Exchange Act of 1934, as amended, and the rules and regulations promulgated thereunder. “Exclusive License” means any outbound license of Intellectual Property that is exclusive (whether as to use, field, geography or otherwise) and (i) has a term that is longer than twelve (12) months from the date of the original effective date of such license or (ii) is not subject to any automatic renewal right or obligation by the parties thereto. “Facility” means, as the context may require, any of the Tranche 1 Facility or the Tranche 2 Facility, and “Facilities” means, collectively, any combination of the foregoing, as the case may be. “FATCA” means Sections 1471 through 1474 of the Code, as of the date of this Agreement (or any amended or successor version that is substantively comparable and not materially more onerous to comply with), any current or future regulations or official interpretations thereof, any agreements entered into pursuant to Section 1471(b)(1) of the Code and any fiscal or regulatory legislation, rules or practices adopted pursuant to any intergovernmental agreement, treaty or convention among Governmental Authorities and implementing such Sections of the Code. “FD&C Act” means the U.S. Food, Drug and Cosmetic Act of 1938 (21 U.S.C. §§ 301), as amended from time to time, and the regulations promulgated thereunder. “FDA” means the U.S. Food and Drug Administration and any successor entity. “Federal Funds Effective Rate” means, for any day, the greater of (i) the rate calculated by the Federal Reserve Bank of New York based on such day’s federal funds transactions by depositary institutions (as determined in such manner as the Federal Reserve Bank of New York sets forth on its public website from time to time) and published on the next succeeding Business Day by the Federal Reserve Bank of New York as the federal funds effective rate and (ii) zero percent (0%). “Foreign Benefit Event” means, with respect to any Foreign Pension Plan, (a) the existence of unfunded liabilities in excess of the amount permitted under any material applicable Law, or in excess of the amount that would be permitted absent a waiver from a Governmental Authority, (b) the failure to make the required contributions or payments, under any material applicable Law, on or before the due date for such contributions or payments, (c) the receipt of a written notice by a Governmental Authority relating to the termination of any such Foreign Pension Plan or to appoint a trustee or similar official to administer any such Foreign Pension Plan, or alleging the insolvency of any such Foreign Pension Plan, (d) the incurrence of any liability the Issuer or any of its Subsidiaries under applicable Law on account of the complete or partial termination of such Foreign Pension Plan or the complete or partial withdrawal of any participating employer therein, or (e) the occurrence of any transaction that is prohibited under any applicable Law and that could reasonably be expected to result in the incurrence of any liability by the Issuer or any of its Subsidiaries, or the imposition on the Issuer or any of its Subsidiaries of any fine, excise tax or penalty resulting from any noncompliance with any applicable Law. 10 “Foreign Collateral Security Documents” means (i) the English Law Security Agreement, (ii) the English Law Share Charge, (iii) the Irish Security Agreement, (iv) the Irish Share Charge, and (v) any other document evidencing or creating a Lien over any asset to secure any obligation of any Obligor to the Secured Parties under the Notes Documents. “Foreign Pension Plan” means any benefit plan that under applicable Law, other than the Laws of the United States or any political subdivision thereof, is required to be funded through a trust or other funding vehicle other than a trust or funding vehicle maintained exclusively by a Governmental Authority. “Foreign Real Property Security Document” means any Contract evidencing or creating a Lien over any Manufacturing Facility entered into in accordance with Section 8.17. “GAAP” means generally accepted accounting principles in the United States, as in effect from time to time, set forth in the opinions and pronouncements of the Accounting Principles Board and the American Institute of Certified Public Accountants, in the statements and pronouncements of the Financial Accounting Standards Board and in such other statements by such other entity as may be in general use by significant segments of the accounting profession that are applicable to the circumstances as of the date of determination. Unless otherwise mutually agreed upon by the Issuer and the Administrative Agent pursuant to Section 1.02(b), all references to “GAAP” used herein shall be to GAAP applied consistently with the principles used in the preparation of the financial statements delivered pursuant to Section 6.01(e)(i). “Governmental Approval” means any consent, authorization, approval, order, license, franchise, permit (including any Healthcare Permit), certification, accreditation, registration, clearance, exemption, filing or notice that is issued or granted by or from (or pursuant to any act of) any Governmental Authority pursuant to or in connection with any Law (including any Healthcare Law). including without “Governmental Authority” means any nation, government, branch of power (whether executive, legislative or judicial), state, province or municipality or other political subdivision thereof and any entity exercising executive, legislative, judicial, monetary, regulatory or administrative functions of or pertaining to government, limitation regulatory authorities, governmental departments, agencies, commissions, bureaus, officials, ministers, courts, bodies, boards, tribunals and dispute settlement panels, and other law-, rule- or regulation-making organizations or entities of any state, territory, county, city or other political subdivision of any country, in each case whether U.S. or non-U.S., including the FDA and any other agency, branch or other governmental body that has regulatory, supervisory or administrative authority or oversight over, or is charged with the responsibility or vested with the authority to administer or enforce, any Healthcare Laws or issue or approve any Healthcare Permits under or in connection with any such Healthcare Laws. “Guarantee” of or by any Person (the “guarantor”) means any obligation, contingent or otherwise, of the guarantor guaranteeing or having the economic effect of guaranteeing any Indebtedness or other monetary obligation of any other Person (the “primary obligor”) in any manner, whether directly or indirectly, and including any obligation of the guarantor, direct or indirect, (i) to purchase or pay (or advance or supply funds for the purchase or payment of) such 11 Indebtedness or other monetary obligation or to purchase (or to advance or supply funds for the purchase of) any security for the payment thereof, (ii) to purchase or lease property, securities or services for the purpose of assuring the owner of such Indebtedness or other monetary obligation of the payment thereof, (iii) to maintain working capital, equity capital or any other financial statement condition or liquidity of the primary obligor so as to enable the primary obligor to pay such Indebtedness or other monetary obligation or (iv) as an account party in respect of any letter of credit or letter of guaranty issued to support such Indebtedness or monetary obligation; provided, that the term “Guarantee” shall not include endorsements for collection or deposit in the ordinary course of business. “Guarantee Assumption Agreement” means a Guarantee Assumption Agreement substantially in the form of Exhibit C, executed by any entity that, pursuant to Section 8.12 is required to become a “Subsidiary Guarantor”. “Guaranteed Obligations” has the meaning set forth in Section 13.01. “Hazardous Material” means any substance, element, chemical, compound, product, solid, gas, liquid, waste, by-product, pollutant, contaminant or material which is hazardous or toxic, and includes, without limitation, (i) asbestos, polychlorinated biphenyls and petroleum (including crude oil or any fraction thereof) and (ii) any material classified or regulated as “hazardous” or “toxic” or words of like import pursuant to an Environmental Law. “Headlease” means a lease under which an Obligor holds title to all or any part of a Manufacturing Facility. “Healthcare Laws” means all applicable healthcare Laws, whether U.S. or non-U.S., the federal Anti- kickback Statute (42 U.S.C. § 1320a-7b(b)) (the “Federal Anti-Kickback Statute”), the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h), the civil False Claims Act (31 U.S.C. §§ 3729 et seq.), the criminal False Claims Act (42 U.S.C. § 1320a-7b(a)), all criminal laws relating to health care fraud and abuse, including but not limited to 18 U.S.C. Sections 286, 287, 1035, 1347 and 1349, the exclusion law (42 U.S.C. § 1320a-7), the civil monetary penalties law (42 U.S.C. § 1320a-7a), Health Insurance Portability and Accountability Act of 1996 (42 U.S.C. §§ 1320d et seq.), as amended by the Health Information Technology for Economic and Clinical Health Act (42 U.S.C. §§ 17921 et seq.), the FD&C Act, the statutes, regulations and binding directives of applicable federal healthcare programs, including but not limited to Medicare (Title XVIII of the Social Security Act) and Medicaid (Title XIX of the Social Security Act), any rules and regulations promulgated pursuant to the statutes listed herein and any and all comparable U.S. and non-U.S. Laws and other applicable healthcare laws and regulations. “Healthcare Permit” means, with respect to any Person and with respect to its ordinary course business or commercial activities (including the commercialization and development of its products), any Governmental Approval (i) issued or required under any Healthcare Laws applicable to such activities of such Person, or (ii) issued to such Person or required to be held by such Person under any Healthcare Laws with respect to its ordinary course business or commercial activities (including the commercialization and development of its products). 12 “Hedging Agreement” means any interest rate exchange agreement, foreign currency exchange agreement, commodity price protection agreement or other interest or currency exchange rate or commodity price hedging arrangement. For the avoidance of doubt, no Permitted Bond Hedge Transaction or Permitted Warrant Transaction shall constitute Hedging Agreements. “HMRC” means HM Revenue & Customs. “IDA Grant” means the transactions and grant awarded by the Industrial Development Agency (Ireland) to the Irish Subsidiary Guarantor pursuant to the IDA Grant Agreement. “IDA Grant Agreement” means the IDA Grant Agreement, dated as of August 27, 2021, by and between the Industrial Development Agency (Ireland) and the Irish Subsidiary Guarantor, as amended, restated, supplemented or otherwise modified from time to time. “Immaterial Subsidiary” means, as of any date of determination, any Subsidiary of an Obligor (i) the unconsolidated assets of which does not exceed 5.0% of the consolidated assets of the Issuer and its consolidated Subsidiaries as set forth in the financial statements most recently delivered pursuant to Sections 6.01, 8.01(a) or 8.01(b), as applicable, and (ii) the unconsolidated revenues of which does not exceed 5.0% of the consolidated revenues of the Issuer and its consolidated Subsidiaries as set forth in the financial statements most recently delivered pursuant to Sections 6.01, 8.01(a) or 8.01(b), as applicable; provided that no Subsidiary of the Obligors shall qualify as an Immaterial Subsidiary if the assets or revenue of such Subsidiary taken together with the consolidated assets or revenue of all then existing Immaterial Subsidiaries exceeds 10.0% of the consolidated assets or revenue, as applicable, of the Issuer and its consolidated Subsidiaries. “Impermissible Specified Assets Exclusive License” means any outbound license (or similar transaction or arrangement) of any Specified Asset, in whole or in part, to a Person that is not an Affiliate that (i) qualifies as an Exclusive License, and (ii) is not terminable by its terms (or automatically terminates) or by the licensor within twenty (20) years from either (x) the original date of such outbound license or (y) if the term of such outbound license is extended and so long as such extension does not result from an automatic renewal right or equivalent, the date of such extension. “Indebtedness” of any Person means, without duplication, (i) all obligations of such Person for borrowed money, (ii) all obligations of such Person evidenced by bonds, debentures, notes, loan agreements, or similar instruments, (iii) all obligations of such Person upon which interest charges are customarily paid (excluding trade account payables), (iv) all obligations of such Person under conditional sale or other title retention agreements relating to property acquired by such Person, (v) all obligations of such Person in respect of the deferred purchase price of property or services ((A) excluding accounts payable incurred in the ordinary course of business, but (B) including earn-out payments, purchase price adjustments and similar contingent payment obligations relating to any Acquisition (such obligations arising pursuant to clause (B), collectively, “Contingent Acquisition Obligations”)), (vi) all Indebtedness of others secured by (or for which the holder of such Indebtedness has an existing right, contingent or otherwise, to be secured by) any Lien on property owned or acquired by such Person, whether or not the Indebtedness secured thereby has been assumed, (vii) all Guarantees by such Person of Indebtedness of others, (viii) all Capital Lease Obligations of such Person, (ix) all obligations, 13 contingent or otherwise, of such Person as an account party in respect of letters of credit and letters of guaranty, (x) obligations under any Hedging Agreement, currency swaps, forwards, futures or derivatives transactions, (xi) all obligations, contingent or otherwise, of such Person in respect of bankers’ acceptances, (xii) all obligations of such Person under license or other agreements containing a guaranteed minimum payment or purchase by such Person other than operating leases entered into in the ordinary course of business and any such license or other agreement for the purchase of goods, software and other intangibles, services or supplies in the ordinary course of business, (xiii) any Disqualified Equity Interests of such Person, and (xiv) all other obligations required to be classified as indebtedness of such Person under GAAP, excluding any of the foregoing to the extent comprised of an obligation in respect of a trade payable, a commercial letter of credit supporting one or more trade payables or similar obligations to a trade creditor, in each case in the ordinary course of business. The Indebtedness of any Person shall include the Indebtedness of any other entity (including any partnership in which such Person is a general partner) to the extent such Person is liable therefor as a result of such Person’s ownership interest in or other relationship with such entity, except to the extent the terms of such Indebtedness provide that such Person is not liable therefor. Notwithstanding the foregoing, no Permitted Bond Hedge Transaction or Permitted Warrant Transaction shall constitute Indebtedness. “Indemnified Party” has the meaning set forth in Section 14.03(b). “Indemnified Taxes” means (i) Taxes, other than Excluded Taxes, imposed on or with respect to any payment made by or on account of any Obligation, (ii) to the extent not otherwise described in clause (i), Other Taxes or (iii) any UK Tax Deduction in respect of a payment made by a Withholding Agent under a Notes Document to Perceptive Credit Holdings III, LP. “Independent Appraiser” has the meaning set forth in Section 6.01(p). “Information Certificate” means an Information and Collateral Certificate, in substantially the form set forth in Exhibit G. “Insolvency Proceeding” means (i) any case, action or proceeding before any court or other Governmental Authority relating to bankruptcy, reorganization, insolvency, liquidation, receivership, examinership, dissolution, winding-up or relief of debtors, or (ii) any general assignment for the benefit of creditors, composition, marshaling of assets for creditors, or other, similar arrangement in respect of any Person’s creditors generally or any substantial portion of such Person’s creditors, in each case undertaken under U.S. federal, state or foreign Law, including the Bankruptcy Code, or similar laws of Ireland or other applicable jurisdictions from time to time. “Intellectual Property” means all Patents, Trademarks, Copyrights, and Technical Information, whether registered or not, U.S. or non-U.S., including (without limitation) all of the following: (i) Property; applications, registrations, amendments and extensions relating to such Intellectual (ii) rights and privileges arising under any applicable Laws with respect to such Intellectual Property; 14 (iii) rights to sue for or collect any damages for any past, present or future infringements of such Intellectual Property; and (iv) rights of the same or similar effect or nature in any jurisdiction corresponding to such Intellectual Property throughout the world. “Intercompany Subordination Agreement” means a subordination agreement to be executed and delivered by the Issuer and each of its Subsidiaries, pursuant to which all obligations in respect of any Indebtedness owing to any such Person by the Issuer or any of its Subsidiaries shall be subordinated to the prior payment in full in cash of all Obligations, such agreement to be substantially in the form attached hereto as Exhibit H. “Interest Period” means (i) initially, the period commencing on (and including) the Closing Date and ending on (and including) the last day of the calendar quarter in which the Closing Date occurred, and (ii) thereafter, the period beginning on (and including) the first day of each succeeding calendar quarter and ending on the earlier of (and including) (x) the last day of such calendar quarter and (y) the Maturity Date. “Interest Rate” means, for any Interest Period, the sum of (i) the Applicable Margin plus (ii) the greater of (x) the Reference Rate as of the second Business Day immediately preceding the first day of such Interest Period and (y) one percent (1.00%). “Invention” means any novel, inventive or useful art, apparatus, method, process, machine (including any article or device), manufacture or composition of matter, or any novel, inventive and useful improvement in any art, method, process, machine (including article or device), manufacture or composition of matter. “Investment” means, for any Person: (i) the acquisition (whether for cash, property, services or securities or otherwise) of Equity Interests, bonds, notes, debentures, partnership or other ownership interests or other securities of any other Person or any agreement to make any such acquisition (including any “short sale” or any sale of any securities at a time when such securities are not owned by the Person entering into such sale); (ii) the making of any deposit with, or advance, loan, assumption of debt, or other extension of credit to, or capital contribution in any other Person (including the purchase of property from another Person subject to an understanding or agreement, contingent or otherwise, to resell such property to such Person), but excluding any such advance, loan or extension of credit having a term not exceeding one hundred eighty (180) days arising in connection with the sale of inventory, services or supplies by such Person in the ordinary course of business; (iii) the entering into of any Guarantee of, or other contingent obligation with respect to, Indebtedness or other liability of any other Person and (without duplication) any amount committed to be advanced, lent or extended to such Person; or (iv) the entering into of any Hedging Agreement. The amount of an Investment will be determined at the time the Investment is made without giving effect to any subsequent changes in value. “Irish Companies Act” means the Companies Act of Ireland, 2014 (as amended). “Irish Security Agreement” means the Irish law debenture to be executed and delivered by the Irish Subsidiary Guarantor and the Administrative Agent, as amended, restated, amended and restated, supplemented or otherwise modified from time to time. 15 “Irish Share Charge” means an Irish law share charge over the shares of MeiraGTx Ireland DAC, to be executed and delivered by MeiraGTx Limited and the Administrative Agent, as amended, restated, amended and restated, supplemented or otherwise modified from time to time. “Irish Subsidiary Guarantor” means MeiraGTx Ireland DAC, a designated activity company limited by shares incorporated in Ireland under registration number 672472 and with its registered address at 25-28 North Wall Quay, Dublin 1, D01 H104 and any other company incorporated in Ireland who accedes to this Agreement as a Subsidiary Guarantor from time to time. “IRS” means the U.S. Internal Revenue Service. “Issuer” has the meaning set forth in the preamble hereto. “Issuer DTTP Filing” means a HMRC Form DTTP2 duly completed and filed by the Issuer, which: (a) where it relates to a UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities) that is a party hereto as at the date of this Agreement, contains the UK DTTP Scheme reference number and jurisdiction of tax residence stated opposite that Noteholder’s name in Schedule 1 (Commitments), and is filed with HMRC within 30 days of the date of this Agreement; or (b) where it relates to a UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities) that becomes a party hereto after the date of this Agreement, contains the UK DTTP Scheme reference number and jurisdiction of tax residence stated in respect of that Noteholder in the relevant documentation which it executes on becoming a party hereto, and is filed with HMRC within 30 days of that date. “Janssen Collaboration Agreement” means that certain Collaboration, Option and License Agreement, dated January 30, 2019, by and between Janssen Pharmaceuticals, Inc. and Issuer, as may be amended, restated, supplemented or otherwise modified from time to time. “Law” means any U.S. or non-U.S. federal, state, provincial, territorial, municipal or local statute, treaty, rule, regulation, ordinance, code or administrative or judicial precedent or authority, including any interpretation or administration thereof by any Governmental Authority charged with the enforcement, interpretation or administration thereof, and all applicable administrative orders, directed duties, requests, licenses, authorizations and permits of, and agreements with, any Governmental Authority, in each case having the force of law. “Legal Reservations” means, solely in respect of the English Guarantor and the Irish Subsidiary Guarantor, (i) the principle that equitable or discretionary remedies may be granted or refused at the discretion of a court and the limitation of enforcement by laws relating to insolvency, reorganisation and other laws generally affecting the rights of creditors; (ii) the time barring of claims under the UK Limitation Acts or the Statute of Limitations 1957 (Ireland) (as applicable), the possibility that an undertaking to assume liability for or indemnify a person against non-payment of stamp duty may be void and defences of set-off or counterclaim; (iii) the limitation of the enforcement of the terms of leases of real property by laws of general application to those 16 leases; (iv) similar principles, rights and remedies under the laws of any Relevant Jurisdiction; and (v) any other matters which are set out as qualifications or reservations as to matters of law of general application in any legal opinions supplied to the Noteholders under this Agreement. “Lien” means any mortgage, lien, pledge, charge, assignment by way of security or other security interest, or any lease, title retention agreement, mortgage, restriction, easement, right-of-way, option or adverse claim (of ownership or possession) or other encumbrance of any kind or character whatsoever or any preferential arrangement that has the practical effect of creating a security interest. “London Manufacturing Facility” means the leasehold interest held by the UK Subsidiary Guarantor with Land Registry title number EGL434767 and known as Pharmacy Manufacturing Unit, Britannia Walk, London (N1 7LU) and located at 92 Britannia Walk, London, United Kingdom. “Loss” means judgments, debts, liabilities, expenses, costs, damages or losses, contingent or otherwise, whether liquidated or unliquidated, matured or unmatured, disputed or undisputed, contractual, legal or equitable, including loss of value, professional fees, including fees and disbursements of legal counsel on a full indemnity basis, and all costs incurred in investigating or pursuing any Claim or any proceeding relating to any Claim. “Majority Noteholders” means, at any time, Noteholders having at such time in excess of fifty percent (50%) of the aggregate Commitments (or, if such Commitments are terminated, the outstanding principal amount of the Notes) then in effect, ignoring, in such calculation, the Commitments of and outstanding Notes owing to any Noteholder that has failed to perform its funding obligations in respect of its Commitment to make subscriptions for Notes hereunder. “Manufacturing Facility” means (i) the Shannon Manufacturing Facility and (ii) the London Manufacturing Facility. “Margin Stock” means “margin stock” within the meaning of Regulation U and Regulation X. “Material Adverse Change” and “Material Adverse Effect” mean a material adverse change in or effect on (i) the business, assets, operations or condition (financial or otherwise) of the Issuer and its Subsidiaries, taken as a whole, (ii) the ability of any Obligor to perform its obligations under the Notes Documents, as and when due, or (iii) the legality, validity, binding effect or enforceability of the Notes Documents or the rights and remedies of the Administrative Agent or the Noteholders under any of the Notes Documents. “Material Agreement” means (i) any Contract to which the Issuer or any of its Subsidiaries is a party or a beneficiary from time to time, the absence or termination of which could reasonably be expected to result in a Material Adverse Effect, and (ii) without duplication, any other Contract to which the Issuer or any of its Subsidiaries is a party or a guarantor (or equivalent) that, during any period of twelve (12) consecutive months is reasonably expected to (1) result in payments or receipts (including royalty, licensing or similar payments) made to the Issuer or any of its Subsidiaries in an aggregate amount in excess of $5,000,000, or (2) require payments or 17 expenditures (including royalty, licensing or similar payments) to be made by the Issuer or any of its Subsidiaries in an aggregate amount in excess of $5,000,000. “Material Indebtedness” means, at any time, any Indebtedness of any Obligor or any Subsidiary thereof (excluding any intercompany Indebtedness by and among the Obligors and their respective Subsidiaries that is permitted hereunder), the outstanding principal amount of which, individually or in the aggregate, exceeds $5,000,000 (or the Equivalent Amount in other currencies). “Material Intellectual Property” means any Intellectual Property of the Obligors, whether currently owned or licensed, or acquired, developed or otherwise licensed or obtained after the date hereof the loss of which could reasonably be expected to result in a Material Adverse Effect. “Maturity Date” means August 2, 2026. “MD&A” has the meaning set forth in Section 8.01(c). “Medicaid” means that government-sponsored entitlement program under Title XIX, P.L. 89-97 of the Social Security Act, which provides federal grants to states for medical assistance based on specific eligibility criteria, as set forth on Section 1396, et seq. of Title 42 of the United States Code. “Medicare” means that government-sponsored insurance program under Title XVIII, P.L. 89-97, of the Social Security Act, which provides for a health insurance system for eligible elderly and disabled individuals, as set forth at Section 1395, et seq. of Title 42 of the United States Code. “Minimum Liquidity Account” has the meaning set forth in Section 10.01. “Multiemployer Plan” means any multiemployer plan, as defined in Section 400l(a)(3) of ERISA, to which any ERISA Affiliate incurs or otherwise has any obligation or liability, contingent or otherwise. “Net Cash Proceeds”, means, (i) with respect to any Casualty Event experienced or suffered by the Issuer or any of its Subsidiaries, the amount of cash proceeds received (directly or indirectly) including, without limitation, in the form of insurance proceeds or condemnation awards in respect of such Casualty Event, from time to time by or on behalf of such Person after deducting therefrom only (x) reasonable fees, costs and expenses related thereto incurred by the Issuer or such Subsidiary in connection therewith, (y) amounts required to be repaid on account of any Permitted Indebtedness (other than the Obligations) required to be repaid as a result of such Casualty Event, (y) amounts required to be reserved in accordance with GAAP for indemnities and against liabilities associated with the property damaged, destructed or condemned in such Casualty Event, and (z) Taxes (including transfer Taxes or net income Taxes) paid or payable in connection therewith; and (ii) with respect to any Asset Sale by the Issuer or any of its Subsidiaries, the amount of cash proceeds received (directly or indirectly) from time to time by or on behalf of such Person after deducting therefrom only (x) reasonable fees, costs and expenses related thereto incurred by the Issuer or such Subsidiary in connection therewith, (y) amounts required to be repaid on account of any Permitted Indebtedness (other than the Obligations) required to be repaid as a result of such Asset Sale, and (z) Taxes (including transfer Taxes or net income Taxes) paid or 18 payable in connection therewith; provided that, in each case of clauses (i) and (ii), costs and expenses shall only be deducted to the extent, that the amounts so deducted are (x) actually paid to a Person that is not an Affiliate of the Issuer or any of its Subsidiaries and (y) properly attributable to such Casualty Event or Asset Sale, as the case may be. “Noteholders” has the meaning set forth in the preamble hereto. “Notes” means, as the context may require, any of the Tranche 1 Notes or the Tranche 2 Notes, and “Notes” means, collectively, any combination of the foregoing, as the case may be. “Notes Certificate” means a notes certificate in the form set out in Exhibit A. “Notes Documents” means, collectively, this Agreement, the Notes Certificates, the Security Documents, any Guarantee, any Notes Subscription Request, any Assignment Agreement, any Transfer Certificate, any Warrant Certificate, the Intercompany Subordination Agreement, and any other guaranty, security agreement, subordination agreement, intercreditor agreement or other present or future document, instrument, agreement, certificate or other amendment, waiver or modification of the foregoing, delivered to the Administrative Agent or any Noteholder in connection with this Agreement or any of the other Notes Documents, in each case, as amended or otherwise modified. “Notes Register” has the meaning set forth in Section 14.05(d). “Notes Subscription” means a subscription for Tranche 1 Notes or Tranche 2 Notes. “Notes Subscription Date” means the Closing Date and each Tranche 2 Notes Subscription Date as applicable. “Notes Subscription Request” means a written notice substantially in the form of Exhibit B. “NY UCC” means the UCC as in effect from time to time in New York. “Obligations” means, with respect to any Obligor, all amounts, obligations, liabilities, covenants and duties of every type and description (including all Guaranteed Obligations) owing by such Obligor to any Secured Party, any indemnitee hereunder or any participant, arising out of, under, or in connection with, any Notes Document, whether direct or indirect (regardless of whether acquired by assignment), absolute or contingent, due or to become due, whether liquidated or not, now existing or hereafter arising and however acquired, and whether or not evidenced by any instrument or for the payment of money, including, without duplication, (i) if such Obligor is the Issuer, all Notes, (ii) all interest, whether or not accruing after the filing of any petition in bankruptcy or after the commencement of any insolvency, reorganization or similar proceeding, and whether or not a claim for post-filing or post-petition interest is allowed in any such proceeding, and (iii) all other fees, expenses (including fees, charges and disbursement of counsel), interest, commissions, charges, costs, disbursements, indemnities and reimbursement of amounts paid and other sums chargeable to such Obligor under any Notes Document. Notwithstanding the foregoing, the “Obligations” shall not include the Warrant Obligations and any obligations under any other warrant or other instrument or any equity or other investment. 19 “Obligors” means, collectively, the Issuer, the Subsidiary Guarantors and their respective successors and permitted assigns. “OFAC” means the U.S. Department of the Treasury’s Office of Foreign Assets Control. “One-Month Term SOFR” means, the Term SOFR Reference Rate (expressed, as a decimal, rounded upwards, if necessary, to the nearest 1/100th of 1%) for a one month tenor on the day (such day, the “Periodic Term SOFR Determination Day”) that is two (2) U.S. Government Securities Business Days prior to the first day of the Interest Period, as such rate is published by the Term SOFR Administrator; provided, however, that if as of 5:00 p.m. (New York City time) on any Periodic Term SOFR Determination Day the Term SOFR Reference Rate for the one month tenor has not been published by the Term SOFR Administrator, then Term SOFR will be the Term SOFR Reference Rate for a one month tenor as published by the Term SOFR Administrator on the first preceding U.S. Government Securities Business Day for which such Term SOFR Reference Rate for such tenor was published by the Term SOFR Administrator so long as such first preceding U.S. Government Securities Business Day is not more than three (3) U.S. Government Securities Business Days prior to such Periodic Term SOFR Determination Day. “Organic Document” means, for any Person, such Person’s formation documents, including, as applicable its certificate of incorporation, by-laws, constitution, memorandum and articles of association, certificate of partnership, partnership agreement, certificate of formation, limited liability agreement, constitution, operating agreement and all shareholder agreements, voting trusts and similar arrangements applicable to such Person’s Equity Interests, or any equivalent document of any of the foregoing. “Original Noteholder” has the meaning set forth in the preamble hereto. “Other Connection Taxes” means, with respect to any Recipient, Taxes imposed as a result of a present or former connection between such Recipient and the jurisdiction imposing such Tax (other than connections arising from such Recipient having executed, delivered, become a party to, performed its obligations under, received payments under, received or perfected a security interest under, engaged in any other transaction pursuant to or enforced any Notes Documents, or sold or assigned an interest in any Notes or Notes Documents). “Other Taxes” means all present or future stamp, court or documentary, intangible, recording, filing or similar Taxes that arise from any payment made under, from the execution, delivery, performance, enforcement or registration of, from the receipt or perfection of a security interest under, or otherwise with respect to, any Notes Documents, except any such Taxes that are Other Connection Taxes imposed with respect to an assignment (other than an assignment made pursuant to Section 5.03(h)). “Overage Deed” means an overage deed relating to the London Manufacturing Facility made between (1) the English Guarantor and (2) Moorfields Eye Hospital NHS Foundation Trust dated 14 December 2018. “Participant” has the meaning set forth in Section 14.05(e). “Participant Register” has the meaning set forth in Section 14.05(e). 20 “Patents” means all patents and patent applications, including (i) the reissues, divisions, continuations, renewals, extensions, and continuations in part thereof, (ii) all rights to recover for all past, present and future infringements thereof and all rights to sue therefor, and (iii) all rights whatsoever accruing thereunder or pertaining thereto throughout the world. “Patriot Act” has the meaning set forth in Section 14.20. “Payment Date” means (i) the last day of each Interest Period; provided that if such last day of any Interest Period is not a Business Day, then the Payment Date shall be the next succeeding Business Day, and (ii) the Maturity Date. “PBGC” means the United States Pension Benefit Guaranty Corporation referred to and defined in ERISA and any successor entity performing similar functions. “Perfection Requirements” means, solely in respect of the English Guarantor and the Irish Subsidiary Guarantor, the making or the procuring of filings, stampings, registrations, notarisations, endorsements, translations and/or notifications of any Notes Document (and/or any Liens created under it) necessary for the validity, enforceability (as against the relevant Obligor or any relevant third party) and/or perfection of that Notes Document. “Periodic Term SOFR Determination Day” has the meaning set forth in the definition of “One-Month Term SOFR”. “Permitted Acquisition” means any Acquisition by the Issuer or any of its Subsidiaries that satisfies each of the following conditions: (a) immediately prior to, and after giving effect to such Acquisition, (i) all representations and warranties contained in this Agreement and the other Notes Documents that are qualified by materiality, Material Adverse Effect or the like are, in each case, true and correct, (ii) all representations and warranties contained in this Agreement and the other Notes Documents that are not qualified by materiality, Material Adverse Effect or the like are, in each case, true and correct in all material respects, and (iii) no Event of Default shall have occurred and be continuing or could reasonably be expected to result therefrom; (b) all transactions in connection therewith shall be consummated in accordance with all applicable Laws and in conformity with all applicable Governmental Approvals, in each case, in all material respects; (c) in the case of an Acquisition of Equity Interests of any Person, all of such Equity Interests (except for any such securities in the nature of directors’ qualifying shares required pursuant to any applicable Law) acquired, or otherwise issued by such Person or any newly formed Subsidiary of the Issuer in connection with such acquisition, shall be owned by an Obligor or a wholly-owned Subsidiary of an Obligor, and the Issuer shall have taken, or caused to be taken, as of the date such Person becomes a Subsidiary of the Issuer, each of the actions set forth in Section 8.12(a), if applicable; 21 (d) the Person (in the case of an Acquisition of Equity Interests), business, property, or assets that is the subject of such Acquisition shall be engaged or used, as the case may be, in substantially the same business or lines of business in which the Issuer and its Subsidiaries are engaged as of the Closing Date; (e) on a pro forma basis after giving effect to such Acquisition, the Issuer and its Subsidiaries shall be in compliance with the financial covenant set forth in Section 10.01; (f) with respect to any Acquisition, the consideration paid for such Acquisition (i) when taken together with consideration paid for all other Acquisitions consummated or effected during the prior period of twelve (12) consecutive months ending on the date such Acquisition becomes effective, does not exceed $20,000,000 in the aggregate (which amount shall include the aggregate amount of outstanding principal and unpaid interest (or equivalent if an equivalent concept exists in its jurisdiction of organization or incorporation) in respect of any Indebtedness assumed, incurred or otherwise created in connection with any such applicable Acquisitions, including all related Contingent Acquisition Obligations), and (ii) when taken together with consideration paid for all other Acquisitions consummated or effected since the Closing Date, does not exceed $50,000,000 in the aggregate (which amount shall also include, without duplication, the aggregate amount of outstanding principal and unpaid interest (or equivalent) in respect of any Indebtedness assumed, incurred or otherwise created in connection with any such applicable Acquisitions, including all related Contingent Acquisition Obligations); provided that for purposes of determining amounts to be calculated for purposes of this clause (f), non-cash consideration shall be determined on the basis of fair market value as determined by the Issuer’s Board acting in good faith; (g) the Issuer shall have provided the Administrative Agent with at least ten (10) calendar days’ prior written notice of any such Acquisition, together with any available summaries, prepared in reasonable detail, of all material non-confidential due diligence conducted by or on behalf of the Issuer or the applicable Subsidiary, as applicable, prior to such Acquisition; (h) at least three (3) Business Days prior to the proposed date of the Acquisition, the Administrative Agent shall have received a certificate of a Responsible Officer of the Issuer (prepared in reasonable detail), certifying that the Acquisition complies with the requirements of this definition; (i) to the extent that the purchase price for any such Acquisition is paid in Equity Interests, all such Equity Interests shall be Qualified Equity Interests; (j) promptly upon request by the Administrative Agent in the case of any Acquisition that has a purchase price in excess of $25,000,000, the Issuer shall provide (i) a copy of the draft purchase agreement related to the proposed Acquisition (and any related documents reasonably requested by the Administrative Agent), (ii) any available quarterly and annual financial statements of the Person whose Equity Interests or assets are being acquired for the twelve (12) month period ending forty-five (45) days immediately prior to 22 such Acquisition, including any audited financial statements that are available, and (iii) any other information reasonably requested by the Administrative Agent and available to the Obligors; and (k) neither the Issuer nor any of its Subsidiaries shall, in connection with any such Acquisition, assume or remain subject to or liable with respect to (x) any Indebtedness of the related seller or the business, Person or properties acquired, except to the extent permitted pursuant to Section 9.01, (y) any Lien on any business, Person or assets acquired, except to the extent permitted pursuant to Section 9.02, or (z) any other liability (including Tax, ERISA and environmental liabilities), except (with respect to liabilities under this clause (k)), to the extent the assumption of any such liability could not reasonably be expected to result in a Material Adverse Effect; provided that any other such Indebtedness, liabilities or Liens not permitted to be assumed, continued or otherwise supported by the Issuer or any of its Subsidiaries hereunder shall be paid in full or released as to the business, Persons or properties being so acquired substantially on or before the consummation of such Acquisition. “Permitted Bond Hedge Transaction” means any bond hedge, capped call or similar option transaction entered into by the Issuer in respect of the Issuer’s ordinary shares and entered into in connection with the issuance of Permitted Convertible Indebtedness; provided that (i) the terms, conditions and covenants of each such transaction shall be customary for transactions of such type, as determined in good faith by the Issuer, (ii) such transaction is consummated substantially concurrently with the issuance of such Permitted Convertible Indebtedness, and (iii) the purchase price for such Permitted Bond Hedge Transaction (net of any proceeds to Issuer from the sale of any related Permitted Warrant Transaction) (x) does not exceed the Net Cash Proceeds received by the Issuer from the issuance of Permitted Convertible Indebtedness and (y) is financed with the proceeds of such issuance. “Permitted Cash Equivalent Investments” means (i) marketable direct obligations issued or unconditionally guaranteed by the United States or any agency or any state thereof having maturities of not more than one year from the date of acquisition, (ii) commercial paper maturing no more than one year after the date of its creation and having the highest rating from either Standard & Poor’s Ratings Group or Moody’s Investors Service, Inc., (iii) certificates of deposit, or bankers’ acceptance maturing no more than one year after issue provided that the account in which any such certificate of deposit is maintained is subject to an account control agreement in favor of the Administrative Agent, (iv) money market funds at least ninety five percent (95%) of the assets of which constitute Permitted Cash Equivalent Investments of the kinds described in clauses (i) through (iii) of this definition, (v) fully collateralized repurchase agreements with a term of not more than 30 days for securities described in clause (i) above, and (vi) investments permitted pursuant to an investment policy approved by the Issuer’s Board, as amended from time to time, provided that such investment policy (and any such amendment thereto) shall have been approved in advance in writing by the Administrative Agent. “Permitted Convertible Indebtedness” means unsecured Indebtedness in the form of notes issued by the Issuer that (i) as of the date of issuance thereof contains terms, conditions, covenants, conversion or exchange rights, redemption rights and offer to repurchase rights, in each case, as are typical and customary for notes of such type, as determined by the Issuer, (ii) is convertible or 23 exchangeable into a fixed number of shares of ordinary shares of the Issuer (or Qualified Equity Interests following a merger event or other conversion or exchange of ordinary shares of the Issuer), cash or a combination thereof (such amount of cash determined by reference to the price of the Issuer’s ordinary shares or such Qualified Equity Interests), and cash in lieu of fractional shares of ordinary shares of the Issuer or such Qualified Equity Interests, (iii) has a stated final maturity date that is no earlier than the date that is one hundred eighty (180) days after the Maturity Date (the “Earliest Date”), (iv) shall not be required to be repaid, prepaid, redeemed, repurchased or defeased (whether through scheduled amortization, principal payments, mandatory redemptions, payments of principal or otherwise), whether on one or more fixed dates, prior to the Earliest Date, except (x) upon the occurrence of an event of default, “fundamental change” or equivalent or (y) following the Issuer’s election to redeem such notes; provided that the right to convert such Indebtedness into Qualified Equity Interests, cash or any combination thereof shall not be deemed to violate this clause (iv), and (v) is not supported by a Guarantee made or issued by any Subsidiary of the Issuer that is not an Obligor. “Permitted Indebtedness” means any Indebtedness permitted under Section 9.01. “Permitted Liens” means any Liens permitted under Section 9.02. “Permitted Refinancing” means, with respect to any Indebtedness permitted to be refinanced, extended, renewed or replaced hereunder, any refinancings, extensions, renewals and replacements of such Indebtedness; provided that such refinancing, extension, renewal or replacement shall not (i) increase the outstanding principal amount of the Indebtedness being refinanced, extended, renewed or replaced, (ii) contain terms relating to outstanding principal amount, amortization, maturity, collateral security (if any) or subordination (if any), or other material terms that, taken as a whole, are less favorable in any material respect to the Issuer and its Subsidiaries or the Secured Parties than the terms of any agreement or instrument governing the Indebtedness being refinanced, (iii) have an applicable interest rate or equivalent yield that exceeds the interest rate or equivalent yield of the Indebtedness being refinanced, (iv) contain any new requirement to grant any Lien or to give any Guarantee that was not an existing requirement of the Indebtedness being refinanced and (v) after giving effect to such refinancing, extension, renewal or replacement, no Event of Default shall have occurred (or could reasonably be expected to occur) as a result thereof. “Permitted Warrant Transaction” means any call option, warrant or right to purchase (or substantively equivalent derivative transaction) relating to ordinary shares (or other securities or property following a merger event or other change of the ordinary shares) and/or cash (in an amount determined by reference to the price of such ordinary shares) sold by Issuer substantially concurrently with any purchase by Issuer of a related Permitted Bond Hedge Transaction and as may be amended in accordance with its terms; provided that (x) that the terms, conditions and covenants of each such call option transaction are customary for agreements of such type, as determined in good faith by Issuer and (y) such call option transaction would be classified as an equity instrument in accordance with GAAP. “Person” means any individual, corporation, company, voluntary association, partnership, limited liability company, exempted company, joint venture, trust, unincorporated organization or Governmental Authority or other entity of whatever nature. 24 “Plan” means any employee pension benefit plan (other than a Multiemployer Plan) subject to the provisions of Title IV of ERISA or Section 412 of the Code or Section 302 of ERISA, and in respect of which the Issuer or any ERISA Affiliate is (or, if such plan were terminated, would under Section 4069 of ERISA be deemed to be) an “employer” as defined in Section 3(5) of ERISA. “Proceeding” has the meaning set forth in Section 14.03(c). “Prohibited Payment” means any bribe, rebate, payoff, influence payment, kickback or other payment or gift of money or anything of value (including meals or entertainment) to any officer, employee or ceremonial office holder of any government or instrumentality thereof, political party or supra-national organization (such as the United Nations), any political candidate, any royal family member or any other person who is connected or associated personally with any of the foregoing for the purpose of influencing any act or decision of such payee in his official capacity, inducing such payee to do or omit to do any act in violation of his lawful duty, securing any improper advantage or inducing such payee to use his influence with a government or instrumentality thereof to affect or influence any act or decision of such government or instrumentality, in each case that is prohibited under any applicable Law. “Proportionate Share” means, with respect to each Noteholder, the percentage obtained by dividing (i) the sum of all Commitments (or, if the Commitments are terminated, the outstanding principal amount of the Notes) of such Noteholder then in effect by (ii) the sum of all Commitments (or, if the Commitments are terminated, the outstanding principal amount of the Notes) of all Noteholders then in effect. “Proposal Letter” means the Proposal Letter, dated July 7, 2022, between the Issuer and Perceptive Advisors LLC (as supplemented by the outline of proposed terms and conditions attached thereto). “QEB Exemption” has the meaning set forth in Section 3.02(f). “Qualified Equity Interest” means, with respect to any Person, any Equity Interest of such Person that is not a Disqualified Equity Interest. “Qualified Plan” means an employee benefit plan (as defined in Section 3(3) of ERISA) other than a Multiemployer Plan (i) that is or was at any time maintained or sponsored by any Obligor or any ERISA Affiliate thereof or to which any Obligor or any ERISA Affiliate thereof has ever made, or was ever obligated to make, contributions, and (ii) that is intended to be tax qualified under Section 401(a) of the Code. “Real Property Collateral Security Documents” means any mortgage or deed of trust or any other real property security document executed or required hereunder to be executed by the applicable Obligors and granting a security interest in real property owned or leased (as tenant) by such Obligor in favor of the Secured Parties for purposes of securing the Obligations. “Recipient” means any Noteholder, the Administrative Agent or any other recipient of any payment to be made by or on account of any Obligation, as applicable. 25 “Recognised Stock Exchange” has the meaning given to that term in section 1005 of the UK ITA. “Reference Rate” means One-Month Term SOFR; provided that if the Administrative Agent determines (which determination shall be conclusive absent manifest or demonstrable error) that One-Month Term SOFR cannot be determined pursuant to the definition thereof or a Reference Rate Transition Event has occurred with respect to One-Month Term SOFR or the then-current Reference Rate, then “Reference Rate” means the applicable “Reference Rate Replacement” to the extent that such Reference Rate Replacement has replaced such prior reference rate pursuant to Section 1.05. “Reference Rate Replacement” means, with respect to any Reference Rate Transition Event, an alternate reference rate that has been selected by the Administrative Agent and the Issuer, each of which agree, in good faith, to establish an alternate reference rate of interest to One-Month Term SOFR that gives due consideration to the then prevailing market convention for determining a rate of interest for middle-market loans in the United States at such time, and shall enter into an amendment to this Agreement to reflect such alternate rate of interest and such other related changes to this Agreement as may be applicable; provided, further that, until such alternate rate of interest is agreed upon by the Administrative Agent and the Issuer, the Reference Rate for purposes hereof and of each other Notes Document shall be the Wall Street Journal Prime Rate. “Reference Rate Transition Event” means the occurrence of one or more of the following events with respect to the Reference Rate then in effect: (a) a public statement or publication of information by or on behalf of the administrator of such Reference Rate announcing that such administrator has ceased or will cease to provide such Reference Rate, permanently or indefinitely; provided that, at the time of such statement or publication, there is no successor administrator that will continue to provide such Reference Rate; (b) a public statement or publication of information by the Governmental Authority governing or regulating the administrator of such Reference Rate, the U.S. Federal Reserve System, an insolvency official with jurisdiction over the then-current administrator for such Reference Rate, a resolution authority with jurisdiction over the then-current administrator for such Reference Rate or a court or an entity with similar insolvency or resolution authority over the administrator for such Reference Rate, which in any case states that the then-current administrator of such Reference Rate has ceased or will cease to provide such Reference Rate permanently or indefinitely; provided that, at the time of such statement or publication, there is no successor administrator that will continue to provide such Reference Rate; or (c) a public statement or publication of information by the Governmental Authority governing or regulating the then-current administrator of such Reference Rate announcing that such Reference Rate is no longer representative. For the avoidance of doubt, a “Reference Rate Transition Event” will be deemed to have occurred with respect to any Reference Rate if a public statement or publication of information set 26 forth above has occurred with respect to each then-current available tenor of such Reference Rate (or the published component used in the calculation thereof). “Regulation T” means Regulation T of the Board of Governors of the Federal Reserve System, as amended. “Regulation U” means Regulation U of the Board of Governors of the Federal Reserve System, as amended. “Regulation X” means Regulation X of the Board of Governors of the Federal Reserve System, as amended. “Related Fund” means, with respect to any Noteholder, a fund which is managed or advised by the same investment manager or investment adviser as such Noteholder or, if it is managed by a different investment manager or investment adviser, a fund whose investment manager or investment adviser is an Affiliate of the investment manager or investment adviser of such Noteholder. “Related Parties” has the meaning set forth in Section 14.16. “Requisite Consents” has the meaning set forth in Section 8.19(c)(ii). “Resolution Authority” means an EEA Resolution Authority or, with respect to any UK Financial Institution, a UK Resolution Authority. “Responsible Officer” of any Person means each of the president, chief executive officer, chief financial officer, chief accounting officer, director, secretary, treasurer, general counsel and similar officer of such Person. “Restricted Payment” means any dividend or other distribution (whether in cash, Equity Interests or other property) with respect to any Equity Interests of the Issuer or any of its Subsidiaries, any payment of interest, principal or fees in respect of any Indebtedness owed by the Issuer or any of its Subsidiaries to any holder of any Equity Interests of the Issuer or any of its Subsidiaries, or any payment (whether in cash, Equity Interests or other property), including any sinking fund or similar deposit, on account of the purchase, redemption, retirement, acquisition, cancellation or termination of any such Equity Interests of the Issuer or any of its Subsidiaries, or any option, warrant or other right to acquire any such Equity Interests of the Issuer or any of its Subsidiaries. “Restrictive Agreement” means any Contract or other arrangement that prohibits, restricts or imposes any condition upon (i) the ability of the Issuer or any of its Subsidiaries to create, incur or permit to exist any Lien upon any of its properties or assets (other than (x) customary provisions in Contracts (including without limitation anti-assignment clauses, leases and licenses of Intellectual Property) restricting the assignment thereof and (y) restrictions or conditions imposed by any Contract governing secured Permitted Indebtedness permitted under Section 9.01(g), to the extent that such restrictions or conditions apply only to the property or assets securing such Indebtedness), or (ii) the ability of the Issuer or any of its Subsidiaries to make Restricted Payments with respect to any of their respective Equity Interests or to make or repay loans or advances to 27 the Issuer or any of its Subsidiaries or such other Obligor or to Guarantee Indebtedness of the Issuer or any of its Subsidiaries thereof or such other Obligor. “Sanction” means any international economic sanction administered or enforced by the United States government (including, without limitation, OFAC), the United Nations Security Council, the European Union or its Member States, Her Majesty’s Treasury or other relevant sanctions authority. “Secured Party” means each Noteholder, the Administrative Agent, each other Indemnified Party, any other holder of any Obligation, and any of their respective permitted transferees or assigns. “Securities Account” means any securities account, as such term is defined in Section 8-501 of the NY UCC. “Securities Act” means the Securities Act of 1933, as amended, and the rules and regulations promulgated thereunder. “Security Documents” means, collectively, the Account Pledge Agreement, each Real Property Collateral Security Document (if any), each Foreign Collateral Security Document, each Foreign Real Property Security Document and each other security agreement, control agreement or financing statement, registration, recordation, filing, instrument or approval required, entered into or recommended to grant, perfect and otherwise render enforceable Liens in favor of the Secured Parties for purposes of securing the Obligations, including (without limitation) pursuant to Section 8.12. “Shannon Manufacturing Facility” means Buildings 2 & 3, Block K, Shannon Free Zone, Shannon, Co. Clare. “SOFR” means a rate equal to the secured overnight financing rate as administered by the SOFR Administrator. “SOFR Administrator” means the Federal Reserve Bank of New York (or a successor administrator of the secured overnight financing rate). “Solvent” means, at any time of determination and with respect to any Person and its Subsidiaries, taken as a whole, that (i) the present fair saleable value of the property of such Person and its Subsidiaries is greater than the total amount of liabilities (including contingent liabilities) of such Person and its Subsidiaries, (ii) the present fair saleable value of the property of such Person and its Subsidiaries is not less than the amount that will be required to pay the probable aggregate liabilities of such Person and its Subsidiaries on their collective debts as they become absolute and matured, (iii) such Person and its Subsidiaries have not incurred and does not intend to, and does not believe that it will, incur debts or liabilities beyond such Person’s and its Subsidiaries’ ability to pay as such aggregate debts and liabilities mature. “Specified Assets” means any of the Issuer’s (i) gene regulation platform technologies, (ii) AAV-AQP1 program, or (iii) AAV-GAD program, as further described in reasonable detail on Schedule B hereto, and all assets and properties of the Issuer and its Subsidiaries reasonably 28 related thereto (including Intellectual Property); provided that the Specified Assets shall not at any time include any assets or property of the Issuer or any of its Subsidiaries that constitutes Collateral. “Specified Assets Conditions” means with respect to any Specified Asset, in whole or in part, (i) no Event of Default has occurred and is continuing, or could reasonably be expected to occur, as a result of the entry into such transaction, (ii) such transaction does not result in, nor could it reasonably be expected to result in, the outright sale or disposition of any Specified Asset, in whole or in part, (iii) such transaction does not constitute, nor could it reasonably be expected to constitute, an Impermissible Specified Assets Exclusive License and (iv) such transaction does not interfere with or adversely affect, nor could it reasonably be expected to interfere with or adversely affect, the Secured Parties’ Liens on any Collateral or its rights or remedies in respect thereof. “Sterling” or “£” means lawful money of the United Kingdom. “Subsidiary” means, with respect to any Person (for purposes of this definition, the “parent”) at any date, any corporation, limited liability company, exempted company, partnership, association or other entity the accounts of which would be consolidated with those of the parent in the parent’s consolidated financial statements if such financial statements were prepared in accordance with GAAP as of such date, as well as any other corporation, limited liability company, exempted company, partnership, association or other entity (i) of which securities or other ownership interests representing more than fifty percent (50%) of the equity or more than fifty percent (50%) of the ordinary voting power or, in the case of a partnership, more than fifty percent (50%) of the general partnership interests are, as of such date, owned, controlled or held, directly or indirectly or (ii) that is, as of such date, otherwise Controlled, by the parent or one or more direct or indirect subsidiaries of the parent or by the parent and one or more direct or indirect subsidiaries of the parent. Unless otherwise specified, all references herein to a “Subsidiary” or to “Subsidiaries” shall refer to a Subsidiary or Subsidiaries of the Issuer. “Subsidiary Guarantor” means, initially as of the Closing Date, each Subsidiary of the Issuer identified under the caption “SUBSIDIARY GUARANTORS” on the signature pages hereto and, thereafter, each Subsidiary of such Subsidiary Guarantors (i.e. the Subsidiary Guarantors as of the Closing Date) that becomes, or is required to become, a “Subsidiary Guarantor” after the Closing Date pursuant to Section 8.12. “Taxes” means all present or future taxes, levies, imposts, duties, deductions, withholdings (including backup withholding), assessments, fees or other charges imposed by any Governmental Authority, including any interest, additions to tax or penalties applicable thereto. “Technical Information” means all trade secrets and other proprietary or confidential information, public information, non-proprietary know-how, any information of a scientific, technical, or business nature in any form or medium, standards and specifications, conceptions, ideas, innovations, discoveries, Invention disclosures, all documented research, developmental, demonstration or engineering work and all other information, data, plans, specifications, reports, summaries, experimental data, manuals, models, samples, know-how, technical information, systems, methodologies, computer programs, information technology and any other information. 29 “Term SOFR Administrator” means CME Group Benchmark Administration Limited (CBA) (or a successor administrator of the Term SOFR Reference Rate selected by the Administrative Agent in its reasonable discretion). “Term SOFR Reference Rate” means the forward-looking term rate based on SOFR. “Title IV Plan” means an employee benefit plan (as defined in Section 3(3) of ERISA) other than a Multiemployer Plan (i) that is or was at any time maintained or sponsored by any Obligor or any ERISA Affiliate thereof or to which any Obligor or any ERISA Affiliate thereof has ever made, or was obligated to make, contributions, and (ii) that is or was subject to Section 412 of the Code, Section 302 of ERISA or Title IV of ERISA. “Trademarks” means all trade names, trademarks and service marks, logos, trademark and service mark registrations, and applications for trademark and service mark registrations, including (i) all renewals of trademark and service mark registrations, (ii) all rights to recover for all past, present and future infringements thereof and all rights to sue therefor, and (iii) all rights whatsoever accruing thereunder or pertaining thereto throughout the world, together, in each case, with the goodwill of the business connected with the use thereof. “Tranche 1 Facility” means the term notes facility made available under this Agreement as described in Section 2.01(a). “Tranche 1 Facility Fee” has the meaning set forth in Section 3.05. “Tranche 2 Maximum Issue Amount” means $25,000,000. “Tranche 1 Notes” has the meaning set forth in the recitals hereto. “Tranche 2 Facility” means the term notes facility made available under this Agreement as described in Section 2.01(b). “Tranche 2 Facility Fee” has the meaning set forth in Section 3.05. “Tranche 2 Issue Date” means any date on which Tranche 2 Notes are issued and subscribed for pursuant to the terms and conditions hereof. “Tranche 2 Notes” has the meaning set forth in the recitals hereto. “Tranche 2 Notes Draw Period” has the meaning set forth in in the recitals hereto. “Transactions” means the negotiation, preparation, execution, delivery and performance by each Obligor of this Agreement and the other Notes Documents to which such Obligor is (or is intended to be) a party, the issuance and sale of the Notes hereunder, and all other transactions contemplated pursuant to this Agreement and the other Notes Documents. “UCC” means, with respect to any applicable jurisdictions, the Uniform Commercial Code as in effect in such jurisdiction, as may be modified from time to time. 30 “UCL Licenses” means each stand alone license agreement entered into from January to February 2019, by and between the English Guarantor and UCL Business plc, in each case, as may be amended, restated, supplemented or otherwise modified from time to time. “UK CTA” means the Corporation Tax Act 2009 of the United Kingdom (as amended). “UK DTTP Scheme” means HMRC’s Double Taxation Treaty Passport scheme, as modified from time to time. “UK Excluded Taxes” means any UK Tax Deduction from a payment by a Withholding Agent under a Notes Document, if on the date on which the payment falls due: (i) the payment could have been made to the relevant Noteholder without a UK Tax Deduction if that Noteholder had been a UK Qualifying Noteholder, but on that date such Noteholder is not or has ceased to be a UK Qualifying Noteholder other than as a result of any Change of Law; (ii) the relevant Noteholder is a UK Qualifying Noteholder solely by virtue of sub-paragraph (a)(ii) of the definition of UK Qualifying Noteholder and (i) that relevant Noteholder has not given a UK Tax Confirmation to the Administrative Agent, and (ii) the payment could have been made to the relevant Noteholder without a UK Tax Deduction if that Noteholder had given a UK Tax Confirmation to the Administrative Agent, on the basis that the UK Tax Confirmation would have enabled the Withholding Agent making the payment to have formed a reasonable belief that the payment was an “excepted payment” for the purpose of section 930 of the UK ITA; (iii) the relevant Noteholder is a UK Qualifying Noteholder solely under sub-paragraph (a)(ii) of the definition of UK Qualifying Noteholder and (i) an officer of HMRC has given (and not revoked) a direction (a “UK Direction”) under section 931 of the UK ITA which relates to that payment and that Noteholder has received from the Issuer a certified copy of that UK Direction, and (ii) the payment could have been made to the Noteholder without any UK Tax Deduction if that UK Direction had not been made; or (iv) the relevant Noteholder is a UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities) and the payment could have been made to the Noteholder without a UK Tax Deduction had that Noteholder complied with its obligations under paragraphs (i) or (j) of Section 5.03; provided that any UK Tax Deduction from a payment by a Withholding Agent to Perceptive Credit Holdings III, LP (but not its any of its successors or assigns) shall not be treated as UK Excluded Taxes for the purposes of this Agreement. For the avoidance of doubt, it is clarified that once the Notes are listed on a Recognised Stock Exchange pursuant to Section 3.02(f), no UK Tax Deduction shall be treated as a UK Excluded Tax for the purposes of this Agreement. “UK Financial Institution” means any BRRD Undertaking (as such term is defined under the PRA Rulebook (as amended from time to time) promulgated by the United Kingdom Prudential Regulation Authority) or any Person falling within IFPRU 11.6 of the FCA Handbook (as amended from time to time) promulgated by the United Kingdom Financial Conduct 31 Authority, which includes certain credit institutions and investment firms, and certain affiliates of such credit institutions or investment firms. “UK ITA” means the Income Tax Act 2007 of the United Kingdom (as amended). “UK Limitation Acts” means the Limitation Act 1980 and the Foreign Limitation Periods Act 1984. “UK Non-Bank Noteholder” means a Noteholder which falls within clause (a)(ii) of the definition of “UK Qualifying Noteholder” and: (a) where such Noteholder is a party hereto as at the date of this Agreement, is described as such in Schedule 1 (Commitments); or (b) where such a Noteholder becomes a party hereto after the date of this Agreement, gives a UK Tax Confirmation in the documentation which it executes on becoming a party hereto. “UK Qualifying Noteholder” means a successor or assignee of Perceptive Credit Holdings III, LP that is: (a) a Noteholder which is beneficially entitled to interest payable to that Noteholder in respect of an advance under a Notes Document and is: (i) a Noteholder: (A) which is a bank (as defined for the purpose of section 879 of the UK ITA) making an advance under a Notes Document and is within the charge to United Kingdom corporation tax as respects any payments of interest made in respect of that advance or would be within such charge as respects such payments apart from section 18A of the UK CTA; or (B) in respect of an advance made under a Notes Document by a person that was a bank (as defined for the purpose of section 879 of the UK ITA) at the time that such advance was made and is within the charge to United Kingdom corporation tax as respects any payments of interest made in respect of that advance; or (ii) a Noteholder which is: (A) (B) (1) a company resident in the United Kingdom for United Kingdom tax purposes; a partnership, each member of which is: a company so resident in the United Kingdom; or (2) a company not so resident in the United Kingdom which carries on a trade in the United Kingdom through a permanent establishment and which brings into account in computing its chargeable profits (within the meaning of section 19 of the UK CTA) the whole of any share of interest 32 payable in respect of that advance that falls to it by reason of Part 17 of the UK CTA; or (C) a company not so resident in the United Kingdom which carries on a trade in the United Kingdom through a permanent establishment and which brings into account interest payable in respect of that advance in computing the chargeable profits (within the meaning of section 19 of the UK CTA) of that company; or (iii) a UK Treaty Noteholder; or (b) a Noteholder which is a building society (as defined for the purposes of section 880 of the UK ITA) making an advance under a Notes Document. “UK Resolution Authority” means the Bank of England or any other public administrative authority having responsibility for the resolution of any UK Financial Institution. “UK Shareholder” means MeiraGTx Limited, a private limited company incorporated in England and Wales with registration number 09501998 and whose registered office address is at 92 Britannia Walk, London, England, N1 7NQ. “UK Subsidiary Guarantor” means MeiraGTx UK II Limited, a private limited company incorporated in England and Wales with registration number 09348737 and whose registered office address is at 92 Britannia Walk, London, England, N1 7NQ. “UK Tax Confirmation” means a confirmation in writing by a Noteholder that the person beneficially entitled to interest payable to that Noteholder in respect of an advance under a Notes Document is either: (i) a company resident in the UK for UK tax purposes; (ii) a partnership each member of which is: (A) a company so resident in the UK; or (B) a company not so resident in the UK which carries on a trade in the UK through a permanent establishment and which brings into account in computing its chargeable profits (within the meaning of section 19 of the UK CTA) the whole of any share of interest payable in respect of that advance that falls to it by reason of Part 17 of the UK CTA; or (iii) a company not so resident in the UK which carries on a trade in the UK through a permanent establishment and which brings into account interest payable in respect of that advance in computing the chargeable profits (within the meaning of section 19 of the UK CTA) of that company. “UK Tax Deduction” means a deduction or withholding from a payment under any Notes Document for and on account of any Taxes imposed by the United Kingdom. “UK Treaty Noteholder” means a Noteholder which is a successor or assignee of Perceptive Credit Holdings III, LP and: (i) is treated as a resident of a UK Treaty State for the purposes of the relevant Treaty; (ii) does not carry on a business in the United Kingdom through a permanent establishment with which that Noteholder’s participation in any advance is effectively 33 connected; and (iii) meets all other conditions applicable to that Noteholder in the relevant Treaty in order to obtain full exemption from Tax imposed by the United Kingdom on payments of interest, including the completion of any necessary procedural formalities. “UK Treaty State” means a jurisdiction having a double taxation agreement (a “Treaty”) with the United Kingdom which makes provision for full exemption from tax imposed by the United Kingdom on payments of interest. “United Kingdom” and “UK” each means the United Kingdom of Great Britain and Northern Ireland. “United States” or “U.S.” means the United States of America, its fifty (50) states and the District of Columbia. “U.S. Government Securities Business Day” means any day except for (a) a Saturday, (b) a Sunday or (c) a day on which the Securities Industry and Financial Markets Association recommends that the fixed income departments of its members be closed for the entire day for purposes of trading in United States government securities. “Valuation Report” has the meaning set forth in Section 8.19(a). “VAT” means: (i) any value added tax imposed by the UK Value Added Tax Act 1994 (as amended); (ii) any tax imposed in compliance with the Council Directive of 28 November 2006 on the common system of value added tax (EC Directive 2006/112); and (iii) any other tax of a similar nature, whether imposed in the UK or in a member state of the European Union in substitution for, or levied in addition to, such tax referred to in paragraph (i) or (ii) above, or imposed elsewhere. “Wall Street Journal Prime Rate” means the Wall Street Journal Prime Rate, as published and defined in The Wall Street Journal. “Warrant Certificate” means a Warrant Certificate in substantially the form of Exhibit J hereto, to be delivered pursuant to Section 6.01(g), as amended or otherwise modified pursuant to the terms thereof. “Warrant Obligations” means all Obligations of the Issuer arising out of, under or in connection with the Warrant Certificates. “Withdrawal Liability” means, at any time, any liability incurred (whether or not assessed) by any ERISA Affiliate and not yet satisfied or paid in full at such time with respect to any Multiemployer Plan pursuant to Section 4201 of ERISA. “Withholding Agent” means the Issuer, any other Obligor and the Administrative Agent. “Works” means means the fit out and other construction works currently being carried out, on the instruction of the Issuer, to the Shannon Manufacturing Facility to include works carried out pursuant to planning permissions references 20/840, 20/841, 21/45, 21/58, 21/222, 21/426, 21/488, 21/1242, 21/1356, 22/134 and 22/204. 34 “Write-Down and Conversion Powers” means (a) with respect to any EEA Resolution Authority, the write-down and conversion powers of such EEA Resolution Authority from time to time under the Bail-In Legislation for the applicable EEA Member Country, which write-down and conversion powers are described in the EU Bail-In Legislation Schedule and (b) with respect to the United Kingdom, any powers of the applicable Resolution Authority under the Bail-In Legislation to cancel, reduce, modify or change the form of a liability of any UK Financial Institution or any contract or instrument under which that liability arises, to convert all or part of that liability into shares, securities or obligations of that Person or any other Person, to provide that any such contract or instrument is to have effect as if a right had been exercised under it or to suspend any obligation in respect of that liability or any of the powers under that Bail-In Legislation that are related to or ancillary to any of those powers. 1.02 Accounting Terms and Principles. (a) Unless otherwise specified, all accounting terms used in each Notes Document shall be interpreted, and all accounting determinations and computations thereunder (including under Section 10 and any definitions used in such calculations) shall be made, in accordance with GAAP. Unless otherwise expressly provided, all financial covenants and defined financial terms shall be computed on a consolidated basis for the Issuer and its Subsidiaries, in each case without duplication. Notwithstanding the foregoing, the representations and warranties made in Section 7.08 and the covenants made in Section 8.04 shall be construed in accordance with UK GAAP, as applicable. (b) If at any time any change in GAAP or the application thereof would affect the computation of any financial term, covenant, ratio or requirement set forth in any Notes Document, and either the Issuer or the Administrative Agent shall so request, the Administrative Agent and the Issuer shall negotiate in good faith to amend such term, covenant, ratio or requirement to preserve the original intent thereof set forth in the applicable Notes Document in light of such change in GAAP or application thereof; provided that, until so amended, such term, covenant, ratio or requirement shall continue to be computed in accordance with GAAP prior to such change therein for all purposes hereof. Interpretation. For all purposes of this Agreement, except as otherwise expressly provided herein or 1.03 unless the context otherwise requires, (a) (b) (c) the terms defined in this Agreement include the plural as well as the singular and vice versa; words importing gender include all genders; any reference to a Section, Annex, Schedule or Exhibit refers to a Section of, or Annex, Schedule or Exhibit to, this Agreement; (d) any reference to “this Agreement” refers to this Agreement, including all Annexes, Schedules and Exhibits hereto, and the words herein, hereof, hereto and hereunder and words of similar import refer to this Agreement and its Annexes, Schedules and Exhibits as a whole and not to any particular Section, Annex, Schedule, Exhibit or any other subdivision; 35 (e) (f) references to days, months and years refer to calendar days, months and years, respectively; all references herein to “include” or “including” shall be deemed to be followed by the words “without limitation”; (g) the word “from” when used in connection with a period of time means “from and including” and the word “until” means “to but not including”; (h) the words “asset” and “property” shall be construed to have the same meaning and effect and to refer broadly to any and all assets and properties, whether tangible or intangible, real or personal, including cash, securities, rights under contractual obligations and permits and any right or interest in any such assets or property; (i) accounting terms not specifically defined herein (other than “property” and “asset”) shall be construed in accordance with GAAP; (j) the word “will” shall have the same meaning as the word “shall”; (k) where any provision in this Agreement or any other Notes Document refers to an action to be taken by any Person, or an action which such Person is prohibited from taking, such provision shall be applicable whether such action is taken directly or indirectly; (l) references to any Lien granted or created hereunder or pursuant to any other Notes Document securing any Obligations shall be deemed to be a Lien for the benefit of the Secured Parties; and (m) references to any Law will include all statutory and regulatory provisions amending, consolidating, replacing, supplementing or interpreting such Law from time to time. Unless otherwise expressly provided herein, references to organizational documents, agreements (including the Notes Documents) and other contractual instruments shall be deemed to include all subsequent amendments, restatements, extensions, supplements and other modifications thereto permitted by the Notes Documents. If any obligation to pay any amount pursuant to the terms and conditions of any Notes Document falls due on a day which is not a Business Day, then such required payment date shall be extended to the immediately following Business Day. For the purposes of calculations made pursuant to the terms of this Agreement or otherwise for purposes of compliance herewith, GAAP will be deemed to treat operating leases as set forth in the definition of Capitalized Lease Obligations. For the avoidance of doubt, any lease that would have been characterized as an operating lease under Accounting Standards Codification Topic No. 840, Leases, shall be accounted for as an operating lease (and not as a capital lease or otherwise reflected on the Issuer’s consolidated balance sheet) for purposes of this Agreement regardless of the implementation of Accounting Standards Codification Topic No. 842, Leases, or any change in GAAP following the Closing Date that would otherwise require such lease to be characterized or re-characterized (on a prospective or retroactive basis or otherwise) as a capital lease. 36 1.04 Divisions. For all purposes under the Notes Documents, in connection with any division or plan of division under Delaware law (or any comparable event under a different jurisdiction’s laws): (i) if any asset, right, obligation or liability of any Person becomes the asset, right, obligation or liability of a different Person, then it shall be deemed to have been transferred from the original Person to the subsequent Person, and (ii) if any new Person comes into existence, such new Person shall be deemed to have been organized on the first date of its existence by the holders of its Equity Interests at such time. 1.05 Reference Rate Replacement. Upon the occurrence of an event of the type described in the definition of “Reference Rate Transition Event”, the Administrative Agent will promptly notify the Issuer thereof and as set forth in the definition of “Reference Rate Replacement”, the Administrative Agent and the Issuer shall endeavor, in good faith, to establish an alternate rate of interest to One-Month Term SOFR. 1.06 Times of Day; Times of Performance. (a) Unless otherwise specified, all references herein to times of day shall be references to New York City time (daylight or standard, as applicable). (b) If any delivery or other performance obligation hereunder (other than payments) falls due on a day which is not a Business Day, then such due date shall be extended to the immediately following Business Day. 1.07 Rates. The Administrative Agent does not warrant or accept responsibility for, and shall not have any liability with respect to (a) the continuation of, administration of, submission of, calculation of or any other matter related to the Term SOFR Reference Rate or One-Month Term SOFR, or any component definition thereof or rates referred to in the definition thereof, or any alternative, successor or replacement rate thereto, including whether the composition or characteristics of any such alternative, successor or replacement rate will be similar to, or produce the same value or economic equivalence of, or have the same volume or liquidity as, the Term SOFR Reference Rate or One-Month Term SOFR prior to its discontinuance or unavailability, or (b) the effect, implementation or composition of any Conforming Changes. There is no assurance that the composition or characteristics of any such alternative, successor or replacement Reference Rate will be similar to or produce the same value or economic equivalence as One-Month Term SOFR or that it will have the same volume or liquidity as did One-Month Term SOFR prior to its discontinuance or unavailability. The Administrative Agent and its affiliates or other related entities may engage in transactions that affect the calculation of the Term SOFR Reference Rate or One-Month Term SOFR, any alternative, successor or replacement rate or any relevant adjustments thereto, in each case, in a manner that is adverse to the Issuer. The Administrative Agent may select information sources or services in its reasonable discretion to ascertain the Term SOFR Reference Rate or One- Month Term SOFR, in each case pursuant to the terms of this Agreement, and shall have no liability to the Issuer, any Noteholder or any other Person for damages of any kind, including direct or indirect, special, punitive, incidental or consequential damages, costs, losses or expenses (whether in tort, contract or otherwise and whether at law or in equity), for any error or calculation of any such rate (or component thereof) provided by any such information source or service. 37 1.08 Miscellaneous. (a) (b) The “date of this Agreement” is August 2, 2022. The term “redemption” when used in relation to a Note means any prepayment of that Note (or a portion thereof), by prepayment, redemption, purchase or any other means prior to the Maturity Date. SECTION 2 THE COMMITMENTS AND THE NOTES 2.01 Issuance of Notes. (a) The parties to this Agreement acknowledge and agree that, prior to the amendment and restatement of this Agreement as of the Amendment and Restatement Date, this Agreement provided for the borrowing of certain loans, and such loans (in the aggregate principal amount of $75,000,000) were borrowed by the Issuer and, immediately following such amendment and restatement, $75,000,000 in aggregate principal amount remains outstanding under this Agreement as the Tranche 1 Notes pursuant to Section 2.01(b) below. (b) Accordingly, on the terms and subject to the conditions of this Agreement, (i) each Noteholder subscribed for the Tranche 1 Notes, and the Issuer issued such Tranche 1 Notes, on the Closing Date in an aggregate principal amount for all Noteholders in an aggregate amount of $75,000,000 and (ii) in the sole discretion of the Majority Noteholders, during the Tranche 2 Notes Draw Period, the Issuer may request the subscription by the Noteholders of the Tranche 2 Notes in an aggregate amount not to exceed the Tranche 2 Maximum Issue Amount. (c) No amount paid, repaid or prepaid by the Issuer or any Guarantor with respect to any Note may be required to be subscribed or readvanced under the Notes Documents. (d) Any term or provision hereof (or of any other Notes Document) to the contrary notwithstanding, Notes issued and the subscriptions hereunder will be denominated solely in Dollars and no other currency. 2.02 [Reserved]. 2.03 Noteholder Representations. Each Noteholder hereby represents and warrants to the Issuer that: (a) The Noteholder is, and on the Closing Date was, (i) an “accredited investor” as that term is defined in Rule 501(a) of Regulation D under the Securities Act and (ii) a “qualified institutional buyer” (as that term is defined in Rule 144A of the Securities Act). The Noteholder is acquiring, or acquired on the Closing Date, the Notes for investment for its own account and not with a current view towards, or for resale in connection with, the public sale or distribution of the Notes, except pursuant to sales registered or exempted under the Securities Act. (b) The Noteholder understands and acknowledges that the Notes issued, or to be issued, are “restricted securities” under the Securities Act inasmuch as they are being acquired 38 from the Company in a transaction not involving a public offering and that, under such Laws and applicable regulations, such securities may be resold without registration under the Securities Act only in certain limited circumstances. In addition, the Holder represents that it is familiar with Rules 144 and 144A, as presently in effect, and understands the resale limitations imposed thereby and by the Securities Act. (c) The Noteholder acknowledges that it can bear the economic and financial risk of its investment for an indefinite period and has such knowledge and experience in financial or business matters that it is capable of evaluating the merits and risks of the investment in the Notes. The Noteholder has had an opportunity to ask questions and receive answers from the Issuer regarding the terms and conditions of the Notes and the business, properties, prospects and financial condition of the Issuer. 2.04 Use of Proceeds. The Issuer shall use the proceeds of the issuance of Notes for working capital and general corporate purposes, including the payment of fees and expenses associated with this Agreement and the other Notes Documents and the transactions contemplated hereby and thereby. 2.05 Constitution of the Notes. The Notes will be: (a) (b) 14.05(d); and issued in a minimum amount of $1,000,000 and integral multiples thereof; considered issued when their details are registered in the Notes Register referred to in Section (c) subject to the terms and conditions of this Agreement. Signing and authenticating Notes Certificates. A Notes Certificate shall not be considered to have been 2.06 issued unless and until it has been signed by the Issuer and authenticated by the Administrative Agent. Status of Notes Certificate. A Notes Certificate shall serve as evidence of the relevant records in the 2.07 Notes Register and shall not represent title to the Notes. In the event of a conflict between information in a Notes Certificate and information in the Notes Register, the information in the Notes Register will prevail. Stocks of blank Notes Certificates. The Issuer shall execute and deliver to the Administrative Agent such 2.08 number of blank Notes Certificates, duly signed by it, as the Administrative Agent may from time to time reasonably require. 2.09 Delivery of replacements. Subject to receipt of sufficient blank Notes Certificates, the Administrative Agent shall, upon and in accordance with the instructions of the Issuer (which instructions may, without limitation, include terms as to the payment of expenses and as to 39 evidence, security and indemnity), complete, authenticate and deliver replacement Notes Certificates. 2.10 Replacement Notes Certificates. The Administrative Agent shall not deliver or issue any replacement Notes Certificate: (a) if the Notes Certificate being replaced has been mutilated or defaced otherwise than against the surrender of the same; and (b) until the claimant of the Notes Certificate has: (i) provided to the Administrative Agent such evidence, security and indemnity as the Issuer and/or Administrative Agent may reasonably require; and (ii) paid such costs and expenses as may be incurred in connection with such replacement. 2.11 Replacements to be numbered. Each replacement Notes Certificate shall bear a unique serial number. 2.12 Cancellation and destruction. The Administrative Agent shall cancel and destroy each mutilated or defaced Notes Certificate surrendered to it in respect of which a replacement Notes Certificate has been delivered. 2.13 Notification. The Administrative Agent shall notify the Issuer of the delivery by it of any replacement Notes Certificate surrendered to it in respect of which a replacement Notes Certificate has been delivered. 2.14 Legend. The Notes may only be transferred or disposed of in compliance with applicable state and federal securities Laws. For so long as such restrictions apply, the Noteholder agrees to the imprinting of a legend in the Note Register and on the Notes in the following form: THIS NOTE HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ACT”) OR UNDER THE SECURITIES LAWS OF CERTAIN STATES, AND MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED, CHARGED, HYPOTHECATED OR OTHERWISE TRANSFERRED EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION STATEMENT FILED UNDER THE ACT AND APPLICABLE STATE SECURITIES LAWS OR PURSUANT TO AN AVAILABLE EXEMPTION FROM REGISTRATION UNDER THE ACT AND APPLICABLE STATE SECURITIES LAWS OR UNLESS SOLD IN ACCORDANCE WITH RULE 144 UNDER THE ACT. SECTION 3 PAYMENTS, REDEMPTION AND INTEREST 3.01 Payments and Redemption Generally; Application. (a) There will be no scheduled redemptions of principal on the Notes prior to the Maturity Date. 40 (b) On the Maturity Date, the Issuer shall redeem the entire remaining outstanding principal amount of the Notes at par in full and in cash. (c) The Issuer agrees that all amounts payable hereunder or under any other Notes Document, whether in respect of any Notes, fees or interest accrued or accruing thereon, or any other Obligations, shall be paid, repaid and prepaid, as the case may be, solely in Dollars and no other currency pursuant to the terms of this Section 3. Except as otherwise provided in this Agreement, proceeds of each payment (including each redemption of Notes) by the Issuer shall be, and shall be deemed to be, made ratably to the Noteholders in accordance with their respective Proportionate Shares. 3.02 Interest. (a) Interest Generally. The outstanding principal amount of the Notes, as well as the amount of all other outstanding Obligations, shall accrue interest at the Interest Rate on and from the Closing Date. The Administrative Agent’s determination of the Interest Rate shall be binding on the Issuer, its Subsidiaries and the Noteholders in the absence of manifest error. (b) Default Interest. Notwithstanding the foregoing, unless the Administrative Agent otherwise agrees in writing, upon the occurrence and during the continuance of any Event of Default, the Applicable Margin shall increase automatically by three percent (3.0%) per annum (the Interest Rate, as increased pursuant to this Section 3.02(b), being the “Default Rate”). If any Obligation is not paid when due under any applicable Notes Document, the amount thereof shall accrue interest at the Default Rate. For the avoidance of doubt, the Default Rate shall not be cumulative and no more than three percent (3.00%) per annum can be applicable to the Notes or any past due Obligation at any time, and further for the avoidance of doubt, once an Event of Default is waived by the Administrative Agent or the Majority Noteholders, the Default Rate shall cease to apply. (c) Interest Payment Dates. Accrued interest on the Notes shall be payable in cash, in arrears, on each Payment Date with respect to the most recently completed Interest Period, and upon the payment or redemption of the Notes (on the principal amount being so paid or redeemed); provided that interest payable at the Default Rate, or any accrued interest not paid on or before the Maturity Date, shall be payable from time to time in cash on the Administrative Agent’s demand until paid in full. (d) Conforming Changes. In connection with the use or administration of One-Month Term SOFR, the Administrative Agent will have the right to make Conforming Changes from time to time and, notwithstanding anything to the contrary herein or in any other Notes Document, any amendments implementing such Conforming Changes will become effective without any further action or consent of any other party to this Agreement or any other Notes Document. The Administrative Agent will promptly notify the Issuer and the Noteholders of the effectiveness of any Conforming Changes in connection with the use or administration of One- Month Term SOFR. (e) Compensation for Loss. In the event of the payment or redemption of any principal of any Note other than on the last day of the Interest Period applicable thereto (including as a result of an Event of Default), then, in any such event, the Issuer shall compensate each 41 Noteholder for any reasonable and documented loss, cost and expense attributable to such event, including any reasonable and documented loss, cost or expense arising from the liquidation or redeployment of funds. A certificate of any Noteholder including documentary evidence of any amount or amounts that such Noteholder is entitled to receive pursuant to this Section shall be delivered to the Issuer and shall be conclusive absent manifest error. The Issuer shall pay such Noteholder the amount shown as due on any such certificate within 30 days after receipt thereof. (f) Listing and Co-operation Obligations. The parties agree to co-operate in good faith to ensure that the Notes are listed on a Recognised Stock Exchange promptly after the date of this Agreement, and to use commercially reasonable best efforts to assist the Obligors to obtain and maintain a listing of such Notes on a Recognised Stock Exchange such that the exemption from UK withholding tax under section 882 of the UK ITA (“QEB Exemption”) applies. If the Notes are not listed on a Recognised Stock Exchange within six months after the date of this Agreement, or if the QEB Exemption is otherwise unavailable, each Noteholder shall use all commercially reasonable best efforts to ensure that the Issuer is able to make payments to that Noteholder, to the maximum extent possible, without a UK Tax Deduction, including the completion of any procedural formalities necessary for the Issuer to obtain authorization to make such payments without a UK Tax Deduction; provided, however, that notwithstanding anything to the contrary in this Agreement, (i) Perceptive Credit Holdings III, LP shall not be obligated to take any actions that would (x) disclose the identity of its partners, or (y) be disadvantageous to its interests hereunder or under any other Notes Document in any material respect, and (ii) as provided pursuant to Section 14.03 hereof, the Issuer shall reimburse Perceptive Credit Holdings III, LP for all reasonable costs and expenses incurred by it in connection with actions taken by it pursuant to this Section 3.02(f). Any conversion of the existing indebtedness which shall comprise the Notes issued under this Agreement or any equivalent transaction will be conducted pursuant to a valid exemption from the registration and prospectus delivery requirements under the Securities Act and the qualification requirements under applicable state and foreign Law and otherwise in compliance with the securities Laws of the United States. Any costs arising in connection with the listing shall be borne by the Obligors. (g) Interest Deferral. Notwithstanding any other provision of this Agreement, the payment of any interest in respect of the Notes shall automatically be deferred, at no additional cost to the Obligors, in respect of all Payment Dates, until the first Payment Date following the earlier of: (i) the date the Issuer receives confirmation that the Notes have been listed on a Recognised Stock Exchange; and (ii) February 2, 2023. 3.03 Early Redemption; Early Redemption Premium. (a) Optional Redemption of Notes (i) Subject to prior written notice pursuant to clause (a)(ii) below and the applicable portion of the payment of the Early Redemption Fee pursuant to clause (c) below, the Issuer shall have the right to optionally redeem, in whole or in part, the outstanding principal amount of the Notes at par on any Business Day (an “Early Redemption Date”); provided that in addition to such redeemed principal amount and the Early Redemption Fee applicable to such redeemed principal amount, the Issuer shall also make payment in full in cash on such Early Redemption Date the applicable portion of all accrued but unpaid interest on the principal amount 42 of the Notes being redeemed (such aggregate amount of Early Redemption Fee, redeemed principal and accrued interest being herein referred to as the “Early Redemption Price”). (ii) A notice of optional redemption shall be effective only if received by the Administrative Agent not later than 2:00 p.m. (New York City time) on a date at least three (3) (but not more than five (5)) Business Days prior to the proposed Early Redemption Date. Each notice of optional redemption shall specify the proposed Early Redemption Date (and may be revocable), the principal amount of the Notes to be prepaid, the amount of accrued and unpaid interest that will be paid on the Early Redemption Date, and, in reasonable detail, a calculation of the Early Redemption Fee payable on such Early Redemption Date in connection with such proposed redemption. (b) Mandatory Redemptions. Within ten (10) Business Days of the receipt of Net Cash Proceeds from the occurrence of any Casualty Event or Asset Sale (other than any Asset Sale permitted pursuant to Sections 9.09 (a), (b), (c), (d), (e), (g), (j) and (k)), to the extent that the aggregate amount of Net Cash Proceeds received by Issuer and its Subsidiaries (and not paid to the Administrative Agent as a redemption of the Notes) in respect of all such Casualty Events or Asset Sales, when taken together, exceeds $2,500,000 in any fiscal year, the Issuer shall apply an amount equal to one hundred percent (100%) of the Net Cash Proceeds received by the Issuer or any of its Subsidiaries with respect to such Casualty Event or Asset Sale, as the case may be with such amount of Net Cash Proceeds being allocated, to (i) the redemption of principal outstanding under the Notes, and (ii) the payment of accrued and unpaid interest on such principal amount of the Notes being prepaid and the payment of the applicable portion of the Early Redemption Fee being paid. Such Net Cash Proceeds shall be allocated to such redemption and payments such that the full amount of the applicable Early Redemption Price shall be paid with such Net Cash Proceeds. Notwithstanding the foregoing, so long as no Event of Default has occurred and is continuing or shall immediately result therefrom, if, within seven (7) Business Days following the occurrence of any such Casualty Event or Asset Sale, a Responsible Officer of the Issuer delivers to the Administrative Agent a notice to the effect that the Issuer or the applicable Subsidiary intends to apply the Net Cash Proceeds from such Casualty Event or Asset Sale to repair, refurbish, restore, replace or rebuild the asset subject to such Casualty Event or Asset Sale, then such Net Cash Proceeds of such Casualty Event or Asset Sale may be applied for such purpose in lieu of such mandatory redemption otherwise required pursuant to this clause (b) to the extent such Net Cash Proceeds of such Casualty Event or Asset Sale are actually applied for such purpose; provided that, in the event that Net Cash Proceeds have not been so applied within one hundred eighty (180) days following the occurrence of such Casualty Event or Asset Sale, the Issuer shall make a mandatory redemption of the Notes in an aggregate amount equal to one hundred percent (100%) of the unused balance of such Net Cash Proceeds received by the Issuer or any of its Subsidiaries with respect to such Casualty Event or Asset Sale, as the case may be, together with payment of accrued and unpaid interest on the principal amount of the Notes being so prepaid and the applicable Early Redemption Fee, with such amount of Net Cash Proceeds being allocated to the redemption of principal, the payment of accrued and unpaid interest on such principal amount of the Notes being redeemed and the payment of the applicable portion of the Early Redemption Fee being paid such that the full payable with respect to such mandatory redemption is paid with such unused balance of Net Cash Proceeds. Notwithstanding the foregoing, in respect of a Casualty Event relating to a Manufacturing Facility, to the extent required by the basis of settlement under any policy of insurance relating to that Manufacturing Facility or pursuant to the 43 terms of any lease under which the Issuer or any of its Subsidiaries holds an interest in that Manufacturing Facility, the Issuer or the applicable Subsidiary shall apply moneys received under any policy of insurance in respect of that Manufacturing Facility towards replacing, restoring or reinstating that Manufacturing Facility. (c) Early Redemption Fee. Without limiting the foregoing, whenever any redemption of Notes is made hereunder pursuant to Section 3.03(a) or Section 3.03(b), acceleration or otherwise, the applicable portion of the Early Redemption Fee being paid shall be due and payable in full in cash on the applicable Early Redemption Date for such redemption. (d) Application. Proceeds of any redemption made pursuant to clauses (a) or (b) above shall be applied in the following order of priority, with proceeds being applied to a succeeding level of priority only if amounts owing pursuant to the immediately preceding level of priority have been paid in full in cash; provided that all such redemptions made to Noteholders shall be applied pro rata in accordance with their respective Proportionate Shares: (i) first, to the payment of that portion of the Obligations payable to the Administrative Agent constituting fees, indemnities, costs, expenses, and other amounts then due and owing (including costs, Losses and fees and disbursements and other charges of counsel payable under Section 14.03); (ii) second, to the payment of that portion of the Obligations payable to the Noteholders constituting fees (other than any Early Redemption Fee), indemnities, expenses, and other amounts then due and owing (including fees and disbursements and other charges of counsel payable under Section 14.03) ratably among them in proportion to the respective amounts described in this clause (ii) payable to them; (iii) third, to the payment of any accrued and unpaid interest and any fees then due and owing; (iv) fourth, to the redemption of unpaid principal of the Notes of the Noteholders at par; (v) fifth, to the payment of any Early Redemption Fee then due and payable; (vi) sixth, to the payment in full of all other Obligations then due and payable to the Administrative Agent and the Noteholders, ratably among them in proportion to the respective amounts described in this clause (vi) payable to them; and (vii) seventh, to the Issuer or such other Persons as may lawfully be entitled to or directed by the Issuer to receive the remainder. 3.04 Facility Fees. The Issuer (i) paid on the Closing Date, to the Administrative Agent (for the pro rata benefit of the Noteholders) a fee equal to [***] (the “Tranche 1 Facility Fee”) by way of deduction from the proceeds of the Tranche 1 Notes issued by the Issuer by the Noteholders and (ii) shall pay, on any Tranche 2 Notes Subscription Date, to the Administrative Agent (for the pro rata benefit of the Noteholders) a fee equal to 0.75% of the aggregate principal amount of the Tranche 2 Notes subscribed for on such Tranche 2 Issue Date (the “Tranche 2 Facility Fee” and 44 together with the Tranche 1 Facility Fee, the “Facility Fees”). Upon receipt of payment from the Issuer, the Administrative Agent will promptly thereafter distribute like funds relating to any such payment to the Noteholders pro rata on the basis of each Noteholder’s Proportionate Share. Once paid by the Issuer, such Facility Fees shall be non-refundable. SECTION 4 PAYMENTS, ETC. 4.01 Payments. (a) Payments Generally. Each payment of principal, interest and other amounts to be made by the Obligors under this Agreement or any other Notes Document shall be made (i) in Dollars, in immediately available funds, without deduction, set off or counterclaim, to the applicable Noteholder to which such payment is owed, to the deposit account of such Noteholder designated by it by notice to the Issuer, and (ii) not later than 2:00 p.m. (New York City time) on the date on which such payment is due (each such payment made after such time on such due date shall be deemed to have been made on the next succeeding Business Day). (b) Application of Payments. All such payments referenced in clause (a) above shall be applied as set forth in Section 3.03(d) above. (c) Non-Business Days. If the due date of any payment under this Agreement (whether in respect of principal, interest, fees, costs or otherwise) would otherwise fall on a day that is not a Business Day, such date shall be extended to the next succeeding Business Day; provided that if such next succeeding Business Day would fall after the Maturity Date, payment shall be made on the immediately preceding Business Day. 4.02 Computations. All computations of interest and fees hereunder shall be computed on the basis of a year of three hundred and sixty (360) days and actual days elapsed during the period for which payable. 4.03 Set-Off. (a) Set-Off Generally. Upon the occurrence and during the continuance of any Event of Default, the Administrative Agent, each of the Noteholders is hereby authorized at any time and from time to time, to the fullest extent permitted by Law, to set off and apply any and all deposits (general or special, time or demand, provisional or final, in whatever currency) at any time held and other obligations (in whatever currency) at any time owing by the Administrative Agent, any Noteholder to or for the credit or the account of any Obligor against any and all of the Obligations, whether or not such Person shall have made any demand and although such obligations may be unmatured. Any Person exercising rights of set off hereunder agrees to promptly notify the Issuer after any such set-off and application; provided that the failure to give such notice shall not affect the validity of such set-off and application. The rights of the Administrative Agent, the Noteholders under this Section 4.03 are in addition to other rights and remedies (including other rights of set-off) that such Persons may have. (b) Exercise of Rights Not Required. Nothing contained in Section 4.03(a) shall require the Administrative Agent or any Noteholder to exercise any such right or shall affect the 45 right of such Persons to exercise, and retain the benefits of exercising, any such right with respect to any other indebtedness or obligation of any Obligor. (c) Payments Set Aside. To the extent that any payment by or on behalf of any Obligor is made to the Administrative Agent or any Noteholder, or the Administrative Agent, any Noteholder or any Affiliate of the foregoing exercises its right of setoff, and such payment or the proceeds of such setoff or any part thereof is subsequently invalidated, declared to be fraudulent, or preferential, set aside or required (including pursuant to any settlement entered into by the Administrative Agent, such Noteholder or such Affiliate in its discretion) to be repaid to a trustee, receiver, examiner or any other party, in connection with any Insolvency Proceeding or otherwise, then to the extent of such recovery, the obligation or part thereof originally intended to be satisfied shall be revived and continued in full force and effect as if such payment had not been made or such setoff had not occurred. (d) To the extent permitted under applicable Law, any Participant acquiring a participation pursuant to Section 14.05(e) hereof (as well as any Noteholder acquiring a participation pursuant to Section 14.05(e) hereof) may exercise against the Obligors rights of setoff and counterclaim with respect to such participation as fully as if such Participant was a direct creditor of the Obligor in the amount of such participation. SECTION 5 YIELD PROTECTION, ETC. 5.01 Additional Costs. (a) Changes in Law Generally. If, on or after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement), the adoption of any Law, or any change in any applicable Law, or any change in the interpretation or administration thereof by any court or other Governmental Authority charged with the interpretation or administration thereof, or compliance by the Administrative Agent or any of the Noteholders (or the office to which any of its Notes are booked) with any request or directive (whether or not having the force of Law) of any such Governmental Authority, shall impose, modify or deem applicable any reserve (including any such requirement imposed by the Board of Governors of the Federal Reserve System), special deposit, contribution, insurance assessment or similar requirement, in each case that becomes effective after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement) against assets of, deposits with or for the account of, or credit extended by, a Noteholder (or its office to which any of its Notes are booked) or other Recipient or shall impose on a Noteholder (or the office to which any of its Notes are booked) or other Recipient any other condition affecting the Notes or the Commitment, and the result of any of the foregoing is to increase the cost to such Noteholder or such other Recipient of making or maintaining the Notes, or to reduce the amount of any sum received or receivable by such Noteholder or other Recipient under this Agreement or any other Notes Document, or subject any Noteholder to any Taxes on its Notes, Commitment or other obligations, or its deposits, reserves, other liabilities or capital (if any) attributable thereto by an amount reasonably deemed by such Noteholder in good faith to be material (other than (i) Indemnified Taxes, (ii) Taxes described in clauses (ii) and (iii) of the definition of “Excluded Taxes”, (iii) Connection Income Taxes and (iv) any Bank Levy or any payment attributable to, or 46 liability arising as a consequence of, a Bank Levy), then the Issuer shall pay to such Noteholder within three (3) Business Days after written demand such additional amount or amounts as will compensate such Noteholder for such increased cost or reduction. (b) Change in Capital Requirements. If a Noteholder shall have determined that, on or after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement), the adoption of any applicable Law regarding capital adequacy, or any change therein, or any change in the interpretation or administration thereof by any Governmental Authority charged with the interpretation or administration thereof, or any request or directive regarding capital adequacy (whether or not having the force of Law) of any such Governmental Authority, in each case that becomes effective after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement), has or would have the effect of reducing the rate of return on capital of a Noteholder (or its parent) as a consequence of a Noteholder’s obligations hereunder or the Notes to a level below that which a Noteholder (or its parent) could have achieved but for such adoption, change, request or directive by an amount reasonably deemed by it to be material, then the Issuer shall pay to such Noteholder on demand such additional amount or amounts as will compensate such Noteholder (or its parent) for such reduction. (c) Notification by Noteholder. Each Noteholder shall promptly notify the Issuer of any event of which it has knowledge, occurring after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement), which will entitle such Noteholder to compensation pursuant to this Section 5.01. Before giving any such notice pursuant to this Section 5.01(c) such Noteholder shall designate a different office for booking its Notes if such designation (x) will, in the reasonable judgment of such Noteholder, avoid the need for, or reduce the amount of, such compensation and (y) will not, in the reasonable judgment of such Noteholder, be materially disadvantageous to such Noteholder. A certificate of such Noteholder claiming compensation under this Section 5.01, setting forth in reasonable detail the additional amount or amounts to be paid to it hereunder and also setting forth in reasonable detail the basis for calculating the additional amounts claimed to be owed to such Noteholder, shall be conclusive and binding on the Issuer in the absence of manifest error. (d) Delays in Requests. Failure or delay on the part of any Noteholder to demand compensation pursuant to the foregoing provisions of this Section shall not constitute a waiver of such Noteholder’s right to demand such compensation; provided that the Issuer shall not be required to compensate a Noteholder pursuant to the foregoing provisions of this Section for any increased costs unless the Noteholder notifies the Issuer within ninety (90) days following the receipt by such Noteholder of its audited annual financial statements of the change in Law giving rise to such increased costs or reductions and of such Noteholder’s intention to claim compensation therefor. (e) Other Changes. Notwithstanding anything herein to the contrary, (x) the Dodd-Frank Wall Street Reform and Consumer Protection Act and all requests, rules, guidelines or directives thereunder or issued in connection therewith and (y) all requests, rules, guidelines or directives promulgated by the Bank for International Settlements, the Basel Committee on Banking Supervision (or any successor or similar authority) or the United States or foreign regulatory 47 authorities, in each case pursuant to Basel III, shall in each case be deemed to constitute a change in Law for all purposes of this Section 5.01, regardless of the date enacted, adopted or issued. 5.02 Illegality. Notwithstanding any other provision of this Agreement, in the event that on or after the Closing Date (or, with respect to any Noteholder, such later date on which such Noteholder becomes party to this Agreement), the adoption of or any change in any applicable Law or in the interpretation or application thereof by any competent Governmental Authority shall make it unlawful for a Noteholder or the office to which any of its Notes are booked to perform any of its obligations or to subscribe for or maintain its participation in any Note (and, in the opinion of such Noteholder, the designation of a different office for the booking of its Notes would either not avoid such unlawfulness or would be disadvantageous to such Noteholder), then such Noteholder shall promptly notify the Issuer thereof, following which (i) such Noteholder’s Commitment shall be suspended until such time as such Noteholder may again subscribe for and maintain its participation in the Notes hereunder and (ii) if such Law shall so mandate, the Notes shall be redeemed by the Issuer on or before such date as shall be mandated by such Law in an amount equal to the Early Redemption Price applicable on such Early Redemption Date in accordance with Section 3.03(a). 5.03 Taxes. (a) Payments Free of Taxes. Any and all payments by or on account of any Obligations shall be made without deduction or withholding for any Taxes, except as required by applicable Law. If any applicable Law (as determined in the good faith discretion of an applicable Withholding Agent) requires the deduction or withholding of any Tax from any such payment by a Withholding Agent, then the applicable Withholding Agent shall be entitled to make such deduction or withholding and shall timely pay the full amount deducted or withheld to the relevant Governmental Authority in accordance with applicable Law and, if such Tax is an Indemnified Tax, then the sum payable by such Obligor shall be increased as necessary so that after such deduction or withholding has been made (including such deductions and withholdings applicable to additional sums payable under this Section 5.03) the applicable Recipient receives an amount equal to the sum it would have received had no such deduction or withholding been made. (b) Payment of Other Taxes by the Issuer. The Issuer shall timely pay to the relevant Governmental Authority in accordance with applicable Law, or at the option of the Administrative Agent or each Noteholder, timely reimburse it for the payment of any Other Taxes. (c) Evidence of Payments. As soon as reasonably practicable after any payment of Taxes by the Issuer to a Governmental Authority pursuant to this Section 5, the Issuer shall deliver to the Administrative Agent the original or a certified copy of a receipt issued by such Governmental Authority evidencing such payment, a copy of the return reporting such payment or other evidence of such payment reasonably satisfactory to the Administrative Agent. (d) Indemnification by the Issuer. The Issuer shall reimburse and indemnify each Recipient, within ten (10) days after demand therefor, for the full amount of any Indemnified Taxes (including Indemnified Taxes imposed or asserted on or attributable to amounts payable under this Section 5) payable or paid by such Recipient or required to be withheld or deducted from a payment to such Recipient and any reasonable expenses arising therefrom or with respect thereto, 48 whether or not such Indemnified Taxes were correctly or legally imposed or asserted by the relevant Governmental Authority, but excluding, for the avoidance of doubt, any Indemnified Tax which is suffered or incurred in respect of any Bank Levy, or any payment attributable to, or liability arising as a consequence of, a Bank Levy. A certificate as to the amount of such payment or liability delivered to the Issuer by a Noteholder (with a copy to the Administrative Agent), or by the Administrative Agent on its own behalf or on behalf of a Noteholder shall be conclusive absent manifest error. (e) indemnify the Indemnification by the Noteholders. Each Noteholder shall severally Administrative Agent, within ten (10) days after demand therefor, for (i) any Indemnified Taxes attributable to such Noteholder (but only to the extent that the Issuer has not already indemnified the Administrative Agent for such Indemnified Taxes and without limiting the obligation of the Issuer to do so), (ii) any Taxes attributable to such Noteholder’s failure to comply with the provisions of Section 14.05(g) relating to the maintenance of a Participant Register, and (iii) any Excluded Taxes attributable to such Noteholder, in each case, that are payable or paid by (or withheld from payments to) the Administrative Agent in connection with any Notes Documents, and any reasonable expenses arising therefrom or with respect thereto, whether or not such Taxes were correctly or legally imposed or asserted by the relevant Governmental Authority. A certificate as to the amount of such payment or liability delivered to any Noteholder by the Administrative Agent shall be conclusive absent manifest error. Each Noteholder hereby authorizes the Administrative Agent to set off and apply any and all amounts at any time owing to such Noteholder under any Notes Documents or otherwise payable by the Administrative Agent to the Noteholder from any other source against any amount due to the Administrative Agent under this clause (e). (f) Status of Successors and Assignees. (i) Any Noteholder that is a successor or assignee of Perceptive Credit Holdings III, LP and that is entitled to an exemption from or reduction of withholding Tax with respect to payments made under any Notes Document shall deliver to the Issuer and the Administrative Agent at the time or times reasonably requested by the Issuer or the Administrative Agent, such properly completed and executed documentation reasonably requested by the Issuer or the Administrative Agent as will permit such payments to be made without withholding or at a reduced rate of withholding. Notwithstanding anything to the contrary in the preceding sentence, the completion, execution and submission of such documentation (other than such documentation set forth in Section 5.03(f)(ii)) shall not be required if in such Noteholder’s reasonable judgment such completion, execution or submission would subject such Noteholder to any material unreimbursed cost or expense or could materially prejudice the legal or commercial position of such Noteholder. For the avoidance of doubt, notwithstanding anything to the contrary in this Agreement, Perceptive Credit Holdings III, LP shall not be obligated to take any actions that would disclose the identity of its partners. (ii) If a payment made to any Noteholder under any Notes Documents would be subject to U.S. federal withholding Tax imposed by FATCA if such Noteholder were to fail to comply with the applicable reporting requirements of FATCA (including those contained in Section 1471(b) or 1472(b) of the Code, as applicable), such Noteholder shall deliver to the Issuer and the Administrative Agent at the time or times prescribed by Law and at such time or times 49 reasonably requested by the Issuer or the Administrative Agent such documentation prescribed by applicable Law (including as prescribed by Section 1471(b)(3)(C)(i) of the Code) and such additional documentation reasonably requested by the Issuer or the Administrative Agent as may be necessary for the Issuer and the Administrative Agent to comply with their obligations under FATCA and to determine that such Noteholder has complied with such Noteholder’s obligations under FATCA or to determine the amount, if any, to deduct and withhold from such payment. Solely for purposes of this clause (ii), “FATCA” shall include any amendments made to FATCA after the date of this Agreement. Each Recipient agrees that if any form or certification it previously delivered expires or becomes obsolete or inaccurate in any respect, it shall update such form or certification or promptly notify the Issuer and the Administrative Agent in writing of its legal inability to do so. (g) Treatment of Certain Tax Benefits. If any party to this Agreement determines, in its sole discretion exercised in good faith, that it has received a refund of any Taxes as to which it has been indemnified pursuant to this Section 5.03 (including by the payment of additional amounts pursuant to this Section 5.03), it shall pay to the indemnifying party an amount equal to such refund (but only to the extent of indemnity payments made under this Section 5.03 with respect to the Taxes giving rise to such refund), net of all out-of-pocket expenses (including Taxes) of such indemnified party and without interest (other than any interest paid by the relevant Governmental Authority with respect to such refund). Such indemnifying party, upon the request of such indemnified party, shall repay to such indemnified party the amount paid over pursuant to this Section 5.03 (plus any penalties, interest or other charges imposed by the relevant Governmental Authority) in the event that such indemnified party is required to repay such refund to such Governmental Authority. Notwithstanding anything to the contrary in this Section 5.03(g), in no event will the indemnified party be required to pay any amount to an indemnifying party pursuant to this Section 5.03(g) the payment of which would place the indemnified party in a less favorable net after-Tax position than the indemnified party would have been in if Tax subject to indemnification and giving rise to such refund had not been deducted, withheld or otherwise imposed and the indemnification payments or additional amounts with respect to such Tax had never been paid. This Section 5.03(g) shall not be construed to require any indemnified party to make available its Tax returns (or any other information relating to its Taxes that it deems confidential) to the indemnifying party or any other Person. (h) Mitigation Obligations. If the Issuer is required to pay any Indemnified Taxes or additional amounts to any Noteholder or to any Governmental Authority for the account of any Noteholder pursuant to Section 5.01, then such Noteholder shall (at the request of the Issuer) use reasonable efforts to designate a different office for subscribing for or booking its participation in the Notes hereunder or to assign and delegate its rights and obligations hereunder to another of its offices, branches or Affiliates if, in the sole, reasonable judgment of such Noteholder, such designation or assignment and delegation would (i) eliminate or reduce amounts payable pursuant to Section 5.01, as the case may be, in the future, (ii) not subject such Noteholder to any unreimbursed cost or expense and (iii) not otherwise be disadvantageous to such Noteholder. The Issuer hereby agrees to pay all reasonable costs and expenses incurred by any Noteholder in connection with any such designation or assignment and delegation. (i) United Kingdom Requirements. 50 (i) Subject to sub-paragraph (ii) below, a UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities) and each Withholding Agent which makes a payment to which that Noteholder is entitled shall co-operate in completing any procedural formalities necessary for that Withholding Agent to obtain authorization to make that payment without a UK Tax Deduction. (ii) Each UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities): (A) which is a Noteholder as at the date of this Agreement and that holds a passport under the UK DTTP Scheme, and which wishes that scheme to apply to this Agreement, shall confirm its UK DTTP Scheme reference number and its jurisdiction of tax residence opposite its name on Schedule 1; and (B) that becomes a Noteholder after the date of this Agreement and that holds a passport under the UK DTTP Scheme, and which wishes that scheme apply to such Noteholder’s participation in this Agreement, shall confirm its UK DTTP Scheme reference number and its jurisdiction of tax residence in the documentation which it executes on becoming a party hereto as a Noteholder, and in each case under (A) and (B) above, having done so, that Noteholder shall be under no further obligation pursuant to sub-paragraph (i) above. (iii) If a Noteholder has confirmed its UK DTTP Scheme reference number and its jurisdiction of tax residence in accordance with sub-paragraph (i)(ii) above and: in respect of that Noteholder; or (A) the Issuer making a payment to that Noteholder has not made an Issuer DTTP Filing (B) the Issuer making a payment to that Noteholder has made an Issuer DTTP Filing in respect of that Noteholder but (1) that Issuer DTTP Filing has been rejected by HMRC, (2) HMRC has not given the Issuer authority to make payments to that Noteholder without a UK Tax Deduction within 60 days of the date of the Issuer DTTP Filing, or (3) HMRC has given authority for the Issuer to make payments to that Noteholder without a UK Tax Deduction but such authority has subsequently been revoked, suspended or expired, and in each case, the Issuer has notified that Noteholder in writing, then the applicable Noteholder shall co-operate with the Issuer in completing any additional procedural formalities necessary for that Issuer to obtain authorization to make that payment without a UK Tax Deduction. (iv) If a Noteholder has not confirmed its UK DTTP Scheme reference number and jurisdiction of tax residence in accordance with sub-paragraph (i)(ii) above, no Withholding Agent shall make an Issuer DTTP Filing or file any other form relating to the UK DTTP Scheme in respect of a Commitment by such Noteholder or its participation in any advance unless the Noteholder otherwise agrees. (v) The Issuer shall, promptly on making any Issuer DTTP Filing, deliver a copy of that Issuer DTTP Filing to the Administrative Agent for delivery to the relevant Noteholder. 51 (vi) A UK Non-Bank Noteholder shall promptly notify the Administrative Agent if there is any change in the position from that set out in the applicable UK Tax Confirmation. (vii) If the Administrative Agent receives a UK Tax Confirmation from a UK Non-Bank Noteholder it shall promptly provide a copy of such UK Tax Confirmation to the Issuer. (viii) The Issuer shall upon becoming aware that the Issuer must make a UK Tax Deduction (or that there is any change in the rate or the basis of a UK Tax Deduction) notify the Administrative Agent accordingly. Similarly, a Noteholder shall notify the Administrative Agent on becoming aware that a Withholding Agent must make a UK Tax Deduction (or that there is any change in the rate or the basis of a UK Tax Deduction). If the Administrative Agent receives such notification from a Noteholder, it shall promptly notify the Issuer. (j) Noteholder Status Confirmation. (i) Each Noteholder which becomes a party after the date of this Agreement shall indicate in the documentation which it executes on becoming a party which of the following categories it falls into: (A) not a UK Qualifying Noteholder; (B) a UK Qualifying Noteholder (other than a UK Treaty Noteholder); or (C) a UK Treaty Noteholder (or a Noteholder which would be a UK Treaty Noteholder upon the completion of any necessary procedural formalities). (ii) If a Noteholder fails to indicate its status in respect of the Issuer in accordance with paragraph (j)(i) above, then such Noteholder shall be treated for the purposes of this Agreement (including by each Withholding Agent) as if it is not a UK Qualifying Noteholder until such time as it notifies the Administrative Agent which categories apply (and the Administrative Agent, upon receipt of such notification, shall promptly inform the Issuer). For the avoidance of doubt, the documentation which a Noteholder executes on becoming a Party as a Noteholder shall not be invalidated by any failure of such Noteholder to comply with this clause 5.03(j). (iii) Where a Noteholder will become be a UK Treaty Noteholder only upon the completion of certain procedural formalities, it shall be treated for the purposes of this Agreement (including by each Withholding Agent) as if it is not a UK Qualifying Noteholder until such time as it notifies the Administrative Agent that such procedural formalities are complete (and the Administrative Agent, upon receipt of such notification, shall promptly inform the Issuer). (k) VAT. (i) All amounts expressed to be payable under any Notes Documents by any party to any Secured Party which (in whole or in part) constitute the consideration for a supply or supplies for VAT purposes shall be deemed to be exclusive of any VAT which is chargeable on such supply or supplies, and accordingly, subject to paragraph (ii) below, if VAT is or becomes chargeable on any supply made by any Secured Party to any party under any Notes Documents and: that party shall pay to the Secured Party (in addition to and at the same time (A) such Secured Party is required to account to the relevant tax authority for the VAT, 52 as paying any other consideration for such supply) an amount equal to the amount of such VAT (and such Secured Party shall promptly provide an appropriate VAT invoice to such party); or (B) if such party is required to directly account for such VAT under the reverse charge procedure provided for by article 44 of the Council Directive 2006/112/EC, or section 7A of the Value Added Tax Act 1994 of the United Kingdom, in each case, as amended, or any relevant VAT provisions of the jurisdiction in which such party received such supply, then such party shall account for the VAT at the appropriate rate (and the relevant Secured Party must promptly provide an appropriate VAT invoice to such party stating that the amount is charged in respect of a supply that is subject to VAT but that the reverse charge procedure applies). (ii) If VAT is or becomes chargeable on any supply made by any Secured Party (the “VAT Supplier”) to any other Secured Party (the “VAT Recipient”) under any Notes Documents, and any party other than the VAT Recipient (the “Relevant Party”) is required by the terms of any Notes Documents to pay an amount equal to the consideration for that supply to the VAT Supplier (rather than being required to reimburse or indemnify the VAT Recipient in respect of that consideration): (iii) where the VAT Supplier is the person required to account to the relevant tax authority for the VAT, the Relevant Party must also pay to the VAT Supplier (at the same time as paying that amount) an additional amount equal to the amount of VAT. The VAT Recipient must (where this sub-paragraph (ii)(A) applies) promptly pay to the Relevant Party an amount equal to any credit or repayment the VAT Recipient receives from the relevant tax authority which the VAT Recipient reasonably determines relates to the VAT chargeable on that supply; and (iv) where the VAT Recipient is the person required to account to the relevant tax authority for the VAT, the Relevant Party must promptly, following demand from the VAT Recipient, pay to the VAT Recipient an amount equal to the VAT chargeable on that supply but only to the extent that the VAT Recipient reasonably determines that it is not entitled to credit or repayment from the relevant tax authority in respect of that VAT. (v) Where any Notes Documents require any party to reimburse or indemnify a Secured Party for any cost or expense in connection with such Notes Documents, the reimbursement or indemnity (as the case may be) shall be for the full amount of such cost or expense, including such part thereof as represents VAT, save to the extent that such Secured Party reasonably determines that it is entitled to credit or repayment in respect of such VAT from the relevant tax authority. (vi) Any reference in this clause 5.03(k) to any party shall, at any time when such party is treated as a member of a group or unity (or fiscal unity) for VAT purposes, include (where appropriate and unless the context otherwise requires) a reference to the representative member of such group at such time as making the supply, or (as appropriate) receiving the supply, under the grouping rules (as provided for in Article 11 of Council Directive 2006/112/EC (or as implemented by the relevant member state of the European Union) or any other similar provision in any jurisdiction which is not a member state of the European Union, including, for the avoidance of doubt, in accordance with section 43 of the UK Value Added Tax Act 1994) so that a reference to a party shall be construed as a reference to that party or the relevant group or unity (or fiscal 53 unity) of which that party is a member for VAT purposes at the relevant time or the relevant representative member (or head) of that group or unity (or fiscal unity) at the relevant time (as the case may be). (vii) In relation to any supply made by a Secured Party to any party under a Notes Document, if reasonably requested by such Secured Party, that party must as promptly as reasonably practicable provide such Secured Party with details of that party’s VAT registration and such other information as is reasonably requested in connection with such Secured Party’s VAT reporting requirements in relation to such supply. (l) Hybrid Mismatch Rules. Each Noteholder agrees to use commercially reasonable efforts to assist the Issuer in preparing an analysis of available interest deductions to the Issuer under the UK hybrid mismatch rules contained in Part 6A of the Taxation (International and Other Provisions) Act 2010 at Issuer’s cost; provided, however, that notwithstanding anything to the contrary in this Agreement, no Noteholder shall be obligated to take any actions that would disclose the identity of its partners. (m) Survival. Each party’s obligations under this Section 5.03 shall survive the resignation or replacement of the Administrative Agent or any assignment of rights by, or the replacement of, a Noteholder, the termination of the Commitments and the repayment, satisfaction or discharge of all Obligations under any Notes Documents. SECTION 6 CONDITIONS PRECEDENT 6.01 Conditions to the issuance and subscription of the Tranche 1 Notes. The obligation of the Noteholders to subscribe for the Tranche 1 Notes on the Closing Date was subject to the execution and delivery of this Agreement by the parties hereto, the delivery of a funds flow memorandum summarizing, in reasonable detail, the use of proceeds of the Tranche 1 Notes, and the prior or concurrent satisfaction (or waiver thereof by the Administrative Agent) of each of the conditions precedent set forth below in this Section 6.01, each of which was satisfied or waived as of the Closing Date. (a) Secretary’s Certificate, Etc. The Administrative Agent received from each Obligor party to a Notes Document on the Closing Date: (i) a copy of a good standing certificate or the equivalent thereof, dated a date reasonably close to the Closing Date, for each such Person; and (ii) a certificate, dated as of the Closing Date, duly executed and delivered by such Person’s director, secretary or assistant secretary, managing member, general partner, authorized signatory or equivalent, as to: resolutions of each such Person’s Board then in full force and effect authorizing the execution, delivery and performance of each Notes Document and the Transactions, to be executed and delivered by such Person; (A) 54 the incumbency and signatures of those of its officers, directors, managing member or general partner or equivalent authorized to act with respect to each Notes Document to be executed and delivered by such Person; and (B) true and complete copies of each Organic Document of such Person and, in relation to any Person that is a Cayman Islands exempted company or limited liability company, its register of directors and officers and register of mortgages and charges; (C) (iii) solely with respect to the Irish Subsidiary Guarantor: the registration of the transfer of secured shares and does not apply any company lien over shares; and (A) evidence that the constitution of such Irish Subsidiary Guarantor does not restrict Documents by it would not breach Sections 82 and 239 of the Irish Companies Act; (B) a certificate from such Subsidiary Guarantor certifying that entry into the Notes which certificates were in form and substance reasonably satisfactory to the Administrative Agent and upon which the Administrative Agent and the Noteholders may conclusively rely until they shall have received a further certificate of the director, secretary, assistant secretary, managing member, general partner or equivalent of any such Person cancelling or amending the prior certificate of such Person. (b) Information Certificate. The Administrative Agent received a fully completed Information Certificate, in form and substance reasonably satisfactory to the Administrative Agent, dated as of the Closing Date, duly executed and delivered by a Responsible Officer of the Issuer, which was true and correct in all material respects as of the Closing Date. All documents and agreements required to be appended to the Information Certificate, if any, were in form and substance reasonably satisfactory to the Administrative Agent, were executed and delivered by the requisite parties and were in full force and effect. (c) Closing Date Certificate. The following statements were true and correct, and the Administrative Agent received a certificate, dated as of the Closing Date in form and substance reasonably satisfactory to the Administrative Agent, duly executed and delivered by a Responsible Officer of the Issuer certifying that: (i) both immediately before and after the issuance of the Tranche 1 Notes on the Closing Date, (x) the representations and warranties set forth in each Notes Document qualified by materiality, Material Adverse Effect or the like were, in each case, true and correct, (y) the representations and warranties set forth in each Notes Document not qualified by materiality, Material Adverse Effect or the like were, in each case, true and correct in all material respects, and (z) no Event of Default had occurred and was continuing, or could reasonably be expected to result from the issuance of the Tranche 1 Notes, or the consummation of any Transactions contemplated to occur on the Closing Date, and (ii) all of the conditions set forth in this Section 6.01 had been satisfied (except to the extent waived in writing by the Administrative Agent). All documents and agreements required to be appended to the certificate delivered pursuant to this Section 6.01(c), if any, were in form and substance reasonably satisfactory to the Administrative Agent, were executed (if applicable) and delivered by the requisite parties, and were in full force and effect. 55 (d) (e) [Reserved]. Financial Information, Etc. The Administrative Agent received: (i) audited consolidated financial statements of the Issuer and its Subsidiaries for the fiscal year ended December 31, 2021; and (ii) unaudited consolidated balance sheets of the Issuer and its Subsidiaries for each fiscal quarter ended after December 31, 2021 and at least thirty (30) Business Days prior to the Closing Date, together with the related consolidated statement of operations, shareholder’s equity and cash flows for each such fiscal quarter. (f) Minimum Liquidity Compliance. The Administrative Agent received evidence reasonably satisfactory to it that, immediately after giving effect to the issuance of the Tranche 1 Notes on the Closing Date, the Issuer was in compliance with the covenant set forth in Section 10.01. (g) Closing Date Warrant Certificates. The Administrative Agent received (i) an executed counterpart of a Warrant Certificate, exercisable into 400,000 shares of the Issuer’s ordinary shares with a per share exercise price of $15.00 and (ii) an executed counterpart of a Warrant Certificate, exercisable into 300,000 shares of the Issuer’s ordinary shares with a per share exercise price of $20.00, in each case duly executed and delivered by the Issuer. (h) Insurance. The Administrative Agent received certificates of insurance evidencing that the insurance required to be maintained pursuant to Section 8.05 was at the Closing Date in full force and effect, together with endorsements naming the Administrative Agent, for the benefit of the Noteholders, as additional insured and loss payee thereunder, in each case, in form and substance reasonably satisfactory to the Administrative Agent. (i) Solvency. The Administrative Agent received a solvency certificate substantially in the form of Exhibit I, duly executed and delivered by the chief financial or other Responsible Officer of the Issuer, dated as of the Closing Date, in form and substance reasonably satisfactory to the Administrative Agent. (j) Security Documents. The Administrative Agent received executed counterparts of all Security Documents, each dated as of the Closing Date, duly executed and delivered by the applicable Obligors, together with: (i) The delivery of all certificates (in the case of Equity Interests that are securities (as defined in the UCC)) evidencing the issued and outstanding capital securities of the Subsidiary Guarantors that were required to be pledged under any Security Document, which certificates in each case were accompanied by undated instruments of transfer duly executed in blank, or, in the case of Equity Interests that were uncertificated securities (as defined in the UCC), confirmation and evidence satisfactory to the Administrative Agent and the Noteholders that the security interest required to be pledged therein under any Security Document had been transferred to and perfected by the Administrative Agent for the benefit of the Secured Parties in accordance with Articles 8 and 9 of the NY UCC and all Laws otherwise applicable to the perfection of the pledge of such Equity Interests; 56 (ii) financing statements naming each Obligor as a debtor and the Administrative Agent as the secured party, or other similar instruments, registrations, or documents, in each case suitable for filing, filed under the UCC (or equivalent Law) of all jurisdictions as was reasonably necessary to perfect the Liens of the Secured Parties pursuant to any Security Document; (iii) evidence that the Minimum Liquidity Account and all deposit accounts, lockboxes, disbursement accounts, investment accounts (or other similar cash or bank accounts) of the Subsidiary Guarantors were at the Closing Date Controlled Accounts; (iv) evidence that all such Controlled Accounts were subject to one or more account control agreements, or the equivalent in a foreign law jurisdiction, in favor of, and satisfactory in form and substance to, the Administrative Agent; and (v) all notices of assignment, share deliverables and other ancillary documents necessary to perfect the Liens of the Secured Parties pursuant to any Foreign Collateral Security Document. (k) Lien Searches. The Administrative Agent was satisfied with scope and results of Lien searches (or equivalents) regarding the Collateral made within thirty (30) days prior to the Closing Date. (l) Opinions of Counsel. The Administrative Agent received one or more legal opinions, dated the Closing Date and addressed to the Administrative Agent and the Noteholders, from independent legal counsel to the Issuer, in each case, in form and substance reasonably acceptable to the Administrative Agent. (m) Material Adverse Change. No Material Adverse Change had, as at the Closing Date, occurred since December 31, 2021. (n) Anti-Terrorism Laws. The Administrative Agent received, as applicable, all documentation and other information required by bank regulatory authorities requested by the Administrative Agent at least three (3) Business Days prior to the Closing Date with respect to applicable “know your customer” and anti-money laundering rules and regulations, including the Patriot Act. (o) Fees, Expenses, Etc. The Administrative Agent received for its account and the account of each Noteholder, the Tranche 1 Facility Fee, together with payment and reimbursement of all other fees, costs and expenses due and payable pursuant to the Proposal Letter and Section 14.03, including all closing costs and fees and all unpaid reasonable expenses of the Administrative Agent and the Noteholders incurred as of the Closing Date in connection with the Transactions in excess of the Expense Deposit (as defined in the Proposal Letter) (including the Administrative Agent’s and the Noteholders’ legal fees and expenses). (p) Independent Appraisal of Manufacturing Facilities. The Administrative Agent received a satisfactory initial draft valuation and appraisal report, prepared by a reputable independent appraiser (the “Independent Appraiser”) instructed and appointed by the 57 Administrative Agent, which report was in scope and substance reasonably satisfactory to the Administrative Agent. (q) Certificates of Title and Foreign Real Property Security Documents. The Issuer delivered to the Administrative Agent: (i) a duly executed Foreign Real Property Security Document in respect of each of the London Manufacturing Facility and the Shannon Manufacturing Facility; (ii) copies of all lease and title documents for the London Manufacturing Facility in electronic format; (iii) a clear (save in respect of pending applications which have been disclosed in the Certificate of Title) Land Registry Priority Search (OS1) in favour of the Administrative Agent against the title number of the London Manufacturing Facility and: (A) giving not less than 20 Business Days’ priority beyond the date of the relevant Security Document; and (B) showing no adverse entries (save in respect of pending applications which have been disclosed in the relevant Certificate of Title); (iv) the Certificates of Title; (v) an overview report prepared by the Administrative Agent’s solicitors on the Certificates of Title addressed to the Secured Parties; (vi) all necessary HM Land Registry application forms in relation to the charging of the London Manufacturing Facility in favour of the Administrative Agent (including a form to note the obligation to make further advances and a form to register the restriction contained in the relevant Security Document), duly completed, accompanied by payment of the applicable HM Land Registry fees or an acceptable undertaking in relation to the same; (vii) copies of all Authorisations (if any) required in connection with the charging of the London Manufacturing Facility and the Shannon Manufacturing Facility in favour of the Administrative Agent; (viii) all title documents relating to the Shannon Manufacturing Facility or an acceptable undertaking to hold the same to the order of the Secured Parties; (ix) all necessary Property Registration Authority forms in relation to the charging of the Shannon Manufacturing Facility in favour of the Administrative Agent; (x) an acceptable undertaking to assist with Property Registration Authority queries relating to the registration of the Shannon Manufacturing Facility in the name of the Irish Subsidiary Guarantor and the registration of the charge over the Shannon Manufacturing Facility in favour of the Administrative Agent; (xi) undertaking from of the Irish Subsidiary Guarantor to assist with Property Registration Authority queries relating to the registration of the Shannon Manufacturing Facility 58 in the name of the Irish Subsidiary Guarantor and the registration of the charge over the Shannon Manufacturing Facility in favour of the Administrative Agent; (xii) Clear or duly explained and certified Land Registry / Registry of Deeds and planning searches in respect of the Shannon Manufacturing Facility showing no adverse acts appearing; (xiii) Sworn Family Home Declaration in relation to the Shannon Manufacturing Facility; (xiv) Sworn Declaration re compliance with leasehold covenants in relation to the Shannon Manufacturing Facility; and (xv) over dealing D2022LR029852T. Letter from ALG addressed to the Land Registry authorising William Fry to take control In this Section, an “acceptable undertaking” means a solicitor’s undertaking from a firm of solicitors regulated by the Solicitors Regulation Authority or the Irish Law Society (as applicable) and approved for this purpose by the Administrative Agent and in form and substance reasonably satisfactory to the Administrative Agent. (r) Process Agent. Evidence that any process agent referred to in clause 21 (Service of process) of the English Law Security Agreement had accepted its appointment. 6.02 Conditions to the issuance and sale of the Tranche 2 Notes. During the Tranche 2 Notes Draw Period, the Issuer may request that the Noteholders subscribe for the Tranche 2 Notes in an aggregate principal amount of $25,000,000; provided that the making of the subscription for the Tranche 2 Notes shall be subject to the prior consent of the Majority Noteholders in their sole discretion after receiving such request from the Issuer, and no Noteholder shall have any commitment to make or participate in the subscription for the Tranche 2 Notes unless the Majority Noteholders have provided such consent in writing to the Issuer, the Administrative Agent and the other Noteholders hereunder. In the event (and only in the event) the Majority Noteholders so consent to subscribe for the Tranche 2 Notes, in whole or in part, as provided above, the obligation of the Noteholders to fund their respective Proportionate Shares of the subscription for the Tranche 2 Notes at their sole discretion shall be subject to the delivery of a Notes Subscription Request by the Issuer, the delivery of a funds flow memorandum by the Issuer summarizing, in reasonable detail, the use of proceeds of the Tranche 2 Facility, and the prior or concurrent satisfaction (or waiver thereof by the Administrative Agent) of such customary additional conditions as the Majority Noteholders may reasonably request (including some or all conditions of the type set forth in Section 6.01). SECTION 7 REPRESENTATIONS AND WARRANTIES The Issuer and each other Obligor hereby jointly and severally represent and warrant to the Administrative Agent and each Noteholder that: 59 7.01 Power and Authority. The Issuer and each of its Subsidiaries (i) is duly organized or incorporated, as applicable, and validly existing under the laws of its jurisdiction of organization or incorporation, as applicable, (ii) has all requisite corporate or other power, and has all Governmental Approvals necessary to own or lease its assets and carry on its business as now being or as proposed to be conducted, including all Healthcare Permits, other than could not reasonably be expected to result in a Material Adverse Effect, (iii) is qualified to do business and is in good standing (or equivalent) in all jurisdictions in which the nature of the business conducted by it makes such qualification necessary and where failure so to qualify, individually or in the aggregate, could reasonably be expected to result in a Material Adverse Effect, and (iv) has full power, authority and legal right to execute, deliver and perform its obligations under each of the Notes Documents to which it is a party and, in the case of the Issuer, to issue the Notes hereunder. 7.02 Authorization; Enforceability. Each Transaction to which an Obligor is a party (or to which it or any of its assets or properties is subject) are within such Obligor’s corporate or other powers and have been duly authorized by all necessary corporate action including, if required, approval by all necessary holders of Equity Interests. This Agreement has been duly executed and delivered by such Obligor and constitutes, and each of the other Notes Documents to which it is a party when executed and delivered by such Obligor, will constitute, a legal, valid and binding obligation of such Obligor, enforceable against such Obligor in accordance with its terms, except as such enforceability may be limited by (i) bankruptcy, insolvency, reorganization, moratorium or similar laws of general applicability affecting the enforcement of creditors’ rights; (ii) the application of general principles of equity (regardless of whether such enforceability is considered in a proceeding in equity or at law); and (iii) solely in respect of the English Guarantor and the Irish Subsidiary Guarantor, the Legal Reservations or the Perfection Requirements. 7.03 Governmental and Other Approvals for Execution and Delivery of the Notes Document, etc.; No Conflicts. No authorization or approval or other action by, and no notice to or filing with, any Governmental Authority or any other Person (other than those that have been duly obtained or made and which are in full force and effect) is required in connection with the due execution, delivery or performance by, any Obligor of any Notes Document to which it is a party, except for such approvals, consents, exemptions, authorizations, actions or notices (including such filings and recordings that have been or will be made on the Closing Date in respect of perfecting or recording the Liens created pursuant to the Security Documents) that have been duly obtained, taken or made and that are in full force and effect. None of the Transactions will (i) violate or conflict with any Law, other than any such violation that could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Effect, (ii) violate or conflict with any Organic Document of the Issuer or any of its Subsidiaries, (iii) violate or conflict with any Governmental Approval of any Governmental Authority binding upon the Issuer or any of its Subsidiaries other than any such violation that could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Effect, (iv) violate or result in a default under any Material Agreement other than any such violation that could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Effect, or (v) result in the creation or imposition of any Lien (other than Permitted Liens) on any asset of such Obligor. The Issuer, its Subsidiaries and their respective properties and businesses are in compliance in all material respects with all applicable Laws (including Healthcare Laws) and Governmental Approvals applicable to such Person and its properties or businesses, as the case may be. 60 7.04 Financial Statements; Material Adverse Change. (a) Financial Statements. The Issuer has heretofore furnished to the Administrative Agent and the Noteholders certain consolidated financial statements as provided for in Section 6.01(e). Such financial statements, and all other financial statements delivered by the Issuer pursuant hereto (including Section 6.01) present fairly, in all material respects, the consolidated financial position and results of operations and cash flows of the Issuer and its Subsidiaries as of such dates and for such periods in accordance with GAAP, subject to year- end audit adjustments and the absence of footnotes in the case of the statements of the type described in Sections 8.01(a) and 8.01(b). Neither the Issuer nor any of its Subsidiaries has any material contingent liabilities or unusual forward or long-term commitments required to be disclosed in the aforementioned financial statements and related footnotes in accordance with GAAP that are not disclosed therein. (b) No Material Adverse Change. Since December 31, 2021, there has been no Material Adverse Change. 7.05 Properties. (a) Property Generally. With respect to all real and personal assets and properties of the Issuer and each of its Subsidiaries (other than Intellectual Property which is covered in clause (b) below), the Issuer and each of its Subsidiaries has good and marketable fee simple title to, valid leasehold interests or other equivalent rights in, all such real and personal assets and property, whether tangible or intangible, material to its respective business and except as disclosed in a Certificate of Title, subject only to Permitted Liens and except for defects in title that do not, and are not reasonably anticipated to materially interfere with the ability of the Issuer or any such Subsidiaries, as the case may be, to utilize such assets and properties in the ordinary course of business as currently conducted and anticipated to be conducted. (b) Intellectual Property. (i) Schedule 7.05(b) contains, with respect to the Obligors and their respective Material Intellectual Property (set forth on an Obligor-by-Obligor basis and designated as to whether such Material Intellectual Property is owned or in-licensed): a complete and accurate list of all applied for, issued, or registered Patents owned by or licensed to the Obligors, including the jurisdiction and patent number, which would qualify as Material Intellectual Property; (A) a complete and accurate list of all material applied for, or registered active Trademarks owned by or licensed to the Obligors, including the jurisdiction, trademark application or registration number and the application or registration date, which would qualify as Material Intellectual Property; and (B) licensed to the Obligors, which would qualify as Material Intellectual Property. (C) a complete and accurate list of all applied for or registered Copyrights owned by or 61 (ii) With respect to any such Intellectual Property listed on Schedule 7.05(b) that is designated as being in-licensed by the Obligors from a third party, there are no unpaid fees or royalties (or similar payment obligations) currently due and payable under or in respect of any such in-licensed Material Intellectual Property (or any license or other Contract related thereto) and, to the knowledge of the Issuer, such license is legal, valid, binding, enforceable, and in full force and effect. No Obligor is in material breach or default of any such license and, to the knowledge of the Issuer, no third party (including the licensor of any such licensed Material Intellectual Property) is in material breach or default of any such license that, in either case, could reasonably be expected to give rise to a right of rescission, termination, revision or amendment of any of any such license. (iii) With respect to any such Material Intellectual Property listed on Schedule 7.05(b) that is designated as being owned by the Obligors, each Obligor, as the case may be, is the beneficial owner of all right, title and interest in and to such Person’s Material Intellectual Property that it owns, with no breaks in chain of title and with good and marketable title, free and clear of any Liens or Claims of any kind whatsoever (other than Permitted Liens), and the Issuer or the applicable Obligor, as the case may be, has the right to use such Material Intellectual Property in the ordinary course of its respective business as currently conducted and as anticipated to be conducted. Without limiting the foregoing, and except as set forth on Schedule 7.05(b): other than as permitted by Section 9.09, neither the Issuer nor any Subsidiary Guarantor, has transferred ownership of any such Material Intellectual Property, in whole or in part, to any Person who is not an Obligor; (A) (B) other than (1) customary restrictions in in-bound licenses of Intellectual Property and non-disclosure agreements, in each case as permitted pursuant to Section 9.19 or (2) licenses granted to the Issuer’s or any of its Subsidiaries’ customers or development partners in the ordinary course of business, there are no judgments, covenants not to sue, permits, grants, licenses, Liens (other than Permitted Liens), Claims, or other agreements or arrangements relating to any such Material Intellectual Property, including any development, submission, services, research, license or support agreements, which bind, obligate or otherwise restrict the Issuer or any of its Subsidiaries with respect to any such Material Intellectual Property in any material respect; (C) the use by the Issuer or any of its Subsidiaries of any such Material Intellectual Property in the ordinary course of such Person’s businesses does not breach, violate, infringe or interfere with or constitute a misappropriation of any valid rights arising under any Intellectual Property of any other Person that, individually or in the aggregate, could reasonably be expected to result in a Material Adverse Effect; (D) (1) there are no pending or, to the Issuer’s knowledge, threatened in writing Claims against the Issuer or any of its Subsidiaries asserted by any other Person relating to any such Material Intellectual Property, including any Claims of adverse ownership, invalidity, infringement, misappropriation, violation or other opposition to or conflict with such Material Intellectual Property; and (2) neither the Issuer nor any of its Subsidiaries has received any written notice from, or Claim by, any other Person that the business of the Issuer or any of its Subsidiaries, the use of any such Material Intellectual Property by the Issuer or any of its Subsidiaries materially 62 infringes upon, violates or constitutes a misappropriation of, or may infringe upon, violate or constitute a misappropriation of, or otherwise interfere with, or otherwise offer a license with respect to any Intellectual Property of any such other Person; and (E) to the Issuer’s knowledge, no such Material Intellectual Property is being infringed, violated, misappropriated or otherwise used by any other Person without the express authorization of the Issuer; and, without limiting the foregoing, neither the Issuer nor any of its Subsidiaries has put any other Person on notice of actual or potential infringement, violation or misappropriation of any such Material Intellectual Property, and neither the Issuer nor any of its Subsidiaries has initiated the enforcement of any Claim with respect to any such Material Intellectual Property. (iv) With respect to the owned Material Intellectual Property of the Obligors consisting of Patents listed on Schedule 7.05(b), except as set forth on Schedule 7.05(b), and without limiting the representations and warranties in Section 7.05(b)(iii): (A) each of the issued claims in such Patents is valid and enforceable; (B) each inventor named in such Patents has executed written Contracts with the Issuer or one of its Subsidiaries (or a predecessor-in-interest) that properly and irrevocably assigns to the Issuer or such Subsidiary (or such predecessor-in-interest) all of such inventor’s rights, title and interest to any of the Inventions claimed in such Patents; claimed in any such Patent, have been dedicated to the public; (C) all such Patents are in good standing and none of the Patents, or the Inventions all prior art material to such Patents was adequately disclosed, to the extent such disclosure is required, to the relevant patent office or, to the Issuer’s knowledge, considered by the respective patent offices during prosecution of such Patents; (D) subsequent to the issuance of such Patents, none of the Issuer, any of its Subsidiaries or any of their respective predecessors-in-interest, has filed any disclaimer or made or permitted any other voluntary reduction in the scope of the Inventions claimed in such Patents; (E) (F) no subject matter designated allowable or allowed by the U.S. Patent and Trademark Office of such Patents is subject to any competing conception claims of allowable or allowed subject matter of any patent applications or patents of any third party and have not been the subject of any interference, and such Patents are not and have not been the subject of any re-examination, opposition or any other post-grant proceedings, and neither the Issuer nor any of its Subsidiaries has knowledge of any basis for any such interference, re-examination, opposition, inter partes review, post grant review, or any other post-grant proceedings; (G) no such Patents have ever been finally adjudicated to be invalid, unpatentable or unenforceable for any reason in any administrative, arbitration, judicial or other proceeding, and, with the exception of publicly available documents in the applicable patent office recorded with respect to any Patents, neither the Issuer nor any of its Subsidiaries has received any written, or to its knowledge, other notice asserting that such Patents are invalid, unpatentable or 63 unenforceable; if any of such Patents is terminally disclaimed to another patent or patent application, all patents and patent applications subject to such terminal disclaimer are included in the Collateral; neither the Issuer nor any of its Subsidiaries has received an opinion, whether preliminary in nature or qualified in any manner, which concludes that a challenge to the validity or enforceability of any such Patents is more likely than not to succeed; (H) (I) (i) neither the Issuer nor any of its Subsidiaries, nor, any of their respective agents or representatives, have engaged in any conduct, or omitted to perform any necessary act, the result of which would invalidate or render unpatentable or unenforceable any such Patent and (ii) to the Issuer’s knowledge, no prior owner of any such Patent of the Issuer or any of its Subsidiaries, nor any of such prior owner’s agents or representatives, have engaged in any conduct, or omitted to perform any necessary act, the result of which would invalidate or render unpatentable or unenforceable any such Patent; and all maintenance fees, annuities, and the like due or payable on or with respect to any such Patents have been timely paid or the failure to so pay could not, individually or in the aggregate, reasonably be expected to result in a Material Adverse Change. (J) (v) The Material Intellectual Property listed on Schedule 7.05(b), together with the Issuer’s and its Subsidiaries’ lawful use of open source, freeware, is all the Intellectual Property necessary for the operation of the business of the Issuer and its Subsidiaries as it is currently conducted or as currently contemplated to be conducted. Issuer and each of its Subsidiaries have taken commercially reasonable precautions to protect the secrecy, confidentiality and value of its Material Intellectual Property consisting of trade secrets and confidential information, including unregistered Intellectual Property that is material to their respective businesses. 7.06 No Actions or Proceedings. (a) Litigation. Except as set forth on Schedule 7.06(a), there is no litigation, investigation or proceeding pending or, to the knowledge of the Issuer, threatened in writing, with respect to the Issuer or any of its Subsidiaries by or before any Governmental Authority or arbitrator that (i) could, individually or in the aggregate, reasonably be expected to result in an Event of Default or (ii) involves this Agreement, any other Notes Document, the Transactions or any Material Intellectual Property. (b) Environmental Matters. The operations and property of the Issuer and each of its Subsidiaries comply with all applicable Environmental Laws, except to the extent the failure to so comply (either individually or in the aggregate) could not reasonably be expected to result in Material Adverse Effect. (c) Labor Matters. There are no strikes, lockouts or other material labor disputes against the Issuer or any of its Subsidiaries or, to the Issuer’s knowledge, threatened in writing against or directly affecting the Issuer or any of its Subsidiaries, and no material unfair labor practice complaint is pending against the Issuer or any Subsidiary or, to the knowledge of the Issuer, threatened in writing against any of them before any Governmental Authority, in each case, that could reasonably be expected to result in a Material Adverse Effect. Except as set forth on 64 Schedule 7.06(c), neither the Issuer nor any of its Subsidiaries is a party to any collective bargaining agreements or similar Contracts, no union representation exists on any facilities of the Issuer or any of its Subsidiaries and the Issuer and its Subsidiaries do not have any knowledge of any union organizing activities that are taking place. 7.07 Compliance with Laws and Agreements. (a) Each of the Issuer and its Subsidiaries is in compliance with all applicable Laws and all Contracts binding upon it or its property, except (other than with respect to Material Intellectual Property) where the failure to do so, individually or in the aggregate, could not reasonably be expected to result in a Material Adverse Effect. No Default has occurred and is continuing, or will occur as a result of the issuing of any Notes hereunder. (b) Without limiting the generality of the foregoing, (i) each of the Issuer and its Subsidiaries is in material compliance with all applicable Healthcare Laws and Healthcare Permits, and (ii) during the past four (4) years neither the Issuer nor any of its Subsidiaries has received written notice by a Governmental Authority of any material violation (or of any investigation, audit, or other proceeding involving allegations of any violation) of any Healthcare Laws, and no such investigation, inspection, audit or other proceeding involving allegations of any such violation has been, to the knowledge of the Issuer, threatened in writing. 7.08 Taxes. Except as set forth on Schedule 7.08, the Issuer and each of its Subsidiaries has timely filed or caused to be filed all federal and state income tax returns and other material tax returns and reports required to have been filed and has paid or caused to be paid all material Taxes required to have been paid by it, except for Taxes that are being contested in good faith by appropriate proceedings and for which, in each case, the Issuer or such Subsidiary, as applicable, has set aside on its books adequate reserves with respect thereto in accordance with GAAP. 7.09 Full Disclosure. None of the reports, financial statements, certificates (other than the Certificates of Title) or other information furnished by or on behalf of the Obligors to the Administrative Agent or any Noteholder in connection with the negotiation of this Agreement and the other Notes Documents or delivered hereunder or thereunder (as modified or supplemented by other information so furnished) contains any material misstatement of material fact or omits to state any material fact necessary to make the statements therein, in the light of the circumstances under which they were made, not misleading; provided that, with respect to projected financial information, the Issuer represents only that such information was prepared in good faith based upon assumptions believed to be reasonable at the time (it being understood by the Administrative Agent and the Noteholders that such projected financial information is not to be viewed as facts, and that no assurances can be given that any particular projections will be realized and that actual results during the period or periods covered by any such projections may differ from the projected results and such differences may be material). In respect of the Certificates of Title, the information supplied by or on behalf of the Obligors to the lawyers who prepared any Certificate of Title for the purpose of that Certificate of Title was true, complete and accurate as at the date of the Certificate of Title or (if appropriate) as at the date (if any) at which it is stated to be given and did not omit any information which, if disclosed, would make that information untrue or misleading in any material respect. 65 7.10 Investment Company Act and Margin Stock Regulation. (a) Investment Company Act. Neither the Issuer nor any of its Subsidiaries is an “investment company” as defined in, or subject to regulation under, the Investment Company Act of 1940, as amended. (b) Margin Stock. Neither the Issuer nor any of its Subsidiaries is engaged principally, or as one of its important activities, in the business of extending credit for the purpose, whether immediate, incidental or ultimate, of buying or carrying Margin Stock, and no part of the proceeds of the Notes will be used to buy or carry any Margin Stock in violation of Regulation T, Regulation U or Regulation X. Solvency. The Issuer and its Subsidiaries, on a consolidated basis, are, and, immediately after issuing the 7.11 Notes and the use of proceeds thereof, will be Solvent. 7.12 Equity Holders, Subsidiaries and Other Investments. (a) Set forth on Schedule 7.12(a) is a complete and correct list of all direct and indirect Subsidiaries of the Issuer. Each such Subsidiary is duly organized or incorporated, as applicable and validly existing under the jurisdiction of its organization or incorporation, as applicable shown in Schedule 7.12(a), and the percentage ownership by the Issuer of each such Subsidiary thereof is as shown in Schedule 7.12(a). (b) Set forth on Schedule 7.12(b) is a complete and correct list of all other Equity Interests owned or held by the Issuer or any of its direct or indirect Subsidiaries in any Person that does not qualify as a direct or indirect Subsidiary of the Issuer. Schedule 7.12(b) also sets forth, in reasonable detail, the type of Equity Interest held by each Obligor in such other Person and the fully-diluted percentage ownership held beneficially by the Issuer or one or more of its Subsidiaries, as the case may be, such other Person. 7.13 Continuing Secured Indebtedness. Set forth on Schedule 7.13 is a complete and correct list of all Indebtedness of the Issuer and each of its Subsidiaries outstanding as of the date hereof that (i) will remain outstanding immediately after the issuing of the Notes and the application of proceeds therefrom on the Closing Date and (ii) is secured by a Lien on assets or property of the Issuer or any of its Subsidiaries. 7.14 Material Agreements. Except as set forth on Schedule 7.14, as of the Closing Date, all Material Agreements have been publically disclosed. Neither the Issuer nor any of its Subsidiaries is in default under any such Material Agreement, and the Issuer does not have knowledge of any material default by any counterparty to any such Material Agreement and there are no pending or, to the Issuer’s knowledge, threatened material adverse Claims against the Issuer or any of its Subsidiaries asserted by any other Person relating to any such Material Agreements, including any such Claims of breach or default thereunder. 7.15 Restrictive Agreements. Except as set forth on Schedule 7.15, neither the Issuer nor any of its Subsidiaries is subject to any Restrictive Agreement, except those permitted under Section 9.11. 66 7.16 Real Property. Except as set forth on Schedule 7.16, neither the Issuer nor any of its Subsidiaries owns or leases (as a tenant) any real property. 7.17 Pension Matters. Except as, in the aggregate, could not reasonably be expected to result in a Material Adverse Effect, (a) each Benefit Plan, and each trust thereunder, intended to qualify for tax-exempt status under Section 401 or 501 of the Code or other applicable Law so qualifies, (b) each Benefit Plan and Foreign Pension Plan is in compliance with all applicable provisions of ERISA, the Code or other applicable Law, (c) no ERISA Event has occurred or is reasonably expected to occur, (d) the Issuer and each of its ERISA Affiliates has met all applicable requirements under the ERISA Funding Rules with respect to each Title IV Plan, and no waiver of the minimum funding standards under the ERISA Funding Rules has been applied for or obtained, (e) as of the most recent valuation date for any Title IV Plan, the funding target attainment percentage (as defined in Section 430(d) (2) of the Code) is at least sixty percent (60%), and none of the Issuer, any of its Subsidiaries nor any of their ERISA Affiliates knows of any facts or circumstances that could reasonably be expected to cause the funding target attainment percentage to fall below sixty percent (60%) as of the most recent valuation date and (f) neither the Issuer nor any of its ERISA Affiliates has or would have any Withdrawal Liability as a result of a complete withdrawal from any Multiemployer Plan on the date this representation is made. 7.18 Priority of Obligations; Collateral; Security Interest. No monetary Obligation arising hereunder or under any Notes Document, or arising in connection herewith or therewith, is contractually subordinated to any other Indebtedness of the Obligors. Subject to the Legal Reservations and Perfection Requirements solely in respect of the English Guarantor and the Irish Subsidiary Guarantor, each Security Document is effective to create in favor of the Secured Parties a legal, valid and enforceable security interest in the Collateral subject to such Security Document, each such security interest is legal, valid and enforceable, and each such security interest is perfected to the extent required by the applicable Security Document on a first-priority basis (subject to Permitted Liens that may apply to specific items of Collateral permitted pursuant to Section 9.02) and secures the Obligations. 7.19 Governmental Approvals in Respect of Ordinary Course Activities, Etc. The Issuer and each of its Subsidiaries hold, and will continue to hold, either directly or through licensees or agents, all Governmental Approvals, including all Healthcare Permits, necessary or required for the Issuer and each of its Subsidiaries to engage in and otherwise conduct their respective operations and businesses in the ordinary course, including their commercialization and development of products. 7.20 Transactions with Affiliates. Except as set forth on Schedule 7.20, neither the Issuer nor any of its Subsidiaries is a party to any transaction with any Affiliate that would be prohibited pursuant to Section 9.10 hereof. 7.21 Sanctions. Neither the Issuer nor any of its Subsidiaries, any of their respective directors, officers, or employees nor, to the knowledge of the Issuer, agents or other Persons acting on behalf of any of the foregoing (i) is currently the target of any Sanctions, (ii) is operating, organized or resident in any Designated Jurisdiction, (iii) is engaged in any transactions with, or for the benefit of, any Person who is the target of Sanctions or who is operating, organized or resident in any Designated Jurisdiction in violation of Sanctions or (iv) is in violation of Sanctions. No Notes, 67 nor the proceeds from any Notes, will be used, directly or indirectly, to lend, contribute or provide to, or has been or will be otherwise made available to fund, any activity or business in any Designated Jurisdiction or any activity or business of any Person located, organized or residing in any Designated Jurisdiction, in violation of Sanctions or who is the subject of any Sanctions, or in any other manner that will result in any violation by any Person (including the Administrative Agent, the Noteholders and their Affiliates) of Sanctions. 7.22 Anti-Corruption. Neither the Issuer nor any of its Subsidiaries, any of their respective directors, officers or employees nor, to the knowledge of the Issuer, any agents or other Persons acting on behalf of any of the foregoing, directly or indirectly, has (i) violated or is in violation of any applicable anti-corruption Law or (ii) made, offered to make, promised to make or authorized the payment or giving of, directly or indirectly, any Prohibited Payment. 7.23 Deposit and Disbursement Accounts and Investment Accounts. Schedule 7.23 contains a list of all banks and other financial institutions at which the Obligors maintain deposit accounts, lockboxes, disbursement accounts, investment accounts or other similar accounts, and such Schedule correctly identifies the name and address of each bank or financial institution, the name in which the account is held, the type of account, and the complete account number therefor. 7.24 Centre of Main Interests. For the purposes of Regulation (EU) 2015/848 of 20 May 2015 on insolvency proceedings (recast) (the Regulation), the Issuer’s centre of main interest (as that term is used in Article 3(1) of the Regulation) is situated in its jurisdiction of organization and it has no "establishment" (as that term is used in Article 2(10) of the Regulations) in any other jurisdiction. SECTION 8 AFFIRMATIVE COVENANTS The Obligors jointly and severally covenant and agree with the Administrative Agent and the Noteholders that, until the Commitments have expired or been terminated and all Obligations (other than inchoate indemnification and expense reimbursement obligations for which no Claim has been made) have been paid in full in cash: Financial Statements and Other Information. The Issuer shall furnish to the Administrative Agent (with 8.01 sufficient copies for each Noteholder): (a) As soon as available and in any event within (i) forty five (45) days after the end of each of the first three fiscal quarters of each fiscal year and (ii) ninety (90) days after the end of the last fiscal quarter of each fiscal year, (i) a consolidated balance sheet of the Issuer and its Subsidiaries as of the end of such fiscal quarter, and (ii) the related consolidated statements of income, shareholders’ equity and cash flows of the Issuer and its Subsidiaries for such quarter and the portion of the fiscal year through the end of such fiscal quarter, in each case, prepared in accordance with GAAP consistently applied, all in reasonable detail and setting forth in comparative form the figures for the corresponding period in the preceding fiscal year, together with (iii) a certificate of a Responsible Officer of the Issuer stating that (x) such financial statements fairly present in all material respects the financial condition of the Issuer and its Subsidiaries as at such date and (y) the results of operations of the Issuer and its Subsidiaries for 68 the period ended on such date have been prepared in accordance with GAAP consistently applied, subject to changes resulting from normal, year-end audit adjustments and except for the absence of notes; provided that documents required to be furnished pursuant to this Section 8.01(a) shall be deemed furnished on the date that such documents are publicly available on “EDGAR” (with the related certificate separately delivered). (b) As soon as available and in any event within ninety (90) days after the end of each fiscal year, (i) the consolidated balance sheets of the Issuer and its Subsidiaries as of the end of such fiscal year, and (ii) the related consolidated statements of income, shareholders’ equity and cash flows of the Issuer and its Subsidiaries for such fiscal year, in each case prepared in accordance with GAAP consistently applied, all in reasonable detail and setting forth in comparative form the figures for the previous fiscal year, accompanied by a report and opinion thereon of independent certified public accountants of recognized national standing reasonably acceptable to the Administrative Agent, which report and opinion shall be prepared in accordance with Public Company Accounting Oversight Board standards and shall not be subject to (x) with respect to any such reports or opinions prepared for any fiscal year ending after December 31, 2022, any “ going concern” or similar qualification or exception (other than any such qualification or exception in respect of the Issuer’s failure to have access to sufficient cash to pay the Obligations in full on the Maturity Date) or (y) any qualification or exception as to the scope of such audit, and in the case of such consolidating financial statements, certified by a Responsible Officer of the Issuer; provided that documents required to be furnished pursuant to this Section 8.01(b) shall be deemed furnished on the date that such documents are publicly available on “EDGAR”. (c) Together with the financial statements required pursuant to Sections 8.01(a) and 8.01(b), (i) a management discussion and analysis (“MD&A”), prepared in writing and in reasonable detail in a manner consistent with the requirements of Item 303 of Regulation S–K of the Securities Act, discussing the Issuer’s financial condition and results of operations as set forth in such financial statements; provided that for so long as Issuer remains (A) a “smaller reporting company” as defined in the Securities Act and Exchange Act and/or (B) an emerging growth company (as defined in the Jumpstart Our Business Startups Act of 2012) through the end of an applicable reporting period, any reduced disclosure obligations under SEC rules relating to the MD&A applicable to smaller reporting companies and/or emerging growth companies shall apply and (ii) a compliance certificate of a Responsible Officer, substantially in the form of Exhibit E (a “Compliance Certificate”), as of the end of the applicable accounting period, including, with respect to the financial statement delivered pursuant to Section 8.01(b), details of any issues that are material that are raised by the Issuer’s auditors. In addition, promptly following the Administrative Agent’s reasonable request, reasonable proof of the Issuer’s compliance with Section 10.01. (d) [Reserved]. (e) Promptly after the same are released, copies of all press releases; provided that documents required to be furnished pursuant to this Section 8.01(e) shall be deemed furnished on the date that such documents are publicly available on “EDGAR” or on the Issuer’s website. (f) Promptly, and in any event within five (5) Business Days after receipt, by an Obligor thereof, copies of each material notice or other material correspondence received from any 69 securities regulator or exchange to the authority of which the Issuer or any Obligor may become subject from time to time concerning any investigation or possible investigation or other inquiry by such agency regarding financial or other operational results of the Issuer or any Obligor; provided that documents required to be furnished pursuant to this Section 8.01(f) shall be deemed furnished on the date that such documents are publicly available on “EDGAR”. (g) Promptly (and in any event within five (5) Business Days of delivery) after the same are available, copies of each annual report, proxy or financial statement and any other statements, reports, communications and notices (including board kits) made available to the Issuer’s Board or holders of the Equity Interests of the Issuer or any of its Subsidiaries (including copies of all annual, regular, periodic and special reports and registration statements which the Issuer or any its Subsidiaries may file or be required to file with any securities regulator or exchange to the authority of which the Issuer or such Subsidiary, as applicable, may become subject from time to time); provided that documents required to be furnished pursuant to this Section 8.01(g) shall be deemed furnished on the date that such documents are publicly available on “EDGAR”. Notwithstanding the foregoing, any materials delivered to a member of the Board of Issuer that is a representative of Administrative Agent or its Affiliates shall satisfy the requirements of this clause (g) so long as such member is permitted to provide such materials to the Administrative Agent. (h) Promptly following Administrative Agent’s reasonable request, the information regarding insurance maintained by the Issuer and its Subsidiaries as required under Section 8.05. (i) Within thirty (30) days following the end of each calendar month, evidence satisfactory to the Administrative Agent, based upon the Issuer’s bank account statements, that the Issuer has met its minimum liquidity requirement set forth in Section 10.01. (j) Such other information respecting the operations, properties, business, liabilities or condition (financial or otherwise) of the Obligors (including with respect to the Collateral) as the Administrative Agent may from time to time reasonably request. The Issuer hereby acknowledges that the Administrative Agent or the Noteholders may not wish to receive material non-public information with respect to the Issuer or its Affiliates, or the respective securities of any of the foregoing, and the Administrative Agent, the Noteholders or their respective personnel may be engaged in investment and other market-related activities with respect to such Persons’ securities. In order to avoid disclosing material non-public information, the parties hereto covenant and agree that Issuer will not become obligated to provide the Administrative Agent, any Noteholder or their respective representatives or agents with any information pursuant to this Section 8.01 other than information that is required to be publicly disclosed by the SEC and is publicly available on “EDGAR”, unless (x) the Administrative Agent or its Affiliates have a representative on the Board of the Issuer or (y) prior thereto, the Administrative Agent or a Noteholder, as the case may be, shall have notified the Issuer in writing that it consents to receive such information. 8.02 Notices of Material Events. On or within five (5) Business Days (or such longer or shorter period as may be expressly set forth below) after a Responsible Officer of the Issuer first learns of 70 or acquires knowledge with respect to any of the below events or circumstances, the Issuer shall furnish to the Administrative Agent written notice thereof (prepared in reasonable detail): (a) (b) The occurrence of any Default. The occurrence of any event with respect to any property or assets of the Issuer or any of its Subsidiaries resulting in a Loss aggregating $2,500,000 (or the Equivalent Amount in other currencies) or more. (c) Any written or filed Claim, action, suit, notice of violation, hearing, investigation or other proceedings pending, or to the best of the Issuer’s knowledge, threatened against or affecting the Issuer or any of its Subsidiaries or with respect to the ownership, use, maintenance and operation of their respective businesses, operations or properties, whether made by a Governmental Authority or other Person that, if adversely determined could reasonably be expected to result in a Loss of $2,500,000 or more. (d) (i) On or prior to the date of any filing by Issuer or any of its ERISA Affiliates of any notice of intent to terminate any Title IV Plan that could reasonably be expected to result in a Material Adverse Effect, a copy of such notice and (ii) promptly, and in any event within ten (10) days, after any Responsible Officer of the Issuer knows (A) that an ERISA Event that could reasonably be expected to result in a Material Adverse Effect has occurred or is reasonably expected to occur or (B) that a request for a minimum funding waiver under Section 412 of the Code has been filed with respect to any Title IV Plan or Multiemployer Plan and could reasonably be expected to result in a Material Adverse Effect, a notice (which may be made by telephone if promptly confirmed in writing) describing such waiver request and any action that any ERISA Affiliate proposes to take with respect to either of the foregoing, together with a copy of any notice filed with the PBGC or the IRS pertaining thereto. (e) Concurrently with the delivery of the Compliance Certificate pursuant to Section 8.01(c), the receipt by the Issuer or any of its Subsidiaries of any notice of a material breach, subject to any applicable cure period, under or in respect of any Material Agreement. (f) The reports and notices as required by the Security Documents. (g) Within thirty (30) days of the date thereof, or, if earlier, on the date of delivery of any financial statements pursuant to Section 8.01 with respect to the first fiscal period to which such change is applicable, notice of any material change in accounting policies or financial reporting practices by the Obligors; provided that disclosure in the notes to such financial statements, if any, shall be deemed to satisfy the requirements of this Section 8.02(g). (h) Notice of any labor controversy resulting in or threatening to result in any strike, permanent work stoppage, boycott, shutdown or other material labor disruption against or involving the Issuer or any of its Subsidiaries. (i) Notice of infringement or alleged infringement of any Material Intellectual Property of another Person by Issuer or any of its Subsidiaries that, if adversely determined could reasonably be expected to result in a Loss of $2,500,000 or more. 71 (j) Within seven (7) Business Days, any change to Obligors’ ownership of Deposit Accounts, Securities Accounts and Commodity Accounts, by delivering to the Administrative Agent, a notice setting forth a complete and correct list of all such accounts as of the date of such change. Each notice delivered under this Section 8.02 shall be accompanied by a statement of a Responsible Officer of the Issuer setting forth the details of the event or development requiring such notice and any action taken or proposed to be taken with respect thereto. Information required to be delivered pursuant to this Section 8.02 shall be deemed to have been delivered on the date that such information shall have been made publicly available on “EDGAR” so long as such information has been made publicly available within the five (5) Business Day period set forth above. Nothing in this Section 8.02 is intended to waive, consent to or otherwise permit any action or omission that is otherwise prohibited by this Agreement or any other Notes Document. The Issuer hereby acknowledges that the Administrative Agent or the Noteholders may not wish to receive material non-public information with respect to the Issuer or its Affiliates, or the respective securities of any of the foregoing, and the Administrative Agent, the Noteholders or their respective personnel may be engaged in investment and other market-related activities with respect to such Persons’ securities. In order to avoid disclosing material non-public information, the parties hereto covenant and agree that, as except for any notice required pursuant to clause (a) above, Issuer will not become obligated to provide the Administrative Agent, any Noteholder or their respective representatives or agents with any information pursuant to this Section 8.02 other than information that is required to be publicly disclosed by the SEC and is publicly available on “EDGAR”, unless (x) the Administrative Agent or its Affiliates have a representative on the Board of the Issuer or (y) prior thereto, the Administrative Agent or a Noteholder, as the case may be, shall have notified the Issuer in writing that it consents to receive such information. 8.03 Existence; Conduct of Business. The Issuer shall, and shall cause each of its Subsidiaries to, do or cause to be done all things necessary to preserve, renew and maintain in full force and effect its legal existence and all Governmental Approvals material to the conduct of its business; provided that the foregoing shall not prohibit any merger, amalgamation, consolidation, liquidation or dissolution permitted under Section 9.03. 8.04 Payment of Obligations. The Issuer shall, and shall cause each of its Subsidiaries to, pay and discharge its material obligations, including (i) all material Taxes, fees, assessments and governmental charges or levies imposed upon it or upon its properties or assets prior to the date on which penalties attach thereto, and all lawful Claims for labor, materials and supplies which, if unpaid, might become a Lien upon any properties or assets of the Issuer or any of its Subsidiaries, except to the extent such Taxes, fees, assessments or governmental charges or levies, or such claims are being contested in good faith by appropriate proceedings and are adequately reserved against in accordance with GAAP, and (ii) all other lawful Claims which, if unpaid, would by Law become a Lien upon any properties or assets of the Issuer or any of its Subsidiaries, other than any Permitted Lien. 8.05 Insurance. The Issuer shall, and shall cause each of its Subsidiaries to maintain, with financially sound and reputable insurance companies, insurance in such amounts and against such risks as are customarily maintained by companies engaged in the same or similar businesses 72 operating in the same or similar locations, and with coverage amounts of at least $2,000,000 in general liability insurance with a $5,000,000 umbrella. Upon the request of the Administrative Agent, the Issuer shall furnish to the Administrative Agent from time to time: (i) full information as to the insurance carried by the Issuer and each of its Subsidiaries and, if so requested, copies of all such insurance policies and (ii) a certificate from the Issuer’s insurance broker or other insurance specialist stating that all premiums then due on the policies relating to insurance in respect of the Collateral have been paid and that such policies are in full force and effect. The Issuer shall use commercially reasonable efforts to ensure, or cause others to ensure, that all insurance policies in respect of the Collateral shall provide that they shall not be terminated or cancelled without at least thirty (30) days’ (ten (10) days for nonpayment of premium) prior written notice to the Issuer and the Administrative Agent. Receipt of notice of cancellation or modification of any such insurance policies or reduction of coverage or amounts thereunder shall entitle any Secured Party to renew any such policies, cause the coverage and amounts thereof to be maintained at levels required pursuant to the first sentence of this Section 8.05 or otherwise to obtain similar insurance in place of such policies, in each case at the expense of the Issuer (payable on demand). 8.06 Books and Records; Inspection Rights. The Issuer shall, and shall cause each of its Subsidiaries to, keep proper books of record and account in which full, true and correct entries are made of all dealings and transactions in relation to its business and activities. The Issuer shall, and shall cause each of its Subsidiaries to, permit any representatives designated by the Administrative Agent or any Noteholder, upon reasonable prior written notice and during normal business hours, to visit and reasonably inspect its properties, to reasonably examine and make extracts from its books and records (excluding records subject to attorney-client privilege, subject to binding confidentiality agreements with third parties that preclude disclosure to any Secured Party (acting in such capacity) not entered into in contemplation of this Section 8.06 or subject to confidentiality restrictions pursuant to applicable Law (including HIPAA)), and to discuss its affairs, finances and condition (financial or otherwise) with its officers and, if necessary after such discussions with such Obligor’s officers, its independent accountants, all at such reasonable times (but not more often than once per year unless an Event of Default has occurred and is continuing) as the Administrative Agent or the Noteholders may reasonably request; provided that no notice shall be required if an Event of Default has occurred and is continuing. The Issuer shall pay all reasonable and documented costs and expenses of all such inspections. 8.07 Compliance with Laws and Material Agreements. The Issuer shall, and shall cause each of its Subsidiaries to, (i) comply in all material respects with all applicable Laws and Governmental Approvals (including Environmental Laws and all Healthcare Laws and Healthcare Permits), and (ii) use commercially reasonable efforts to remain in compliance with, and perform all obligations under or in connection with, all Healthcare Permits and Material Agreements in accordance with the terms and conditions set forth in Section 9.12(b). 8.08 Maintenance of Properties, Etc. The Issuer shall, and shall cause each of its Subsidiaries to, maintain and preserve all of its assets and properties, whether tangible or intangible, necessary or useful in the proper conduct of its business in good working order and condition in accordance with the general practice of other Persons of similar character and size or, in accordance with the terms of any lease of a Manufacturing Facility under which the Issuer or its Subsidiaries holds an interest, ordinary wear and tear and damage from casualty or condemnation excepted. 73 8.09 Governmental Approvals, Etc. The Issuer shall, and shall cause each of its Subsidiaries to, obtain and maintain all Governmental Approvals (including all Healthcare Permits) necessary in connection with (i) the execution, delivery and performance of the Notes Documents, (ii) the consummation of the Transactions and (iii) the operation and conduct of their respective businesses and the ownership of their respective properties, except, in the case of clause (iii) above, where the failure to do so could not reasonably be expected to have a Material Adverse Effect on the Issuer’s and its Subsidiaries’ business. 8.10 Action under Environmental Laws. The Issuer shall, and shall cause each of its Subsidiaries to, upon becoming aware of the release of any Hazardous Materials or the existence of any environmental liability under applicable Environmental Laws with respect to their respective businesses, operations or properties, take all commercially reasonable actions, at their cost and expense, as shall be necessary or advisable to investigate and clean up the condition of their respective businesses, operations or properties, including all required removal, containment and remedial actions, to restore their respective businesses, operations and properties to a condition in each case, in material compliance with applicable Environmental Laws. 8.11 Use of Proceeds. The proceeds of the Commitments or any amounts extended for the subscription for Tranche 2 Notes shall be used only as provided in Section 2.04. Without limiting the foregoing, no part of the proceeds of the Commitments or any amounts extended for the subscription for Tranche 2 Notes shall be used, whether directly or indirectly, for any purpose that entails a violation of any of the Regulations of the Board of Governors of the Federal Reserve System, including Regulation T, Regulation U and Regulation X. 8.12 Certain Obligations Respecting Subsidiaries; Further Assurances. (a) Subsidiary Guarantors. The Issuer shall take such action from time to time as shall be necessary to ensure that (x) each of its Subsidiaries that is a party to this Agreement as of the Closing Date will be and will remain an Obligor and Subsidiary Guarantor hereunder (except as otherwise permitted by Section 9.03), and (y) each direct or indirect Subsidiary of the Subsidiary Guarantors (other than any Immaterial Subsidiary), whether direct or indirect, now existing or hereafter created, will, within thirty (30) days of becoming a Subsidiary of a Subsidiary Guarantor, become a “Subsidiary Guarantor” pursuant to this Section 8.12. Without limiting the generality of the foregoing, in the event that any Subsidiary Guarantor shall form or acquire any new Subsidiary (other than any Immaterial Subsidiary), the Issuer shall, within thirty (30) days (or such longer period as the Administrative Agent, in its reasonable discretion, may consent to) of such formation or acquisition, cause such Subsidiary (other than any Immaterial Subsidiary) to become a “Subsidiary Guarantor” hereunder, a “Grantor” (or the equivalent thereof) under any applicable Security Document, and a “Subsidiary Party” under the Intercompany Subordination Agreement; (b) The Issuer shall, except with respect to any Immaterial Subsidiary, take such action or cause such new Subsidiary to take such action (including joining the applicable Security Document and delivering any certificated Equity Interests together with undated transfer powers executed in blank, applicable control agreements and other instruments) as shall be reasonably necessary or reasonably requested by the Administrative Agent to create and perfect, in favor of the Administrative Agent, for the benefit of the Secured Parties, valid and enforceable first priority 74 Liens (other than Permitted Liens) on all Deposit Accounts, Securities Accounts and Commodity Accounts of such new Subsidiary as collateral security for the Obligations hereunder; provided that any such security interest or Lien shall be subject to the applicable Security Documents; (i) to the extent that the parent of such new Subsidiary (other than any Immaterial Subsidiary) has not pledged Equity Interests in its Subsidiaries in accordance with the terms of the relevant Security Document and this Agreement, cause the parent of such Subsidiary to execute and deliver a pledge agreement in favor of the Administrative Agent, for the benefit of the Secured Parties, in respect of all outstanding issued Equity Interests of such new Subsidiary; and (ii) deliver such proof of corporate action, incumbency of officers, opinions of counsel and other documents as is consistent with those delivered by the Issuer pursuant to Section 6.01 or as the Administrative Agent shall have reasonably requested. (c) Further Assurances. (i) The Issuer shall, and shall cause each of its direct or indirect Subsidiaries (including any newly formed or newly acquired Subsidiaries (other than any Immaterial Subsidiary)) to take such action from time to time as shall reasonably be requested by the Administrative Agent to effectuate the purposes and objectives of this Agreement and the applicable Security Documents. (ii) Without limiting the generality of the foregoing, within thirty (30) days following written request from the Administrative Agent, the Issuer shall cause each Person that is required to be a Subsidiary Guarantor or an Obligor hereunder to take such action from time to time (including executing and delivering such Security Documents and delivering its certificated Equity Interests together with undated transfer powers executed in blank) as shall be reasonably requested by the Administrative Agent to create, in favor of the Secured Parties, perfected security interests and Liens on the Manufacturing Facilities and all Deposit Accounts, Securities Accounts and Commodity Accounts of such Person and all Equity Interests in each Subsidiary Guarantor as collateral security for the Obligations; provided that any such security interest or Lien shall be subject to Permitted Liens and the relevant requirements of the applicable Security Documents. 8.13 Termination of Non-Permitted Liens. In the event that the Issuer or any of its Subsidiaries shall obtain knowledge of, or be notified by the Administrative Agent or any Noteholder of the existence of, any outstanding Lien against any assets or property of the Issuer or any of its Subsidiaries, which Lien is not a Permitted Lien, the Issuer shall use commercially reasonable efforts to promptly terminate or cause the termination of such Lien. 8.14 Maintenance of the Governmental Approvals and Intellectual Property. The Issuer shall cause each of its Subsidiaries (to the extent applicable) to, (i) maintain in full force and effect all material Governmental Approvals, Healthcare Permits, Material Intellectual Property and other rights, interest or assets (whether tangible or intangible) reasonably necessary for its ordinary course of business and commercial efforts as currently conducted and as anticipated to be conducted, in each case, except where the failure to do so could not reasonably be expected to result in a Material Adverse Effect, (ii) promptly upon obtaining knowledge thereof, notify the 75 Administrative Agent of any infringement or other violation by any Person of the Issuer’s or Subsidiary Guarantors’ Material Intellectual Property, and take commercially reasonable efforts to pursue any such infringement or other violation, except in any specific circumstance where the Issuer reasonably determines in good faith that it is not commercially reasonable to do so, (iii) use commercially reasonable efforts to pursue and maintain in full force and effect all new Material Intellectual Property created, developed, or acquired by the Issuer or any of its Subsidiaries, as the case may be, that are necessary for ordinary course commercial or business activities or operations of such Person, and (iv) promptly after obtaining knowledge thereof, notify the Administrative Agent of any written Claim by any Person that the conduct of the business of the Issuer or any of its Subsidiaries has infringed upon any Intellectual Property of such Person that could reasonably be expected to result in a Material Adverse Effect. 8.15 ERISA and Foreign Pension Plan Compliance. Except as could not reasonably be expected to result in a Material Adverse Effect, the Issuer shall comply, and shall cause each of its Subsidiaries to comply, with the provisions of ERISA or applicable Law with respect to any Plans or Foreign Pension Plans to which the Issuer or any such Subsidiary is a party as an employer. 8.16 Cash Management. The Issuer shall, and shall cause the Subsidiary Guarantors to: (a) maintain at all times the Minimum Liquidity Account and all deposit accounts, disbursement accounts, investment accounts (and other similar cash or bank accounts) and lockboxes located in the U.S. or non- U.S. and held by any Subsidiary Guarantor with a bank or financial institution, except as permitted pursuant to clause (b) below, that has executed and delivered to the Administrative Agent an account control agreement (or, in respect of an account in the United Kingdom and Ireland, evidence that each relevant Obligor delivered to the relevant account bank a notice of assignment in respect of the account and has used reasonable endeavors to ensure that each Account Bank acknowledges the notice), in form and substance reasonably acceptable to the Administrative Agent (each of the Minimum Liquidity Account and such deposit account, disbursement account, investment account (or other similar cash or bank account) and lockbox, a “Controlled Account”); each such Controlled Account shall secure payment of the Obligations, and each Obligor shall have granted a Lien to the Administrative Agent, for the benefit of the Secured Parties, over such Controlled Accounts. For the avoidance of doubt, no account control agreements shall be required in respect of any bank account held in Ireland or England; and (b) deposit promptly, and in any event no later than five (5) Business Days after the date of receipt thereof (if and to the extent received), all cash, checks, drafts or other similar items of payment relating to or constituting payments made in respect of any and all accounts receivable, Contracts or any other rights and interests into the applicable Controlled Accounts. Notwithstanding the foregoing or in any Notes Document to the contrary, neither the Issuer nor any of its Subsidiaries shall be required to obtain an account control agreement (or, in respect of an account in the United Kingdom and Ireland, evidence that each relevant Obligor delivered to the relevant account bank a notice of assignment in respect of the account) for any deposit accounts, disbursement accounts, investment accounts (and other similar cash or bank accounts) and lockboxes that (i) in respect of the Irish Subsidiary Guarantor, are established and maintained in connection with any IDA Grant, in an amount not to exceed €2,200,000 in aggregate at any one 76 time or (ii) in respect of the English Guarantor, are for the sole purpose of holding cash or cash equivalents that serves as collateral security under any letter of credit or other obligation not prohibited by this Agreement. 8.17 Title, Headleases, Power to Remedy. The Issuer shall, and shall cause each of its Subsidiaries to, (i) exercise its rights and comply in all respects with any covenant, stipulation or obligation (restrictive or otherwise) at any time affecting a Manufacturing Facility, (ii) exercise its rights and comply with its obligations under each Headlease in a proper and timely manner, (iii) use its reasonable endeavours to ensure that each landlord complies with its obligations under each Headlease in a proper and timely manner, (iv) if so required by the Administrative Agent, apply for relief against forfeiture of any Headlease in a proper and timely manner, and (v) in the event that an Obligor fails to perform any obligations under the Notes Documents affecting its Manufacturing Facility, that Obligor must allow the Administrative Agent or its agents and contractors (A) to enter any part of its Manufacturing Facility, (B) to comply with or object to any notice served on the Obligor in respect of its Manufacturing Facility and (C) to take any action that the Administrative Agent may reasonably consider necessary or desirable to prevent or remedy any breach of any such term or to comply with or object to any such notice. 8.18 Register of Mortgages and Charges. The Issuer shall, within three (3) Business Days of the Closing Date, update its register of mortgages and charges to reflect the security granted by the Issuer pursuant to the applicable Security Documents, in form and substance reasonably satisfactory to the Administrative Agent. 8.19 Post-Closing Covenants. (a) Within twenty (20) Business Days of the Closing Date (or such later date as an Independent Appraiser may reasonably request or as the Administrative Agent may agree in its reasonable discretion), the Administrative Agent shall have received a valuation and appraisal report, prepared by an Independent Appraiser instructed and appointed by the Administrative Agent (the “Valuation Report”), which report shall be in scope and substance reasonably satisfactory to the Administrative Agent and shall confirm the fair market value of: (i) (ii) the London Manufacturing Facility is not less than [***] (or Equivalent Amount); and the Shannon Manufacturing Facility is not less than [***] (or Equivalent Amount). (b) If the fair market value of the London Manufacturing Facility confirmed by the Valuation Report exceeds [***] (or Equivalent Amount) then within 10 Business Days of the receipt of the Valuation Report by the Issuer, the Issuer shall have delivered to the Administrative Agent an endorsement of: (i) the Dual Asset no-search insurance policy dated 29 July 2022 (with reference 00- 87868222N0); and (ii) the Dual Asset title insurance policy dated 14 December 2018 and varied by an endorsement dated 29 July 2022 (with reference 00-39858418K0), 77 increasing the indemnity limit of each policy from [***] to the sum equal to the fair market value of the London Manufacturing Facility confirmed by the Valuation Report (or Equivalent Amount) and the Issuer shall pay the premium for each endorsement when it falls due. (c) Within six (6) weeks of the issue of a certificate of practical completion in relation to the Works, the Issuer shall furnish to the Noteholders and their solicitors copies of the following: (i) an architect’s opinion on compliance with planning permission and an architect's opinion on compliance with the building regulations in RIAI format which shall include all confirmations and other documents referred to or relied upon therein; (ii) a copy of any approvals, consents, permissions and licences of any competent authority that may from time to time be required to enable the Issuer to commence and carry out the Works including without limitation any planning permission, commencement notice, fire safety certificate or disability access certificate required by the Building Control Acts 1990 to 2014 required or obtained in relation to the Works (the “Requisite Consents”); (iii) a copy of the receipts for any financial contributions payable by the Issuer pursuant to the Requisite Consents; and (iv) (Amendment) Regulations 2014. certificate of compliance on completion within the meaning of the Building Control (d) Within thirty (30) Business Days of the Closing Date, (or such later date as the Administrative Agent may agree in its reasonable discretion), the Issuer shall deliver to the Administrative Agent short form security agreements, in form and substance reasonably satisfactory to the Administrative Agent, evidencing a grant of security over Issuer’s rights to insurance proceeds. 8.20 Undertaking to list. The Issuer shall use reasonable endeavours to list all the Notes hereunder on a Recognised Stock Exchange promptly following issuance and in any event prior to February 2, 2023, and thereafter to maintain a listing of all the Notes hereunder on a Recognised Stock Exchange for so long as such Notes are outstanding; provided that if the Issuer is unable to obtain admission to such listing or if at any time the Issuer determines that it will not maintain such listing, it will use its reasonable endeavours to obtain (prior to the delisting of the Notes from such Recognised Stock Exchange) and thereafter maintain a listing of such Notes on another Recognised Stock Exchange. SECTION 9 NEGATIVE COVENANTS The Obligors jointly and severally covenant and agree with the Administrative Agent and the Noteholders that, until the Commitments have expired or been terminated and all Obligations (other than inchoate indemnification and expense reimbursement obligations for which no Claim has been made) have been paid in full in cash: Indebtedness. The Issuer shall not, and shall not permit any of its Subsidiaries to, create, incur, assume or 9.01 permit to exist any Indebtedness, whether directly or indirectly, except: 78 (a) the Obligations; (b) Indebtedness existing on the Closing Date and set forth on Schedule 7.13 and Permitted Refinancings thereof; provided that, in each case, such Indebtedness is subordinated to the Obligations on terms reasonably satisfactory to the Administrative Agent; (c) accounts payable to trade creditors for goods and services and current operating liabilities (not the result of the borrowing of money) incurred in the ordinary course of the Issuer’s or such Subsidiary’s business in accordance with customary terms and paid within one hundred twenty (120) days of becoming due, unless contested in good faith by appropriate proceedings and reserved for in accordance with GAAP for any such amounts over $5,000,000; (d) Indebtedness consisting of guarantees resulting from the endorsement of negotiable instruments for collection in the ordinary course of business; (e) Indebtedness of any Obligor owing to any of its Subsidiaries or to another Obligor; provided that, in each case, such Indebtedness is subordinated to the Obligations subject to the Intercompany Subordination Agreement; (f) Guarantees by any Obligor of outstanding Permitted Indebtedness of any other Obligor; provided that to the extent that any such Permitted Indebtedness is subordinated to the Obligations, such Guarantees shall be similarly subordinated; (g) ordinary course of business equipment financing, leasing and Capital Lease Obligations; provided that (i) if secured, the collateral therefor consists solely of the assets being financed, the products and proceeds thereof and books and records related thereto, and (ii) the aggregate outstanding principal amount of such Indebtedness does not exceed $7,000,000 (or the Equivalent Amount in other currencies) in the aggregate at any time; (h) Indebtedness under Hedging Agreements permitted by Section 9.05(e); (i) with respect to any Permitted Acquisition, Indebtedness assumed in connection with such Permitted Acquisition; provided that, (i) no such Indebtedness shall have been created or incurred in connection with, or in contemplation of, such Acquisition or this Section 9.01(i), and (ii) the aggregate amount of Indebtedness permitted pursuant to this Section 9.01(i) shall not exceed $5,000,000 (or the Equivalent Amount in other currencies) at any time outstanding, inclusive of all related Contingent Acquisition Obligations; (j) Indebtedness consisting of the financing of insurance premiums in respect of insurance policies insuring assets or businesses of an Obligor written or arranged in such Obligor’s ordinary course of business; (k) Indebtedness incurred in connection with cash management services, including treasury, depository, overdraft, credit or debit card, purchasing cards, electronic funds transfer, automatic clearing house arrangements, cash pooling arrangements, netting services, over draft protections, merchant services and other cash management and similar arrangements of an Obligor or any of its Subsidiaries, in each case incurred in the ordinary course of business; 79 (l) Indebtedness incurred under performance, surety, bid, statutory and appeal bonds, completion guarantees and other similar obligations, in each case in the ordinary course of business; (m) Indebtedness in respect of worker’s compensation claims, payment obligations in connection with health, disability or other types of social security benefits, unemployment or other insurance obligations and reclamation and statutory obligations, in each case incurred in the ordinary course of business; (n) Indebtedness in respect of letters of credit, bank guarantees or similar instruments incurred in the ordinary course of business; provided that the aggregate face amount of all such letters of credit, bank guarantees or other instruments (including letters of credit outstanding on the Closing Date) shall not exceed $5,000,000 at any time outstanding; (o) Indebtedness consisting of Investments permitted pursuant to Section 9.05; (p) Permitted Convertible Indebtedness; provided that the aggregate amount of all such Indebtedness permitted pursuant to this Section 9.01(p) shall not exceed $150,000,000 (or the Equivalent Amount in other currencies) at any time outstanding; (q) (r) advances or deposits from customers or vendors received in the ordinary course of business; Indebtedness incurred in connection with IDA Grants not to exceed €2,200,000 in the aggregate at any time outstanding; and (s) other unsecured Indebtedness in an aggregate amount not to exceed $5,000,000 in the aggregate at any time outstanding. 9.02 Liens. The Issuer shall not, and shall not permit any of its Subsidiaries to, create, incur, assume or permit to exist any Lien on any property now owned by it or such Subsidiary, except: (a) Liens securing the Obligations; (b) any Lien on any property or asset of the Issuer or any of its Subsidiaries existing on the Closing Date and set forth on Schedule 9.02; provided that (i) no such Lien shall extend to any other property or asset of the Issuer or any of its Subsidiaries and (ii) any such Lien shall secure only those obligations which it secures on the Closing Date and extensions, renewals and replacements thereof that do not increase the outstanding principal amount thereof; (c) Liens securing Indebtedness permitted under Section 9.01(g); provided that such Liens are restricted solely to the collateral permitted to be secured by Section 9.01(g); (d) Liens imposed by any applicable Law arising in the ordinary course of business, including (but not limited to) carriers’, warehousemen’s and mechanics’ liens, materialmen and other similar Liens arising in the ordinary course of business and which (x) do not in the aggregate materially detract from the value of the property subject thereto or materially impair the use thereof in the operations of the business of such Person or (y) are being contested in good faith by 80 appropriate proceedings, which proceedings have the effect of preventing the forfeiture or sale of the property subject to such Liens and for which adequate reserves have been made if required in accordance with GAAP; (e) pledges or deposits made in the ordinary course of business in connection with (i) real property leases entered into in the ordinary course of business, (ii) obligations in respect of workers’ compensation, unemployment insurance or other similar social security legislation, to the extent permitted pursuant to Section 9.01(m), or (iii) obligations in respect of surety or appeal bonds, bid or performance bonds, or other obligations of a like nature, to the extent permitted pursuant to Section 9.01(l); (f) Liens securing Taxes, assessments and other governmental charges, the payment of which is not yet due or is being contested in good faith by appropriate proceedings promptly initiated and diligently conducted and for which such reserve or other appropriate provisions, if any, as shall be required by GAAP shall have been made; (g) servitudes, easements, rights of way, restrictions and other similar encumbrances on real property imposed by any applicable Law or by any lease pursuant to which an Obligor holds its interest in a Manufacturing Facility and Liens consisting of zoning or building restrictions, easements, licenses, restrictions on the use of property or minor imperfections in title thereto which, in the aggregate, are not material, and which do not in any case materially detract from the value of the property subject thereto or interfere in any material respects with the ordinary conduct of the business of any of the Obligors or any of their Subsidiaries; (h) with respect to any real property, (i) such defects or encroachments as might be revealed by an up- to-date survey of such real property; (ii) the reservations, limitations, provisos and conditions expressed in the original grant, deed or patent of such property by the original owner of such real property pursuant to applicable Law or expressed in any lease pursuant to which an Obligor holds its interest in a Manufacturing Facility; (iii) rights of expropriation, access or user or any similar right conferred or reserved by or in any applicable Law, which, in the aggregate for clauses (i), (ii) and (iii), are not material, and which do not in any case materially detract from the value of the property subject thereto or interfere in any material respects with the ordinary conduct of the business of any of the Obligors or its Subsidiaries and (iv) leases or subleases of real property in the ordinary course of business; (i) bankers’ liens, rights of setoff and similar Liens incurred on deposits made to a bank on deposit accounts to the extent permitted to be made hereunder in the ordinary course of business; (j) any judgment Lien not constituting an Event of Default; (k) interests of lessors and sublessors under operating leases, interests of licensors or sublicensors under license agreements, and with respect to any realty occupied by any Obligor or any of its Subsidiaries, all easements, rights of way, reservations, licenses, covenants encroachments, variations and similar restrictions, charges and encumbrances on title that, in any such case or event, do not secure monetary obligations (other than any Permitted Lien set out in Schedule 9.02) and do not materially impair the use of such property for its intended purposes; 81 (l) Liens on cash held on deposit to secure letters of credit, bank guarantees or similar instruments permitted under Section 9.01(n) in an amount not to exceed the face amount of such letters of credit, bank guarantees or similar instruments, so long as such cash is held in segregated accounts maintained with the issuers of such letters of credit, bank guarantees or similar instruments; (m) Liens securing Indebtedness permitted under Section 9.01(i); provided that (i) such Lien is not created in contemplation of or in connection with such Permitted Acquisition or this Agreement, (ii) such Lien shall not apply to any other property or assets of the Issuer or any of its Subsidiaries other than the property or assets being acquired pursuant to such Permitted Acquisition, (iii) such Lien shall secure only those obligations that it secured immediately prior to the consummation of such Permitted Acquisition and extensions, renewals and replacements thereof that do not increase the outstanding principal amount thereof and (iv) such Lien does not secure any Contingent Acquisition Obligation; (n) (i) Liens arising from rights of licensees or licensors, as the case may be, arising under licenses permitted pursuant to Section 9.19, and (ii) any ordinary course interest or title of a licensor, sublicensor, lessor or sublessor with respect to any assets under any inbound license or lease agreement permitted pursuant to Section 9.19; (o) Liens securing Indebtedness permitted by Section 9.01(j); provided that such Lien shall be solely limited to the applicable insurance policies, supporting documentation relating thereto and the Obligor’s right to receive proceeds under such insurance policy with respect to which such Indebtedness has been incurred; (p) Liens in favor of customs and revenue authorities arising as a matter of law to secure payment of customs duties in connection with the importation of goods; (q) (r) (s) Liens referred to in any Certificate of Title; Liens securing Indebtedness permitted under Section 9.01(r); or Liens on the Specified Assets so long as the Specified Assets Conditions are satisfied both immediately before and after giving effect to the creation of any such Lien. 9.03 Fundamental Changes, Acquisitions, Etc. The Issuer shall not, and shall not permit any of its Subsidiaries to, (i) enter into any transaction of merger, amalgamation or consolidation, (ii) liquidate, wind up or dissolve itself (or suffer any liquidation or dissolution), (iii) sell or issue any Disqualified Equity Interests, or (iv) other than Permitted Acquisitions, make any Acquisition or otherwise acquire any business or substantially all the property from, or Equity Interests of, or be a party to any Acquisition of, any Person, except, so long as no Event of Default has occurred and is continuing or could reasonably be expected to occur as a result therefrom, for the following: (a) (b) Investments permitted under Section 9.05; any Permitted Acquisitions; 82 (c) the merger, amalgamation or consolidation of (i) any Subsidiary with or into any Obligor; provided that with respect to any such transaction involving the Issuer or any other Obligor, the Issuer or such Obligor, as the case may be, must be the surviving or successor entity of such transaction and (ii) any Immaterial Subsidiary with or into any other Immaterial Subsidiary; (d) the sale, lease, transfer or other disposition by any Subsidiary of any or all of its property (upon voluntary liquidation or otherwise) to any other Obligor; (e) (i) the sale, lease, transfer or other disposition by any Immaterial Subsidiary of any or all of its property (upon voluntary liquidation or otherwise) to any other Immaterial Subsidiary or to any Obligor, or (ii) the sale, transfer or other disposition of the Equity Interests of any Immaterial Subsidiary to any other Immaterial Subsidiary or to any Obligor; and (f) the issuance, sale, transfer or other disposition of the Equity Interests of any Subsidiary Guarantor to any other Obligor. 9.04 Lines of Business. The Issuer shall not, and shall not permit any of its Subsidiaries to, engage in any business other than the business engaged in on the Closing Date by such Persons or a business reasonably related or ancillary thereto or a reasonable extension thereof. Investments. The Issuer shall not, and shall not permit any of its Subsidiaries to, make, directly or 9.05 indirectly, or permit to remain outstanding any Investments except: (a) Investments outstanding on the Closing Date and identified on Schedule 9.05 and any modification, replacement, renewal or extension thereof to the extent not involving new or additional Investments; (b) extensions of credit in the nature of accounts receivable or notes receivable arising from (i) the sales of goods or services in the ordinary course of business and prepaid royalties, (ii) the satisfaction or partial satisfaction thereof to the extent reasonably necessary in order to prevent or limit loss and any prepayments and other credits to suppliers made in good faith and in the ordinary course of business or (iii) the satisfaction, partial satisfaction or enforcement of Indebtedness or Claims due or owing to an Obligor or its Subsidiaries (in bankruptcy of customers or suppliers or otherwise outside the ordinary course of business) or as security for any such Indebtedness or Claims in good faith and in the ordinary course of business; (c) Permitted Cash Equivalent Investments; (d) Investments by Issuer or any other Subsidiary of the Issuer in (i) the Issuer, (ii) any Subsidiary Guarantor, or (iii) any other Subsidiary of the Issuer for (A) operating expenses incurred in the ordinary course of business and consistent with past practices or (B) other Investments to any other Subsidiary of the Issuer; provided that the fair value of all such Investments made pursuant to this clause (iii)(B) shall not exceed $2,000,000 in the aggregate per fiscal year; (e) Hedging Agreements entered into in the Issuer’s or any of its Subsidiaries’ ordinary course of business for the purpose of hedging currency risks or interest rate risks (but not for 83 speculative purposes) and in an aggregate notional amount for all such Hedging Agreements not in excess of $5,000,000 (or the Equivalent Amount in other currencies); (f) Investments consisting of prepaid expenses, negotiable instruments held for collection or deposit, security deposits with utilities and landlords to secure office space and other like Persons and deposits in connection with workers’ compensation and similar deposits, in each case, made in the ordinary course of business; (g) employee loans, travel advances and guarantees in accordance with the Issuer’s usual and customary practices with respect thereto (if permitted by applicable Law) which in the aggregate shall not exceed $1,000,000 outstanding at any time (or the Equivalent Amount in other currencies); (h) Investments received in connection with any Insolvency Proceedings in respect of any customers, suppliers or clients and in settlement of delinquent obligations of, and other disputes with, customers, suppliers or clients; (i) (j) Investments permitted under Section 9.03; advances and extensions of credit (including to trade creditors) in the nature of trade payables made in connection with the purchases of goods or services in the ordinary course of business; (k) Investments made or acquired as a result of consideration received in connection with any Asset Sale permitted under Section 9.09 or Permitted Acquisition; provided that all such Investments made pursuant to this clause (k) shall not exceed €2,200,000 in the aggregate since the Closing Date; (l) Investments in the form of non-cash loans and advances in an aggregate amount not to exceed $2,500,000 outstanding at any one time to employees, officers, and directors of any Obligor or any of its Subsidiaries for the purpose of purchasing Qualified Equity Interests in the Issuer so long as the proceeds of such loans are used in their entirety to purchase such Qualified Equity Interests in the Issuer; (m) the entry into and payment of any premium in connection with any Permitted Bond Hedge Transaction; (n) Investments involving the Specified Assets so long as the Specified Assets Conditions are met and satisfied; (o) Investments in connection with IDA Grants in an aggregate amount not to exceed €2,200,000 at any time outstanding; (p) Investments by the Obligors in Subsidiaries pursuant to Tax sharing arrangements, transfer pricing arrangements or cost plus arrangements, in each case, solely as between or among the Obligors and one or more of their Subsidiaries; and 84 (q) other Investments in an aggregate amount not to exceed $2,500,000 in the aggregate since the Closing Date. 9.06 Restricted Payments. The Issuer shall not, and shall not permit any of its Subsidiaries to, declare or make, or agree to pay or make, directly or indirectly, any Restricted Payment; provided that the following Restricted Payments shall be permitted so long as no Event of Default has occurred and is continuing or could reasonably be expected to occur or result from such Restricted Payment: (a) dividends with respect to the Issuer’s Equity Interests payable solely in shares of its Qualified Equity Interests (or the equivalent thereof); (b) the Issuer’s purchase, redemption, retirement or other acquisition of its Equity Interests that (i) with respect to any such Person, the aggregate purchase, redemption, retirement or other acquisition cost or price does not exceed $1,000,000 in the aggregate since the Closing Date and (ii) with respect to all such purchases, redemptions, retirements or other acquisitions made pursuant to this Section 9.06(b) since the Closing Date, the aggregate cost or price does not exceed $4,000,000; (c) dividends paid by any Subsidiary Guarantor to any other Obligor; (d) upon the death, incapacity or termination of any natural person that is a holder of Qualified Equity Interests of the Issuer or the exercise of a right of first refusal or similar right in respect of any such holder, the Issuer may repurchase the stock of such Qualified Equity Interests of such holder or such holder’s family, trusts, estates and heirs pursuant to stock repurchase agreements in an amount not to exceed $1,000,000 per fiscal year; (e) (f) cash in lieu of the issuance of fractional shares not to exceed $1,000,000 per fiscal year; dividends paid by any Immaterial Subsidiary to any other Immaterial Subsidiary or to any Obligor; (g) repurchases of Qualified Equity Interests deemed to occur upon the exercise of stock options or warrants if such repurchased Qualified Equity Interests represents a portion of the exercise price of such options or warrants pursuant to a “cashless exercise” or similar feature; (h) repurchases of Qualified Equity Interests deemed to occur upon withholding of a portion of the Qualified Equity Interests granted or awarded to a current or former director, officer, employee or consultant to pay for the taxes payable by such Person upon such grant or award (or upon vesting thereof); provided that, in each case, no such repurchases shall exceed $1,000,000 per year (calculated since the Closing Date), in the aggregate for all employees; and (i) (i) the payment of the purchase price of any Permitted Bond Hedge Transaction or (ii) the settlement, unwinding or termination of all or any portion of any Permitted Warrant Transaction by (I) set-off against the concurrent settlement, unwind or other termination of all or any portion of any related Permitted Bond Hedge Transaction or (II) delivery of ordinary shares. 85 Notwithstanding anything to the contrary in the foregoing, the issuance of, performance of obligations under (including any payments of interest), and conversion, exercise, repurchase, redemption (including, for the avoidance of doubt, a required repurchase in connection with the redemption of Permitted Convertible Indebtedness upon satisfaction of a condition related to the stock price of the ordinary shares), settlement or early termination or cancellation of (whether in whole or in part and including by netting or set-off) (in each case, whether in cash, ordinary shares, following a merger event or other change of the ordinary shares, other securities or property), or the satisfaction of any condition that would permit or require any of the foregoing, any Permitted Convertible Indebtedness shall not constitute a Restricted Payment by the Issuer for the purposes of this Section 9.06; provided that, to the extent both (a) the aggregate amount of cash payable upon conversion or payment of any Permitted Convertible Indebtedness (excluding any required payment of interest with respect to such Permitted Convertible Indebtedness and excluding any payment of cash in lieu of a fractional share due upon conversion thereof) exceeds the aggregate principal amount thereof and (b) such conversion or payment does not trigger or correspond to an exercise or early unwind or settlement of a corresponding portion of the Permitted Bond Hedge Transactions relating to such Permitted Convertible Indebtedness (including, for the avoidance of doubt, the case where there is no Bond Hedge Transaction relating to such Permitted Convertible Indebtedness), the payment of such excess cash shall not be permitted by this paragraph. Notwithstanding the foregoing, the Issuer may repurchase, exchange or induce the conversion of Permitted Convertible Indebtedness by delivery of shares of ordinary shares and/or a different series of Permitted Convertible Indebtedness and/or by payment of cash (in an amount that does not exceed the proceeds received by Issuer from the substantially concurrent issuance of ordinary shares and/or Permitted Convertible Indebtedness plus the net cash proceeds, if any, received by Issuer pursuant to the related exercise or early unwind or termination of the related Permitted Bond Hedge Transactions and Permitted Warrant Transactions, if any, pursuant to the immediately following proviso); provided that, substantially concurrently with, or a commercially reasonable period of time before or after, the related settlement date for the Permitted Convertible Indebtedness that is so repurchased, exchanged or converted, Issuer shall exercise or unwind or terminate early (whether in cash, shares or any combination thereof) the portion of the Permitted Bond Hedge Transactions and Permitted Warrant Transactions, if any, corresponding to such Permitted Convertible Indebtedness that are so repurchased, exchanged or converted. Payments of Indebtedness. The Issuer shall not, and shall not permit any of its Subsidiaries to, make any 9.07 payments in respect of any Indebtedness other than (i) payments of the Obligations and (ii) scheduled or other mandatory payments of other Permitted Indebtedness (other than any Permitted Convertible Indebtedness) that are not otherwise prohibited or limited pursuant to any subordination or similar contract that is binding upon the Issuer, any such Subsidiary or any holder of such Permitted Indebtedness. Notwithstanding anything to the contrary in the foregoing, the issuance of, performance of obligations under (including any payments of interest), and conversion, exercise, repurchase, redemption (including, for the avoidance of doubt, a required repurchase in connection with the redemption of Permitted Convertible Indebtedness upon satisfaction of a condition related to the stock price of the ordinary shares), settlement or early termination or cancellation of (whether in whole or in part and including by netting or set-off) (in each case, whether in cash, ordinary shares, following a merger event or other change of the ordinary shares, other securities or property), or 86 the satisfaction of any condition that would permit or require any of the foregoing, any Permitted Convertible Indebtedness shall not violate this Section 9.07; provided that, to the extent both (a) the aggregate amount of cash payable upon conversion or payment of any Permitted Convertible Indebtedness (excluding any required payment of interest with respect to such Permitted Convertible Indebtedness and excluding any payment of cash in lieu of a fractional share due upon conversion thereof) exceeds the aggregate principal amount thereof and (b) such conversion or payment does not trigger or correspond to an exercise or early unwind or settlement of a corresponding portion of the Permitted Bond Hedge Transactions relating to such Permitted Convertible Indebtedness (including, for the avoidance of doubt, the case where there is no Bond Hedge Transaction relating to such Permitted Convertible Indebtedness), the payment of such excess cash shall not be permitted by the preceding sentence. Notwithstanding the foregoing, Issuer may repurchase, exchange or induce the conversion of Permitted Convertible Indebtedness by delivery of shares of ordinary shares and/or a different series of Permitted Convertible Indebtedness and/or by payment of cash (in an amount that does not exceed the proceeds received by Issuer from the substantially concurrent issuance of ordinary shares and/or Permitted Convertible Indebtedness plus the net cash proceeds, if any, received by Issuer pursuant to the related exercise or early unwind or termination of the related Permitted Bond Hedge Transactions and Permitted Warrant Transactions, if any, pursuant to the immediately following proviso); provided that, substantially concurrently with, or a commercially reasonable period of time before or after, the related settlement date for the Permitted Convertible Indebtedness that is so repurchased, exchanged or converted, Issuer shall exercise or unwind or terminate early (whether in cash, shares or any combination thereof) the portion of the Permitted Bond Hedge Transactions and Permitted Warrant Transactions, if any, corresponding to such Permitted Convertible Indebtedness that are so repurchased, exchanged or converted. 9.08 Change in Fiscal Year. The Issuer shall not, and shall not permit any of its Subsidiaries to, change the last day of its fiscal year from that in effect on the Closing Date, except to change the fiscal year of a Subsidiary acquired in connection with a Permitted Acquisition to conform its fiscal year to that of the Issuer. 9.09 Sales of Assets, Etc. Except as set forth below, the Issuer shall not, and shall not permit any of its Subsidiaries to sell, lease, transfer, or otherwise dispose of any of its assets or property (including accounts receivable, Material Intellectual Property or Equity Interests of Subsidiaries), grant or enter into any Exclusive License (other than any Exclusive License that is not prohibited by this Agreement), forgive, release or compromise any amount owed to the Issuer or such Subsidiary, in each case, in one transaction or series of transactions (any thereof, an “Asset Sale”); provided that Asset Sales of the type described in clauses (c), (d), (e), (f), (i), (l) and (m) shall only be permitted so long as no Event of Default has occurred or could reasonably be expected to result from such Asset Sale: (a) (b) sales of inventory in the ordinary course of its business on ordinary business terms; the forgiveness, release or compromise of any amount owed to any Obligor or Subsidiary in the ordinary course of business; (c) transfers of assets or property by any Subsidiary to an Obligor; 87 (d) transfers of assets or property by an Immaterial Subsidiary to any other Immaterial Subsidiary; (e) Business; dispositions of any assets or property that is obsolete or worn out or no longer used or useful in the (f) in connection with any transaction permitted under Sections 9.02, 9.03, 9.05 or 9.06 or 9.10; (g) the sale, assignment, transfer, disposition or discount, in each case, without recourse, of accounts receivable arising in the ordinary course of business that have been written down by the Issuer acting in good faith and consistent with its historical collection practices; (h) any dispositions as a result of any involuntary loss, damage or destruction of property as a result of a Casualty Event or transfers of property to insurance companies in exchange for casualty insurance proceeds; (i) the sale or issuance of Qualified Equity Interests of the Issuer and the issuance by any of the Issuer’s Subsidiaries of Qualified Equity Interests to the Issuer or any Obligor; (j) the abandonment of issued Patents, issued Trademarks and issued Copyrights of the Issuer and its Subsidiaries to the extent such issued Patents, issued Trademarks and issued Copyrights do not qualify as Material Intellectual Property and are not in the good faith judgment of the Issuer useful to, or required in, the conduct of the business of the Obligors or any of their Subsidiaries; (k) the abandonment or other disposition of a lease or sublease of real property that is, in the commercially reasonable judgment of the Issuer, not used or useful in the conduct of the business of the Obligors or any of their Subsidiaries; (l) licenses, development and other collaborative agreements where such arrangement provide for the license of Patents, Trademarks, Copyrights and other Intellectual Property Rights to the extent permitted pursuant to Section 9.19 hereof; (m) dispositions of property to the extent that such property is exchanged for credit against the purchase price of similar replacement property; (n) and satisfied; and dispositions or licenses of the Specified Assets so long as the Specified Assets Conditions are met (o) dispositions of assets (other than accounts receivable or Intellectual Property) not otherwise permitted pursuant to clauses (a) through (n) above; provided that such dispositions are made at fair market value for cash and the aggregate fair market value of all assets disposed of in all such dispositions (including the proposed disposition) would not exceed $2,500,000 in the aggregate since the Closing Date. 9.10 Transactions with Affiliates. The Issuer shall not, and shall not permit any of its Subsidiaries to, sell, lease, license or otherwise transfer any assets to, or purchase, lease, license 88 or otherwise acquire any assets from, or otherwise engage in any other transactions or arrangements with, any of its Affiliates, except: (a) transactions between or among Obligors and their Subsidiaries to the extent permitted hereunder (including, for the avoidance of doubt, any such transactions that are permitted by Section 9.05); (b) customary compensation and indemnification of, and other employment arrangements with, directors, officers and employees of the Issuer or any of its Subsidiaries in the ordinary course of business; (c) payments by the Obligors and their Subsidiaries pursuant to Tax sharing arrangements, transfer pricing arrangements or cost plus arrangements, in each case, solely as between or among the Obligors and one or more of their Subsidiaries; (d) hereunder; (e) (f) issuance of Qualified Equity Interests not resulting in a Change of Control and otherwise permitted transactions between or involving Perceptive Credit Holdings III, LP and its Affiliates; transactions in connection with the Janssen Collaboration Agreement; and (g) any other transaction of any Obligor or any of its Subsidiaries that is (i) on fair and reasonable terms that are no less favorable (including with respect to the amount of cash or other consideration receivable or payable in connection therewith) to such Obligor or such Subsidiary, as applicable, than it could obtain in an arm’s-length transaction with a Person that is not an Affiliate of such Obligor or such Subsidiary and (ii) of the kind which would be entered into by a prudent Person in the position of such Obligor or such Subsidiary, as applicable, with another Person that is not an Affiliate of such Obligor or such Subsidiary, as applicable. 9.11 Restrictive Agreements. The Issuer shall not, and shall not permit any of its Subsidiaries to, directly or indirectly, enter into, incur or permit to exist any Restrictive Agreement other than (i) restrictions and conditions imposed by applicable Laws or by the Notes Documents, (ii) customary restrictions and conditions contained in agreements relating to an Asset Sale permitted pursuant to Section 9.09; provided that such restrictions and conditions apply only to the Subsidiary or property or asset that is to be sold and were not created or imposed in contemplation of this Agreement, (iii) restrictions and conditions imposed by any agreement relating to Permitted Indebtedness that is secured by a Permitted Lien so long as such restrictions or conditions apply only to the property or assets securing such Permitted Indebtedness and were not created or imposed in contemplation of this Agreement, (iv) any agreement or restriction or condition in effect at the time any Person becomes a Subsidiary pursuant to a Permitted Acquisition, so long as such agreement or restriction or condition was not entered into in contemplation of such Person becoming a Subsidiary and does not extend to any assets, properties or businesses other than those acquired pursuant to such Permitted Acquisition, (v) customary provisions in leases and subleases entered into in compliance with Section 9.13 or licenses entered into in compliance with Section 9.19, in either case restricting the assignment thereof or restricting the grant of Liens in such lease, sublease or license, as the case may be, (vi) restrictions on pledges or deposits made in the ordinary 89 course of business in connection with leases or obligations permitted pursuant to Section 9.02(e), and (vii) Restrictive Agreements set forth on Schedule 7.15; provided further that, any term or provision of the foregoing notwithstanding, no such Restrictive Agreement otherwise permitted under this Section shall be permitted in the event it in any way restricts, prohibits or otherwise prevents (x) the execution, delivery and performance of the Obligations or any Secured Party’s rights or remedies in respect thereof, (y) the exercise of remedies by the Administrative Agent against the Issuer or any Subsidiary following an Event of Default as contemplated by the Notes Documents or (z) the performance of the obligations of the Issuer pursuant to Section 8.12 hereof. 9.12 Modifications of Organic Documents; Termination of Material Agreements.. The Issuer shall not, and shall not permit any of its Subsidiaries to: (a) waive, amend, terminate, replace or otherwise modify any term or provision of any Organic Document that could reasonably be expected to have a negative adverse effect on (x) any Obligations or any interests, rights or remedies of any Secured Party in respect of the Notes Documents or (y) any rights or remedies of any Noteholder in respect of any Warrant Certificate (or, to the extent the Noteholder has exercised its rights under any Warrant Certificate, such Noteholder’s rights as a holder of the Issuer’s Equity Interests) except, for purposes of this clause (y) only, to the extent such modification would not negatively adversely and disproportionately affect such Noteholder when compared with the effect of such modification on all other holders of the same series or class of Equity Interests; or (b) Except with respect to the Material Agreements set forth on Schedule 9.12(b), take or omit to take any action that results in the termination of, or permits any other Person to terminate, any Material Agreement or; or take any action that permits any Material Agreement to be terminated by any counterparty thereto prior to its stated date of expiration, in each case, only to the extent such termination would negatively adversely and disproportionately affect the Administrative Agent or the Noteholders. 9.13 Sales and Leasebacks. Except as disclosed on Schedule 9.13, the Issuer shall not, and shall not permit any of its Subsidiaries to, become liable, directly or indirectly, with respect to any lease, whether an operating lease or a Capital Lease Obligation, of any property (whether real, personal, or mixed), whether now owned or hereafter acquired, (i) which such Person has sold or transferred or is to sell or transfer to any other Person and (ii) which such Person intends to use for substantially the same purposes as property which has been or is to be sold or transferred. 9.14 Hazardous Material. The Issuer shall not, and shall not permit any of its Subsidiaries to, use, generate, manufacture, install, treat, release, store or dispose of any Hazardous Material, except in compliance with all applicable Environmental Laws or where the failure to comply, individually or in the aggregate, could not reasonably be expected to result in a Material Adverse Effect. 9.15 Accounting Changes. The Issuer shall not, and shall not permit any of its Subsidiaries to, make any significant change in accounting treatment or reporting practices, except as required or permitted by GAAP. 90 9.16 Compliance with ERISA. Neither Issuer nor any of its ERISA Affiliates shall cause or suffer to exist (i) any event that could result in the imposition of a Lien with respect to any Title IV Plan or Multiemployer Plan or (ii) any other ERISA Event that, in the aggregate, could reasonably be expected to result in a Material Adverse Effect. Neither the Issuer nor any of its Subsidiaries shall cause or suffer to exist any event that could result in the imposition of a Lien with respect to any Benefit Plan that could reasonably be expected to result in a Material Adverse Effect. 9.17 [Reserved]. 9.18 Sanctions; Anti-Corruption Use of Proceeds. The Issuer shall not, directly or knowingly indirectly, use the proceeds of the Notes, or lend, contribute or otherwise make available such proceeds to any Subsidiary, joint venture partner or other Person, (i) in furtherance of an offer, payment, promise to pay, or authorization of the payment or giving of money, or anything else of value, to any Person in violation of any applicable anti-corruption Law, or (ii) (A) to fund any activities or business of or with any Person, that, at the time of such funding, is, or whose government is, the subject of Sanctions or in any Designated Jurisdiction, or (B) in any other manner that would result in a violation of Sanctions by any Person (including any Person participating in the Notes, whether as Administrative Agent, Noteholder, underwriter, advisor, investor, or otherwise). 9.19 Inbound and Outbound Licenses. (a) Inbound Licenses. Except for the UCL Licenses and Janssen Collaboration Agreement, the Issuer shall not, and shall not permit any of its Subsidiaries to, enter into or become bound by any inbound license agreement that, individually or in the aggregate, could reasonably be expected to result in a Material Adverse Effect, which agreement, and that requires the Issuer or any of its Subsidiaries, as the case may be, during any twelve (12) month period during the term of such license agreement, to make aggregate payments in excess of [***] unless (i) the licensor under such license is a non-Affiliated third party and (ii) such license has been entered into by the Issuer or one of its Subsidiaries as the case may be, in the ordinary course of business and the commercial terms of such license otherwise comply with Section 9.10; provided that inbound license agreements in the nature of ordinary course customer contracts, application programming interfaces (APIs), over the counter software that are commercially available to the public shall not be prohibited by this clause (a). (b) Outbound Licenses. The Issuer shall not, and shall not permit any of its Subsidiaries to, enter into or become bound by any outbound license of Material Intellectual Property that, individually or in the aggregate, could reasonably be expected to result in a Material Adverse Effect unless such outbound license (i) does not impair the Administrative Agent or any Secured Party from fully exercising their respective rights in respect of Collateral under any of the Notes Documents in the event of the exercise of remedies, including a disposition or liquidation in connection with a foreclosure of any such Collateral, or any rights, assets or property related thereto, and (ii) is not an Exclusive License; provided that, any term or provision of this Section 9.19(b) or otherwise in this Agreement to the contrary notwithstanding, so long as the Specified Assets Conditions are met and satisfied as of the effective time of any outbound license (or similar 91 arrangement) of Specified Assets, this Section 9.19(b) shall not apply to any outbound license of Specified Assets. 9.20 Title, Headleases, Development. The Issuer shall not, and shall not permit any of its Subsidiaries to, (i) agree to any amendment, supplement, waiver, surrender or release of any covenant, stipulation or obligation (restrictive or otherwise) at any time affecting a Manufacturing Facility, (ii) agree to any amendment, supplement, waiver, surrender or release of any Headlease, (iii) exercise any right to break, determine or extend any Headlease, (iv) agree to any rent review in respect of any Headlease, (v) do or allow to be done any act as a result of which any Headlease may become liable to forfeiture or otherwise be terminated, (vi) do or allow to be done any act as a result of which the Overage Deed may be amended or triggered or (vii) make or allow to be made any application for planning permission in respect of any part of any Manufacturing Facility or carry out, or allow to be carried out, any demolition, construction, structural alterations or additions, development or other similar operations in respect of any part of any Manufacturing Facility, other than (A) the maintenance of the buildings, plant, machinery, fixtures and fittings in accordance with the Notes Documents, (B) any alterations or improvements which a tenant is entitled to undertake in accordance with the terms of the relevant Lease Document and in respect of which an Obligor in its capacity as landlord is required to give its consent pursuant to the terms of that Lease Document, (C) the carrying out of non-structural improvements or alterations which affect only the interior of any building on any Manufacturing Facility or (D) as disclosed in the Certificate of Title for the Shannon Manufacturing Facility and the continued planned buildout of the Shannon Manufacturing Facility up to an aggregate principal amount of [***] pursuant to Issuer’s Board approved projected budget; provided that, to the extent (A) through (D) do not apply, any such actions can be undertaken by the Issuer or its Subsidiaries with the consent of the Administrative Agent (not to be unreasonably withheld or delayed). SECTION 10 FINANCIAL COVENANTS 10.01 Minimum Liquidity. The Issuer shall at all times maintain a minimum aggregate balance of three million dollars ($3,000,000) in cash and Permitted Cash Equivalent Investments in a Controlled Account maintained with a commercial bank or similar deposit-taking institution in the U.S. (such Controlled Account, the “Minimum Liquidity Account”) that is free and clear of all Liens, other than Permitted Liens. 10.02 Phase III Trial. The Issuer shall have enrolled in a Phase III trial for AAV–RPGR with Johnson & Johnson on or before June 30, 2023. 10.03 Shannon Manufacturing Facility. The Shannon Manufacturing Facility meets or satisfies all applicable “good manufacturing practice” requirements on or before December 31, 2023 and any additional quality standards the facility markets or represents it satisfies, including without limitation cGMP. 11.01 Events of Default. Each of the following events shall constitute an “Event of Default”: SECTION 11 EVENTS OF DEFAULT 92 (a) Principal or Interest Payment Default. The Issuer shall fail to pay any principal of the Notes, when and as the same shall become due and payable, whether at the due date thereof, at a date fixed for redemption thereof or otherwise. (b) Other Payment Defaults. Any Obligor shall fail to pay any Obligation (other than an amount referred to in Section 11.01(a)) when and as the same shall become due and payable, and such failure shall continue unremedied for a period of three (3) Business Days of the due date thereof. (c) Representations and Warranties. Any representation or warranty made or deemed made by or on behalf of the Issuer or any of its Subsidiaries in or in connection with this Agreement or any other Notes Document or any amendment or modification hereof or thereof, or in any report, certificate, financial statement or other document furnished pursuant to or in connection with this Agreement or any other Notes Document or any amendment or modification hereof or thereof, shall, when taken as a whole: (i) prove to have been incorrect when made or deemed made to the extent that such representation or warranty contains any materiality or Material Adverse Effect qualifier; or (ii) prove to have been incorrect in any material respect when made or deemed made to the extent that such representation or warranty does not otherwise contain any materiality or Material Adverse Effect qualifier. (d) Certain Covenants. Any Obligor shall fail to observe or perform any covenant, condition or agreement contained in Sections 8.02, 8.03 (with respect to the Issuer’s existence) 8.11, 8.12, 8.19, Section 9 or Sections 10.01 or 10.02. (e) Other Covenants. Any Obligor shall fail to observe or perform any covenant, condition or agreement contained in this Agreement (other than those specified in Section 11.01(a), 11.01(b) or 11.01(d)) or any other Notes Document, and in the case of any failure that is capable of cure, such failure shall continue unremedied for a period of thirty (30) or more days. (f) Payment Default on Other Indebtedness. Any Obligor or any of its Subsidiaries shall fail to make any payment (whether of principal or interest and regardless of amount) in respect of any Material Indebtedness, when and as the same shall become due and payable after giving effect to any applicable grace or cure period as originally provided by the terms of such Indebtedness. (g) Other Defaults on Other Indebtedness. Any material breach of, or “event of default” or similar event under, any Contract governing any Material Indebtedness shall occur, or and shall continue after the applicable grace period, if any, (x) that results in any Material Indebtedness becoming due prior to its scheduled maturity or (y) that enables or permits (with or without the giving of notice, the lapse of time or both) the holder or holders of such Material Indebtedness or any trustee or agent on its or their behalf to cause such Material Indebtedness to become due, or to require the prepayment, repurchase, redemption or defeasance thereof, prior to its scheduled maturity; provided that this Section 11.01(g) shall not apply to (x) secured Indebtedness that becomes due as a result of the voluntary sale or transfer of the property or assets securing such Material Indebtedness, or (y) any redemption, exchange, repurchase, conversion or settlement with respect to any Permitted Convertible Indebtedness, or satisfaction of any condition 93 giving rise to or permitting the foregoing, pursuant to their terms unless such redemption, repurchase, conversion or settlement results from a default thereunder or an event of the type that constitutes an Event of Default. (h) Insolvency, Bankruptcy, Etc. (i) Any Obligor does not or becomes unable to pay its debts or meet its liabilities as the same become due, or admits in writing its inability to pay its debts generally, or declares any general moratorium on its indebtedness, or enters into a compromise or arrangement or deed of company arrangement between it and any class of its creditors. (ii) Any Obligor commits an act of bankruptcy or makes an assignment of its property for the general benefit of its creditors or makes a proposal (or files a notice of its intention to do so). (iii) Any Obligor institutes any proceeding seeking to adjudicate it an insolvent, or seeking liquidation, dissolution, winding-up, reorganization, compromise, arrangement, adjustment, protection, moratorium, relief, stay of proceedings of creditors generally (or any class of creditors), or composition of it or its debts or any other relief, under any applicable Law, whether U.S. or non-U.S., now or hereafter in effect relating to bankruptcy, winding-up, insolvency, reorganization, receivership, examinership, plans of arrangement or relief or protection of debtors or at common law or in equity, or files an answer admitting the material allegations of a petition filed against it in any such proceeding (in each case, other than any liquidation, dissolution or winding-up permitted pursuant to Section 9.03). (iv) Any Obligor applies for the appointment of, or the taking of possession by, a receiver, interim receiver, receiver/manager, sequestrator, conservator, custodian, administrator, trustee, liquidator, provisional liquidator, voluntary administrator, receiver and manager or other similar official for it or any substantial part of its property. (v) Any Obligor takes any action, corporate or otherwise, to approve, effect, consent to or authorize any of the actions described in this Section 11.01(h), or otherwise acts in furtherance thereof or fails to act in a timely and appropriate manner in defense thereof. (vi) Any petition is filed, application made or other proceeding instituted in a court of competent jurisdiction against or in respect of any Obligor: (A) seeking to adjudicate it as insolvent; (B) seeking a receiving order against it; (C) seeking liquidation, dissolution, winding-up, reorganization, compromise, arrangement, adjustment, protection, moratorium, relief, stay of proceedings of creditors generally (or any class of creditors), deed of company arrangement or composition of it or its debts or any other relief under any applicable Law, whether U.S. or non-U.S., now or hereafter in effect relating to bankruptcy, winding-up, insolvency, reorganization, receivership, examinership, plans of arrangement or relief or protection of debtors or at common law or in equity; or 94 (D) seeking the entry of an order for relief or the appointment of, or the taking of possession by, a receiver, interim receiver, receiver/manager, sequestrator, conservator, custodian, administrator, trustee, liquidator, provisional liquidator, voluntary administrator, receiver and manager or other similar official for it or any substantial part of its property, and such petition, application or proceeding (i.e. clauses (A) through (D) of this provision) continues undismissed, or unstayed and in effect, for a period of sixty (60) days after the institution thereof; provided that if an order, decree or judgment is granted or entered (whether or not entered or subject to appeal) against any Obligor thereunder in the interim, such grace period will cease to apply; provided, further, that if such Obligor files an answer admitting the material allegations of a petition filed against it in any such proceeding, such grace period will cease to apply. (vii) Any other event occurs which, under the applicable Law of any applicable jurisdiction, has an effect equivalent to any of the events referred to in Section 11.01(h). (i) Judgments. One or more final judgments for the payment of money in an aggregate amount in excess of $2,000,000 (or the Equivalent Amount in other currencies) (exclusive of any amounts fully covered by insurance (less any applicable deductible) and as to which the insurer has not rejected responsibility to cover such judgment) shall be rendered against the Issuer or any Obligor or any combination thereof and the same shall remain undismissed, unsatisfied or undischarged for a period of sixty (60) calendar days during which execution shall not be effectively stayed, or any action shall be legally taken by a judgment creditor to attach or levy upon any assets of any Obligor to enforce any such judgment. (j) ERISA and Pension Plans. An ERISA Event shall have occurred that, when taken together with all other ERISA Events that have occurred, could reasonably be expected to result in a Material Adverse Effect. (k) (l) have occurred. Change of Control. A Change of Control shall have occurred. Material Adverse Change, Etc. A Material Adverse Change or Material Adverse Effect shall (m) Impairment of Security, Etc. If any of the following events occurs, and with respect to the following clause (i), other than as a result of the acts or omissions of the Administrative Agent or any Noteholder: (i) any Lien created by any of the Security Documents shall at any time not constitute a valid and perfected Lien on the applicable Collateral in favor of the Secured Parties, free and clear of all other Liens (other than Permitted Liens) to the extent perfection is required herein or therein, other than solely as the result of any action(s) taken by the Administrative Agent or the failure of the Administrative Agent to take any action(s) within its control, or any combination thereof, which does not arise from a breach of any Notes Document by an Obligor, (ii) except for expiration in accordance with its terms, any of the Security Documents or any Guarantee of any of the Obligations (including that contained in Section 13) shall for whatever reason cease to be in full force and effect, or (iii) any Obligor shall, directly or indirectly, contest in any manner such effectiveness, validity, binding nature or enforceability of any such Lien or any Notes Document. 95 11.02 Remedies. Upon the occurrence and during the continuance of any Event of Default, then, and in every such event (other than an Event of Default described in Section 11.01(h)), the Administrative Agent may, by notice to the Issuer, declare the Notes then outstanding to be due and payable in whole (or in part, in which case any principal not so declared to be due and payable may thereafter be declared to be due and payable), and thereupon the principal of the Notes so declared to be due and payable, together with accrued interest thereon and all fees and other Obligations, shall become due and payable immediately (in the case of the Notes, at the Early Redemption Price therefor), without presentment, demand, protest or other notice of any kind, all of which are hereby waived by each Obligor; and in case of an Event of Default described in Section 11.01(h), the principal of the Notes then outstanding, together with accrued interest thereon and all fees and other Obligations, shall automatically become due and payable immediately (in the case of the Notes, at the Early Redemption Price therefor), without presentment, demand, protest or other notice of any kind, all of which are hereby waived by each Obligor. 11.03 Additional Remedies. In the event any Event of Default has occurred and is continuing, if the Issuer or any of its Subsidiaries shall be in uncured default under a Material Agreement, the Administrative Agent or the Noteholders shall have the right (but not the obligation) to cause the default or defaults under such Material Agreement to be remedied (including without limitation by paying any unpaid amount thereunder) and otherwise exercise any and all rights of the Issuer or such Subsidiary, as the case may be, thereunder, as may be necessary to prevent or cure any default. Without limiting the foregoing, upon any such default, the Issuer and each of its Subsidiaries shall promptly execute, acknowledge and deliver to the Administrative Agent such instruments as may reasonably be required of the Issuer or such Subsidiary to permit the Administrative Agent and the Noteholders to cure any default under the applicable Material Agreement or permit the Administrative Agent and the Noteholders to take such other action required to enable the Administrative Agent and the Noteholders to cure or remedy the matter in default and preserve the interests of the Administrative Agent or Noteholders. Any amounts paid by the Administrative Agent or Noteholders pursuant to this Section 11.04 shall be payable on demand by Obligors, shall accrue interest at the Default Rate if not paid on demand, and shall constitute “Obligations.” SECTION 12 THE ADMINISTRATIVE AGENT 12.01 Appointment and Duties. Subject in all cases to clause (c) below: (a) Appointment of the Administrative Agent. Each of the Noteholders hereby irrevocably appoints Perceptive Credit Holdings III, LP (together with any successor the Administrative Agent pursuant to Section 12.09) as the Administrative Agent hereunder and authorizes the Administrative Agent to (i) execute and deliver the Notes Document and accept delivery thereof on its behalf from the Issuer or any of its Subsidiaries, (ii) take such action on its behalf and to exercise all rights, powers and remedies and perform the duties as are expressly delegated to the Administrative Agent under such Notes Document and (iii) exercise such powers as are reasonably incidental thereto. 96 (b) Duties as Collateral and Disbursing Agent. Without limiting the generality of Section 12.01(a), the Administrative Agent shall have the sole and exclusive right and authority (to the exclusion of the Noteholders), and is hereby authorized, to (i) act as the disbursing and collecting agent for the Noteholders with respect to all payments and collections arising in connection with the Notes Documents (including in any proceeding described in Section 11.01(h) or any other bankruptcy, insolvency or similar proceeding); provided that (i) the Administrative Agent shall only be required to act in such agency capacity if it has notified the Issuer and the Noteholders in writing that it has elected to do so, and (ii) so long as the Administrative Agent has not delivered any such election notice it shall not be deemed to be acting as a disbursing and collecting agent for any other Noteholder or Secured Party and no Person (including any Withholding Agent) shall be authorized to make any payment to the Administrative Agent for such purpose, (ii) file and prove claims and file other documents necessary or desirable to allow the claims of the Secured Parties with respect to any Obligation in any proceeding described in Section 11.01(h) or any other bankruptcy, insolvency or similar proceeding (but not to vote, consent or otherwise act on behalf of such Secured Party), (iii) act as collateral agent for each Secured Party for purposes of the perfection of all Liens created by such agreements and all other purposes stated therein, (iv) manage, supervise and otherwise deal with the Collateral, (v) take such other action as is necessary or desirable to maintain the perfection and priority of the Liens created or purported to be created by the Notes Documents, (vi) except as may be otherwise specified in any Notes Document, exercise all remedies given to the Administrative Agent and the other Secured Parties with respect to the Collateral, whether under the Notes Documents, applicable Laws or otherwise and (vii) execute any amendment, consent or waiver under the Notes Documents on behalf of any Noteholder that has consented in writing to such amendment, consent or waiver; provided that the Administrative Agent hereby appoints, authorizes and directs each Noteholder to act as collateral sub-agent for the Administrative Agent and the Noteholders for purposes of the perfection of all Liens with respect to the Collateral, including any deposit account maintained by any Obligor with, and cash and Permitted Cash Equivalent Investments held by, such Noteholder, and may further authorize and direct the Noteholders to take further actions as collateral sub- agents for purposes of enforcing such Liens or otherwise to transfer the Collateral subject thereto to the Administrative Agent, and each Noteholder hereby agrees to take such further actions to the extent, and only to the extent, so authorized and directed. (c) Limited Duties. The Noteholders and the Obligors hereby each acknowledge and agree that the Administrative Agent (i) has undertaken its role hereunder purely as an accommodation to the parties hereto and the Transactions, (ii) is receiving no compensation for undertaking such role and (iii) subject only to the notice provisions set forth in Section 12.09, may resign from such role at any time for any reason or no reason whatsoever. Without limiting the foregoing, the parties hereto further acknowledge and agree that under the Notes Documents, the Administrative Agent (i) is acting solely on behalf of the Noteholders (except to the limited extent provided in Section 12.11), with duties that are entirely administrative in nature and do not (and are not intended to) create any fiduciary obligations, notwithstanding the use of the defined term “the Administrative Agent”, the terms “agent”, “administrative agent” and “collateral agent” and similar terms in any Notes Document to refer to the Administrative Agent, which terms are used for title purposes only, (ii) is not assuming any obligation under any Notes Document other than as expressly set forth therein or any role as agent, fiduciary or trustee of or for any Noteholder or any other Secured Party and (iii) shall have no implied functions, responsibilities, duties, obligations or other liabilities under any Notes Document (fiduciary or otherwise), and each 97 Noteholder hereby waives and agrees not to assert any claim against the Administrative Agent based on the roles, duties and legal relationships expressly disclaimed in this clause (c). 12.02 Binding Effect. Each Noteholder agrees that (i) any action taken by the Administrative Agent or the Majority Noteholders (or, if expressly required hereby, a greater proportion of the Noteholders) in accordance with the provisions of the Notes Documents, (ii) any action taken by the Administrative Agent in reliance upon the instructions of the Majority Noteholders (or, where so required, such greater proportion) and (iii) the exercise by the Administrative Agent or the Majority Noteholders (or, where so required, such greater proportion) of the powers set forth herein or therein, together with such other powers as are reasonably incidental thereto, shall be authorized and binding upon all of the Secured Parties. 12.03 Use of Discretion. (a) No Action without Instructions. The Administrative Agent shall not be required to exercise any discretion or take, or to omit to take, any action, including with respect to enforcement or collection, except (subject to clause (b) below) any action it is required to take or omit to take (i) under any Notes Document or (ii) pursuant to instructions from the Majority Noteholders (or, where expressly required by the terms of this Agreement, a greater proportion of the Noteholders). (b) Right Not to Follow Certain Instructions. Notwithstanding Section 12.03(a) or any other term or provision of this Section 12, the Administrative Agent shall not be required to take, or to omit to take, any action (i) unless, upon demand, the Administrative Agent receives an indemnification satisfactory to it from the Noteholders (or, to the extent applicable and acceptable to the Administrative Agent, any other Secured Party) against all liabilities that, by reason of such action or omission, may be imposed on, incurred by or asserted against the Administrative Agent or any Related Parties thereof or (ii) that is, in the opinion of the Administrative Agent, in its sole and absolute discretion, contrary to any Notes Document, applicable Law or the best interests of the Administrative Agent or any of its Affiliates or Related Parties. 12.04 Delegation of Rights and Duties. The Administrative Agent may, upon any term or condition it specifies, delegate or exercise any of its rights, powers and remedies under, and delegate or perform any of its duties or any other action with respect to, any Notes Document by or through any trustee, co-agent, employee, attorney-in-fact and any other Person (including any Secured Party). Any such Person shall benefit from this Section 12 to the extent provided by the Administrative Agent. 12.05 Reliance and Liability. (a) The Administrative Agent may, without incurring any liability hereunder, (i) consult with any of its Related Parties and, whether or not selected by it, any other advisors, accountants and other experts (including advisors to, and accountants and experts engaged by, any Obligor) and (ii) rely and act upon any document and information and any telephone message or conversation, in each case believed by it to be genuine and transmitted, signed or otherwise authenticated by the appropriate parties. 98 (b) Neither the Administrative Agent nor any of its Related Parties shall be liable for any action taken or omitted to be taken by any of them under or in connection with any Notes Document, and each Noteholder and the Issuer hereby waives and shall not assert (and the Issuer shall cause each other Obligor to waive and agree not to assert) any right, claim or cause of action based thereon, except to the extent of liabilities resulting primarily from the fraudulent conduct or behavior of the Administrative Agent or, as the case may be, such Related Party (each as determined in a final, non-appealable judgment or order by a court of competent jurisdiction) in connection with the duties expressly set forth herein. Without limiting the foregoing, the Administrative Agent: (i) shall not be responsible or otherwise incur liability for any action or omission taken in reliance upon the instructions of the Majority Noteholders or for the actions or omissions of any of their Related Parties selected with reasonable care (other than employees, officers and directors of the Administrative Agent, when acting on behalf of the Administrative Agent); (ii) shall not be responsible to any Secured Party for the due execution, legality, validity, enforceability, effectiveness, genuineness, sufficiency or value of, or the attachment, perfection or priority of any Lien created or purported to be created under or in connection with, any Notes Document; (iii) makes no warranty or representation, and shall not be responsible, to any Secured Party for any statement, document, information, representation or warranty made or furnished by or on behalf of any Related Party, in or in connection with any Notes Document or any transaction contemplated therein, whether or not transmitted by the Administrative Agent, including as to completeness, accuracy, scope or adequacy thereof, or for the scope, nature or results of any due diligence performed by the Administrative Agent in connection with the Notes Documents; and (iv) shall not have any duty to ascertain or to inquire as to the performance or observance of any provision of any Notes Document, whether any condition set forth in any Notes Document is satisfied or waived, as to the financial condition of any Obligor or as to the existence or continuation or possible occurrence or continuation of any Default or Event of Default and shall not be deemed to have notice or knowledge of such occurrence or continuation unless it has received a notice from the Issuer, any Noteholder describing such Default or Event of Default clearly labeled “notice of default” (in which case the Administrative Agent shall promptly give notice of such receipt to all Noteholders); and, for each of the items set forth in clauses (i) through (iv) above, each Noteholder and the Issuer hereby waives and agrees not to assert (and the Issuer shall cause each other Obligor to waive and agree not to assert) any right, claim or cause of action it might have against the Administrative Agent based thereon. 12.06 Administrative Agent Individually. The Administrative Agent and its Affiliates may make loans and other extensions of credit to, acquire Equity Interests of, engage in any kind of business with, any Obligor or Affiliate thereof as though it were not acting as the Administrative Agent and may receive separate fees and other payments therefor. To the extent the Administrative 99 Agent or any of its Affiliates subscribes for or purchases any Notes or otherwise becomes a Noteholder hereunder, it shall have and may exercise the same rights and powers hereunder and shall be subject to the same obligations and liabilities as any other Noteholder and the terms “Noteholder”, “Majority Noteholder”, and any similar terms shall, except where otherwise expressly provided in any Notes Document, include, without limitation, the Administrative Agent or such Affiliate, as the case may be, in its individual capacity as Noteholder or as one of the Majority Noteholders, respectively. 12.07 Noteholder Credit Decision. Each Noteholder acknowledges that it has, independently and without reliance upon the Administrative Agent, any Noteholder or any of their Related Parties or upon any document solely or in part because such document was transmitted by the Administrative Agent or any of its Related Parties, conducted its own independent investigation of the financial condition and affairs of each Obligor and has made and continues to make its own credit decisions in connection with entering into, and taking or not taking any action under, any Notes Document or with respect to any transaction contemplated in any Notes Document, in each case based on such documents and information as it shall deem appropriate. 12.08 Expenses; Indemnities. (a) Each Noteholder agrees to reimburse the Administrative Agent and each of its Related Parties (to the extent not reimbursed by any Obligor) promptly upon demand for such Noteholder’s Proportionate Share of any costs and expenses (including fees, charges and disbursements of financial, legal and other advisors and Other Taxes paid in the name of, or on behalf of, any Obligor) that may be incurred by the Administrative Agent or any of its Related Parties in connection with the preparation, syndication, execution, delivery, administration, modification, consent, waiver or enforcement (whether through negotiations, through any work-out, bankruptcy, restructuring or other legal or other proceeding or otherwise) of, or legal advice in respect of its rights or responsibilities under, any Notes Document. (b) Each Noteholder further agrees to indemnify the Administrative Agent and each of its Related Parties (to the extent not reimbursed by any Obligor), from and against such Noteholder’s aggregate Proportionate Share of the liabilities (including taxes, interests and penalties imposed for not properly withholding or backup withholding on payments made to on or for the account of any Noteholder) that may be imposed on, incurred by or asserted against the Administrative Agent or any of its Related Parties in any matter relating to or arising out of, in connection with or as a result of any Notes Document or any other act, event or transaction related, contemplated in or attendant to any such Notes Document, or, in each case, any action taken or omitted to be taken by the Administrative Agent or any of its Related Parties under or with respect to any of the foregoing; provided that no Noteholder shall be liable to the Administrative Agent or any of its Related Parties to the extent such liability has resulted primarily from the gross negligence or willful misconduct of the Administrative Agent or, as the case may be, such Related Party, as determined by a court of competent jurisdiction in a final non- appealable judgment or order. 12.09 Resignation of the Administrative Agent. 100 (a) At any time upon not less than five (5) Business Days prior written notice, the Administrative Agent may resign as the “the Administrative Agent” hereunder, in whole or in part (in the sole and absolute discretion of the Administrative Agent), effective on the date set forth in such notice, which effective date shall not be less than five (5) (or more than thirty (30)) days following delivery of such notice. If the Administrative Agent delivers any such notice, the Majority Noteholders shall have the right to appoint a successor (which successor shall not be a Disqualified Institution) to the Administrative Agent; provided that if a successor to the Administrative Agent has not been appointed on or before the effectiveness of the resignation of the resigning Administrative Agent, then the resigning Administrative Agent may, on behalf of the Noteholders, appoint any Person reasonably chosen by it (other than a Disqualified Institution) as the successor to the Administrative Agent. (b) Effective immediately upon its resignation, (i) the resigning Administrative Agent shall be discharged from its duties and obligations under the Notes Documents to the extent set forth in the applicable resignation notice, (ii) the Noteholders shall assume and perform all of the duties of the Administrative Agent until a successor the Administrative Agent shall have accepted a valid appointment hereunder, (iii) the resigning Administrative Agent and its Related Parties shall no longer have the benefit of any provision of any Notes Document other than with respect to (x) any actions taken or omitted to be taken while such resigning Administrative Agent was, or because the Administrative Agent had been, validly acting as the Administrative Agent under the Notes Documents or (y) any continuing duties such resigning Administrative Agent continues to perform, and (iv) subject to its rights under Section 12.04, the resigning Administrative Agent shall take such action as may be reasonably necessary to assign to the successor the Administrative Agent its rights as the Administrative Agent under the Notes Documents. Effective immediately upon its acceptance of a valid appointment as the Administrative Agent, a successor the Administrative Agent shall succeed to, and become vested with, all the rights, powers, privileges and duties of the resigning Administrative Agent under the Notes Documents. 12.10 Release of Collateral or Guarantees. Each Noteholder hereby consents to the release and hereby directs the Administrative Agent to release (or, in the case of Section 12.10(b)(ii), release or subordinate) the following: (a) any Subsidiary of the Issuer from its guaranty of any Obligation of any Obligor if all of the Equity Interests in such Subsidiary owned by any Obligor or any of its Subsidiaries are disposed of in an Asset Sale permitted under the Notes Documents (including pursuant to a waiver or consent), to the extent that, after giving effect to such Asset Sale, such Subsidiary would not be required to guaranty any Obligations pursuant to Section 8.12(a); and (b) any Lien held by the Administrative Agent for the benefit of the Secured Parties against (i) any Collateral that is disposed of by an Obligor or any of its Subsidiaries in an Asset Sale permitted by the Notes Documents (including pursuant to a valid waiver or consent), (ii) any property subject to a Lien described in Section 9.02(c) and (iii) all of the Collateral and all Obligors, upon (w) termination of the Commitments, (x) payment and satisfaction in full of the Notes and all other Obligations (other than (i) for the Warrant Obligations and (y) contingent obligations as to which no Claims have been asserted) that the Administrative Agent has been notified in writing are then due and payable, (y) deposit of cash collateral with respect to all contingent Obligations, in amounts and on terms and conditions and with parties satisfactory to 101 the Administrative Agent and each Indemnified Party that is owed such Obligations and (z) to the extent requested by the Administrative Agent, receipt by the Secured Parties of liability releases from the Obligors each in form and substance acceptable to the Administrative Agent. Each Noteholder hereby directs the Administrative Agent, and the Administrative Agent hereby agrees, upon receipt of reasonable advance notice from the Issuer, to execute and deliver or file such documents and to perform other actions reasonably necessary to release the guarantees and Liens when and as directed in this Section 12.10. 12.11 Additional Secured Parties. The benefit of the provisions of the Notes Documents directly relating to the Collateral or any Lien granted thereunder shall extend to and be available to any Secured Party that is not a Noteholder so long as, by accepting such benefits, such Secured Party agrees, as among the Administrative Agent and all other Secured Parties, that such Secured Party is bound by (and, if requested by the Administrative Agent, shall confirm such agreement in a writing in form and substance acceptable to the Administrative Agent) this Section 12 and the decisions and actions of the Administrative Agent and the Majority Noteholders (or, where expressly required by the terms of this Agreement, a greater proportion of the Noteholders) to the same extent a Noteholder is bound; provided that, notwithstanding the foregoing, (i) such Secured Party shall be bound by Section 12.08 only to the extent of liabilities, costs and expenses with respect to or otherwise relating to the Collateral held for the benefit of such Secured Party, in which case the obligations of such Secured Party thereunder shall not be limited by any concept of Proportionate Share or similar concept, (ii) each of the Administrative Agent and each Noteholder shall be entitled to act at its sole discretion, without regard to the interest of such Secured Party, regardless of whether any Obligation to such Secured Party thereafter remains outstanding, is deprived of the benefit of the Collateral, becomes unsecured or is otherwise affected or put in jeopardy thereby, and without any duty or liability to such Secured Party or any such Obligation and (iii) such Secured Party shall not have any right to be notified of, consent to, direct, require or be heard with respect to, any action taken or omitted in respect of the Collateral or under any Notes Document. SECTION 13 GUARANTEE 13.01 The Guarantee. The Subsidiary Guarantors hereby jointly and severally guarantee to the Administrative Agent and the Noteholders, and their successors and assigns, the prompt payment in full when due (whether at stated maturity, by acceleration or otherwise) of the principal of and interest on the Notes, all fees and other amounts and Obligations from time to time owing to the Administrative Agent and the Noteholders by the Issuer and each other Obligor under this Agreement or under any other Notes Document (other than in the case of the Irish Subsidiary Guarantor, the Warrant Certificate), in each case strictly in accordance with the terms hereof and thereof (such obligations being herein collectively called the “Guaranteed Obligations”). The Subsidiary Guarantors hereby further jointly and severally agree that if the Issuer or any other Obligor shall fail to pay in full when due (whether at stated maturity, by acceleration or otherwise) any of the Guaranteed Obligations, the Subsidiary Guarantors shall promptly pay the same, without any demand or notice whatsoever, and that in the case of any extension of time of payment or renewal of any of the Guaranteed Obligations, the same shall be promptly paid in full when due 102 (whether at extended maturity, by acceleration or otherwise) in accordance with the terms of such extension or renewal. 13.02 Obligations Unconditional. The obligations of the Subsidiary Guarantors under Section 13.01 are absolute and unconditional, joint and several, irrespective of the value, genuineness, validity, regularity or enforceability of the obligations of the Issuer or any other Subsidiary Guarantor under this Agreement or any other agreement or instrument referred to herein, or any substitution, release or exchange of any other guarantee of or security for any of the Guaranteed Obligations, and, to the fullest extent permitted by all applicable Laws, irrespective of any other circumstance whatsoever that might otherwise constitute a legal or equitable discharge or defense of a surety or guarantor, it being the intent of this Section 13.02 that the obligations of the Subsidiary Guarantors hereunder shall be absolute and unconditional, joint and several, under any and all circumstances. Without limiting the generality of the foregoing, it is agreed that the occurrence of any one or more of the following shall not alter or impair the liability of the Subsidiary Guarantors hereunder, which shall remain absolute and unconditional as described above: (a) at any time or from time to time, without notice to the Subsidiary Guarantors, the time for any performance of or compliance with any of the Guaranteed Obligations shall be extended, or such performance or compliance shall be waived; (b) any of the acts mentioned in any of the provisions of this Agreement or any other agreement or instrument referred to herein shall be done or omitted; (c) the maturity of any of the Guaranteed Obligations shall be accelerated, or any of the Guaranteed Obligations shall be modified, supplemented or amended in any respect, or any right under this Agreement or any other agreement or instrument referred to herein shall be waived or any other guarantee of any of the Guaranteed Obligations or any security therefor shall be released or exchanged in whole or in part or otherwise dealt with; or (d) any lien or security interest granted to, or in favor of, the Secured Parties as security for any of the Guaranteed Obligations shall fail to be perfected. The Subsidiary Guarantors hereby expressly waive diligence, presentment, demand of payment, protest and all notices whatsoever, and any requirement that the Administrative Agent or any Noteholder exhaust any right, power or remedy or proceed against the Issuer or any other Subsidiary Guarantor under this Agreement or any other agreement or instrument referred to herein, or against any other Person under any other guarantee of, or security for, any of the Guaranteed Obligations. 13.03 Reinstatement. The obligations of the Subsidiary Guarantors under this Section 13 shall be automatically reinstated if and to the extent that for any reason any payment by or on behalf of the Issuer in respect of the Guaranteed Obligations is rescinded or must be otherwise restored by any holder of any of the Guaranteed Obligations, whether as a result of any proceedings in bankruptcy or reorganization or otherwise, and the Subsidiary Guarantors jointly and severally agree that they shall indemnify the Secured Parties on demand for all reasonable costs and expenses (including reasonable and documented fees of counsel) properly incurred by such 103 Persons in connection with such rescission or restoration, including any such costs and expenses properly incurred in defending against any claim alleging that such payment constituted a preference, fraudulent transfer or similar payment under any bankruptcy, insolvency or similar law. 13.04 Subrogation. The Subsidiary Guarantors hereby jointly and severally agree that, until the payment and satisfaction in full in cash of all Guaranteed Obligations (other than contingent obligations for which no Claim has been asserted) and the expiration and termination of the Commitments, they shall not exercise any right or remedy arising by reason of any performance by them of their guarantee in Section 13.01, whether by subrogation or otherwise, against the Issuer or any other guarantor of any of the Guaranteed Obligations or any security for any of the Guaranteed Obligations. 13.05 Remedies. The Subsidiary Guarantors jointly and severally agree that, as between the Subsidiary Guarantors, on one hand, and the Administrative Agent and the Noteholders, on the other hand, the obligations of the Issuer under this Agreement and under the other Notes Documents may be declared to be forthwith due and payable as provided in Section 11 (and shall be deemed to have become automatically due and payable in the circumstances provided in Section 11) for purposes of Section 13.01 notwithstanding any stay, injunction or other prohibition preventing such declaration (or such obligations from becoming automatically due and payable) as against the Issuer and that, in the event of such declaration (or such obligations being deemed to have become automatically due and payable), such obligations (whether or not due and payable by the Issuer) shall forthwith become due and payable by the Subsidiary Guarantors for purposes of Section 13.01. 13.06 Instrument for the Payment of Money. Each Subsidiary Guarantor hereby acknowledges that the guarantee in this Section 13 constitutes an instrument for the payment of money, and consents and agrees that the Administrative Agent and the Noteholders, at their sole option, in the event of a dispute by such Subsidiary Guarantor in the payment of any moneys due hereunder, shall have the right to proceed by motion for summary judgment in lieu of complaint pursuant to N.Y. Civ. Prac. L&R § 3213. 13.07 Continuing Guarantee. The guarantee in this Section 13 is a continuing guarantee, and shall apply to all Guaranteed Obligations whenever arising. (a) 13.08 General Limitation on Guarantee Obligations. In any action or proceeding involving any provincial, territorial or state corporate Law, or any state or federal bankruptcy, insolvency, reorganization or other Law affecting the rights of creditors generally, if the obligations of any Subsidiary Guarantor under Section 13.01 would otherwise be held or determined to be void, invalid or unenforceable, or subordinated to the claims of any other creditors, on account of the amount of its liability under Section 13.01, then, notwithstanding any other provision hereof to the contrary, the amount of such liability shall, without any further action by such Subsidiary Guarantor, the Administrative Agent, any Noteholder or any other Person, be automatically limited and reduced to the highest amount that is valid and enforceable and not subordinated to the claims of other creditors as determined in such action or proceeding; and (b) notwithstanding anything to the contrary in this Agreement, the obligations, liabilities and undertakings under this Agreement (including in the guarantee in this section 13) shall not be 104 deemed to be undertaken or incurred by an Irish Subsidiary Guarantor to the extent that the same would constitute unlawful financial assistance prohibited by Section 82 of the Irish Companies Act (or any analogous provision of any other applicable Law). SECTION 14 MISCELLANEOUS 14.01 No Waiver. No failure on the part of the Administrative Agent or the Noteholders to exercise and no delay in exercising, and no course of dealing with respect to, any right, power or privilege under any Notes Document shall operate as a waiver thereof, nor shall any single or partial exercise of any right, power or privilege under any Notes Document preclude any other or further exercise thereof or the exercise of any other right, power or privilege. The remedies provided herein are cumulative and not exclusive of any remedies provided by Law. 14.02 Notices. All notices, requests, instructions, directions and other communications provided for herein (including any modifications of, or waivers, requests or consents under, this Agreement) or in the other Notes Documents shall be given or made in writing (including by telecopy or email) delivered, if to the Issuer, another Obligor, the Administrative Agent or any Noteholder, to its address specified on the signature pages hereto or its Guarantee Assumption Agreement, as the case may be, or at such other address as shall be designated by such party in a written notice to the other parties. Except as otherwise provided in this Agreement or therein, all such communications shall be deemed to have been duly given upon receipt of a legible copy thereof, in each case given or addressed as aforesaid. All such communications provided for herein by telecopy shall be confirmed in writing promptly after the delivery of such communication (it being understood that non-receipt of written confirmation of such communication shall not invalidate such communication). Notwithstanding anything to the contrary in this Agreement or any other Notes Document, notices, documents, certificates and other deliverables to the Noteholders by any Obligor may be made solely to the Administrative Agent and the Administrative Agent shall promptly deliver such notices, documents, certificates and other deliverables to the Noteholders. 14.03 Expenses, Indemnification, Etc. (a) Expenses. Issuer agrees to pay or reimburse (i) the Administrative Agent and the Noteholders for all of their reasonable and documented out of pocket costs and expenses (including the reasonable and documented fees and expenses of Morrison & Foerster LLP, counsel to the Administrative Agent, and printing, reproduction, document delivery, communication and travel costs) in connection with (x) the negotiation, preparation, execution and delivery of this Agreement and the other Notes Documents and the issuing of the Notes (exclusive of post-closing costs), (y) post-closing costs and expenses (including in connection with the listing of the Notes on a Recognised Stock Exchange in accordance with Section 8.20), any amendments, consents, waivers or other modifications, if any) and (z) the negotiation or preparation of any modification, supplement or waiver of any of the terms of this Agreement or any of the other Notes Documents (whether or not consummated) and (ii) the Administrative Agent and the Noteholders for all of their reasonable and documented out of pocket costs and expenses (including the reasonable and documented out of pocket fees and expenses of legal counsel) in connection with any enforcement or collection proceedings resulting from the occurrence of an Event of Default. 105 (b) Exculpation, Indemnification, etc. (i) In no event shall any party hereto, any successor, transferee or assignee of any party hereto, or any of their respective Affiliates, directors, officers, employees, attorneys, agents, advisors or controlling parties (each, an “Exculpated Party”) have any obligation or responsibility for (and the Obligors and the Secured Parties, as applicable, jointly and severally waive any claims they may have in respect of) any Loss, on any theory of liability, for consequential, indirect, special or punitive damages arising out of or otherwise relating to this Agreement or any of the other Notes Document or any of the Transactions or the actual or proposed use of the proceeds of the Notes; provided that, nothing in this clause (i) shall relieve any Obligor of any obligation such Obligor may have to indemnify an Indemnified Party, as provided in clause (ii) below, against any special, indirect, consequential or punitive damages asserted against such Indemnified Party by a third party. Each party hereto agrees, to the fullest extent permitted by applicable Law, that it will not assert, directly or indirectly, any Claim against any Exculpated Party with respect to any of the foregoing. (c) Each Obligor, jointly and severally, hereby indemnifies the Administrative Agent, each Noteholder, each of their respective permitted successors, transferees and assigns and each of their respective Affiliates, directors, officers, employees, attorneys, agents, advisors and controlling parties (each, an “Indemnified Party”) from and against, and agrees to hold them harmless against, any and all Claims and Losses of any kind (including reasonable fees and disbursements of counsel), joint or several, that may be incurred by or asserted or awarded against any Indemnified Party, in each case arising out of or in connection with or relating to any investigation, litigation or proceeding (each, a “Proceeding”) or the preparation of any defense with respect thereto arising out of or in connection with or relating to this Agreement or any of the other Notes Documents or the Transactions or any use made or proposed to be made with the proceeds of the Notes, whether or not such Proceeding is brought by any Obligor, any of its Subsidiaries, any of its shareholders or creditors, an Indemnified Party or any other Person, or an Indemnified Party is otherwise a party thereto, and whether or not any of the conditions precedent set forth in Section 6 are satisfied or the other transactions contemplated by this Agreement are consummated, except to the extent such Claim or Loss is found in a final, non-appealable judgment by a court of competent jurisdiction to have resulted from such Indemnified Party’s gross negligence or willful misconduct. No Obligor shall assert any Claim against any Indemnified Party, on any theory of liability, for consequential, indirect, special or punitive damages arising out of or otherwise relating to this Agreement or any of the other Notes Documents or any of the Transactions or the actual or proposed use of the proceeds of the Notes. This Section 14.03(b) shall not apply with respect to Taxes other than any Taxes that represent Losses arising from any non-Tax Claim. 14.04 Amendments, Etc. Except as otherwise expressly provided in this Agreement, any provision of this Agreement and any other Notes Document may be modified or supplemented only by an instrument in writing signed by the Issuer, the Administrative Agent and the Majority Noteholders; provided that: (a) any such modification or supplement that is disproportionately adverse to any Noteholder as compared to other Noteholders or subjects any Noteholder to any additional obligation shall not be effective without the consent of such affected Noteholder; 106 (b) the consent of all of the Noteholders shall be required to: (i) amend, modify, discharge, terminate or waive any of the terms of this Agreement or any other Notes Document if such amendment, modification, discharge, termination or waiver would increase the amount of the Notes or any Commitment; (ii) postpone or delay any date fixed for, or reduce or waive, any scheduled installment of principal or any payment of interest, fees or other amounts (other than principal) due to the Noteholders; (iii) reduce the principal of, or the rate of interest specified herein (it being agreed that waiver of the default interest shall only require the consent of Majority Noteholders) or the amount of interest payable in cash specified herein in respect of any Note, or of any fees or other amounts payable hereunder or under any other Notes Document; (iv) to subscribe for Notes in Section 6; amend or waive compliance with the conditions precedent to the obligations of Noteholders (v) amend, modify, discharge, terminate or waive any Security Document if the effect is to discharge the Issuer or any Subsidiary from their respective Obligations, or release a material part of the Collateral, in each case other than pursuant to the terms of hereof and thereof; or (vi) amend this Section 14.04 or the definition of “Majority Noteholders”. (c) if the Administrative Agent and the Issuer shall have jointly identified an obvious error or any error or omission of a technical nature, in each case, in any provision of the Notes Documents, then the Administrative Agent and the Issuer shall be permitted to amend such provision, and, in each case, such amendment shall become effective without any further action or consent of any other party to any Notes Document if the same is not objected to in writing by the Majority Noteholders to the Administrative Agent within ten (10) Business Days following receipt of notice thereof. 14.05 Successors and Assigns. (a) General. The provisions of this Agreement and the other Notes Documents shall be binding upon and shall inure to the benefit of the parties hereto or thereto and their respective successors and assigns permitted hereby or thereby, except that no Obligor may assign or otherwise transfer any of its rights or obligations hereunder without the prior written consent of the Administrative Agent. Any Noteholder may assign or otherwise transfer any of its rights or obligations hereunder or under any of the other Notes Documents (i) to an assignee in accordance with the provisions of Section 14.05(b), (ii) by way of participation in accordance with the provisions of Section 14.05(e), or (iii) by way of pledge or assignment of a security interest subject to the restrictions of Section 14.05(h). Nothing in this Agreement, expressed or implied, shall be construed to confer upon any Person (other than the parties hereto, their respective successors and assigns permitted hereby, Participants to the extent provided in Section 14.05(f) and, to the extent expressly contemplated hereby, the Related Parties of each of the Administrative Agent and the Noteholders) any legal or equitable right, remedy or claim under or by reason of this Agreement. 107 (b) Assignments by Noteholder. Any Noteholder may at any time transfer or assign to one or more Eligible Transferees (or, if an Event of Default has occurred and is continuing, to any Person) all or a portion of its rights and obligations under this Agreement (including all or a portion of the Notes at the time owing to it) and the other Notes Documents; provided that (i) no such assignment shall be made to any Obligor, any Affiliate of any Obligor, or any employees or directors of any Obligor at any time, (ii) no such assignment shall be made without the prior written consent of the Administrative Agent, and (iii) so long as no Event of Default shall have occurred and is continuing, no such assignment shall be made without the prior written consent of the Issuer (such consents not to be unreasonably withheld, delayed or conditioned) to a Disqualified Institution; provided that the Issuer shall be deemed to have consented to any such assignment unless it shall object thereto by written notice to the Administrative Agent within five (5) Business Days after having received notice thereof. Subject to the recording thereof by the Noteholder pursuant to Section 14.05(d), from and after the effective date specified in each Assignment and Assumption, the assignee thereunder shall be a party to this Agreement and, to the extent of the interest assigned by such Assignment and Assumption, have the rights and obligations of such Noteholder under this Agreement and the other Notes Document, and correspondingly the assigning Noteholder shall, to the extent of the interest assigned by such Assignment and Assumption, be released from its obligations under this Agreement (and, in the case of a transfer or assignment covering all of the Noteholder’s rights and obligations under this Agreement, such Noteholder shall cease to be a party hereto) and the other Notes Documents but shall continue to be entitled to the benefits of Section 5 and Section 14.03. Any assignment or transfer by the Noteholder of rights or obligations under this Agreement that does not comply with this Section 14.05(b) shall be treated for purposes of this Agreement as a sale by such Noteholder of a participation in such rights and obligations in accordance with Section 14.05(e). (c) Amendments to Notes Document. Each of the Administrative Agent, the Noteholders, the Issuer and its Subsidiaries agrees to enter into such amendments to the Notes Documents, and such additional Security Documents and other instruments and agreements, in each case in form and substance reasonably acceptable to the Administrative Agent, the Noteholders the Issuer and its Subsidiaries, as shall reasonably be necessary to implement and give effect to any assignment made under this Section 14.05. (d) Notes Register. The Administrative Agent, acting solely for this purpose as a non-fiduciary agent of the Issuer, shall maintain at one of its offices in the United States a copy of each Assignment and Assumption delivered to it and a register for the recordation of the names and addresses of the Noteholders, and the Commitments of, and principal amounts (and stated interest) of the Notes owing to, each Noteholder pursuant to the terms hereof from time to time (the “Notes Register”). The entries in the Register shall be conclusive absent manifest error, and the Issuer, the Administrative Agent and the Noteholders shall treat each Person whose name is recorded in the Register pursuant to the terms hereof as a Noteholder hereunder for all purposes of this Agreement. The Register shall be available for inspection by the Issuer and any Noteholder, at any reasonable time and from time to time upon reasonable prior notice. (e) Participations. Any Noteholder may at any time, without the consent of, or notice to, the Issuer, sell participations to any Person (other than a Disqualified Institution (so long as no Event of Default shall have occurred and is continuing), natural person or any Obligor or any of its Subsidiaries or Affiliates) (each, a “Participant”) in all or a portion of the Noteholder’s rights 108 and/or obligations under this Agreement (including all or a portion of the Commitment and/or the Notes owing to it); provided that (i) such Noteholder’s obligations under this Agreement shall remain unchanged, (ii) such Noteholder shall remain solely responsible to the other parties hereto for the performance of such obligations and (iii) the Issuer shall continue to deal solely and directly with such Noteholder in connection therewith. Any agreement or instrument pursuant to which any Noteholder sells such a participation shall provide that such Noteholder shall retain the sole right to enforce the Notes Documents and to approve any amendment, modification or waiver of any provision of the Notes Documents; provided that such agreement or instrument may provide that such Noteholder shall not, without the consent of the Participant, agree to any amendment, modification or waiver that would (i) increase or extend the term of such Noteholder’s Commitment, (ii) extend the date fixed for the payment of principal of or interest on the Notes or any portion of any fee hereunder payable to the Participant, (iii) reduce the amount of any such payment of principal, or (iv) reduce the rate at which interest is payable thereon to a level below the rate at which the Participant is entitled to receive such interest. Subject to Section 14.05(f), the Issuer agrees that each Participant shall be entitled to the benefits of Section 5 (subject to the requirements and limitations therein including the requirements under Section 5.03(f) (it being understood that the documentation required under Section 5.03(f) shall be delivered to the participating Noteholder)) to the same extent as if it were a Noteholder and had acquired its interest by assignment pursuant to Section 14.05(b); provided that such Participant agrees to be subject to the provisions of Section 5.03(h) as if it were an assignee under Section 14.05(b) above. To the extent permitted by applicable Law, each Participant also shall be entitled to the benefits of Section 4.03(a) as though it were a Noteholder. (f) Limitations on Rights of Participants. A Participant shall not be entitled to receive any greater payment under Sections 5.01 or 5.03 than such Noteholder would have been entitled to receive with respect to the participation sold to such Participant, except to the extent such entitlement to receive a greater payment results from a Change in Law that occurs after the Participant acquired the applicable participation. (g) Participant Register. Each Noteholder that sells a participation shall, acting solely for this purpose as a non-fiduciary agent of the Issuer, maintain a register on which it enters the name and address of each Participant and the principal amounts (and stated interest) of each Participant’s interest in the Notes or other Obligations under the Notes Documents (the “Participant Register”); provided that no Noteholder shall have any obligation to disclose all or any portion of the Participant Register (including the identity of any Participant or any information relating to a Participant’s interest in any Commitments, Notes, or its other Obligations under any Notes Document) to any Person except to the extent that such disclosure is necessary to establish that such Commitment, Note, or other Obligation is in registered form under Section 5f.103-1(c) of the United States Treasury Regulations. The entries in the Participant Register shall be conclusive absent manifest error, and such Noteholder shall treat each Person whose name is recorded in the Participant Register as the owner of such participation for all purposes of this Agreement notwithstanding any notice to the contrary. For the avoidance of doubt, the Administrative Agent (in its capacity as Administrative Agent) shall have no responsibility for maintaining a Participant Register. (h) Certain Pledges. Any Noteholder may at any time pledge or assign a security interest in all or any portion of its rights under the Notes Documents to secure obligations of such 109 Noteholder, including any pledge or assignment to secure obligations to a Federal Reserve Bank; provided that no such pledge or assignment shall release such Noteholder from any of its obligations hereunder or substitute any such pledgee or assignee for such Noteholder as a party hereto. 14.06 Survival. The obligations of the Issuer under Sections 5.01, 5.02, 5.03, 14.03, 14.05, 14.06, 14.09, 14.10, 14.11, 14.12, 14.13, 14.14 and the obligations of the Subsidiary Guarantors under Section 13 (solely to the extent guaranteeing any of the obligations under the foregoing Sections) shall survive the repayment of the Obligations and the termination of the Commitment and, in the case of the Noteholders’ assignment of any interest in the Commitment or the Notes hereunder, shall survive, in the case of any event or circumstance that occurred prior to the effective date of such assignment, the making of such assignment, notwithstanding that the Noteholders may cease to be “Noteholders” hereunder. In addition, each representation and warranty made, or deemed to be made by a Notes Subscription Request, herein or pursuant hereto shall survive the making of such representation and warranty. 14.07 Captions. The table of contents and captions and section headings appearing herein are included solely for convenience of reference and are not intended to affect the interpretation of any provision of this Agreement. 14.08 Counterparts; Electronic Signatures. This Agreement may be executed in any number of counterparts, all of which taken together shall constitute one and the same instrument and any of the parties hereto may execute this Agreement by signing any such counterpart. Delivery of an executed signature page of this Agreement by facsimile transmission or electronic transmission (in PDF format) shall be effective as delivery of a manually executed counterpart hereof. Any signature (including, without limitation, (x) any electronic symbol or process attached to, or associated with, a contract or other record and adopted by a Person with the intent to sign, authenticate or accept such contract or record and (y) any facsimile or .pdf signature) hereto or to any other certificate, agreement or document related to this Agreement, and any contract formation or record-keeping, in each case, through electronic means, shall have the same legal validity and enforceability as a manually executed signature or use of a paper-based record-keeping system to the fullest extent permitted by applicable Law, including the Federal Electronic Signatures in Global and National Commerce Act, the New York State Electronic Signatures and Records Act, or any similar state law based on the Uniform Electronic Transactions Act, and the parties hereto hereby waive any objection to the contrary. Each party hereby consents to the execution of this Agreement by way of electronic signature. 14.09 Governing Law. This Agreement and the rights and obligations of the parties hereunder shall be governed by, and construed in accordance with, the law of the State of New York, without regard to principles of conflicts of laws that would result in the application of the laws of any other jurisdiction; provided that Section 5-1401 of the New York General Obligations Law shall apply. 14.10 Jurisdiction, Service of Process and Venue. (a) Submission to Jurisdiction. Each Obligor agrees that any suit, action or proceeding with respect to this Agreement or any other Notes Document to which it is a party or any judgment entered by any court in respect thereof may be brought initially in the federal or state 110 courts in New York, New York and irrevocably submits to the non-exclusive jurisdiction of each such court for the purpose of any such suit, action, proceeding or judgment. This Section 14.10(a) is for the benefit of the Administrative Agent and the Noteholders only and, as a result, no Noteholder shall be prevented from taking proceedings in any other courts with jurisdiction. To the extent allowed by any applicable Law, the Noteholders may take concurrent proceedings in any number of jurisdictions. (b) Alternative Process. Nothing herein shall in any way be deemed to limit the ability of the Administrative Agent and the Noteholders to serve any process or summons in any manner permitted by any applicable Law. (c) Waiver of Venue, Etc. Each Obligor irrevocably waives to the fullest extent permitted by law any objection that it may now or hereafter have to the laying of the venue of any suit, action or proceeding arising out of or relating to this Agreement or any other Notes Document and hereby further irrevocably waives to the fullest extent permitted by law any claim that any such suit, action or proceeding brought in any such court has been brought in an inconvenient forum. A final judgment (in respect of which time for all appeals has elapsed) in any such suit, action or proceeding shall be conclusive and may be enforced in any court to the jurisdiction of which the Issuer is or may be subject, by suit upon judgment. 14.11 Waiver of Jury Trial. EACH PARTY HERETO HEREBY IRREVOCABLY WAIVES, TO THE FULLEST EXTENT PERMITTED BY APPLICABLE LAW, ANY AND ALL RIGHT TO TRIAL BY JURY IN ANY SUIT, ACTION OR PROCEEDING ARISING OUT OF OR RELATING TO THIS AGREEMENT, THE OTHER NOTES DOCUMENTS OR THE TRANSACTIONS CONTEMPLATED HEREBY OR THEREBY. 14.12 Waiver of Immunity. To the extent that any Obligor may be or become entitled to claim for itself or its property or revenues any immunity on the ground of sovereignty or the like from suit, court jurisdiction, attachment prior to judgment, attachment in aid of execution of a judgment or execution of a judgment, and to the extent that in any such jurisdiction there may be attributed such an immunity (whether or not claimed), such Obligor hereby irrevocably agrees not to claim and hereby irrevocably waives such immunity with respect to its obligations under this Agreement and the other Notes Documents. 14.13 Entire Agreement. This Agreement and the other Notes Documents constitute the entire agreement among the parties with respect to the subject matter hereof and thereof and supersede any and all previous agreements and understandings, oral or written, relating to the subject matter hereof, including (a) any confidentiality (or similar) agreements and (b) the Proposal Letter. EACH OBLIGOR ACKNOWLEDGES, REPRESENTS AND WARRANTS THAT IN DECIDING TO ENTER INTO THIS AGREEMENT AND THE OTHER NOTES DOCUMENTS OR IN TAKING OR NOT TAKING ANY ACTION HEREUNDER OR THEREUNDER, IT HAS NOT RELIED, AND SHALL NOT RELY, ON ANY STATEMENT, REPRESENTATION, WARRANTY, COVENANT, AGREEMENT OR UNDERSTANDING, WHETHER WRITTEN OR ORAL, OF OR WITH ADMINISTRATIVE AGENT OR THE NOTEHOLDERS OTHER THAN THOSE EXPRESSLY SET FORTH IN THIS AGREEMENT AND THE OTHER NOTES DOCUMENTS. 111 14.14 Severability. If any provision hereof is found by a court to be invalid or unenforceable, to the fullest extent permitted by any applicable Law the parties agree that such invalidity or unenforceability shall not impair the validity or enforceability of any other provision hereof. 14.15 No Fiduciary Relationship. The Issuer acknowledges that the Administrative Agent and the Noteholders have no fiduciary relationship with, or fiduciary duty to, the Issuer arising out of or in connection with this Agreement or the other Notes Documents, and the relationship between the Noteholders and the Issuer is solely that of creditor and debtor. This Agreement and the other Notes Documents do not create a joint venture among the parties. 14.16 Confidentiality. The Administrative Agent and each Noteholder agree to keep confidential all non-public and other confidential information provided to them in writing by any Obligor pursuant to this Agreement that is designated by such Obligor as confidential in accordance with its customary procedures for handling its own confidential information; provided that nothing herein shall prevent the Administrative Agent or any Noteholder from disclosing any such information (i) subject to an agreement to comply with the provisions of this Section, to the Administrative Agent, any other Noteholder, any Affiliate of a Noteholder or any Eligible Transferee or other assignee permitted under Section 14.05(b), (ii) subject to an agreement to comply with the provisions of this Section, to any actual or prospective direct or indirect counterparty to any Hedging Agreement (or any professional advisor to such counterparty), (iii) to its employees, officers, directors, agents, attorneys, accountants, trustees and other professional advisors or those of any of its affiliates (collectively, its “Related Parties”); provided that such Related Parties are subject to obligations of confidentiality at least as restrictive as set forth in this Section 14.16, and the applicable Noteholder shall remain liable hereunder for any breach of this Section 14.16 by any of its Related Parties, (iv) upon the request or demand of any Governmental Authority or any Governmental Authority having jurisdiction over such Person or its Related Parties (including any self-regulatory authority, such as the National Association of Insurance Commissioners), (v) in response to any order of any court or other Governmental Authority or as may otherwise be required pursuant to any applicable Law, (vi) if requested or required to do so in connection with any litigation or similar proceeding; provided that, unless otherwise prohibited by applicable Law, court order or decree, the Administrative Agent and each Noteholder, as applicable, shall provide prior notice to the Obligor to allow such Obligor an opportunity to obtain a protective order, (vii) that has been publicly disclosed (other than as a result of a disclosure in violation of this Section 14.16), (viii) to the National Association of Insurance Commissioners or any similar organization or any nationally recognized rating agency that requires access to information about a Noteholder’s investment portfolio in connection with ratings issued with respect to such Noteholder, (ix) in connection with the exercise of any remedy permitted hereunder or under any other Notes Document, (x) on a confidential basis to (A) any rating agency in connection with rating the Issuer or any of its Subsidiaries or the Notes or (B) the CUSIP Service Bureau or any similar agency in connection with the issuance and monitoring of CUSIP numbers of other market identifiers with respect to the Notes or (xi) to any other party hereto. 14.17 Interest Rate Limitation. Notwithstanding anything herein to the contrary, if at any time the interest rate applicable to any Notes, together with all fees, charges and other amounts that are treated as interest on such Notes under applicable Law (collectively, “charges”), shall exceed the maximum lawful rate (the “Maximum Rate”) that may be contracted for, charged, taken, received or reserved by the Administrative Agent and the Noteholder holding such Notes in accordance 112 with applicable Law, the rate of interest payable in respect of such Notes hereunder, together with all charges payable in respect thereof, shall be limited to the Maximum Rate. To the extent lawful, the interest and charges that would have been paid in respect of such Notes but were not paid as a result of the operation of this Section shall be cumulated and the interest and charges payable to such Noteholder in respect of other Notes or periods shall be increased (but not above the amount collectible at the Maximum Rate therefor) until such cumulated amount, together with interest thereon at the Federal Funds Effective Rate for each day to the date of repayment, shall have been received by such Noteholder. Any amount collected by such Noteholder that exceeds the maximum amount collectible at the Maximum Rate shall be applied to the reduction of the principal balance of such Notes so that at no time shall the interest and charges paid or payable in respect of such Notes exceed the maximum amount collectible at the Maximum Rate. 14.18 Early Redemption Fee. The parties hereto acknowledge and agree that, to the extent the Early Redemption Fee is applicable to any repurchase, repayment or redemption of principal of any Notes at any time, such Early Redemption Fee is not intended to be a penalty assessed as a result of any such repurchase, repayment or redemption of the Notes, but rather is the product of a good faith, arm’s length commercial negotiation between the Issuer and the Noteholders relating to the mutually satisfactory compensation payable to the Noteholders by the Issuer in respect of the Notes made hereunder. In furtherance of the foregoing, to the fullest extent permitted by applicable Law, the Obligors hereby jointly and severally waive any rights or Claims any of them may have under any such applicable Law (whether or not in effect on the Closing Date) that would prohibit or restrict the payment of the Early Redemption Fee under any of the circumstances provided herein or in any other Notes Document, including payment after acceleration of the Notes. 14.19 Judgment Currency. (a) If, for the purposes of obtaining judgment in any court, it is necessary to convert a sum due hereunder in Dollars into another currency, the parties hereto agree, to the fullest extent permitted by Law, that the rate of exchange used shall be that at which, in accordance with normal banking procedures, the Administrative Agent could purchase Dollars with such other currency at the buying spot rate of exchange in the New York foreign exchange market on the Business Day immediately preceding that on which any such judgment, or any relevant part thereof, is given. (b) The obligations of the Obligors in respect of any sum due to the Administrative Agent hereunder and under the other Notes Documents shall, notwithstanding any judgment in a currency other than Dollars, be discharged only to the extent that on the Business Day following receipt by the Administrative Agent of any sum adjudged to be so due in such other currency the Administrative Agent may, in accordance with normal banking procedures, purchase Dollars with such other currency. If the amount of Dollars so purchased is less than the sum originally due to the Administrative Agent in Dollars, the Issuer agrees, to the fullest extent that it may effectively do so, as a separate obligation and notwithstanding any such judgment, to indemnify the Administrative Agent against such loss. If the amount of Dollars so purchased exceeds the sum originally due to the Administrative Agent in Dollars, the Administrative Agent shall remit such excess to the Issuer. 113 14.20 USA PATRIOT Act. The Administrative Agent and the Noteholders hereby notify the Obligors that pursuant to the requirements of the USA PATRIOT Act (Title III of Pub. L. 107-56 (signed into law October 26, 2001)) (the “Patriot Act”), they are required to obtain, verify and record information that identifies the Obligors, which information includes the name and address of each Obligor and other information that will allow such Person to identify such Obligor in accordance with the Patriot Act. 14.21 Acknowledgement and Consent to Bail-In of Affected Financial Institutions. Notwithstanding anything to the contrary in any Notes Document or in any other agreement, arrangement or understanding among any such parties, each party hereto acknowledges that any liability of any Affected Financial Institution arising under any Notes Document, to the extent such liability is unsecured, may be subject to the Write-Down and Conversion Powers of the applicable Resolution Authority and agrees and consents to, and acknowledges and agrees to be bound by: (a) the application of any Write-Down and Conversion Powers by the applicable Resolution Authority to any such liabilities arising hereunder which may be payable to it by any party hereto that is an EEA Financial Institution; and (b) the effects of any Bail-In Action on any such liability, including, if applicable: (i) a reduction in full or in part or cancellation of any such liability; (ii) a conversion of all, or a portion of, such liability into shares or other instruments of ownership in such Affected Financial Institution, its parent undertaking, or a bridge institution that may be issued to it or otherwise conferred on it, and that such shares or other instruments of ownership will be accepted by it in lieu of any rights with respect to any such liability under this Agreement or any other Notes Document; or (iii) the variation of the terms of such liability in connection with the exercise of the Write- Down and Conversion Powers of the applicable Resolution Authority. [Signature Pages Follow] 114 IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly executed and delivered as of the day and year first above written. ISSUER: MEIRAGTX HOLDINGS PLC By /s/ Richard Giroux Name: Richard Giroux Title: Chief Financial Officer and Chief Operating Officer Address for Notices: [***] SUBSIDIARY GUARANTORS: MEIRAGTX UK II LIMITED By /s/ Richard Giroux Name: Richard Giroux Title: Chief Financial Officer and Chief Operating Officer Address for Notices: [***] [Signature Page to Amended and Restated Notes Purchase Agreement And Guaranty] MEIRAGTX IRELAND DAC By /s/ Richard Giroux Name: Richard Giroux Title: Chief Financial Officer and Chief Operating Officer Address for Notices: [***] [Signature Page to Amended and Restated Notes Purchase Agreement And Guaranty] ADMINISTRATIVE AGENT: PERCEPTIVE CREDIT HOLDINGS III, LP By: PERCEPTIVE CREDIT OPPORTUNITIES GP, LLC, its general partner By /s/ Sandeep Dixit Name: Sandeep Dixit Title: Chief Credit Officer By /s/ Sam Chawla Name: Sam Chawla Title: Portfolio Manager Address for Notices: [***] [Signature Page to Amended and Restated Notes Purchase Agreement And Guaranty] NOTEHOLDERS: PERCEPTIVE CREDIT HOLDINGS III, LP By: PERCEPTIVE CREDIT OPPORTUNITIES GP, LLC, its general partner By /s/ Sandeep Dixit Name: Sandeep Dixit Title: Chief Credit Officer By /s/ Sam Chawla Name: Sam Chawla Title: Portfolio Manager Address for Notices: [***] [Signature Page to Amended and Restated Notes Purchase Agreement And Guaranty] NOTE Exhibit 10.38 December 19, 2022 U.S. $75,000,000 FOR VALUE RECEIVED, the undersigned, MeiraGTx Holdings plc, an exempted company incorporated under the laws of the Cayman Islands with registration number 336306 (the “Issuer”), hereby promises to pay to Perceptive Credit Holdings III, LP (the “Noteholder”), in immediately available funds, the aggregate principal sum set forth above, or, if less, the aggregate unpaid principal amount of the Tranche 1 Note made by the Noteholder pursuant to Section 2.01(a) of the Amended and Restated Note Purchase Agreement and Guaranty, dated as of December 19, 2022 (as amended or otherwise modified from time to time, the “Note Purchase Agreement”), among the Issuer, the Subsidiary Guarantors from time to time thereunder, the noteholders from time to time party thereto (the “Noteholders”) and Perceptive Credit Holdings III, LP, a Delaware limited partnership, as administrative agent for the Noteholders (in such capacity, together with its successors and assigns, the “Administrative Agent”), on the date or dates specified in the Note Purchase Agreement, together with interest on the principal amount of such Notes from time to time outstanding thereunder at the rates, and payable in the manner and on the dates, specified in the Note Purchase Agreement. This Note is a Note issued pursuant to the terms of the Note Purchase Agreement, and this Note and the holder hereof are entitled to all the benefits and security provided for thereby or referred to therein, to which Note Purchase Agreement reference is hereby made for a statement thereof. All defined terms used in this Note, except terms otherwise defined herein, shall have the same meaning as in the Note Purchase Agreement. THIS NOTE AND THE RIGHTS AND OBLIGATIONS OF THE PARTIES HEREUNDER SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE LAW OF THE STATE OF NEW YORK, WITHOUT REGARD TO PRINCIPLES OF CONFLICTS OF LAWS THAT WOULD RESULT IN THE APPLICATION OF THE LAWS OF ANY OTHER JURISDICTION; PROVIDED THAT SECTION 5-1401 OF THE NEW YORK GENERAL OBLIGATIONS LAW SHALL APPLY. The Issuer hereby waives demand, presentment, protest or notice of any kind hereunder, other than notices provided for in the Note Documents. The non-exercise by the holder hereof of any of its rights hereunder in any particular instance shall not constitute a waiver thereof in such particular or any subsequent instance. THIS NOTE MAY NOT BE TRANSFERRED EXCEPT IN COMPLIANCE WITH THE TERMS OF THE NOTE PURCHASE AGREEMENT. THIS NOTE HAS BEEN ISSUED WITH “ORIGINAL ISSUE DISCOUNT” (WITHIN THE MEANING OF SECTION 1273 OF THE INTERNAL REVENUE CODE OF 1986, AS AMENDED). UPON WRITTEN REQUEST, THE ISSUER WILL PROMPTLY MAKE AVAILABLE TO ANY HOLDER OF THIS NOTE THE FOLLOWING INFORMATION: (1) THE ISSUE PRICE AND ISSUE DATE OF THIS NOTE, (2) THE AMOUNT OF ORIGINAL ISSUE DISCOUNT ON THIS NOTE AND (3) THE YIELD TO MATURITY OF THIS NOTE. HOLDERS SHOULD CONTACT THE CHIEF FINANCIAL OFFICER OF THE ISSUER AT 450 EAST 29TH STREET, 14TH FLOOR, NEW YORK, NY 10016, ATTN: CHIEF OPERATING OFFICER. THIS NOTE HAS NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ACT”) OR UNDER THE SECURITIES LAWS OF CERTAIN STATES, AND MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED, CHARGED, HYPOTHECATED OR OTHERWISE TRANSFERRED EXCEPT PURSUANT TO AN EFFECTIVE REGISTRATION STATEMENT FILED UNDER THE ACT AND APPLICABLE STATE SECURITIES LAWS OR PURSUANT TO AN AVAILABLE EXEMPTION FROM REGISTRATION UNDER THE ACT AND APPLICABLE STATE SECURITIES LAWS OR UNLESS SOLD IN ACCORDANCE WITH RULE 144 UNDER THE ACT. [Signature Page Follows] MEIRAGTX HOLDINGS PLC By /s/ Rich Giroux Name: Rich Giroux Title: CFO and COO Exhibit 10.39 SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”) is made and entered into as of November 9, 2022 by and among MeiraGTx Holdings plc, a Cayman Islands exempted company (the “Company”), and Johnson & Johnson Innovation – JJDC, Inc. (the “Investor”). RECITALS A. The Company and the Investor are executing and delivering this Agreement in reliance upon the exemption from securities registration afforded by the provisions of Section 4(a)(2) and/or Rule 506 of Regulation D of the Securities Act of 1933, as amended (the “1933 Act”); and B. The Investor wishes to purchase from the Company, and the Company wishes to sell and issue to the Investor, upon the terms and subject to the conditions stated in this Agreement, a certain number (the “Shares”) of ordinary shares of the Company, nominal value $0.00003881 per share (the “Ordinary Shares”). C. Within three days of the sale of the Shares, the parties hereto will execute and deliver a Registration Rights Agreement, substantially in the form attached hereto as Exhibit B (the “Registration Rights Agreement”), pursuant to which the Company will agree to provide certain registration rights in respect of the Shares under the 1933 Act, and the rules and regulations promulgated thereunder, and applicable state securities laws. In consideration of the mutual promises made herein and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto agree as follows: 1. Definitions. For the purposes of this Agreement, the following terms shall have the meanings set forth below: “Affiliate” means, with respect to any Person, any other Person which directly or indirectly through one or more intermediaries Controls, is controlled by, or is under common Control with, such Person. “Business Day” means a day, other than a Saturday or Sunday, on which banks in New York City are open for the general transaction of business. “Closing” has the meaning set forth in Section 3.1. “Closing Date” has the meaning set forth in Section 3.1. “Company’s Knowledge” means the actual knowledge of the executive officers (as defined in Rule 405 under the 1933 Act) of the Company. “Control” (including the terms “controlling”, “controlled by” or “under common control with”) means the possession, direct or indirect, of the power to direct or cause the direction of the management and policies of a Person, whether through the ownership of voting securities, by contract or otherwise. “Environmental Laws” has the meaning set forth in Section 4.17. “GAAP” has the meaning set forth in Section 4.6. “Losses” has the meaning set forth in Section 8.2. “Material Adverse Effect” means a material adverse effect on (i) the assets, liabilities, results of operations, condition (financial or otherwise) or business of the Company and its Subsidiaries taken as a whole, (ii) the legality or enforceability of this Agreement or (iii) the ability of the Company to perform its obligations under this Agreement. “Material Contract” means any contract, instrument or other agreement to which the Company is a party or by which it is bound which is material to the business of the Company, including those that have been filed or were required to have been filed as an exhibit to the SEC Filings pursuant to Item 601(b)(10) of Regulation S-K. “Nasdaq” means The Nasdaq Global Select Market. “Person” means an individual, corporation, partnership, limited liability company, trust, business trust, association, joint stock company, joint venture, sole proprietorship, unincorporated organization, governmental authority or any other form of entity not specifically listed herein. “Press Release” has the meaning set forth in Section 9.7. “SEC” means the United States Securities and Exchange Commission. “SEC Filings” means the Company’s filings with the SEC pursuant to the Securities Exchange of 1934 Act, as amended, filed since January 1, 2022. “Shares” has the meaning set forth in the Recitals. “Short Sales” means all “short sales” as defined in Rule 200 of Regulation SHO under the 1934 Act (but shall not be deemed to include the location and/or reservation of borrowable Ordinary Shares). “Subscription Amount” means the aggregate amount to be paid for the Shares purchased hereunder. “Subsidiary” of any Person means another Person, an amount of the voting securities, other voting ownership or voting partnership interests of which is sufficient to elect at least a majority of its Board of Directors or other governing body (or, if there are no such voting interests, 50% or more of the equity interests of which) is owned directly or indirectly by such first Person. “Trading Day” means a day on which Nasdaq is open for trading. “Transfer Agent” has the meaning set forth in Section 7.8. “Transaction Documents” means this Agreement and the Registration Rights Agreement. “1933 Act” has the meaning set forth in the Recitals. “1934 Act” means the Securities Exchange Act of 1934, as amended, or any successor statute, and the rules and regulations promulgated thereunder. 2. Purchase and Sale of the Shares. On the Closing Date, upon the terms and subject to the conditions set forth herein, the Company will issue and sell, and the Investor will purchase 3,742,514 Shares at a price per Share equal to $6.68, for an aggregate purchase price of $24,999,993.52. 3. Closing. 3.1. The completion of the purchase and sale of the Shares (the “Closing”) shall occur remotely via exchange of documents and signatures at a time (the “Closing Date”) to be agreed to by the Company and the Investor. 3.2. On the Closing Date, the Investor shall deliver or cause to be delivered to the Company the Subscription Amount via wire transfer of immediately available funds pursuant to the wire instructions, as set forth on Exhibit A hereto. 3.3. On or within one business day of the Closing Date, the Company shall deliver or cause to be delivered to the Investor a number of Shares, registered in the name of the Investor, in the amount as set forth in this Agreement. 4. Representations and Warranties of the Company. The Company hereby represents and warrants to the Investor that, except as set forth in the schedules delivered herewith (the “Disclosure Schedules”) and except as described in the SEC Filings (other than in risk factors and other cautionary language regarding forward- looking statements), which qualify these representations and warranties in their entirety: 4.1. Organization, Good Standing and Qualification. The Company is duly incorporated, validly existing and in good standing under the laws of the jurisdiction of its incorporation and has all requisite corporate power and authority to carry on its business as now conducted and to own or lease its properties. The Company is duly qualified to do business as a foreign corporation and is in good standing in each jurisdiction in which the conduct of its business or its ownership or leasing of property makes such qualification or leasing necessary unless the failure to so qualify has not had and could not reasonably be expected to have a Material Adverse Effect. Each of the Company’s “Subsidiaries” (for purposes of this Agreement, as defined in Rule 405 under the 1933 Act) has been duly incorporated or organized, as the case may be, and is validly existing as a corporation, partnership or limited liability company, as applicable, in good standing under the laws of the jurisdiction of its incorporation or organization and has the power and authority (corporate or other) to carry on its business as now conducted and to own or lease its properties. Each of the Company’s Subsidiaries is duly qualified as a foreign corporation, partnership or limited liability company, as applicable, to transact business and is in good standing in each jurisdiction in which the conduct of its business or its ownership or leasing of property makes such qualification or leasing necessary unless the failure to so qualify has not had and could not reasonably be expected to have a Material Adverse Effect. All of the issued and outstanding capital stock or other equity or ownership interests of each of the Company’s Subsidiaries have been duly authorized and validly issued, are fully paid and nonassessable and are owned by the Company, directly or through Subsidiaries, free and clear of any security interest, mortgage, pledge, lien, encumbrance or adverse claim. 4.2. Authorization. The Company has the requisite corporate power and authority and has taken all requisite corporate action necessary for, and no further action on the part of the Company, its officers, directors and shareholders is necessary for, (i) the authorization, execution and delivery of this Agreement, (ii) the authorization of the performance of all obligations of the Company hereunder, and (iii) the authorization, issuance and delivery of the Shares. This Agreement constitutes the legal, valid and binding obligations of the Company, enforceable against the Company in accordance with its terms, subject to bankruptcy, insolvency, fraudulent transfer, reorganization, moratorium and similar laws of general applicability, relating to or affecting creditors’ rights generally and to general equitable principles. 4.3. Capitalization. The SEC Filings accurately reflect as of their respective dates (a) the authorized shares of the Company; (b) the number of shares issued and outstanding; (c) the number of shares issuable pursuant to the Company’s stock plans; and (d) the number of shares issuable and reserved for issuance pursuant to securities (other than the Shares) exercisable for, or convertible into or exchangeable for any shares of the Company. All of the issued and outstanding shares of the Company’s have been duly authorized and validly issued and are fully paid, nonassessable and none of such shares were issued in violation of any pre-emptive rights and such shares were issued in compliance in all material respects with applicable Cayman Islands, state and federal securities law and any rights of third parties. Except as described in the SEC Filings, no Person is entitled to pre-emptive or similar statutory or contractual rights with respect to the issuance by the Company of any securities of the Company. Except as described in the SEC filings, there are no outstanding warrants, options, convertible securities or other rights, agreements or arrangements of any character under which the Company is or may be obligated to issue any equity securities of any kind and except as contemplated by this Agreement. Except as described in the SEC filings, there are no voting agreements, buy-sell agreements, option or right of first purchase agreements or other agreements of any kind among the Company and any of the securityholders of the Company relating to the securities of the Company held by them. Except as described in the SEC filings, no Person has the right to require the Company to register any securities of the Company under the 1933 Act, whether on a demand basis or in connection with the registration of securities of the Company for its own account or for the account of any other Person. The issuance and sale of the Shares hereunder will not obligate the Company to issue Ordinary Shares or other securities to any other Person (other than the Investor) and will not result in the adjustment of the exercise, conversion, exchange or reset price of any outstanding security. The Company does not have outstanding shareholder purchase rights or “poison pill” or any similar arrangement in effect giving any Person the right to purchase any equity interest in the Company upon the occurrence of certain events. 4.4. Valid Issuance. The Shares have been duly and validly authorized and, when issued and paid for pursuant to this Agreement, will be validly issued, fully paid and nonassessable, and shall be free and clear of all encumbrances and restrictions (other than those created by the Investor), except for restrictions on transfer set forth herein or imposed by applicable securities laws. 4.5. No Material Adverse Effect. Since June 30, 2022, (i) there has not been any event, occurrence, development or condition of any character that has had or would reasonably be expected to have a Material Adverse Effect; (ii) there have not been any changes in the authorized capital, assets, liabilities, financial condition, business, Material Contracts or operations of the Company and its Subsidiaries, taken as a whole, from that reflected in the consolidated financial statements of the Company and its Subsidiaries, except for any such changes in the ordinary course of business which have not had or would not reasonably be expected to have a Material Adverse Effect and (iii) the Company has not declared or made any dividend or distribution of cash or other property to its shareholders. No material event, liability, fact, circumstance, occurrence or development has occurred or exists, or is reasonably expected to occur or exist, with respect to the Company or its Subsidiaries or their respective businesses, properties, operations, assets or financial condition that would be required to be disclosed by the Company under applicable Law that has not been publicly disclosed. 4.6. Financial Statements. The financial statements included in each SEC Filing comply in all material respects with applicable accounting requirements and the rules and regulations of the SEC with respect thereto as in effect at the time of filing (or to the extent corrected by a subsequent restatement) and present fairly, in all material respects, the financial position of the Company as of the dates shown and its results of operations and cash flows for the periods shown, and such financial statements have been prepared in conformity with United States generally accepted accounting principles applied on a consistent basis during the periods involved (“GAAP”) (except as may be disclosed therein or in the notes thereto, except that the unaudited quarterly financial statements may not contain all footnotes required by GAAP, as permitted by Form 10-Q under the 1934 Act). 4.7. Consents. The execution, delivery and performance by the Company of the Transaction Documents and the offer, issuance and sale of the Shares require no consent of, action by or in respect of, or filing with, any Person, governmental body, agency, or official other than (a) filings that have been made pursuant to applicable state securities laws, (b) post-sale filings pursuant to applicable state and federal securities laws and (c) filings pursuant to the rules and regulations of Nasdaq, each of which the Company has filed or undertakes to file within the applicable time. Subject to the accuracy of the representations and warranties of the Investor set forth in Section 5 hereof, the Company has taken all action necessary to exempt (i) the issuance and sale of the Shares and (ii) the other transactions contemplated by the Transaction Documents from the provisions of any shareholder rights plan or other “poison pill” arrangement, any anti-takeover, business combination or control share law or statute binding on the Company or to which the Company or any of its assets and properties is subject that is or could reasonably be expected to become applicable to the Investors as a result of the transactions contemplated hereby, including without limitation, the issuance of the Shares and the ownership, disposition or voting of the Shares by the Investors or the exercise of any right granted to the Investors pursuant to this Agreement or the other Transaction Documents. 4.8. Legal Proceedings. Except as described in the SEC Filings or as previously disclosed to the Investor, there are no legal, governmental or regulatory investigations, actions, suits or proceedings pending to which the Company or any of its Subsidiaries is or may reasonably be expected to become a party or to which any property of the Company is or may reasonably be expected to become the subject that, individually or in the aggregate, if determined adversely to the Company or its Subsidiaries, could (i) reasonably be expected to have a Material Adverse Effect or (ii) adversely affect or challenge the legality, validity or enforceability of the Transaction Documents. Neither the Company nor any of its Subsidiaries, nor, to the Company’s Knowledge, any director or officer thereof, is or has been the subject of any action involving a judicially filed claim of violation of or liability under U.S. federal, state or foreign securities laws or a judicially filed claim of breach of fiduciary duty. Except as described in the SEC Filings or as previously disclosed to the Investor, there has not been, and to the Company’s Knowledge, there is not pending or threatened, any investigation by the SEC involving the Company or any current or former director or officer of the Company. The SEC has not issued any stop order or other order suspending the effectiveness of any registration statement filed by the Company or any of its Subsidiaries under the 1933 Act or the 1934 Act. 4.9. SEC Filings; Business. The Company has timely filed all reports, schedules, forms, statements and other documents required to be filed by the Company under 1933 Act and the 1934 Act, including pursuant to Section 13(a) or 15(d) of the 1934 Act, for the one year preceding the date hereof. The Company has further made available to the Investor through the Electronic Data Gathering, Analysis, and Retrieval System (the “EDGAR system”), true and complete copies of the SEC filings. The Company has made all filings required to be made pursuant to the 1934 Act. The Company is engaged in all material respects only in the business described in the SEC Filings and the SEC Filings contain a complete and accurate description in all material respects of the business of the Company. 4.10. Compliance. The Company is not (i) in default under or in violation of (and no event has occurred that has not been waived that, with notice or lapse of time or both, would result in a default by the Company under), nor has the Company received notice of a claim that it is in default under or that it is in violation of, any indenture, loan or credit agreement or any other agreement or instrument to which it is a party or by which it or any of its properties is bound (whether or not such default or violation has been waived), (ii) in violation of any judgment, decree or order of any court, arbitrator or governmental body or (iii) in violation of any statute, rule, ordinance or regulation of any governmental authority, including without limitation all foreign, federal, state and local laws relating to taxes, environmental protection, occupational health and safety, product quality and safety and employment and labor matters, except in each case as could not have or reasonably be expected to result in a Material Adverse Effect. 4.11. Tax Matters. The Company and its Subsidiaries have filed all tax returns required to have been filed by the Company or its Subsidiaries with all appropriate governmental agencies and have paid all taxes shown thereon or otherwise owed by them. The Company has made adequate charges, accruals and reserves in the applicable financial statements referred to in Section 4.6 in respect of all federal, state and foreign income and franchise taxes for all periods as to which the tax liability of the Company or its Subsidiaries has not been finally determined, except to the extent of any inadequacy that would not reasonably be expected to result in a Material Adverse Effect. There are no material tax liens or claims pending, or to the Company’s Knowledge, threatened against the Company or any of its Subsidiaries or any of their respective material assets or properties. 4.12. Use of Proceeds. The net proceeds of the sale of the Shares hereunder shall be used by the Company to (1) maintain and accelerate its existing preclinical and research programs and (2) improve internal manufacturing and quality check capabilities. 4.13. Title to Properties. Except as described in the SEC Filings, the Company and its Subsidiaries have good and marketable title to all real properties and all other properties and assets owned by them, in each case free from liens, encumbrances and defects, except such as would not reasonably be expected, individually or in the aggregate, to have a Material Adverse Effect; and except as disclosed in the SEC Filings, the Company and its Subsidiaries hold any leased real or personal property under valid, subsisting and enforceable leases with which the Company and its Subsidiaries are in compliance and with no exceptions, except such as would not reasonably be expected, individually or in the aggregate, to have a Material Adverse Effect. 4.14. No Conflict, Breach, Violation or Default. The execution, delivery and performance of the Transaction Documents by the Company and the issuance and sale of the Shares in accordance with the provisions thereof will not (i) conflict with or result in a breach or violation of (a) any of the terms and provisions of, or constitute a default under, the Company’s Articles of Association, both as in effect on the date hereof (true and complete copies of which have been made available to the Investor through the EDGAR system), or (b) assuming the accuracy of the representations and warranties in Section 5, any applicable statute, rule, regulation or order of any governmental agency or body or any court, domestic or foreign, having jurisdiction over the Company or its Subsidiaries, or any of their assets or properties. 4.15. Intellectual Property. Except as disclosed in the SEC Filings, the Company and its Subsidiaries own, possess, license or have other rights to use, the patents and patent applications, copyrights, trademarks, service marks, trade names, service names and trade secrets described in the SEC Filings and as necessary or material for use in connection with its business and which the failure to so have would have or reasonably be expected to result in a Material Adverse Effect (collectively, the “Intellectual Property Rights”). There is no pending or, to the Company’s Knowledge, threatened action, suit, proceeding or claim by any Person that the Company’s business or the business of its Subsidiaries as now conducted infringes or otherwise violates any patent, trademark, copyright, trade secret or other proprietary rights of another. To the Company’s Knowledge, there is no existing infringement by another Person of any of the Intellectual Property Rights that would have or would reasonably be expected to have a Material Adverse Effect. The Company and its Subsidiaries have taken reasonable security measures to protect the secrecy, confidentiality and value of all of its Intellectual Property Rights, except where failure to do so would not, individually or in the aggregate, reasonably be expected to have a Material Adverse Effect. All material licenses or other material agreements under which the Company is granted Intellectual Property Rights are in full force and effect and, to the Company’s knowledge, there is no material default by any other party thereto, except as would not reasonably be expected to have a Material Adverse Effect. The Company has no reason to believe that the licensors under such licenses and other agreements do not have and did not have all requisite power and authority to grant the rights to the Intellectual Property Rights purported to be granted thereby. The consummation of the transactions contemplated hereby and by the other Transaction Documents will not result in the alteration, loss, impairment of or restriction on the Company’s or any of its Subsidiaries’ ownership or right to use any Intellectual Property Rights that is material to the conduct of the Company’s business as currently conducted. 4.16. Certificates, Authorities and Permits. The Company and its Subsidiaries possess adequate certificates, authorities or permits issued by appropriate governmental agencies or bodies necessary to conduct the business now operated by them, except where failure to so possess would not reasonably be expected to, individually or in the aggregate, result in a Material Adverse Effect. The Company and its Subsidiaries have not received any notice of proceedings relating to the revocation or modification of any such certificate, authority or permit that, if determined adversely to the Company or its Subsidiaries, would reasonably be expected, individually or in the aggregate, to have a Material Adverse Effect. 4.17. Environmental Matters. Except as would not reasonably be expected, individually or in the aggregate, to have a Material Adverse Effect, neither the Company nor any of its Subsidiaries is in violation of any statute, rule, regulation, decision or order of any governmental agency or body or any court, domestic or foreign, relating to the use, disposal or release of hazardous or toxic substances or relating to the protection or restoration of the environment or human exposure to hazardous or toxic substances (collectively, “Environmental Laws”), has released any hazardous substances regulated by Environmental Law on to any real property that it owns or operates, or has received any written notice or claim it is liable for any off-site disposal or contamination pursuant to any Environmental Laws; and to the Company’s Knowledge, there is no pending or threatened investigation that would reasonably be expected to lead to such a claim. 4.18. Compliance with Nasdaq Continued Listing Requirements. The Company is in compliance with applicable Nasdaq continued listing requirements. There are no proceedings pending or, to the Company’s Knowledge, threatened against the Company relating to the continued listing of the Ordinary Shares on Nasdaq and the Company has not received any notice of, nor to the Company’s Knowledge is there any reasonable basis for, the delisting of the Ordinary Shares from Nasdaq. 4.19. Brokers and Finders. No Person will have as a result of the transactions contemplated hereby any valid right, interest or claim against or upon the Company or the Investor for any commission, fee or other compensation pursuant to any agreement, arrangement or understanding entered into by or on behalf of the Company. 4.20. No Directed Selling Efforts or General Solicitation. Neither the Company nor any of its Subsidiaries nor any Person acting on its behalf has conducted any general solicitation or general advertising (as those terms are used in Regulation D (“Regulation D”) promulgated under the 1933 Act) in connection with the offer or sale of any of the Shares. The Company has offered the Shares for sale only to “accredited investors” within the meaning of Rule 501 under the 1933 Act. 4.21. No Integrated Offering. Neither the Company nor any of its subsidiaries nor any Person acting on its behalf has, directly or indirectly, made any offers or sales of any Company security or solicited any offers to buy any Company security, under circumstances that would adversely affect reliance by the Company on Section 4(a)(2) for the exemption from registration for the transactions contemplated hereby or would require registration of the Shares under the 1933 Act. 4.22. Private Placement. Assuming the accuracy of the representations and warranties of the Investor set forth in Section 5, the offer and sale of the Shares to the Investor as contemplated hereby is exempt from the registration requirements of the 1933 Act. The issuance and sale of the shares does not contravene the rules and regulations of Nasdaq. 4.23. No Unlawful Payments. Neither the Company nor any of its Subsidiaries nor any director, officer, or employee of the Company or any of its Subsidiaries nor, to the knowledge of the Company, any agent, affiliate or other person associated with or acting on behalf of the Company or any of its Subsidiaries has (i) used any corporate funds for any unlawful contribution, gift, entertainment or other unlawful expense relating to political activity; (ii) made or taken an act in furtherance of an offer, promise or authorization of any direct or indirect unlawful payment or benefit to any foreign or domestic government or regulatory official or employee, including of any government-owned or controlled entity or of a public international organization, or any person acting in an official capacity for or on behalf of any of the foregoing, or any political party or party official or candidate for political office; (iii) violated or is in violation of any provision of the Foreign Corrupt Practices Act of 1977, as amended, or any applicable law or regulation implementing the OECD Convention on Combating Bribery of Foreign Public Officials in International Business Transactions, or committed an offence under the Bribery Act 2010 of the United Kingdom, or any other applicable anti-bribery or anti-corruption laws; or (iv) made, offered, agreed, requested or taken an act in furtherance of any unlawful bribe or other unlawful benefit, including, without limitation, any rebate, payoff, influence payment, kickback or other unlawful or improper payment or benefit. The Company and its Subsidiaries have instituted, maintain and enforce, and will continue to maintain and enforce policies and procedures designed to promote and ensure compliance with all applicable anti- bribery and anti-corruption laws. 4.24. Compliance with Anti-Money Laundering Laws. The operations of the Company and its Subsidiaries are and have been conducted at all times in compliance with applicable financial recordkeeping and reporting requirements, including those of the Currency and Foreign Transactions Reporting Act of 1970, as amended, the applicable money laundering statutes of all jurisdictions where the Company or any of its Subsidiaries conducts business, the rules and regulations thereunder and any related or similar rules, regulations or guidelines issued, administered or enforced by any governmental or regulatory agency (collectively, the “Anti-Money Laundering Laws”) and no action, suit or proceeding by or before any court or governmental or regulatory agency, authority or body or any arbitrator involving the Company or any of its Subsidiaries with respect to the Anti-Money Laundering Laws is pending or, to the knowledge of the Company, threatened. 4.25. No Conflicts with Sanctions Laws. Neither the Company nor any of its Subsidiaries, directors, officers or employees, nor, to the knowledge of the Company, any agent, or affiliate or other person associated with or acting on behalf of the Company or any of its Subsidiaries is currently the subject or the target of any sanctions administered or enforced by the U.S. Government, (including, without limitation, the Office of Foreign Assets Control of the U.S. Department of the Treasury or the U.S. Department of State and including, without limitation, the designation as a “specially designated national” or “blocked person”), the United Nations Security Council, the European Union, His Majesty’s Treasury, or other relevant sanctions authority (collectively, “Sanctions”), nor is the Company or any of its Subsidiaries located, organized or resident in a country or territory that is the subject or the target of Sanctions, including, without limitation, Cuba, Iran, North Korea, Sudan, Syria, and the Crimea Region of the Ukraine (each, a “Sanctioned Country”); and the Company will not directly or indirectly use the proceeds of the offering of the Shares hereunder, or lend, contribute or otherwise make available such proceeds to any subsidiary, joint venture partner or other person or entity (i) to fund or facilitate any activities of or business with any person that, at the time of such funding or facilitation, is the subject or the target of Sanctions, (ii) to fund or facilitate any activities of or business in any Sanctioned Country or (iii) in any other manner that will result in a violation by any person (including any person participating in the transaction, whether as underwriter, advisor, investor or otherwise) of Sanctions. For the past five years, the Company and its Subsidiaries have not knowingly engaged in and are not now knowingly engaged in any dealings or transactions with any person that at the time of the dealing or transaction is or was the subject or the target of Sanctions or with any Sanctioned Country. 4.26. Transactions with Affiliates. Except as disclosed in the SEC Filings, none of the executive officers or directors of the Company or its Subsidiaries and, to the Company’s Knowledge, none of the employees of the Company or its Subsidiaries is presently a party to any transaction with the Company (other than as holders of stock options and/or warrants, and for services as employees, officers and directors) that is required to be disclosed under Item 404 of Regulation S-K under the 1933 Act. 4.27. Internal Controls. The Company has established and maintains disclosure controls and procedures (as defined in Rules 13a-15 and 15d-15 under the 1934 Act), which are designed to ensure that material information relating to the Company, including its consolidated Subsidiaries, is made known to the Company’s principal executive officer and its principal financial officer by others within those entities. Except as described in the SEC Filings, since the end of the Company’s most recent audited fiscal year, there have been no significant deficiencies or material weakness in the Company’s internal control over financial reporting (whether or not remediated) and no change in the Company’s internal control over financial reporting that has materially affected, or is reasonably likely to materially affect, the Company’s internal control over financial reporting. The Company is not aware of any change in its internal controls over financial reporting that has occurred during its most recent fiscal quarter that has materially affected, or is reasonably likely to materially affect, the Company’s internal control over financial reporting. 4.28. Required Filings. Except for the transactions contemplated by this Agreement, including the acquisition of the Shares contemplated hereby, no event or circumstance has occurred or information exists with respect to the Company or its business, properties, operations or financial condition, which, under applicable law, rule or regulation, requires public disclosure or announcement by the Company but which has not been so publicly announced or disclosed (assuming for this purpose that the SEC Filings are being incorporated by reference into an effective registration statement filed by the Company under the 1933 Act). 4.29. Investment Company. The Company is not required to be registered as, and is not an Affiliate of, and immediately following the Closing will not be required to register as, an “investment company” within the meaning of the Investment Company Act of 1940, as amended. 4.30. Tests and Preclinical and Clinical Trials. The studies, tests and preclinical and clinical trials conducted by or, to the Company’s Knowledge, on behalf of the Company that are described in the SEC Filings were and, if still pending, are being, conducted in all material respects in accordance with the protocols submitted to the U.S. Food and Drug Administration (the “FDA”) or any foreign governmental body exercising comparable authority, procedures and controls pursuant to, where applicable, accepted professional and scientific standards, and all applicable laws and regulations; the descriptions of the studies, tests and preclinical and clinical trials conducted by or, to the Company’s Knowledge, on behalf of the Company, and the results thereof, contained in the SEC Filings are accurate and complete in all material respects; the Company is not aware of any other studies, tests or preclinical and clinical trials, the results of which call into question the results described in the SEC Filings; and the Company has not received any notices or correspondence from the FDA, any foreign, state or local governmental body exercising comparable authority or any Institutional Review Board requiring the termination, suspension, material modification or clinical hold of any studies, tests or preclinical or clinical trials conducted by or on behalf of the Company. 4.31. Labor. Neither the Company nor any of its Subsidiaries is bound by or subject to any collective bargaining agreement or any similar agreement with any organization representing its employees. No labor problem or dispute with the employees of the Company and its Subsidiaries exists or, to the Company’s Knowledge, is threatened, and the Company is not aware of any existing or imminent labor disturbance by the employees of any of its principal suppliers or contractors, that could have a Material Adverse Effect, whether or not arising from transactions in the ordinary course of business, except as contemplated in the Company SEC Filings. 4.32. Passive Foreign Investment Company; Controlled Foreign Company. Neither the Company nor its Subsidiaries will be deemed to constitute a “passive foreign investment company” within the meaning of 26 USC §1297(a) or a “controlled foreign company” within the meaning of 26 USC §957. 4.33. Regulation M Compliance. The Company has not, and to the Company’s Knowledge no one acting on its behalf has, (i) taken, directly or indirectly, any action designed to cause or to result in the stabilization or manipulation of the price of any security of the Company to facilitate the sale or resale of any of the Shares, (ii) sold, bid for, purchased, or paid any compensation for soliciting purchases of, any of the Shares, or (iii) paid or agreed to pay to any Person any compensation for soliciting another to purchase any other securities of the Company. 4.34. No Disqualification Events. With respect to the Shares to be offered and sold hereunder in reliance on Rule 506 under the 1933 Act, none of the Company, any of its predecessors, any affiliated issuer, any director, executive officer, other officer of the Company participating in the offering hereunder, any beneficial owner of 20% or more of the Company’s outstanding voting equity securities, calculated on the basis of voting power, nor any promoter (as that term is defined in Rule 405 under the 1933 Act) connected with the Company in any capacity at the time of sale (each, an “Issuer Covered Person” and, together, “Issuer Covered Persons”) is subject to any of the “Bad Actor” disqualifications described in Rule 506(d)(1)(i) to (viii) under the Securities Act (a “Disqualification Event”), except for a Disqualification Event covered by Rule 506(d)(2) or (d)(3). The Company has exercised reasonable care to determine whether any Issuer Covered Person is subject to a Disqualification Event. The Company has complied, to the extent applicable, with its disclosure obligations under Rule 506(e), and has furnished to the Purchasers a copy of any disclosures provided thereunder. 4.35. Other Covered Persons. The Company is not aware of any person (other than any Issuer Covered Person) that has been or will be paid (directly or indirectly) remuneration for solicitation of purchasers in connection with the sale of any Shares. 4.36. Notice of Disqualification Events. The Company will notify the Investors in writing, prior to the Closing Date of (i) any Disqualification Event relating to any Issuer Covered Person and (ii) any event that would, with the passage of time, become a Disqualification Event relating to any Issuer Covered Person. 4.37. Full Disclosure. The written materials delivered to the Investors in connection with the transactions contemplated by the Transaction Documents, when considered together with the SEC filings, do not contain any untrue statement of a material fact or omit to state a material fact necessary in order to make the statements contained therein, in light of the circumstances under which they were made, not misleading. The Company understands and confirms that the Investors will rely on the foregoing representations in effecting transactions in securities of the Company. 5. Company that: Representations and Warranties of the Investor. The Investor hereby represents and warrants to the 5.1. Organization and Existence. The Investor is a validly existing corporation and has all requisite corporate power and authority to enter into and consummate the transactions contemplated hereby and to carry out its obligations hereunder and thereunder, and to invest in the Shares pursuant to this Agreement. 5.2. Authorization. The execution, delivery and performance by the Investor of this Agreement has been duly authorized and this Agreement has been duly executed and when delivered will constitute the valid and legally binding obligation of the Investor, enforceable against the Investor in accordance with its terms, subject to bankruptcy, insolvency, fraudulent transfer, reorganization, moratorium and similar laws of general applicability, relating to or affecting creditors’ rights generally. 5.3. Purchase Entirely for Own Account. The Shares to be received by the Investor hereunder will be acquired for the Investor’s own account, not as nominee or agent, and not with a view to the resale or distribution of any part thereof in violation of the 1933 Act, and the Investor has no present intention of selling, granting any participation in, or otherwise distributing the same in violation of the 1933 Act without prejudice, however, to the Investor’s right at all times to sell or otherwise dispose of all or any part of such Shares in compliance with applicable federal and state securities laws. Nothing contained herein shall be deemed a representation or warranty by the Investor to hold the Shares for any period of time. The Investor is not a broker- dealer registered with the SEC under the 1934 Act or an entity engaged in a business that would require it to be so registered. 5.4. Investment Experience. The Investor acknowledges that it can bear the economic risk and complete loss of its investment in the Shares and has such knowledge and experience in financial or business matters that it is capable of evaluating the merits and risks of the investment contemplated hereby. 5.5. Disclosure of Information. The Investor has had an opportunity to receive, review and understand all information related to the Company requested by it and to ask questions of and receive answers from the Company regarding the Company, its business and the terms and conditions of the offering of the Shares, and has conducted and completed its own independent due diligence. Based on the information the Investor has deemed appropriate it has independently made its own analysis and decision to enter into this Agreement. The Investor is relying exclusively on its own sources of information, investment analysis and due diligence (including professional advice it deems appropriate) with respect to the execution, delivery and performance of this Agreement, the Shares and the business, condition (financial and otherwise), management, operations, properties and prospects of the Company, including but not limited to all business, legal, regulatory, accounting, credit and tax matters. Neither such inquiries nor any other due diligence investigation conducted by the Investor shall modify, limit or otherwise affect the Investor’s right to rely on the Company’s representations and warranties contained in this Agreement. 5.6. Restricted Securities. The Investor understands that the Shares are characterized as “restricted securities” under the U.S. federal securities laws inasmuch as they are being acquired from the Company in a transaction not involving a public offering and that under such laws and applicable regulations such securities may be resold without registration under the 1933 Act only in certain limited circumstances. 5.7. Legends. It is understood that, except as provided below, certificates evidencing the Shares may bear the following or any similar legend: “THE SECURITIES REPRESENTED HEREBY HAVE NOT BEEN REGISTERED WITH THE SECURITIES AND EXCHANGE COMMISSION OR THE SECURITIES COMMISSION OF ANY STATE IN RELIANCE UPON AN EXEMPTION FROM REGISTRATION UNDER THE SECURITIES ACT OF 1933, AS AMENDED, AND, ACCORDINGLY, MAY NOT BE TRANSFERRED UNLESS (I) SUCH SECURITIES HAVE BEEN REGISTERED FOR SALE PURSUANT TO THE SECURITIES ACT OF 1933, AS AMENDED, (II) SUCH SECURITIES MAY BE SOLD PURSUANT TO RULE 144 OR OTHER AVAILABLE EXEMPTION, OR (III) THE COMPANY HAS RECEIVED AN OPINION OF COUNSEL REASONABLY SATISFACTORY TO IT THAT SUCH TRANSFER MAY LAWFULLY BE MADE WITHOUT REGISTRATION UNDER THE SECURITIES ACT OF 1933, AS AMENDED.” If required by the authorities of any state in connection with the issuance of sale of the Shares, the legend required by such state authority. 5.8. Accredited Investor. The Investor is (a) an “accredited investor” within the meaning of Rule 501(a)(1), (2), (3) or (7) under the 1933 Act and (b) an Institutional Account as defined in FINRA Rule 4512(c). The investor is a sophisticated institutional investor with sufficient knowledge and experience in investing in private placement transactions to properly evaluate the risks and merits of its purchase of the Shares. 5.9. No General Solicitation. The Investor did not learn of the investment in the Shares as a result of any general solicitation or general advertising. 5.10. Brokers and Finders. No Person will have as a result of the transactions contemplated hereby any valid right, interest or claim against or upon the Company or an Investor for any commission, fee or other compensation pursuant to any agreement, arrangement or understanding entered into by or on behalf of the Investor. 5.11. Short Sales and Confidentiality Prior to the Date Hereof. Other than consummating the transactions contemplated hereunder, the Investor has not, nor has any Person acting on behalf of or pursuant to any understanding with the Investor, directly or indirectly executed any purchases or sales, including Short Sales, of the securities of the Company during the period commencing as of the time that the Investor was first contacted by the Company or any other Person regarding the transactions contemplated hereby. Other than to its authorized representatives and advisors, the Investor has maintained the confidentiality of all disclosures made to it in connection with this transaction (including the existence and terms of this transaction). Notwithstanding the foregoing, for avoidance of doubt, nothing contained herein shall constitute a representation or warranty, or preclude any actions, with respect to the identification of the availability of, or securing of, available shares to borrow in order to effect Short Sales or similar transactions in the future. 5.12. No Government Recommendation or Approval. The Investor understands that no United States federal or state agency, or similar agency of any other country, has reviewed, approved, passed upon, or made any recommendation or endorsement of the Company or the purchase of the Shares. 5.13. No Intent to Effect a Change of Control; Ownership. The Investor has no present intent to effect a “change of control” of the Company as such term is understood under the rules promulgated pursuant to Section 13(d) of the 1934 Act and under the rules of Nasdaq. 5.14. No Conflicts. The execution, delivery and performance by the Investor of this Agreement and the consummation of the transactions contemplated hereby will not (i) result in a violation of the organizational documents of the Investor or (ii) conflict with, or constitute a default (or an event which with notice or lapse of time or both would become a default) under, or give to others any rights of termination, amendment, acceleration or cancellation of, any agreement, indenture or instrument to which the Investor is a party, or (iii) to the Investor’s knowledge, result in a violation of any law, rule, regulation, order, judgment or decree (including federal and state securities laws) applicable to the Investor, except in the case of clauses (ii) and (iii) above, for such conflicts, defaults, rights or violations which would not, individually or in the aggregate, reasonably be expected to have a material adverse effect on the ability of the Investor to perform its obligations hereunder. 5.15. No Rule 506 Disqualifying Activities. The Investor has not taken any of the actions set forth in, and is not subject to, the disqualification provisions of Rule 506(d)(1) of the 1933 Act. 5.16. Residency. The Investor is a resident of the jurisdiction specified in its address in Section 9.4. The Company acknowledges and agrees that the representations contained in this Section 5 shall not modify, amend or affect the Investor’s right to rely on the Company’s representations and warranties contained herein. 6. Conditions to Closing. 6.1. Conditions to the Investor’s Obligations. The obligation of the Investor to purchase Shares at the Closing is subject to the fulfillment to the Investor’s satisfaction, on or prior to the Closing Date, of the following conditions, any of which may be waived by the Investor: (a) The representations and warranties made by the Company in Section 4 hereof shall be true and correct in all material respects (or to the extent representations or warranties are qualified by materiality or Material Adverse Effect, in all respects) as of the date hereof and on the Closing Date, except to the extent any such representation or warranty expressly speaks as of an earlier date, in which case such representation or warranty shall be true and correct as of such earlier date. The Company shall have performed in all material respects all obligations and covenants herein required to be performed by it on or prior to the Closing Date. (b) The Company shall have obtained any and all consents, permits, approvals, registrations and waivers necessary for consummation of the purchase and sale of the Shares and the consummation of the other transactions contemplated by this Agreement, all of which shall be in full force and effect. (c) Registration Rights Agreement. Within three days of the Closing the Company shall have executed and delivered the (d) No judgment, writ, order, injunction, award or decree of or by any court, or judge, justice or magistrate, including any bankruptcy court or judge, or any order of or by any governmental authority, shall have been issued, and no action or proceeding shall have been instituted by any governmental authority, enjoining or preventing the consummation of the transactions contemplated hereby. (e) There shall have been no Material Adverse Effect with respect to the Company since the date hereof. (f) Within three days of the Closing the Company shall have delivered to the Investor a Certificate, executed on behalf of the Company by its Chief Executive Officer or its Chief Financial Officer, dated as of such date, certifying to the fulfillment of the conditions specified in subsections (a), (b), (d) and (e) of this Section 6.1. (g) Within three days of the Closing the Company shall have delivered to the Investor a Certificate, executed on behalf of the Company by its Chief Operating Officer, dated as of such date, certifying the resolutions adopted by the Board of Directors of the Company approving the transactions contemplated by this Agreement and the other Transaction Documents and the issuance of the Shares, certifying the current versions of the Articles of Association of the Company and certifying as to the signatures and authority of persons signing the Transaction Documents and related documents on behalf of the Company. (h) Within three days of the Closing the Investor shall have received an opinion from each of Latham & Watkins LLP, United States counsel for the Company, and Walkers (Cayman) LLP, Cayman Islands counsel for the Company, and dated as of such date, in form and substance reasonably acceptable to the Investor. (i) No stop order or suspension of trading shall have been imposed by Nasdaq, the SEC or any other governmental or regulatory body with respect to public trading in the Ordinary Shares. 6.2. Conditions to Obligations of the Company. The Company’s obligation to sell and issue Shares at the Closing is subject to the fulfillment to the satisfaction of the Company on or prior to the Closing Date of the following conditions, any of which may be waived by the Company: (a) The representations and warranties made by the Investor in Section 5 hereof shall be true and correct in all material respects when made, and shall be true and correct in all material respects on the Closing Date with the same force and effect as if they had been made on and as of said date. The Investor shall have performed in all material respects all obligations and covenants herein required to be performed by them on or prior to the Closing Date. (b) The Investor shall have paid in full its Subscription Amount to the Company. 6.3. Termination of Obligations to Effect Closing; Effects. (a) The obligations of the Company, on the one hand, and the Investor, on the other hand, to effect the Closing shall terminate as follows: (i) (ii) Upon the mutual written consent of the Company and the Investor; By the Company if any of the conditions set forth in Section 6.2 shall have become incapable of fulfillment, and shall not have been waived by the Company; or (iii) By the Investor if any of the conditions set forth in Section 6.1 shall have become incapable of fulfillment, and shall not have been waived by the Investor; provided, however, that, except in the case of clause (i) above, the party seeking to terminate its obligation to effect the Closing shall not then be in breach of any of its representations, warranties, covenants or agreements contained in this Agreement if such breach has resulted in the circumstances giving rise to such party’s seeking to terminate its obligation to effect the Closing. (b) Nothing in this Section 6.3 shall be deemed to release any party from any liability for any breach by such party of the terms and provisions of this Agreement or to impair the right of any party to compel specific performance by any other party of its obligations under this Agreement. 7. Covenants and Agreements of the Parties. 7.1. Reports. The Company will furnish to the Investor and/or its assignees such information relating to the Company as from time to time may reasonably be requested by the Investor and/or its assignees; provided, however, that the Company shall not disclose material nonpublic information to the Investor, or to advisors to or representatives of the Investor, unless prior to disclosure of such information the Company identifies such information as being material nonpublic information and provides the Investor, such advisors and representatives with the opportunity to accept or refuse to accept such material nonpublic information for review and the Investor wishing to obtain such information enters into an appropriate confidentiality agreement with the Company with respect thereto. 7.2. No Conflicting Agreements. The Company will not take any action, enter into any agreement or make any commitment that would conflict or interfere in any material respect with the Company’s obligations to the Investor under the Transaction Documents. 7.3. Form D; Blue Sky Filings. The Company shall take such action as the Company shall reasonably determine is necessary in order to obtain an exemption for, or to qualify the Shares for, sale to each Investor at the Closing under applicable securities or “Blue Sky” laws of the states of the United States, and shall provide evidence of such actions promptly upon request of such Investor. 7.4. Reporting Status. The Company shall timely file all reports required to be filed with the SEC pursuant to the 1934 Act, and the Company shall not terminate its status as an issuer required to file reports under the 1934 Act even if the 1934 Act or the rules and regulations thereunder would otherwise permit such termination. 7.5. Compliance with Laws. The Company will comply in all material respects with all applicable laws, rules, regulations, orders and decrees of all governmental authorities. 7.6. Nasdaq Listing. The Company will use commercially reasonable efforts to continue the listing and trading of its Ordinary Shares on Nasdaq and, in accordance, therewith, will use commercially reasonable efforts to comply in all respects with the Company’s reporting, filing and other obligations under the bylaws or rules of such market or exchange, as applicable. 7.7. Termination of Covenants. The provisions of Sections 7.1 through 7.5 shall terminate and be of no further force and effect on the date on which the Company’s obligations under the Registration Rights Agreement to register or maintain the effectiveness of any registration covering the Registrable Securities (as such term is defined in the Registration Rights Agreement) shall terminate. 7.8. Removal of Legends. In connection with any sale or disposition of the Shares by an Investor pursuant to Rule 144 or pursuant to any other exemption under the 1933 Act such that the purchaser acquires freely tradable shares and upon compliance by the Investor with the requirements of this Agreement, if requested by the Investor, the Company shall cause the transfer agent for the Ordinary Shares (the “Transfer Agent”) to timely remove any restrictive legends related to the book entry account holding such Shares and make a new, unlegended entry for such book entry Shares sold or disposed of without restrictive legends, provided that the Company has received customary representations and other documentation reasonably acceptable to the Company in connection therewith. Subject to receipt by the Company of customary representations and other documentation reasonably acceptable to the Company in connection therewith, upon the earlier of such time as the Shares (i) have been registered under the 1933 Act pursuant to an effective registration statement, (ii) have been sold pursuant to Rule 144, or (iii) are eligible for resale under Rule 144(b)(1) or any successor provision, the Company shall (A) deliver to the Transfer Agent irrevocable instructions that the Transfer Agent shall make a new, unlegended entry for such book entry Shares, and (B) cause its counsel to deliver to the Transfer Agent one or more opinions to the effect that the removal of such legends in such circumstances may be effected under the 1933 Act. The Company shall be responsible for the fees of its Transfer Agent and all DTC fees associated with such issuance. 7.9. Subsequent Equity Sales. From the date hereof until six months after the Closing Date, the Investor shall not, directly or indirectly, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase or otherwise transfer or dispose of any Ordinary Shares or any securities convertible into or exercisable or exchangeable for Ordinary Shares or enter into any swap or any other agreement or any transaction that transfers, in whole or in part, directly or indirectly, the economic consequence of ownership of Ordinary Shares. 7.10. Securities Laws. The Investor hereby acknowledges its obligations under the U.S. federal securities laws, including with respect to the prohibition of any person in possession of “material non-public information” about a company from purchasing or selling, directly or indirectly, securities of such company (including entering into short selling or hedge transactions involving such securities), or from communicating such information to any other person under circumstances in which it is reasonably foreseeable that such person is likely to purchase or sell such securities. 7.11. Passive Foreign Investment Company; Controlled Foreign Corporation. Not later than forty-five (45) days after the end of Company’s fiscal year, the Company will determine whether it and each of its Subsidiaries constitutes a “passive foreign investment company” (a “PFIC”) or a “controlled foreign corporation” (a “CFC”) as defined for U.S. tax purposes for such fiscal year and if Company determines it is a PFIC or CFC, will so advise each Investor. For each fiscal year of the Company, commencing with the first fiscal year for which it is determined to be a PFIC, the Company and each of its Subsidiaries shall no later than ninety (90) days after the end of such fiscal year, furnish the Investor with all information necessary for it to make a qualified electing fund (“QEF”) election, including (i) a PFIC Annual Information Statement under Section 1295(b) of the U.S. Internal Revenue Code, as amended (the “Code”) and (ii) all information necessary for it to complete IRS Form 8621 (or a successor form). All information shall be provided in English. The Company will obtain the advice of one of the “big four” accounting firms to make the determinations and provide the information and statements as described in this paragraph. 8. Survival and Indemnification. 8.1. Survival. The representations, warranties, covenants and agreements contained in this Agreement shall survive the Closing of the transactions contemplated by this Agreement for the applicable statute of limitations. 8.2. Indemnification. The Company agrees to indemnify and hold harmless the Investor and its Affiliates and their respective directors, officers, trustees, members, managers, employees and agents, and their respective successors and assigns, from and against any and all losses, claims, damages, liabilities and expenses, including without limitation reasonable attorney fees and disbursements and other expenses reasonably incurred in connection with investigating, preparing or defending any action, claim or proceeding, pending or threatened and the costs of enforcement thereof (collectively, “Losses”), to which such Person may become subject as a result of or relating to (a) any breach of representation, warranty, covenant or agreement made by or to be performed on the part of the Company under this Agreement or (b) any action instituted against the Investor or its Affiliates by any stockholder of the Company who is not an Affiliate of the Investor, with respect to any of the transactions contemplated by this Agreement (unless such action is based upon a breach of the Investor’s representations, warranties or covenants under this Agreement or any conduct by the Investor or its Affiliates which constitutes fraud, gross negligence, willful misconduct or malfeasance), and will reimburse any such Person for all such amounts as they are incurred by such Person. 8.3. Conduct of Indemnification Proceedings. Any person entitled to indemnification hereunder shall (i) give prompt notice to the indemnifying party of any claim with respect to which it seeks indemnification and (ii) permit such indemnifying party to assume the defense of such claim with counsel reasonably satisfactory to the indemnified party; provided that any person entitled to indemnification hereunder shall have the right to employ separate counsel and to participate in the defense of such claim, but the fees and expenses of such counsel shall be at the expense of such person unless (a) the indemnifying party has agreed to pay such fees or expenses, (b) the indemnifying party shall have failed to assume the defense of such claim and employ counsel reasonably satisfactory to such person or (c) in the reasonable judgment of any such person, based upon written advice of its counsel, a conflict of interest exists between such person and the indemnifying party with respect to such claims (in which case, if the person notifies the indemnifying party in writing that such person elects to employ separate counsel at the expense of the indemnifying party, the indemnifying party shall not have the right to assume the defense of such claim on behalf of such person); and provided, further, that the failure of any indemnified party to give notice as provided herein shall not relieve the indemnifying party of its obligations hereunder, except to the extent that such failure to give notice shall materially adversely affect the indemnifying party in the defense of any such claim or litigation. It is understood that the indemnifying party shall not, in connection with any proceeding in the same jurisdiction, be liable for fees or expenses of more than one separate firm of attorneys at any time for such indemnified party. No indemnifying party will, except with the consent of the indemnified party, which consent shall not be unreasonably withheld, conditioned or delayed, consent to entry of any judgment or enter into any settlement that does not include as an unconditional term thereof the giving by the claimant or plaintiff to such indemnified party of a release from all liability in respect of such claim or litigation. No indemnified party will, except with the consent of the indemnifying party, consent to entry of any judgment or enter into any settlement. The indemnity agreements contained herein shall be in addition to any cause of action or similar right of the Investor or its Affiliates against the Company or others and any liabilities the Company may be subject to pursuant to law. 9. Miscellaneous. 9.1. Successors and Assigns. This Agreement may not be assigned by a party hereto without the prior written consent of the Company or the Investor, as applicable, provided, however, that the Investor may assign its rights and delegate its duties hereunder in whole or in part to an Affiliate or to a third party acquiring some or all of its Shares in a transaction complying with applicable securities laws without the prior written consent of the Company, provided such assignee agrees in writing to be bound by the provisions hereof that apply to the Investor. The provisions of this Agreement shall inure to the benefit of and be binding upon the respective permitted successors and assigns of the parties. Without limiting the generality of the foregoing, in the event that the Company is a party to a merger, consolidation, share exchange or similar business combination transaction in which the Ordinary Shares are converted into the equity securities of another Person, from and after the effective time of such transaction, such Person shall, by virtue of such transaction, be deemed to have assumed the obligations of the Company hereunder, the term “Company” shall be deemed to refer to such Person and the term “Shares” shall be deemed to refer to the securities received by the Investors in connection with such transaction. Nothing in this Agreement, express or implied, is intended to confer upon any party other than the parties hereto or their respective permitted successors and assigns any rights, remedies, obligations, or liabilities under or by reason of this Agreement, except as expressly provided in this Agreement. 9.2. Counterparts; Faxes; E-mail. This Agreement may be executed in one or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. This Agreement may also be executed via facsimile or e-mail, which shall be deemed an original. 9.3. Titles and Subtitles. The titles and subtitles used in this Agreement are used for convenience only and are not to be considered in construing or interpreting this Agreement. 9.4. Notices. Unless otherwise provided, any notice required or permitted under this Agreement shall be given in writing and shall be deemed effectively given as hereinafter described (i) if given by personal delivery, then such notice shall be deemed given upon such delivery, (ii) if given by facsimile, then such notice shall be deemed given upon receipt of confirmation of complete transmittal, (iii) if given by mail, then such notice shall be deemed given upon the earlier of (A) receipt of such notice by the recipient or (B) three days after such notice is deposited in first class mail, postage prepaid, and (iv) if given by an internationally recognized overnight air courier, then such notice shall be deemed given one Business Day after delivery to such carrier. All notices shall be addressed to the party to be notified at the address as follows, or at such other address as such party may designate by ten days’ advance written notice to the other party: If to the Company: MeiraGTx Holdings plc 450 East 29th Street, 14th Floor New York, New York 10016 Attn: Rich Giroux With a copy to: legalnotices@meiragtx.com And a copy to: Latham & Watkins LLP 200 Clarendon Street Boston, Massachusetts 02116 Attn: Peter N. Handrinos, Esq. If to the Investor: Johnson & Johnson Innovation – JJDC, Inc. 410 George Street New Brunswick, New Jersey 08091 Attn: Linda Vogel and Kelvin Lin With a copy to: LVogel@ITS.JNJ.com; KLin18@ITS.JNJ.com; JJDCOperations@its.jnj.com And a copy to: Ropes & Gray LLP 800 Boylston Street Boston, Massachusetts 02199 Attn: Christopher D. Comeau 9.5. Expenses. Within three days of the Closing, the Company has agreed to reimburse the Investor up to $75,000 for its legal fees and expenses. Except as set forth herein to the contrary, the parties hereto shall pay their own costs and expenses in connection herewith regardless of whether the transactions contemplated hereby are consummated; it being understood that each of the Company and the Investor has relied on the advice of its own respective counsel. In the event that legal proceedings are commenced by any party to this Agreement against another party to this Agreement in connection with this Agreement, the party or parties which do not prevail in such proceedings shall severally, but not jointly, pay their pro rata share of the reasonable attorneys’ fees and other reasonable documented out-of-pocket costs and expenses incurred by the prevailing party in such proceedings. 9.6. Amendments and Waivers. Any term of this Agreement may be amended and the observance of any term of this Agreement may be waived (either generally or in a particular instance and either retroactively or prospectively), only with the written consent of the other party hereto. 9.7. Publicity. Except as set forth below, no public release or announcement concerning the transactions contemplated hereby shall be issued by the Investor without the prior written consent of the Company (which consent shall not be unreasonably withheld), except as such release or announcement may be required by law or the applicable rules or regulations of any securities exchange or securities market, in which case the Investor shall allow the Company, to the extent reasonably practicable in the circumstances, reasonable time to comment on such release or announcement in advance of such issuance. Notwithstanding the foregoing, the Investor may identify the Company and the value of the Investor’s security holdings in the Company in accordance with applicable investment reporting and disclosure regulations or internal policies without prior notice to or consent from the Company. The Company shall not include the name of the Investor or any Affiliate or investment adviser of the Investor in any press release or public announcement (which, for the avoidance of doubt, shall not include any SEC Filing to the extent such disclosure is required by SEC rules and regulations) without the prior written consent of the Investor (which consent shall not be unreasonably withheld). Within four trading days following the date this Agreement is executed, the Company shall (i) issue a press release disclosing all material terms of transactions contemplated by this Agreement (the “Press Release”) and/or (ii) file a Current Report on Form 8-K attaching the press release described in the foregoing sentence (as applicable) as well as a copy of this Agreement. In addition, the Company will make such filings and notices in the manner and time required by the SEC or Nasdaq. 9.8. Severability. Any provision of this Agreement that is prohibited or unenforceable in any jurisdiction shall, as to such jurisdiction, be ineffective to the extent of such prohibition or unenforceability without invalidating the remaining provisions hereof but shall be interpreted as if it were written so as to be enforceable to the maximum extent permitted by applicable law, and any such prohibition or unenforceability in any jurisdiction shall not invalidate or render unenforceable such provision in any other jurisdiction. To the extent permitted by applicable law, the parties hereby waive any provision of law which renders any provision hereof prohibited or unenforceable in any respect. 9.9. Entire Agreement. This Agreement, including the signature pages and Exhibits constitute the entire agreement among the parties hereof with respect to the subject matter hereof and thereof and supersede all prior agreements and understandings, both oral and written, between the parties with respect to the subject matter hereof and thereof. 9.10. Further Assurances. The parties shall execute and deliver all such further instruments and documents and take all such other actions as may reasonably be required to carry out the transactions contemplated hereby and to evidence the fulfillment of the agreements herein contained. 9.11. Governing Law; Consent to Jurisdiction; Waiver of Jury Trial. This Agreement shall be governed by, and construed in accordance with, the internal laws of the State of New York without regard to the choice of law principles thereof. Each of the parties hereto irrevocably submits to the exclusive jurisdiction of the courts of the State of New York located in New York County and the United States District Court for the Southern District of New York for the purpose of any suit, action, proceeding or judgment relating to or arising out of this Agreement and the transactions contemplated hereby. Service of process in connection with any such suit, action or proceeding may be served on each party hereto anywhere in the world by the same methods as are specified for the giving of notices under this Agreement. Each of the parties hereto irrevocably consents to the jurisdiction of any such court in any such suit, action or proceeding and to the laying of venue in such court. Each party hereto irrevocably waives any objection to the laying of venue of any such suit, action or proceeding brought in such courts and irrevocably waives any claim that any such suit, action or proceeding brought in any such court has been brought in an inconvenient forum. EACH OF THE PARTIES HERETO WAIVES ANY RIGHT TO REQUEST A TRIAL BY JURY IN ANY LITIGATION WITH RESPECT TO THIS AGREEMENT AND REPRESENTS THAT COUNSEL HAS BEEN CONSULTED SPECIFICALLY AS TO THIS WAIVER. 9.12. Limitation of Liability. Notwithstanding anything herein to the contrary, the Company acknowledges and agrees that the liability of the Investor arising directly or indirectly under this Agreement of any and every nature whatsoever shall be satisfied solely out of the assets of the Investor and that no trustee, officer, other investment vehicle or any other Affiliate of the Investor or any investor, shareholder or holder of shares of beneficial interest of the Investor shall be personally liable for any liabilities of the Investor. [remainder of page intentionally left blank] IN WITNESS WHEREOF, the parties have executed this Agreement or caused their duly authorized officers to execute this Agreement as of the date first above written. COMPANY: MEIRAGTX HOLDINGS PLC By: /s/ Richard Giroux Name: Richard Giroux Title: Chief Operating Officer INVESTOR: Johnson & Johnson Innovation – JJDC, Inc. By: /s/Asish Xavier Name: Asish Xavier Title: VP, Venture Investments REGISTRATION RIGHTS AGREEMENT This REGISTRATION RIGHTS AGREEMENT (this “Agreement”) is made and entered into as of November 9, 2022 by and among MeiraGTx Holdings plc, a Cayman Islands exempted company (the “Company”), and Johnson & Johnson Innovation – JJDC, Inc. (the “Investor”) in connection with that certain Securities Purchase Agreement by and among the Company and the Investor (the “Purchase Agreement”). Capitalized terms used herein have the respective meanings ascribed thereto in the Purchase Agreement unless otherwise defined herein. Exhibit 10.40 The parties hereby agree as follows: 1. Certain Definitions. As used in this Agreement, the following terms shall have the following meanings: “Investor” means the Investor identified above and any Affiliate or permitted transferee of the Investor who is a subsequent holder of Registrable Securities. “Confidential Treatment Request” means any confidential treatment request submitted to the Securities and Exchange Commission (the “SEC”) pursuant to Rule 406 of the Securities Act of 1933, as amended (the “1933 Act”) relating to certain exhibits to be filed with the Registration Statement. “Prospectus” means (i) the prospectus included in any Registration Statement, as amended or supplemented by any prospectus supplement, with respect to the terms of the offering of any portion of the Registrable Securities covered by such Registration Statement and by all other amendments and supplements to the prospectus, including post-effective amendments and all material incorporated by reference in such prospectus, and (ii) any “free writing prospectus” as defined in Rule 405 under the 1933 Act. “Register,” “registered” and “registration” refer to a registration made by preparing and filing a Registration Statement or similar document in compliance with the 1933 Act, and the declaration or ordering of effectiveness of such Registration Statement or document. “Registrable Securities” means (i) the Shares and (ii) any other securities issued or issuable as a dividend or other distribution with respect to, in exchange for or in replacement of the Shares, whether by merger, charter amendment or otherwise; provided, that, a security shall cease to be a Registrable Security upon (A) sale pursuant to a Registration Statement or Rule 144 under the 1933 Act, or (B) such security becoming eligible for sale without restriction (other than volume limitations) by the Investor pursuant to Rule 144 and without the requirement to be in compliance with Rule 144(c)(1) (or any successor thereto) promulgated under the 1933 Act. “Registration Statement” means any registration statement of the Company under the 1933 Act that covers the resale of any of the Registrable Securities pursuant to the provisions of this Agreement, amendments and supplements to such Registration Statement, including post-effective amendments, all exhibits and all material incorporated by reference in such Registration Statement. 2. Registration. (a) Registration Statements. Within 180 days following the date of this Agreement (the “Filing Deadline”), the Company shall prepare and file with the SEC one Registration Statement covering the resale of all of the Registrable Securities. Subject to any SEC comments, such Registration Statement shall include the plan of distribution attached hereto as Exhibit A. Such Registration Statement also shall cover, to the extent allowable under the 1933 Act and the rules promulgated thereunder (including Rule 416), such indeterminate number of additional shares of Ordinary Shares resulting from share splits, share dividends or similar transactions with respect to the Registrable Securities. Such Registration Statement shall not include any Ordinary Shares or other securities for the account of any other holder without the prior written consent of the Investor. Such Registration Statement (and each amendment or supplement thereto) shall be provided in accordance with Section 3(c) to the Investor prior to its filing or other submission. If a Registration Statement covering the Registrable Securities is not filed with the SEC on or prior to the Filing Deadline, the Company will make pro rata payments to the Investor, as liquidated damages and not as a penalty, in an amount equal to 1% of the aggregate amount invested by the Investor for each 30-day period or pro rata for any portion thereof following the Filing Deadline for which no Registration Statement is filed with respect to the Registrable Securities. Such payments shall constitute the Investor’s exclusive monetary remedy for such events, but shall not affect the right of the Investor to seek injunctive relief. Such payments shall be made to the Investor in cash no later than three (3) Business Days after the end of each 30-day period (the “Payment Date”). Interest shall accrue at the rate of 1% per month on any such liquidated damages payments that shall not be paid by the Payment Date until such amount is paid in full. (b) Expenses. The Company will pay all reasonable expenses associated with each Registration Statement, including filing and printing fees, the Company’s counsel and accounting fees and expenses, costs associated with clearing the Registrable Securities for sale under applicable state securities laws, listing fees, fees and expenses of one counsel to the Investor and the Investor’s reasonable expenses in connection with the registration, but excluding discounts, commissions and fees of underwriters, selling brokers, dealer managers or similar securities industry professionals with respect to the Registrable Securities being sold. (c) Effectiveness. (i) The Company shall use reasonable best efforts to have the Registration Statements declared effective as soon as practicable. The Company shall notify the Investor by e-mail as promptly as practicable, and in any event, within forty-eight (48) hours, after any Registration Statement is declared effective and shall simultaneously provide the Investor with copies of any related Prospectus to be used in connection with the sale or other disposition of the securities covered thereby. If (A) a Registration Statement is not declared effective by the SEC prior to the earlier of (i) five (5) Business Days after the SEC informs the Company in writing that no review of such Registration Statement will be made or that the SEC has no further comments on such Registration Statement or (ii) the 30th day after the Filing Deadline (or the 90th day if the SEC reviews such Registration Statement) (the “Effectiveness Deadline”) or (B) after a Registration Statement has been declared effective by the SEC, sales cannot be made pursuant to such Registration Statement for any reason (including without 2 limitation by reason of a stop order, or the Company’s failure to update such Registration Statement), but excluding any Allowed Delay (as defined below), then the Company will make pro rata payments to the Investor then holding Registrable Securities, as liquidated damages and not as a penalty, in an amount equal to 1% of the aggregate amount invested by the Investor for each thirty (30)-day period or pro rata for any portion thereof following the date by which such Registration Statement should have been effective (the “Blackout Period”). Such payments shall constitute the Investor’s exclusive monetary remedy for such events, but shall not affect the right of the Investor to seek injunctive relief. The amounts payable as liquidated damages pursuant to this paragraph shall be paid monthly within three (3) Business Days of the last day of each month following the commencement of the Blackout Period until the termination of the Blackout Period (the “Blackout Period Payment Date”). Such payments shall be made to the Investor in cash. Interest shall accrue at the rate of 1% per month on any such liquidated damages payments that shall not be paid by the Blackout Payment Date until such amount is paid in full. (ii) For not more than thirty (30) consecutive days or for a total of not more than sixty (60) days in any twelve (12) month period, the Company may suspend the use of any Prospectus included in any Registration Statement contemplated by this Section in the event that the Company determines in good faith that such suspension is necessary to (A) delay the disclosure of material non-public information concerning the Company, the disclosure of which at the time is not, in the good faith opinion of the Company, in the best interests of the Company or (B) amend or supplement the affected Registration Statement or the related Prospectus so that such Registration Statement or Prospectus shall not include an untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements therein, in the case of the Prospectus in light of the circumstances under which they were made, not misleading (an “Allowed Delay”); provided, that the Company shall promptly (a) notify the Investor in writing of the commencement of an Allowed Delay, but shall not (without the prior written consent of the Investor) disclose to the Investor any material non- public information giving rise to an Allowed Delay, (b) advise the Investor in writing to cease all sales under such Registration Statement until the end of the Allowed Delay and (c) use reasonable best efforts to terminate an Allowed Delay as promptly as practicable. (d) Rule 415; Cutback. If at any time the SEC takes the position that the offering of some or all of the Registrable Securities in a Registration Statement is not eligible to be made on a delayed or continuous basis under the provisions of Rule 415 under the 1933 Act or requires the Investor to be named as an “underwriter,” the Company shall use reasonable best efforts to persuade the SEC that the offering contemplated by such Registration Statement is a valid secondary offering and not an offering “by or on behalf of the issuer” as defined in Rule 415 and that the Investor is not an “underwriter.” The Investor shall have the right to select one legal counsel to review and oversee any registration or matters pursuant to this Section 2(d), including participation in any meetings or discussions with the SEC regarding the SEC’s position and to comment on any written submission made to the SEC with respect thereto. No such written submission with respect to this matter shall be made to the SEC to which the Investor’s counsel reasonably objects. In the event that, despite the Company’s reasonable best efforts and compliance with the terms of this Section 2(d), the SEC refuses to alter its position, the Company shall (i) remove from such Registration Statement such portion of the Registrable Securities (the “Cut Back Shares”) and/or (ii) agree to such restrictions and limitations on the registration and resale of the Registrable Securities as the SEC may require to assure the Company’s compliance 3 with the requirements of Rule 415 (collectively, the “SEC Restrictions”); provided, however, that the Company shall not agree to name the Investor as an “underwriter” in such Registration Statement without the prior written consent of the Investor. No liquidated damages shall accrue as to any Cut Back Shares until such date as the Company is able to effect the registration of such Cut Back Shares in accordance with any SEC Restrictions applicable to such Cut Back Shares (such date, the “Restriction Termination Date”). In furtherance of the foregoing, the Investor shall provide the Company with prompt written notice of its sale of substantially all of the Registrable Securities under such Registration Statement such that the Company will be able to file one or more additional Registration Statements covering the Cut Back Shares. From and after the Restriction Termination Date applicable to any Cut Back Shares, all of the provisions of this Section 2 (including the Company’s obligations with respect to the filing of a Registration Statement and its obligations to use reasonable best efforts to have such Registration Statement declared effective within the time periods set forth herein and the liquidated damages provisions relating thereto) shall again be applicable to such Cut Back Shares; provided, however, that (i) the Filing Deadline and/or the Qualification Deadline, as applicable, for such Registration Statement including such Cut Back Shares shall be ten (10) Business Days after such Restriction Termination Date, and (ii) the date by which the Company is required to obtain effectiveness with respect to such Cut Back Shares shall be the 60th day immediately after the Restriction Termination Date (or the 90th day if the SEC reviews such Registration Statement). 3. Company Obligations. The Company will use reasonable best efforts to effect the registration of the Registrable Securities in accordance with the terms hereof, and pursuant thereto the Company will, as expeditiously as possible: (a) use reasonable best efforts to cause such Registration Statement to become effective and to remain continuously effective for a period that will terminate upon the earlier of (i) the date on which all Registrable Securities covered by such Registration Statement as amended from time to time, have been sold, and (ii) the date on which all Registrable Securities covered by such Registration Statement may be sold without restriction (other than volume limitations) pursuant to Rule 144 and without the requirement to be in compliance with Rule 144(c)(1) (or any successor thereto) promulgated under the 1933 Act (the “Effectiveness Period”) and advise the Investor promptly in writing when the Effectiveness Period has expired; (b) prepare and file with the SEC such amendments and post-effective amendments to such Registration Statement and the related Prospectus as may be necessary to keep such Registration Statement effective for the Effectiveness Period and to comply with the provisions of the 1933 Act and the 1934 Act with respect to the distribution of all of the Registrable Securities covered thereby; (c) provide copies to and permit a counsel designated by the Investor to review each Registration Statement and all amendments and supplements thereto no fewer than three (3) days prior to their filing with the SEC and not file any document to which such counsel reasonably objects; (d) furnish to the Investor whose Registrable Securities are included in any Registration Statement (i) promptly after the same is prepared and filed with the SEC, if requested by the Investor, one (1) copy of any Registration Statement and any amendment 4 thereto, each preliminary prospectus and Prospectus and each amendment or supplement thereto, and each letter written by or on behalf of the Company to the SEC or the staff of the SEC, and each item of correspondence from the SEC or the staff of the SEC, in each case relating to such Registration Statement (other than any portion of any thereof which contains information for which the Company has sought confidential treatment), and (ii) such number of copies of a Prospectus, including a preliminary prospectus, and all amendments and supplements thereto and such other documents as the Investor may reasonably request in order to facilitate the disposition of the Registrable Securities owned by the Investor; (e) use reasonable best efforts to (i) prevent the issuance of any stop order or other suspension of effectiveness and, (ii) if such order is issued, obtain the withdrawal of any such order at the earliest possible moment; (f) prior to any public offering of Registrable Securities, use reasonable best efforts to register or qualify or cooperate with the Investor and its counsel in connection with the registration or qualification of such Registrable Securities for the offer and sale under the securities or blue sky laws of such jurisdictions requested by the Investor and do any and all other commercially reasonable acts or things necessary or advisable to enable the distribution in such jurisdictions of the Registrable Securities covered by the Registration Statement; provided, however, that the Company shall not be required in connection therewith or as a condition thereto to (i) qualify to do business in any jurisdiction where it would not otherwise be required to qualify but for this Section 3(f), (ii) subject itself to general taxation in any jurisdiction where it would not otherwise be so subject but for this Section 3(f), or (iii) file a general consent to service of process in any such jurisdiction; (g) use reasonable best efforts to cause all Registrable Securities covered by a Registration Statement to be listed on each securities exchange, interdealer quotation system or other market on which similar securities issued by the Company are then listed; (h) promptly notify the Investor, at any time prior to the end of the Effectiveness Period, upon discovery that, or upon the happening of any event as a result of which, the Prospectus includes an untrue statement of a material fact or omits to state any material fact required to be stated therein or necessary to make the statements therein not misleading in light of the circumstances then existing, and promptly prepare, file with the SEC and furnish to such holder a supplement to or an amendment of such Prospectus as may be necessary so that such Prospectus shall not include an untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary to make the statements therein not misleading in light of the circumstances then existing; (i) otherwise use reasonable best efforts to comply with all applicable rules and regulations of the SEC under the 1933 Act and the 1934 Act, including, without limitation, Rule 172 under the 1933 Act, file any final Prospectus, including any supplement or amendment thereof, with the SEC pursuant to Rule 424 under the 1933 Act, promptly inform the Investor in writing if, at any time during the Effectiveness Period, the Company does not satisfy the conditions specified in Rule 172 and, as a result thereof, the Investor is required to deliver a Prospectus in connection with any disposition of Registrable Securities and take such other actions as may be reasonably necessary to facilitate the registration of the Registrable Securities 5 hereunder, and make available to its security holders, as soon as reasonably practicable, but not later than the Availability Date (as defined below), an earnings statement covering a period of at least twelve (12) months, beginning after the effective date of each Registration Statement, which earnings statement shall satisfy the provisions of Section 11(a) of the 1933 Act, including Rule 158 promulgated thereunder (for the purpose of this subsection 3(i), “Availability Date” means the 45th day following the end of the fourth fiscal quarter that includes the effective date of such Registration Statement, except that, if such fourth fiscal quarter is the last quarter of the Company’s fiscal year, “Availability Date” means the 90th day after the end of such fourth fiscal quarter); (j) with a view to making available to the Investor the benefits of Rule 144 (or its successor rule) and any other rule or regulation of the SEC that may at any time permit the Investor to sell Ordinary Shares to the public without registration, the Company covenants and agrees to: (i) make and keep public information available, as those terms are understood and defined in Rule 144, until the earlier of (A) six months after such date as all of the Registrable Securities may be sold without restriction by the holders thereof pursuant to Rule 144 or any other rule of similar effect or (B) such date as there are no longer Registrable Securities; (ii) file with the SEC in a timely manner all reports and other documents required of the Company under the 1934 Act; and (iii) furnish electronically to the Investor upon request, as long as the Investor owns any Registrable Securities, (A) a written statement by the Company that it has complied with the reporting requirements of the 1934 Act, (B) a copy of or electronic access to the Company’s most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q, and (C) such other information as may be reasonably requested in order to avail the Investor of any rule or regulation of the SEC that permits the selling of any such Registrable Securities without registration; and (k) if requested by an Investor, cooperate with the Investor to facilitate the timely preparation and delivery of certificates representing Registrable Securities to be delivered to a transferee pursuant to an effective Registration Statement, which certificates shall be free, to the extent permitted by the Purchase Agreements and applicable law, of all restrictive legends, and to enable such certificates to be in such denominations and registered in such names as the Investor may request. 4. Due Diligence Review; Information. If the Investor is required under applicable securities laws to be described in a Registration Statement as an “underwriter,” the Company shall, upon reasonable prior notice, make available, during normal business hours, for inspection and review by the Investor, advisors to and representatives of the Investor (who may or may not be affiliated with the Investor and who are reasonably acceptable to the Company) (collectively, the “Inspectors”), all pertinent financial and other records, and all other corporate documents and properties of the Company (collectively, the “Records”) as may be reasonably necessary for the purpose of such review, and cause the Company’s officers, directors and employees, within a reasonable time period, to supply all such information reasonably requested by the Inspectors (including, without limitation, in response to all questions and other inquiries reasonably made or submitted by any of them), prior to and from time to time after the filing and effectiveness of such Registration Statement for the sole purpose of enabling the Investor and its accountants and attorneys to conduct such due diligence solely for the purpose of establishing a due diligence defense to underwriter liability under the 1933 Act; provided, however, that each Inspector shall 6 agree to hold in strict confidence and shall not make any disclosure (except to the Investor) or use of any Record or other information which the Company determines in good faith to be confidential, and of which determination the Inspectors are so notified, unless (a) the disclosure of such Records is necessary to avoid or correct a misstatement or omission in any Registration Statement or is otherwise required under the 1933 Act, (b) the release of such Records is ordered pursuant to a final, non-appealable subpoena or order from a court or government body of competent jurisdiction, or (c) the information in such Records has been made generally available to the public other than by disclosure in violation of this or any other Transaction Document. Notwithstanding the foregoing, the Company shall not disclose material nonpublic information to the Investor, or to advisors to or representatives of the Investor, unless prior to disclosure of such information the Company identifies such information as being material nonpublic information and provides the Investor, such advisors and representatives with the opportunity to accept or refuse to accept such material nonpublic information for review and the Investor wishing to obtain such information entered or enters into an appropriate confidentiality agreement with the Company with respect thereto. 5. Obligations of the Investor. (a) The Investor shall furnish in writing to the Company such information regarding itself, the Registrable Securities held by it and the intended method of disposition of the Registrable Securities held by it, as shall be reasonably required to effect the registration of such Registrable Securities and shall execute such documents in connection with such registration as the Company may reasonably request. At least five (5) Business Days prior to the first anticipated filing date of any Registration Statement, the Company shall notify the Investor of the information the Company requires from the Investor if the Investor elects to have any of the Registrable Securities included in such Registration Statement. The Investor shall provide such information to the Company at least two (2) Business Days prior to the first anticipated filing date of such Registration Statement if the Investor elects to have any of the Registrable Securities included in such Registration Statement. (b) The Investor, by its acceptance of the Registrable Securities, agrees to cooperate with the Company as reasonably requested by the Company in connection with the preparation and filing of a Registration Statement hereunder, unless the Investor has notified the Company in writing of its election to exclude all of its Registrable Securities from such Registration Statement. (c) The Investor agrees that, upon receipt of any notice from the Company of either (i) the commencement of an Allowed Delay pursuant to Section 2(c)(ii) or (ii) the happening of an event pursuant to Section 3(h) hereof, the Investor will immediately discontinue disposition of Registrable Securities pursuant to any Registration Statement covering such Registrable Securities, until the Investor is advised by the Company that such dispositions may again be made. (d) The Investor covenants and agrees that it will comply with the prospectus delivery requirements of the 1933 Act as applicable to it or an exemption therefrom in connection with sales of Registrable Securities pursuant to any Registration Statement. 7 6. Indemnification. (a) Indemnification by the Company. The Company will indemnify and hold harmless the Investor and its officers, directors, members, employees and agents, successors and assigns, and each other person, if any, who controls the Investor within the meaning of the 1933 Act, against any losses, claims, damages or liabilities, joint or several, to which they may become subject under the 1933 Act or otherwise, insofar as such losses, claims, damages or liabilities (or actions in respect thereof) arise out of or are based upon any untrue statement or alleged untrue statement or omission or alleged omission of any material fact contained in any Registration Statement, any preliminary Prospectus or final Prospectus, or any amendment or supplement thereof, and will reimburse the Investor, and each such officer, director or member and each such controlling person for any legal or other documented, out-of-pocket expenses reasonably incurred by them in connection with investigating or defending any such loss, claim, damage, liability or action; provided, however, that the Company will not be liable in any such case if and to the extent that any such loss, claim, damage or liability arises out of or is based upon (i) an untrue statement or alleged untrue statement or omission or alleged omission so made in conformity with information furnished by the Investor or any such controlling person in writing specifically for use in such Registration Statement or Prospectus, (ii) the use by the Investor of an outdated or defective Prospectus after the Company has notified the Investor in writing that such Prospectus is outdated or defective or (iii) the Investor’s failure to send or give a copy of the Prospectus or supplement (as then amended or supplemented), if required (and not exempted) to the Persons asserting an untrue statement or omission or alleged untrue statement or omission at or prior to the written confirmation of the sale of Registrable Securities. Indemnification by the Investor. The Investor agrees, severally but not jointly, to indemnify (b) and hold harmless, to the fullest extent permitted by law, the Company, its directors, officers, employees, shareholders and each person who controls the Company (within the meaning of the 1933 Act) against any losses, claims, damages, liabilities and expense (including reasonable attorney fees) resulting from any untrue statement of a material fact or any omission of a material fact required to be stated in any Registration Statement or Prospectus or preliminary Prospectus or amendment or supplement thereto or necessary to make the statements therein not misleading, to the extent, but only to the extent that such untrue statement or omission is contained in any information furnished in writing by the Investor to the Company specifically for inclusion in such Registration Statement or Prospectus or amendment or supplement thereto. In no event shall the liability of the Investor be greater in amount than the dollar amount of the proceeds (net of all expense paid by the Investor in connection with any claim relating to this Section 6 and the amount of any damages the Investor has otherwise been required to pay by reason of such untrue statement or omission) received by the Investor upon the sale of the Registrable Securities included in such Registration Statement giving rise to such indemnification obligation. (c) Conduct of Indemnification Proceedings. Any person entitled to indemnification hereunder shall (i) give prompt notice to the indemnifying party of any claim with respect to which it seeks indemnification and (ii) permit such indemnifying party to assume the defense of such claim with counsel reasonably satisfactory to the indemnified party; provided that any person entitled to indemnification hereunder shall have the right to employ separate counsel and to participate in the defense of such claim, but the fees and expenses of such counsel 8 shall be at the expense of such person unless (a) the indemnifying party has agreed to pay such fees or expenses, (b) the indemnifying party shall have failed to assume the defense of such claim and employ counsel reasonably satisfactory to such person or (c) in the reasonable judgment of any such person, based upon written advice of its counsel, a conflict of interest exists between such person and the indemnifying party with respect to such claims (in which case, if the person notifies the indemnifying party in writing that such person elects to employ separate counsel at the expense of the indemnifying party, the indemnifying party shall not have the right to assume the defense of such claim on behalf of such person); and provided, further that the failure of any indemnified party to give notice as provided herein shall not relieve the indemnifying party of its obligations hereunder, except to the extent that such failure to give notice shall materially adversely affect the indemnifying party in the defense of any such claim or litigation. It is understood that the indemnifying party shall not, in connection with any proceeding in the same jurisdiction, be liable for fees or expenses of more than one separate firm of attorneys at any time for all such indemnified parties. No indemnifying party will, except with the consent of the indemnified party, which shall not be unreasonably withheld or conditioned, consent to entry of any judgment or enter into any settlement that does not include as an unconditional term thereof the giving by the claimant or plaintiff to such indemnified party of a release from all liability in respect of such claim or litigation. (d) Contribution. If for any reason the indemnification provided for in the preceding paragraphs (a) and (b) is unavailable to an indemnified party or insufficient to hold it harmless, other than as expressly specified therein, then the indemnifying party shall contribute to the amount paid or payable by the indemnified party as a result of such loss, claim, damage or liability in such proportion as is appropriate to reflect the relative fault of the indemnified party and the indemnifying party, as well as any other relevant equitable considerations. No person guilty of fraudulent misrepresentation within the meaning of Section 11(f) of the 1933 Act shall be entitled to contribution from any person not guilty of such fraudulent misrepresentation. In no event shall the contribution obligation of a holder of Registrable Securities be greater in amount than the dollar amount of the proceeds (net of all expenses paid by such holder in connection with any claim relating to this Section 6 and the amount of any damages such holder has otherwise been required to pay by reason of such untrue or alleged untrue statement or omission or alleged omission) received by it upon the sale of the Registrable Securities giving rise to such contribution obligation. 7. Miscellaneous. (a) Amendments and Waivers. This Agreement may be amended only by a writing signed by the Company and the Investor. The Company may take any action herein prohibited, or omit to perform any act herein required to be performed by it, only if the Company shall have obtained the written consent to such amendment, action or omission to act, of the Investor. (b) Notices. All notices and other communications provided for or permitted hereunder shall be made as set forth in Section 9.4 of the Purchase Agreement. (c) Assignments and Transfers by Investor. The provisions of this Agreement shall be binding upon and inure to the benefit of the Investor and its respective successors and 9 assigns. The Investor may transfer or assign, in whole or from time to time in part, to one or more persons its rights hereunder in connection with the transfer of Registrable Securities by the Investor to such person, provided that (i) the Investor agrees in writing with the transferee or assignee to assign such rights and a copy of such agreement is furnished to the Company within a reasonable time after such assignment; (ii) the Company is within a reasonable time after such transfer or assignment, furnished with written notice of (A) the name and address of such transferee or assignee and (B) the securities with respect to which such registration rights are being transferred or assigned; (iii) immediately following such transfer or assignment the further disposition of such securities by the transferee or assignee is restricted under the 1933 Act or applicable state securities laws; (iv) at or before the time the Company receives the written notice contemplated by clause (ii) of this sentence the transferee or assignee agrees in writing with the Company to be bound by all of the provisions contained herein and (v) such transfer shall have been made in accordance with the applicable requirements of the Purchase Agreement. (d) Assignments and Transfers by the Company. This Agreement may not be assigned by the Company (whether by operation of law or otherwise) without the prior written consent of the Investor, provided, however, that in the event that the Company is a party to a merger, consolidation, share exchange or similar business combination transaction in which Ordinary Shares are converted into the equity securities of another Person, from and after the effective time of such transaction, such Person shall, by virtue of such transaction, be deemed to have assumed the obligations of the Company hereunder, the term “Company” shall be deemed to refer to such Person and the term “Registrable Securities” shall be deemed to include the securities received by the Investor in connection with such transaction unless such securities are otherwise freely tradable by the Investor after giving effect to such transaction. (e) Benefits of the Agreement. The terms and conditions of this Agreement shall inure to the benefit of and be binding upon the respective permitted successors and assigns of the parties. Nothing in this Agreement, express or implied, is intended to confer upon any party other than the parties hereto or their respective successors and assigns any rights, remedies, obligations, or liabilities under or by reason of this Agreement, except as expressly provided in this Agreement. (f) Counterparts; Faxes. This Agreement may be executed in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. This Agreement may also be executed via facsimile, which shall be deemed an original. (g) Titles and Subtitles. The titles and subtitles used in this Agreement are used for convenience only and are not to be considered in construing or interpreting this Agreement. (h) Severability. Any provision of this Agreement that is prohibited or unenforceable in any jurisdiction shall, as to such jurisdiction, be ineffective to the extent of such prohibition or unenforceability without invalidating the remaining provisions hereof but shall be interpreted as if it were written so as to be enforceable to the maximum extent permitted by applicable law, and any such prohibition or unenforceability in any jurisdiction shall not 10 invalidate or render unenforceable such provision in any other jurisdiction. To the extent permitted by applicable law, the parties hereby waive any provision of law which renders any provisions hereof prohibited or unenforceable in any respect. (i) Further Assurances. The parties shall execute and deliver all such further instruments and documents and take all such other actions as may reasonably be required to carry out the transactions contemplated hereby and to evidence the fulfillment of the agreements herein contained. (j) Entire Agreement. This Agreement is intended by the parties as a final expression of their agreement and intended to be a complete and exclusive statement of the agreement and understanding of the parties hereto in respect of the subject matter contained herein. This Agreement supersedes all prior agreements and understandings between the parties with respect to such subject matter. (k) Governing Law; Consent to Jurisdiction; Waiver of Jury Trial. This Agreement shall be governed by, and construed in accordance with, the internal laws of the State of New York without regard to the choice of law principles thereof. Each of the parties hereto irrevocably submits to the exclusive jurisdiction of the courts of the State of New York located in New York County and the United States District Court for the Southern District of New York for the purpose of any suit, action, proceeding or judgment relating to or arising out of this Agreement and the transactions contemplated hereby. Service of process in connection with any such suit, action or proceeding may be served on each party hereto anywhere in the world by the same methods as are specified for the giving of notices under this Agreement. Each of the parties hereto irrevocably consents to the jurisdiction of any such court in any such suit, action or proceeding and to the laying of venue in such court. Each party hereto irrevocably waives any objection to the laying of venue of any such suit, action or proceeding brought in such courts and irrevocably waives any claim that any such suit, action or proceeding brought in any such court has been brought in an inconvenient forum. EACH OF THE PARTIES HERETO WAIVES ANY RIGHT TO REQUEST A TRIAL BY JURY IN ANY LITIGATION WITH RESPECT TO THIS AGREEMENT AND REPRESENTS THAT COUNSEL HAS BEEN CONSULTED SPECIFICALLY AS TO THIS WAIVER. [remainder of page intentionally left blank] 11 IN WITNESS WHEREOF, the parties have executed this Agreement or caused their duly authorized officers to execute this Agreement as of the date first above written. COMPANY: MEIRAGTX HOLDINGS PLC By:/s/ Richard Giroux Name: Richard Giroux Title: Chief Operating Officer 12 INVESTOR: JOHNSON & JOHNSON INNOVATION – JJDC, INC. By:/s/ Asish Xavier Name: Asish Xavier Title: VP, Venture Investments Exhibit A Plan of Distribution We are registering ordinary shares previously issued to permit the resale of these ordinary shares by the holders of the ordinary shares from time to time after the date of this prospectus. We will not receive any of the proceeds from the sale by the selling shareholders. We will bear all fees and expenses incident to our obligation to register the ordinary shares, except that, if the ordinary shares are sold through underwriters or broker-dealers, the selling shareholders will be responsible for underwriting discounts or commissions or agent’s commissions. The selling shareholders may sell all or a portion of the ordinary shares beneficially owned by them and offered hereby from time to time directly or through one or more underwriters, broker-dealers or agents. The ordinary shares may be sold in one or more transactions at fixed prices, at prevailing market prices at the time of the sale, at varying prices determined at the time of sale, or at negotiated prices. These sales may be effected in transactions, which may involve crosses or block transactions, ● on any national securities exchange or quotation service on which the securities may be listed or quoted at the time of sale; ● in the over-the-counter market; ● in transactions otherwise than on these exchanges or systems or in the over-the-counter market; ● through the writing of options, whether such options are listed on an options exchange or otherwise; ● ordinary brokerage transactions and transactions in which the broker-dealer solicits purchasers; ● block trades in which the broker-dealer will attempt to sell the shares as agent but may position and resell a portion of the block as principal to facilitate the transaction; ● purchases by a broker-dealer as principal and resale by the broker-dealer for its account; ● an exchange distribution in accordance with the rules of the applicable exchange; ● privately negotiated transactions; ● short sales; ● sales pursuant to Rule 144 of the Securities Act; ● broker-dealers may agree with the selling shareholders to sell a specified number of such shares at a stipulated price per share; ● a combination of any such methods of sale; and ● any other method permitted pursuant to applicable law. If the selling shareholders effect such transactions by selling ordinary shares to or through underwriters, broker- dealers or agents, such underwriters, broker-dealers or agents may receive commissions in the form of discounts, concessions or commissions from the selling shareholders or commissions from purchasers of the ordinary shares for whom they may act as agent or to whom they may sell as principal (which discounts, concessions or commissions as to particular underwriters, broker-dealers or agents may be in excess of those customary in the types of transactions involved). In connection with sales of the ordinary shares or otherwise, the selling shareholders may enter into hedging transactions with broker-dealers, which may in turn engage in short sales of our ordinary shares in the course of hedging in positions they assume. The selling shareholders may also sell ordinary shares short and deliver ordinary shares covered by this prospectus to close out short positions and to return borrowed shares in connection with such short sales. The selling shareholders may also loan or pledge ordinary shares to broker-dealers that in turn may sell such shares. The selling shareholders may pledge or grant a security interest in some or all of the shares of our ordinary shares owned by them and, if they default in the performance of their secured obligations, the pledgees or secured parties may offer and sell the ordinary shares from time to time pursuant to this prospectus or other applicable provisions of the Securities Act, amending, if necessary, the list of selling shareholders to include the pledgee, transferee or other successors in interest as selling shareholders under this prospectus. The selling shareholders also may transfer and donate the shares of our ordinary shares in other circumstances in which case the transferees, donees, pledgees or other successors in interest will be the selling beneficial owners for purposes of this prospectus. The selling shareholders and any broker-dealer participating in the distribution of the ordinary shares may be deemed to be “underwriters” within the meaning of the Securities Act, and any commission paid, or any discounts or concessions allowed to, any such broker-dealer may be deemed to be underwriting commissions or discounts under the Securities Act. At the time a particular offering of the ordinary shares is made, a prospectus supplement, if required, will be distributed which will set forth the aggregate amount of shares of our ordinary shares being offered and the terms of the offering, including the name or names of any broker-dealers or agents, any discounts, commissions and other terms constituting compensation from the selling shareholders and any discounts, commissions or concessions allowed or reallowed or paid to broker-dealers. Under the securities laws of some states, the ordinary shares may be sold in such states only through registered or licensed brokers or dealers. In addition, in some states the ordinary shares may not be sold unless such shares have been registered or qualified for sale in such state or an exemption from registration or qualification is available and is complied with. There can be no assurance that any selling shareholder will sell any or all of the ordinary shares registered pursuant to the registration statement, of which this prospectus forms a part. The selling shareholders and any other person participating in such distribution will be subject to applicable provisions of the Exchange Act, and the rules and regulations thereunder, including, without limitation, Regulation M of the Exchange Act, which may limit the timing of purchases and sales of any of the ordinary shares by the selling shareholders and any other participating person. Regulation M may also restrict the ability of any person engaged in the distribution of the ordinary shares to engage in market-making activities with respect to the ordinary shares. All of the foregoing may affect the marketability of the ordinary shares and the ability of any person or entity to engage in market-making activities with respect to the ordinary shares. We will pay all expenses of the registration of the ordinary shares pursuant to the registration statement of which this prospectus forms a part, including, without limitation, SEC filing fees and expenses of compliance with state securities or “blue sky” laws; provided, however, that the selling shareholders will pay all underwriting discounts and selling commissions, if any. We will indemnify the selling shareholders against liabilities, including some liabilities under the Securities Act, or the selling shareholders will be entitled to contribution. We may be indemnified by the selling shareholders against civil liabilities, including liabilities under the Securities Act, that may arise from any written information furnished to us by the selling shareholders specifically for use in this prospectus or we may be entitled to contribution. Once sold under the registration statement of which this prospectus forms a part, the ordinary shares will be freely tradable in the hands of persons other than our affiliates. Legal Name of Subsidiary BRI-Alzan, Inc. MeiraGTx B.V. MeiraGTx Netherlands B.V. MeiraGTx Limited MeiraGTx, LLC MeiraGTx UK Limited MeiraGTx UK II Limited MeiraGTx Ireland DAC MeiraGTx Neurosciences, Inc. MeiraGTx Bio Inc. MeiraGTx Belgium MeiraGTx Therapeutics, Inc. SUBSIDIARIES OF MEIRAGTX HOLDINGS PLC Jurisdiction of Organization Exhibit 21 Delaware Netherlands Netherlands England and Wales Delaware England and Wales England and Wales Ireland Delaware Delaware Belgium Delaware EXHIBIT 23.1 We consent to the incorporation by reference in the following Registration Statements: Consent of Independent Registered Public Accounting Firm (1) Registration Statement (Form S-8 No. 333-225535) pertaining to the 2016 Equity Incentive Plan, 2018 Incentive Award Plan and 2018 Employee Share Purchase Plan of MeiraGTx Holdings plc, (2) Registration Statement (Form S-3 No. 333-232527) of MeiraGTx Holdings plc, (3) Registration Statement (Form S-3 No. 333-232677) of MeiraGTx Holdings plc, and (4) Registration Statement (Form S-8 No. 333-257164) pertaining to the 2018 Incentive Award Plan and 2018 Employee Share Purchase Plan of MeiraGTx Holdings plc; of our report dated March 14, 2023, with respect to the consolidated financial statements of MeiraGTx Holdings plc included in this Annual Report (Form 10-K) of MeiraGTx Holdings plc for the year ended December 31, 2022. /s/ Ernst & Young LLP Jericho, New York March 14, 2023 CERTIFICATION Exhibit 31.1 I, Alexandria Forbes, certify that: 1. I have reviewed this Annual Report on Form 10-K for the fiscal year ended December 31, 2022 of MeiraGTx Holdings plc; 2. 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; 3. 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; 4. 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 14, 2023 By: /s/ Alexandria Forbes Alexandria Forbes President and Chief Executive Officer (Principal Executive Officer) Exhibit 31.2 I, Richard Giroux, certify that: CERTIFICATION 1. I have reviewed this Annual Report on Form 10-K for the fiscal year ended December 31, 2022 of MeiraGTx Holdings plc; 2. 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; 3. 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; 4. 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 14, 2023 By: /s/ Richard Giroux Richard Giroux Chief Financial Officer and Chief Operating Officer (Principal Financial Officer) CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 Exhibit 32.1 In connection with the Annual Report on Form 10-K of MeiraGTx Holdings plc (the “Company”) for the year ended December 31, 2022, as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-Oxley Act of 2002, that to the best of my knowledge: (1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and (2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. Date: March 14, 2023 By: /s/ Alexandria Forbes Alexandria Forbes President and Chief Executive Officer (Principal Executive Officer) CERTIFICATION PURSUANT TO 18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002 Exhibit 32.2 In connection with the Annual Report on Form 10-K of MeiraGTx Holdings plc (the “Company”) for the year ended December 31, 2022, as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-Oxley Act of 2002, that to the best of my knowledge: (1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and (2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company. Date: March 14, 2023 By: /s/ Richard Giroux Richard Giroux Chief Financial Officer and Chief Operating Officer (Principal Financial Officer) 

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