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☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

 For the fiscal year ended March 31, 2021

☐    TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

Delaware						85-3863315
(State or other jurisdiction of incorporation or organization)						(I.R.S. Employer Identification No.)
130 West 42nd St., 26th Floor New York, New York						10036
(Address of principal executive offices)						(Zip Code)

Registrant’s telephone number, including area code: (877) 746-4891

Title of each Class

Trading Symbol

Name of each exchange on which registered

Common Stock, par value $0.00001 per share

SIOX

The Nasdaq Stock Market LLC

Large accelerated filer			☐			Accelerated filer			☐

Non-accelerated filer			ý			Smaller reporting company			ý

						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 7(a)(2)(B) of the Securities 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. ☐

The number of shares outstanding of the Registrant’s common stock, $0.00001 par value per share, on June 7, 2021, was 69,558,434.

			Page
PART I			6
Item 1. Business			8
Item 1A. Risk Factors			45
Item 1B. Unresolved Staff Comments			86
Item 2. Properties			86
Item 3. Legal Proceedings			86
Item 4. Mine Safety Disclosures			86
PART II			87
Item 5. Market For Registrant's Common Equity, Related Shareholder Matters and Issuer Purchases of Equity Securities			87
Item 6. Selected Financial Data			88
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations			89
Item 7A. Quantitative and Qualitative Disclosures About Market Risk			97
Item 8. Financial Statements and Supplementary Data			98
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure			98
Item 9A. Controls and Procedures			98
Item 9B. Other Information			99
PART III			100
Item 10. Directors, Executive Officers and Corporate Governance			100
Item 11. Executive Compensation			109
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Shareholder Matters			115
Item 13. Certain Relationships and Related Transactions, and Director Independence			117
Item 14. Principal Accounting Fees and Services			119
PART IV			120
Item 15. Exhibits And Financial Statement Schedules			120
SIGNATURES			122

•Our business, operations and clinical development plans and timelines could continue to be adversely impacted by the effects of health epidemics, including the recent COVID-19 pandemic, on the manufacturing, clinical trial and other business activities performed by us or by third parties with whom we conduct business, including our contract manufacturers, contract research organizations, or CROs, shippers and others.

•We have a limited operating history and have never generated any product revenues.

•We are heavily dependent on the success of our gene therapy product candidates, which are still in early stages of clinical or preclinical development. If we are unable to successfully develop and commercialize any of our product candidates, our business will be harmed.

•We may be required to make significant payments to third parties under the agreements pursuant to which we acquired our gene therapy product candidates.

•Gene therapies are novel, complex, difficult and expensive to manufacture. We do not have our own manufacturing capabilities and will rely on third parties to produce clinical and commercial supplies of our product candidates. Delays in manufacturing processes, including recently at Oxford, may result in delays in our planned clinical trials that would otherwise harm our business and prospects.

•Our business plan may lead to the initiation of one or more gene therapy development programs, the discontinuation of one or more development programs, or the execution of one or more transactions that you do not agree with or that you do not perceive as favorable to your investment.

•Clinical trials are expensive, time-consuming, difficult to design and implement and involve an uncertain outcome.

•If we are not able to obtain required regulatory approvals, we will not be able to commercialize our gene therapy product candidates, and our ability to generate revenue will be materially impaired.

•The intended tax effects of our corporate structure prior to and following the Domestication (as defined below) and our corporate reorganization to align our corporate structure with current and future business activity (the "Reorganization"), and intercompany arrangements prior to the Domestication and Reorganization, depend on the application of the tax laws of various jurisdictions and on how we operate our business.

•We expect to incur significant losses for the foreseeable future and may never achieve or maintain profitability.

•We will require additional capital to fund our operations, and if we fail to obtain necessary financing, we may not be able to complete the development and commercialization of our product candidates.

•Interim "top-line" 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.

•Our gene therapy product candidates may cause adverse effects or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.

•Enrollment and retention of patients in clinical trials is an expensive and time-consuming process and could be made more difficult or rendered impossible by multiple factors outside our control.

•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, even if approved.

•If the market opportunities for any product candidates we may develop are smaller than we believe they are, our revenues, if any, may be adversely affected, and our business may suffer. Because the target patient populations for many of the product candidates we may develop are small, we must be able to successfully identify patients and achieve a significant market share to achieve and maintain profitability and growth.

•We face significant competition from other biotechnology and pharmaceutical companies, 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 and our operating results will suffer if we fail to compete effectively.

•We may not be able to protect our intellectual property rights throughout the world, which could impair our business.

•Third-party claims or litigation alleging infringement of patents or other proprietary rights or seeking to invalidate patents or other proprietary rights may delay or prevent the development and commercialization of our product candidates.

•The market price of our common stock has been and is likely to continue to be highly volatile, and you may lose some or all of your investment.

•the success and timing of our ongoing development and potential commercialization of our product candidates; 

•our relationships under our license agreements; 

•the success of our interactions with the U.S. Food and Drug Administration ("FDA") and international regulatory authorities; 

•the anticipated start dates, durations and completion dates of our ongoing and future nonclinical studies and clinical trials, as well as subsequent portions or cohorts of our ongoing clinical trials; 

•the receipt of approvals or endorsements by data monitoring or other committees necessary for commencement or continuation of clinical trials; 

•the anticipated designs of our future clinical studies; 

•anticipated future regulatory submissions and the timing of, and our ability to, obtain and maintain regulatory approval for our product candidates; 

•the rate and degree of market acceptance and clinical utility of any approved product candidate; 

•our ability to identify and in-license or acquire additional product candidates;

•our commercialization, marketing and manufacturing capabilities and strategy;

•continued service of our executive officers or other key scientific or management personnel;

•our ability to obtain, maintain and enforce intellectual property rights for our product candidates;

•our anticipated future cash position;

•our estimates regarding our results of operations, financial condition, liquidity, capital requirements, prospects, growth and strategies;

•our ability to maintain and operate our business in light of the COVID-19 pandemic;

•the success of competing therapies that are or may become available; and

•our stated objective of building the world's leading gene therapy company for the treatment of neurological diseases.

Gene Therapy Program			Clinical Indication			Clinical Development Stage
AXO-AAV-GM1			GM1 gangliosidosis			Phase 1/2
AXO-AAV-GM2			GM2 gangliosidosis (including			Phase 1/2
			Tay-Sachs and Sandhoff diseases)
AXO-Lenti-PD			Parkinson's disease			Phase 2

GM1 gangliosidosis is a rare, inherited neurodegenerative lysosomal storage disorder characterized by the accumulation of GM1 ganglioside. This accumulation occurs due to a defect in the galactosidase beta 1 ("GLB1") gene. The GLB1 gene codes for the β-galactosidase ("β-gal") enzyme which catalyzes the hydrolysis of GM1 gangliosides. Impaired β-gal activity results in the toxic accumulation of GM1 gangliosides, causing the progressive destruction of nerve cells in the brain and spinal cord and early death. GM1 gangliosidosis is uniformly fatal, and there are no disease-modifying treatment options. The estimated incidence for GM1 gangliosidosis is approximately one in 100,000 live births worldwide. In 2019, we collaborated with the National Institutes of Health (“NIH”) to publish a comprehensive retrospective study characterizing the natural history of Type I GM1 gangliosidosis in Molecular Genetics and Metabolism (Lang et.al., 2019). This paper describes a rapidly progressive clinical course of Type I GM1 gangliosidosis, in which almost all patients experience significant multi-organ system dysfunction and neurodevelopmental regression between six and 18 months of age.

AXO-AAV-GM1 is an investigational gene therapy currently being developed as a potential one-time disease modifying treatment for GM1 gangliosidosis. The program utilizes an adeno-associated virus ("AAV") vector to deliver a functional copy of the GLB1 gene with the goals of restoring β-gal enzyme activity both systematically and in the CNS, reducing GM1 ganglioside accumulation to ultimately improve neurological function and peripheral manifestations, such as cardiac and skeletal abnormalities, and thereby extend survival. The therapy is administered intravenously and utilizes the AAV9 capsid, which has been shown to cross the blood-brain barrier. Intravenous administration has the potential to broadly transduce the CNS and peripheral tissues, as well as treat peripheral manifestations of the disease. We licensed exclusive worldwide rights for the development and commercialization of AXO-AAV-GM1 from UMMS in December 2018. In November 2019, we announced that the FDA had granted orphan drug designation for AXO-AAV-GM1.

We have completed the enrollment and dosing of the five Type II (late-infantile/juvenile) patients in the low-dose cohort in Stage 1 of the registrational study of both Type I and Type II GM1 patients and announced initial data on the first cohort in December 2020. A total of five Type II patients were included in the initial data announced in December 2020. All patients had documented deficiency of β-gal enzyme activity with a genetic and clinical diagnosis of GM1 gangliosidosis. All five patients exhibited impairment of fine motor skills and change in walking pattern on clinical history at baseline. AXO-AAV-GM1 was generally well-tolerated at the low dose (1.5×1013 vg/kg) delivered intravenously, with no serious adverse events ("SAE" or "SAEs") reported as related to gene therapy. One SAE was described, whereby a single patient was diagnosed with bacterial sepsis resulting from an infection of the line used for drug product administration, which was considered to be unrelated to the investigational drug product, and which resolved within a few days following line removal and administration of antibiotics. The most common adverse events were considered mild to moderate. Transient and mild AST elevations were observed in four subjects, none of which required clinical intervention or had associated clinical consequences. There were no other adverse events indicative of impaired liver function. No clinically relevant changes were observed in platelet count.

We believe the favorable tolerability in the low-dose cohort supports continued enrollment of patients in the high-dose cohort (4.5×1013 vg/kg), in which two Type II patients have now been dosed without complications. At month six, serum enzyme activity increased by an average of 71% from baseline (range: 33%-127%) across the five patients in the first cohort. On average, serum β-gal enzyme activity was restored to 38% of normal reference levels at month six, with individual patients ranging from 23-57% of normal reference levels. The reference level was defined by the lowest level of enzyme activity in serum from 30 healthy adult volunteers using the same validated assay of β-gal enzyme activity as was used to assess the patients in the study. Cerebrospinal fluid ("CSF") samples were collected from all patients through lumbar puncture. Development and validation of biomarker assays for CSF β-gal enzyme is currently ongoing.

AXO-AAV-GM2 is an investigational gene therapy that we are developing as a potential one-time disease modifying treatment for GM2 gangliosidosis (including Tay-Sachs disease and Sandhoff disease). The AXO-AAV-GM2 program utilizes dual AAV vectors to deliver functional copies of both the HEXA gene and the HEXB gene, with the goal of restoring normal Hex A enzyme function in the CNS. AXO-AAV-GM2 is administered directly to the brain and CNS and utilizes the neurotropic AAVrh.8 capsid. The HEXA and HEXB genes will be delivered in a 1:1 ratio using separate AAvrh.8 vectors. As part of the AXO-AAV-GM2 program, we are also exploring a next-generation gene therapy that would utilize a bicistronic vector to deliver both the HEXA and HEXB genes in a single vector using the AAV9 capsid for systemic intravenous administration. We licensed exclusive worldwide rights for the development and commercialization of AXO-AAV-GM2 from UMMS in December 2018.

In October 2020, the FDA granted Rare Pediatric Disease Designation to AXO-AAV-GM2. In November 2020, the FDA cleared an IND to support the initiation of our registrational clinical trial in patients with GM2 gangliosidosis. We have dosed the first infantile patient in the clinical trial under this IND in January 2021. The patient received 1.42×1014 vg divided into bilateral intra-thalamic and intra-thecal dosing.

AXO-Lenti-PD is an in vivo lentiviral gene therapy investigational product candidate currently being developed as a potential one-time treatment of Parkinson’s disease. We licensed the worldwide development and commercialization rights to AXO-Lenti-PD and ProSavin from Oxford Biomedica (UK) Ltd. ("Oxford"), under an exclusive license agreement entered into in June 2018 (the "Oxford Agreement"). Currently, we have six years of data on 15 patients dosed in a Phase 1/2 clinical trial of ProSavin and 24-month data on two patients dosed in Cohort 1 of the Phase 2 clinical trial of the SUNRISE-PD study. We reported six-month data from the four patients dosed in Cohort 2 of the SUNRISE-PD study in October 2020.

ProSavin was evaluated for safety and efficacy in a Phase 1/2 study in patients with advanced Parkinson's disease by Oxford. In this study, ProSavin was observed to be well-tolerated with sustained improvements on motor function as measured by the UPDRS Part III (motor) score in the state "OFF" levodopa medication, which we refer to as UPDRS Part III "OFF." The Phase 1/2 clinical trial was conducted at sites in the United Kingdom ("U.K.") and France on a total of 15 patients with advanced Parkinson's disease. Three target dose levels of ProSavin were assessed in four patient cohorts: Low Dose: 1.9 × 107 transducing units ("TU") in Cohort 1 (n=3); Mid Dose: 4.0 × 107 TU in Cohorts 2a (n=3) and 2b (n=3); High Dose: 1.0 × 108 TU in Cohort 3 (n=6). Cohorts 2b and 3 underwent a modified delivery method to increase the rate of delivery of the viral vector. The primary endpoints were the number and severity of adverse events as well as the UPDRS Part III "OFF" scores at six months after gene therapy administration. No serious adverse events related to ProSavin or the surgical procedure were reported. Reported treatment emergent adverse events were generally mild and related to either Parkinson's disease progression or L-dopa-induced dyskinesias that were ameliorated with reduction of L-dopa administration. The most common adverse events in the first 12 months were dyskinesia (n=11 subjects), "on-off" motor fluctuations (n=9), headache (n=4), and akinesia (n=3).

In vitro experiments in a human neuron model with AXO-Lenti-PD showed up to 10-fold increases in dopamine + L-dopa production over ProSavin. In vivo experiments in non-human primate models showed increased AADC activity in the brain with AXO-Lenti-PD compared to ProSavin as measured by positron emission tomography ("PET") scans. Functionally, in non-human primate models at approximately 1/5th of the dose, AXO-Lenti-PD demonstrated a similar level of improvement in spontaneous locomotor activity compared to ProSavin. A recent placebo-controlled study in a non-human primate model of Parkinson’s disease published in Molecular Therapy: Methods and Clinical Development compared two doses of AXO-Lenti-PD against control-group animals receiving a placebo. The study demonstrated statistically significant differences in Parkinson's disease clinical response scores at six months in this diseased-animal model (p<0.0002 for AXO-Lenti-PD compared to control), dose-dependent increases in PET signaling using a 6-[(18)F]fluoro-m-tyrosine radiotracer (p<0.001 for AXO-Lenti-PD compared to control), and dose-dependent increases in gene expression for AADC, TH, and CH1 in transduced striatal tissue. We believe these data provide evidence that AXO-Lenti-PD may have greater potency compared to ProSavin in terms of dopamine production, enzymatic activity and functional improvement in animal models of Parkinson's disease.

The design of the SUNRISE-PD study is an open label dose-escalation portion studying multiple dose levels. Once the optimal dose has been determined in the dose-escalation study, a sham-controlled study will be conducted with patients randomized either to an active group receiving the optimal dose as determined in the SUNRISE-PD study, or a control group undergoing an imitation "sham" surgical procedure. We are working closely with our manufacturing partner for AXO-Lenti-PD, Oxford Biomedica, to develop a reliable suspension-based manufacturing process. Manufacturing of several GMP batches using a revised suspension-based process has been ongoing at Oxford Biomedica with a goal of generating material for use in future clinical trials. We expect a batch to be released that can be used for dosing of further patients in the SUNRISE-PD study in the fourth calendar quarter of 2021, pending an updated filing with the Medicines and Healthcare products Regulatory Agency (the "MHRA") in the UK. Once the MHRA accepts the filing, we plan on dosing two additional patients at the mid-dose (1.4 × 107 TU) to evaluate a revised surgical procedure before proceeding to dosing patients at the next higher dose (4.2 × 107 TU).

We dosed the first patient in Cohort 2 of the SUNRISE-PD clinical study in April 2019 and the last (fourth) patient in February 2020. The target dose being tested in Cohort 2 is 1.4×107 TU, which is three times higher than the dose used in Cohort 1. In October 2020, we reported that all of the four patients in the cohort were able to complete the evaluations that do not require an inpatient visit (Hauser diary, Levodopa Equivalent Daily Dose), and only two of the four were able to complete the UPDRS Part II and III evaluations – one patient refused this evaluation and the other was not able to be seen in the clinic since it was closed due to COVID-19 response measures. AXO-Lenti-PD was observed to be generally well tolerated, with no serious adverse events attributable to the gene therapy. At month 6, the patients experienced an average improvement from baseline in UPDRS Part III (motor) score, in the state "OFF" levodopa therapy, of 21 points, representing an average improvement of 40% from baseline. Individual patient improvements from baseline at 6 months of 22 and 19 points were observed. Similarly, at six months, the patients experienced an improvement in the UPDRS Part II (quality of life) of 14 points, which represents a 71% improvement. Individual patients’ improvement from baseline were 12 and 15 points. The Hauser diary was completed by all four patients and demonstrated an improvement from baseline of 2.3 hours in OFF time and 2.2 hours in good ON time.

•completion of extensive nonclinical laboratory tests, animal studies, and formulation studies in accordance with the FDA's Good Laboratory Practice ("GLP") regulations;

•submission to the FDA of an IND for human clinical testing, which must become effective before human clinical trials may begin;

•performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice ("GCP") requirements to establish the safety and efficacy of the product for each proposed indication;

•submission to the FDA of a BLA, in the case of biological product candidates including gene therapy product candidates, after completion of all pivotal clinical trials;

•satisfactory completion of an FDA inspection of sites involved in our clinical trials;

•satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the active pharmaceutical ingredient ("API") and finished product are produced and tested to assess compliance with cGMPs; and

•FDA review and approval of the BLA prior to any commercial marketing or sale of the product in the United States.

•Phase 1. The biological product 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. Guidelines on clinical trials with gene therapy products issued by the FDA's Office of Tissues and Advanced Therapies state that the FDA has determined that the benefit-risk ratio of these products does not warrant their evaluation in healthy human subjects.

•Phase 2. The biological product 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.

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 and the investigators for serious and unexpected adverse events, any findings from other studies, 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 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. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

•the second applicant can establish that its product, although similar, is safer, more effective or otherwise clinically superior;

•the applicant consents to a second orphan medicinal product application; or

•the applicant cannot supply enough orphan medicinal product.

We were originally an exempted limited company incorporated under the laws of Bermuda in October 2014 and were named Axovant Gene Therapies Ltd. from March 2019 until November 2020. In November 2020, we became a Delaware corporation in connection with the Domestication and changed our corporate name to Sio Gene Therapies Inc. Our principal executive office is located at 130 West 42nd Street, 26th Floor, New York, New York 10036, and our telephone number is 1 (877) 746-4891.

•the scope of rights granted under the agreement and other interpretation-related issues;

•whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the agreement;

•our right to sublicense patent and other rights to third parties;

•our diligence obligations with respect to the use of the licensed technology in relation to our development and commercialization of our product candidates, and what activities satisfy those diligence obligations;

•the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners;

•our right to transfer or assign our license; and

•the effects of termination.

We may become involved in lawsuits to protect or enforce our patents, the patents of our licensors or our other intellectual property rights, which could be expensive, time consuming and unsuccessful.

Because of the expense and uncertainty of litigation, we may not be in a position to enforce our intellectual property rights against third parties.

Changes in U.S. patent law or the patent law of other countries or jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.

We may not be able to protect our intellectual property rights throughout the world, which could impair our business.

We may 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.

Any trademarks we have obtained or may obtain may be infringed or successfully challenged, resulting in harm to our business.

Intellectual property rights do not necessarily address all potential threats to our competitive advantage.

•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 or other intellectual property rights that we own or that we have exclusively licensed and have the right to enforce;

•we, our licensor or any collaborators might not have been the first to make the inventions covered by the issued patents or pending patent applications that we own or license;

•we or our licensor might not have been the first to file patent applications covering certain of our inventions;

•others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our intellectual property rights;

•it is possible that our pending patent applications will not lead to issued patents;

•issued patents that we own or license may not provide us with any competitive advantages, or may be held invalid or unenforceable as a result of legal challenges;

•our competitors might conduct research and development activities in the United States and other countries that provide a safe harbor from patent infringement claims for certain research and development activities, as well as in countries where we do not have patent rights, and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; and

•we may not develop additional proprietary technologies that are patentable.

•successfully commence and complete clinical trials and obtain regulatory approval for the marketing of our gene therapy product candidates;

•establish effective sales, marketing and distribution systems for our gene therapy product candidates;

•add operational, financial and management information systems and personnel, including personnel to support our clinical, manufacturing and planned future commercialization efforts and operations as a public company;

•initiate and continue relationships with third-party suppliers and manufacturers, including Oxford Biomedica (UK) Ltd. ("Oxford"), Viralgen Vector Core, S.L. and other third-party cGMP manufacturers, and have clinical and commercial quantities of our gene therapy product candidates manufactured at acceptable cost and quality levels;

•attract and retain an experienced management and advisory team;

•raise additional funds when needed and on terms acceptable to us;

•achieve broad market acceptance of our products in the medical community and with third-party payors and consumers;

•launch commercial sales of our products, whether alone or in collaboration with others;

•compete effectively with other biotechnology and gene therapy companies targeting neurological diseases; and

•obtain, maintain, expand and protect necessary intellectual property rights.

•we may not be able to demonstrate that a product candidate is safe and effective as a treatment for our targeted indications to the satisfaction of the applicable regulatory authorities;

•our BLA or other key regulatory filings may be delayed or rejected due to issues, including those related to product quality and manufacturing, timing of results from supporting studies, database lock and data transfer;

•the regulatory authorities may require additional nonclinical studies or clinical studies of the product candidate in Parkinson’s disease or other indications, which would increase our costs and prolong our development;

•the results of our clinical trials may not meet the level of statistical or clinical significance required for marketing approval;

•the regulatory authorities may disagree with the number, design, size, conduct or implementation of our clinical trials;

•the contract research organizations ("CROs") that we retain to conduct clinical trials may take actions outside of our control, or otherwise commit errors or breaches of protocols, that adversely impact our clinical trials;

•the regulatory authorities may not find the data from nonclinical studies and clinical trials sufficient to demonstrate that the clinical and other benefits of the product candidate outweigh its safety risks;

•the regulatory authorities may disagree with our interpretation of data from our nonclinical studies and clinical trials or may require that we conduct additional studies;

•the regulatory authorities may not accept data generated at our clinical trial sites;

•the regulatory authorities may require, as a condition of approval, limitations on approved labeling or distribution and use restrictions;

•the FDA may require development of a risk evaluation and mitigation strategy ("REMS") as a condition of approval;

•the regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-party manufacturers; or

•the regulatory authorities may change their approval policies or adopt new regulations.

•the progress, timing, costs and results of our clinical trials of our product candidates;

•the outcome, timing and cost of meeting regulatory requirements established by the FDA, the EMA, or the PMDA, and other comparable foreign regulatory authorities;

•the achievement of certain development, regulatory and commercialization milestones that give rise to milestone and royalty payments to licensors;

•the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights;

•the cost of obtaining necessary intellectual property and defending potential intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates or any future product candidates;

•the effect of competing technological and market developments;

•the cost and timing of completion of clinical-stage and commercial-scale manufacturing activities, including costs that may result from delays in the development of a suspension-based manufacturing process by our partner, Oxford;

•the cost of establishing sales, marketing and distribution capabilities for our product candidates in regions where we choose to commercialize our products on our own; and

•the initiation, progress, timing and results of our commercialization of our product candidates, if approved for commercial sale.

•multiple, conflicting and changing laws and regulations such as tax laws, export and import restrictions, employment laws, anti-bribery and anti-corruption laws, regulatory requirements and other governmental approvals, permits and licenses;

•failure by us or our distributors to obtain appropriate licenses or regulatory approvals for the sale or use of our product candidates, if approved, in various countries;

•difficulties in managing foreign operations;

•unexpected changes in tariffs or trade barriers;

•complexities associated with managing multiple payor-reimbursement regimes or self-pay systems;

•financial risks, such as longer payment cycles, difficulty enforcing contracts and collecting accounts receivable and exposure to foreign currency exchange rate fluctuations;

•reduced protection for intellectual property rights;

•reduced protection of contractual rights in the event of bankruptcy or insolvency of the other contracting party;

•natural disasters, political and economic instability, including wars, terrorism and political unrest, outbreak of disease, including the recent COVID-19 pandemic and related shelter-in-place orders, travel, social distancing and quarantine policies, boycotts, curtailment of trade and other business restrictions;

•failure to comply with foreign laws, regulations, standards and regulatory guidance governing the collection, use, disclosure, retention, security and transfer of personal data, including the European Union General Data Privacy Regulation ("GDPR"); and

•failure to comply with the United Kingdom Bribery Act 2010 ("U.K. Bribery Act") and similar anti-bribery and anti-corruption laws in other jurisdictions, and the Foreign Corrupt Practices Act, including its books and records provisions and its anti-bribery provisions, including by failing to maintain accurate information and control over sales and distributors’ activities.

•impairment of our business reputation and significant negative media attention;

•withdrawal of participants from our clinical trials;

•significant costs to defend related litigation;

•distraction of management’s attention from our primary business;

•substantial monetary awards to patients or other claimants;

•inability to commercialize our product candidates or any future product candidate;

•product recalls, withdrawals or labeling, marketing or promotional restrictions;

•decreased demand for our product candidates or any future product candidate, if approved for commercial sale; and

•loss of revenue.

•pre-clinical and early clinical results of any product candidates we acquire may not be predictive of future clinical results;

•potential product candidates may, on further study, be shown to have harmful side effects or other characteristics that indicate that they are unlikely to be products that will receive marketing approval and achieve market acceptance; or

•potential product candidates may not be effective in treating their targeted diseases.

•failure to obtain regulatory approval to commence a trial;

•unforeseen safety issues;

•determination of dosing issues;

•lack of effectiveness during clinical trials;

•inability to reach agreement on acceptable terms with prospective CROs and clinical trial sites;

•slower than expected rates of patient recruitment or failure to recruit suitable patients to participate in a trial;

•changes in or modifications to clinical trial design;

•failure to manufacture or obtain supply of sufficient quantities of a gene therapy product candidate or placebo or failure to obtain sufficient quantities of concomitant medication for use in clinical trials;

•inability to monitor patients adequately during or after treatment;

•inability or unwillingness of medical investigators to follow our clinical and other applicable protocols;

•failure to establish sufficient number of clinical trial sites; or

•clinical sites or others deviating from trial protocol, inappropriately unblinding results, or dropping out of a trial.

•develop and commercialize products that are superior to other products in the market;

•demonstrate through our clinical trials that our gene therapy product candidates are differentiated from existing and future therapies;

•attract qualified scientific, product development and commercial personnel;

•obtain patent or other proprietary protection for our medicines;

•obtain required regulatory approvals;

•obtain coverage and adequate reimbursement from, and negotiate competitive pricing with, third-party payors; and

•successfully collaborate with pharmaceutical companies in the discovery, development and commercialization of new medicines.

•regulatory authorities may withdraw their approval of the product or require a REMS to impose restrictions on its distribution or other risk management measures;

•regulatory authorities may require the addition of labeling statements, such as warnings or contraindications;

•we may be required to change the way the product is administered or to conduct additional clinical trials;

•we could be sued and held liable for harm caused to patients;

•we could elect to discontinue the sale of our product; and

•our reputation may suffer.

•restrictions on manufacturing such products;

•restrictions on the labeling or marketing of such products;

•restrictions on product marketing, distribution or use;

•requirements to conduct post-marketing studies or clinical trials;

•warning or untitled letters;

•withdrawal of the products from the market;

•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 such products;

•product seizure; or

•injunctions or the imposition of civil or criminal penalties.

•the efficacy and potential advantages compared to alternative treatments;

•the 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 products for sale at competitive prices;

•the convenience and ease of administration compared to alternative treatments;

•the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

•the ethical, social and legal concerns about gene therapy;

•the strength of marketing and distribution support;

•the availability of third-party coverage and adequate reimbursement and patients’ willingness to pay for our products in the absence of such coverage and adequate reimbursement;

•the prevalence and severity of any side effects; and

•any restrictions on the use of our product together with other medications.

•our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;

•the inability of sales personnel to obtain access to physicians or attain adequate numbers of physicians to prescribe any drugs;

•the inability to negotiate with payors regarding reimbursement for our products; and

•unforeseen costs and expenses associated with creating an independent sales and marketing organization.

•If our product candidates are approved for commercialization, we may enter into agreements with third parties to market them in certain jurisdictions outside the United States. We expect that we will be subject to additional risks related to international operations or entering into international business relationships, including:

•different regulatory requirements for drug approvals and rules governing drug commercialization in foreign countries;

•reduced protection for intellectual property rights;

•unexpected changes in tariffs, trade barriers and regulatory requirements;

•economic weakness, including inflation, or political instability in particular foreign economies and markets;

•compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;

•foreign reimbursement, pricing and insurance regimes;

•foreign taxes;

•foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations incident to doing business in another country;

•workforce uncertainty in countries where labor unrest is more common than in the United States;

•potential noncompliance with the U.S. Foreign Corrupt Practices Act, the U.K. Bribery Act and similar anti-bribery and anti-corruption laws in other jurisdictions;

•production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and

•business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters including earthquakes, typhoons, floods and fires.

•the federal Anti-Kickback Statute prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the federal Anti-Kickback Statute or specific intent to violate it to have committed a violation; in addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act;

•the federal false claims laws including the civil False Claims Act, which can be enforced through civil whistleblower or qui tam actions, and civil monetary penalties laws, which impose criminal and civil penalties against individuals or entities for knowingly presenting, or causing to be presented to the federal government, claims for payment 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 knowingly making, or causing to be made, a false statement to avoid, decrease or conceal an obligation to pay money to the federal government; in addition, the government may assert that a claim including items and services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act;

•HIPAA imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false or fraudulent statements relating to healthcare matters. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;

•HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information on health plans, health care clearing houses, and certain health care providers, known as covered entities, and their business associates, defined as independent contractors or agents of covered entities that create, receive or obtain protected health information in connection with providing a service for or on behalf of a covered entity as well as their covered subcontractors;

•a number of federal, state and foreign laws, regulations, guidance and standards that impose requirements regarding the protection of health data that are applicable to or affect our operations;

•the federal Physician Payments Sunshine Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) to report annually to the government information related to payments or other "transfers of value" made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors) and teaching hospitals, and requires applicable manufacturers and group purchasing organizations to report annually to the government ownership and investment interests held by the physicians described above and their immediate family members. Beginning in 2022, applicable manufacturers also will be required to report such information regarding their relationships with physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists and certified nurse midwives during the previous year; and

•analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, 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 non-governmental third-party payors, including private insurers, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; and state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers, marketing expenditures or drug pricing, as well as state and local laws that require the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

•an annual, nondeductible fee payable by any entity that manufactures or imports specified branded prescription drugs and biologic agents;

•an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;

•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;

•a new Medicare Part D coverage gap discount program, in which manufacturers must now agree to offer point-of-sale discounts of 70% off negotiated prices of applicable brand drugs to eligible beneficiaries under their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

•extension of manufacturers’ Medicaid rebate liability to individuals enrolled in Medicaid managed care organizations;

•expansion of eligibility criteria for Medicaid programs in certain states;

•expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;

•a licensure framework for follow on biologic products;

•a new requirement to annually report drug samples that manufacturers and distributors provide to physicians; and

•a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

•failure to satisfy their contractual duties or obligations;

•inability to meet our product specifications and quality requirements consistently;

•delay or inability to develop, procure or expand sufficient manufacturing capacity;

•manufacturing and/or product quality issues related to manufacturing development and scale-up;

•costs and validation of new equipment and facilities required for scale-up;

•failure to comply with applicable laws, regulations, and standards, including cGMP and similar foreign standards;

•deficient or improper record-keeping;

•contractual restrictions on our ability to engage additional or alternative manufacturers;

•inability to negotiate manufacturing agreements with third parties under commercially reasonable terms;

•termination or nonrenewal of manufacturing agreements with third parties in a manner or at a time that is costly or damaging to us;

•reliance on a limited number of sources, and in some cases, single sources for product components, such that if we are unable to secure a sufficient supply of these product components, we will be unable to manufacture and sell our product candidates or any future product candidate in a timely fashion, in sufficient quantities or under acceptable terms;

•lack of qualified backup suppliers for those components that are currently purchased from a sole or single source supplier;

•lack of access or licenses to proprietary manufacturing methods used by third-party manufacturers to make our product candidates;

•operations of our third-party manufacturers or suppliers could be disrupted by conditions unrelated to our business or operations, including the bankruptcy of the manufacturer or supplier or regulatory sanctions related to the manufacture of our or other company’s products;

•carrier disruptions or increased costs that are beyond our control; and

•failure to deliver our products under specified storage conditions and in a timely manner.

•collaborators have significant discretion in determining the amount and timing of the efforts and resources that they will apply to these collaborations;

•collaborators may not perform their obligations as expected;

•the nonclinical studies and clinical trials conducted as part of these collaborations may not be successful;

•collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs based on nonclinical study or clinical trial results, changes in the collaborators’ strategic focus or available funding or external factors, such as an acquisition, that divert resources or create competing priorities;

•collaborators may delay nonclinical studies and clinical trials, provide insufficient funding for nonclinical studies and clinical trials, stop a nonclinical study or clinical trial or abandon a product candidate, repeat or conduct new nonclinical studies or clinical trials or require a new formulation of a product candidate for nonclinical studies or clinical trials;

•we may not have access to, or may be restricted from disclosing, certain information regarding product candidates being developed or commercialized under a collaboration and, consequently, may have limited ability to inform our stockholders about the status of such product candidates;

•collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

•product candidates developed in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates;

•a collaborator with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of any such product candidate;

•disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development of any product candidates, may cause delays or termination of the research, development or commercialization of such product candidates, may lead to additional responsibilities for us with respect to such product candidates or may result in litigation or arbitration, any of which would be time consuming and expensive;

•collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation;

•disputes may arise with respect to the ownership or inventorship of intellectual property developed pursuant to our collaborations;

•collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;

•the terms of our collaboration agreement may restrict us from entering into certain relationships with other third parties, thereby limiting our options; and

•collaborations may be terminated for the convenience of the collaborator and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.

•any additional delays in the commencement, enrollment and ultimate completion of our clinical trials, including as a result of the clinical hold placed on our AXO-AAV-GM2 program that was lifted in November 2020, and manufacturing delays for our AXO-Lenti-PD program;

•results of clinical trials of our product candidates or those of our competitors;

•any delay in filing applications for marketing approval of our product candidates, and any adverse development or perceived adverse development with respect to applicable regulatory authorities’ review of those applications;

•failure to successfully develop and commercialize our product candidates;

•failure to maintain our relationship with Oxford or UMMS or comply with the terms of the Oxford Agreement or the UMMS Agreement;

•inability to obtain additional funding;

•inability to obtain, protect or maintain necessary intellectual property;

•regulatory or legal developments in the United States and other countries applicable to our product candidates, including gene therapies;

•adverse regulatory decisions or statements;

•changes in the structure of healthcare payment systems;

•inability to obtain adequate product supply for our current product candidates or any future product candidate, or the inability to do so at acceptable prices;

•introduction of new products, services or technologies by our competitors;

•failure to meet or exceed financial projections we provide to the public;

•failure to meet or exceed the estimates and projections of the investment community;

•changes in the market valuations of similar companies;

•market conditions in the pharmaceutical and biotechnology sectors, and the issuance of new or changed securities analysts’ reports or recommendations;

•announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors;

•significant lawsuits, including patent or stockholder litigation, and disputes or other developments relating to our proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies;

•additions or departures of key scientific or management personnel;

•short sales of our common stock;

•sales of shares of our common stock by us or our stockholders in the future;

•negative coverage in the media or analyst reports, whether accurate or not;

•issuance of subpoenas or investigative demands, or the public fact of an investigation by a government agency, whether meritorious or not;

•trading volume of our common stock;

•general economic, industry and market conditions; and

•the other factors described in this "Risk Factors" section.

•stockholders will not be entitled to remove directors other than by a 66 2/3% vote and only for cause;

•stockholders cannot call a special meeting of stockholders;

•stockholders cannot act by written consent in lieu of a meeting; and

•stockholders must give advance notice to nominate directors or submit proposals for consideration at stockholder meetings.

•any derivative action or proceeding brought on our behalf;

•any action asserting a breach of fiduciary duty;

•any action arising pursuant to the Delaware General Corporation Law, our amended and restated certificate of incorporation, or our amended and restated bylaws; and

•any action asserting a claim against us that is governed by the internal-affairs doctrine.

If you are a U.S. holder who owned Sio common shares that had a fair market value of $50,000 or more, but less than 10% (actually or constructively) of (i) the total combined voting power of all classes of our shares entitled to vote at general meetings of Sio on the day of Domestication occurred and (ii) the total value of all classes of our shares at the time the Domestication occurred, then except as noted below, you must generally recognize gain (but not loss) with respect to such common stock of Sio received in the Domestication, even if you continue to hold your stock and have not received any cash as a result of the Domestication. As an alternative to recognizing gain, however, such U.S. holder may elect to include in income the “all earnings and profits amount,” as the term is defined in Treasury Regulation Section 1.367(b)-2(d), attributable to its common shares in Sio provided certain other requirements are satisfied. The income so included pursuant to this election generally would be treated as dividend income. Notwithstanding the foregoing, however, we, in consultation with our tax advisor, believe that Sio's cumulative earnings and profits were not greater than zero through the day of the Domestication. Each shareholder should get their own tax advice, however it is expected that on this basis, the making of an election to include the person’s share of the “all earnings and profits amount” into income as a dividend generally would not be expected to result in an adverse effect to U.S. holders who would otherwise recognize gain with respect to the conversion of the Axovant Gene Therapies Ltd. common shares in the Domestication. THE TAX CONSEQUENCES OF THE DOMESTICATION ARE COMPLEX AND DEPEND ON A HOLDER’S PARTICULAR CIRCUMSTANCES. WE STRONGLY URGE EACH SUCH U.S. HOLDER TO READ CAREFULLY OUR DESCRIPTIONS OF THE ELECTION IN “MATERIAL U.S. FEDERAL INCOME TAX CONSEQUENCES OF THE DOMESTICATION” IN THE CURRENT REPORT, AS WELL AS TO CONSULT ITS OWN TAX ADVISOR FOR A FULL DESCRIPTION OF THE TAX CONSEQUENCES OF THE DOMESTICATION, INCLUDING THE APPLICABILITY AND EFFECT OF U.S. FEDERAL, STATE, LOCAL AND NON-U.S. INCOME AND OTHER TAX LAWS.

If a U.S. holder owned Sio common shares with 10% (actually or constructively) or more of the total combined voting power of all classes of our shares entitled to vote at general meetings of Sio on the day the Domestication occurred or 10% or more of the total value of all classes of our shares at the time the Domestication occurred, such U.S. holder will generally be required to pay taxes on a deemed dividend equal to the “all earnings and profits amount” attributable to its common shares in Sio. As noted above, we, in consultation with our tax advisor, believe that Sio's cumulative earnings and profits were not greater than zero through the day of the Domestication. Complex attribution rules apply in determining whether a U.S. holder owns 10% or more of the total combined voting power of all classes of our shares for U.S. federal tax purposes. EACH U.S. HOLDER IS STRONGLY URGED TO CONSULT ITS OWN TAX ADVISOR.

For a more detailed description of the material U.S. federal income tax consequences associated with the Domestication, please read “Material U.S. Federal Income Tax Consequences of the Domestication” in the S- 4 Registration Statement. THE TAX CONSEQUENCES OF THE DOMESTICATION ARE COMPLEX AND WILL DEPEND ON A HOLDER’S PARTICULAR CIRCUMSTANCES. WE STRONGLY URGE YOU TO CONSULT WITH YOUR OWN TAX ADVISOR FOR A FULL DESCRIPTION OF THE TAX CONSEQUENCES OF THE DOMESTICATION, INCLUDING THE APPLICABILITY AND EFFECT OF U.S. FEDERAL, STATE, LOCAL AND NON-U.S. INCOME AND OTHER TAX LAWS.

If securities or industry analysts cease to publish research or reports about our business, or publish negative reports about our business, our stock price and trading volume could decline.

Our principal and registered offices are located at 130 West 42nd St., 26th Floor, New York, New York 10036. In August 2020, we entered into a lease agreement for office space in New York, New York that commenced in December 2020 and expires in June 2026. In August 2019, we entered into a lease agreement for office space in Durham, North Carolina, which expires in November 2022.

			Years Ended March 31,
			2021						2020						2019						2018						2017
Statements of Operations Data:			(In thousands, except share and per share data)
Operating expenses:
Research and development expenses
(includes $1,583, $2,772, $4,758, $16,597 and $19,186 of stock-based compensation expense for the years ended March 31, 2021, 2020, 2019, 2018 and 2017, respectively)			$	24,903					$	47,110					$	87,552					$	141,412					$	134,778
General and administrative expenses
(includes $2,909, $5,123, $11,671, $15,281 and $17,184 of stock-based compensation expense for the years ended March 31, 2021, 2020, 2019, 2018 and 2017, respectively)			17,294						22,061						39,466						71,906						45,721
Total operating expenses			42,197						69,171						127,018						213,318						180,499
Interest expense			799						4,377						7,530						7,545						1,143
Other (income) expense			(10,359)						(1,358)						(5,616)						(211)						369
Loss before income tax (benefit) expense			(32,637)						(72,190)						(128,932)						(220,652)						(182,011)
Income tax (benefit) expense			(212)						438						133						921						(1,060)
Net loss			$	(32,425)					$	(72,628)					$	(129,065)					$	(221,573)					$	(180,951)
Net loss per share of common stock — basic and diluted			$	(0.62)					$	(2.93)					$	(8.02)					$	(16.51)					$	(14.60)
Weighted average shares of common stock outstanding — basic and diluted			52,181,398						24,812,536						16,100,686						13,421,984						12,394,837

			As of March 31,
			2021						2020						2019						2018						2017
Balance Sheet Data:			(In thousands)
Cash and cash equivalents			$	118,986					$	80,752					$	106,999					$	154,337					$	212,573
Working capital			121,485						53,387						71,085						111,687						173,422
Total assets			135,147						93,680						122,706						160,786						222,539
Long-term liabilities			932						79						22,994						42,925						51,436
Accumulated deficit			(791,069)						(758,644)						(686,016)						(556,951)						(335,143)
Total shareholders’ equity			123,367						61,558						56,213						71,286						124,837

Item 7.         Management’s Discussion and Analysis of Financial Condition and Results of Operations

•direct third-party costs, which include expenses incurred under agreements with CROs and contract manufacturing organizations, the cost of consultants who assist with the development of our product candidates on a program-specific basis, investigator grants, sponsored research, manufacturing costs in connection with producing materials for use in conducting nonclinical and clinical studies, and any other third-party expenses directly attributable to the development of our product candidates; and

•upfront payments for the purchase of in-process research and development and milestone payments, which include costs incurred under our agreements with UMMS and Oxford, as well as costs incurred for our discontinued AXO-AAV-OPMD program.

•stock-based compensation expense for research and development personnel;

•personnel-related expenses, which include employee-related expenses, such as salaries, benefits and travel expenses, for research and development personnel; and

•other expenses, which includes the cost of consultants who assist with our research and development but are not allocated to a specific program.

•the number of trials required for approval;

•the per patient trial costs;

•the number of patients who participate in the trials;

•the number of sites included in the trials;

•the countries in which the trials are conducted;

•the length of time required to enroll eligible patients;

•the dose that patients receive;

•the drop-out or discontinuation rates of patients;

•the potential additional safety monitoring or other studies requested by regulatory agencies;

•the duration of patient follow-up;

•any delays in key trial activities and patient enrollment or diversion of healthcare resources as a result of the COVID-19 pandemic;

•production shortages or other supply interruptions in clinical trial materials resulting from the COVID-19 pandemic;

•the timing and receipt of regulatory approvals; and

•the efficacy and safety profile of the product candidates.

									Years Ended March 31,
									2021						2020
Operating expenses:
Research and development expenses
(includes $1,583 and $2,772 of stock-based compensation expense for the years ended March 31, 2021 and 2020, respectively)									$	24,903					$	47,110
General and administrative expenses
(includes $2,909 and $5,123 of stock-based compensation expense for the years ended March 31, 2021 and 2020, respectively)									17,294						22,061
Total operating expenses									42,197						69,171
Interest expense									799						4,377
Other income									(10,359)						(1,358)
Income tax (benefit) expense									(212)						438
Net loss									$	(32,425)					$	(72,628)

			Years Ended March 31,
			2021						2020						Change
Program-specific costs:
AXO-Lenti-PD			$	5,668					$	22,182					$	(16,514)
AXO-AAV-GM1 and AXO-AAV-GM2			6,907						9,785						(2,878)
AXO-AAV-OPMD (discontinued)			—						1,791						(1,791)
Unallocated internal costs:
Stock-based compensation			1,583						2,772						(1,189)
Personnel-related			7,058						7,149						(91)
Other			3,687						3,431						256
Total research and development expenses			$	24,903					$	47,110					$	(22,207)

•the progress, timing, costs and results of our clinical trials of our product candidates;

•the outcome, timing and cost of meeting regulatory requirements established by the FDA, the EMA, or the PMDA, and other comparable foreign regulatory authorities;

•the achievement of certain development, regulatory and commercialization milestones that give rise to milestone and royalty payments to licensors;

•the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights;

•the cost of obtaining necessary intellectual property and defending potential intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates or any future product candidates;

•the effect of competing technological and market developments;

•the cost and timing of completion of clinical-stage and commercial-scale manufacturing activities, including costs that may result from delays in the development of a suspension-based manufacturing process by our partner, Oxford;

•the cost of establishing sales, marketing and distribution capabilities for our product candidates in regions where we choose to commercialize our products on our own; and

•the initiation, progress, timing and results of our commercialization of our product candidates, if approved for commercial sale.

			Years Ended March 31,
			2021						2020
Net cash used in operating activities			$	(46,589)					$	(67,473)
Net cash provided by (used in) investing activities			12,386						(255)
Net cash provided by financing activities			73,621						41,481

For the year ended March 31, 2021, net cash used in operating activities was $46.6 million and was primarily attributable to a net loss of $32.4 million, which includes costs incurred for research and development activities, including CRO fees, manufacturing, regulatory and other clinical trial costs, as well as our general and administrative expenses, in addition to other income of $11.3 million associated with gains on our investment in Arvelle, an increase of $4.4 million in prepaid expenses and other current assets and decreases of $3.1 million in accounts payable and $2.1 million in accrued expenses, which were partially offset by $4.5 million of non-cash stock-based compensation expense and $1.5 million of operating lease right-of-use asset amortization expense

Contractual Obligations (in thousands) (1)			Total						Under 1 year						1-3 years						3-5 years						Over 5 years
Real property lease obligations (2)			$	1,561					$	327					$	567					$	667					$	—
Total			$	1,561					$	327					$	567					$	667					$	—
(1) This table does not include any milestone and royalty payments which may become payable to third parties for which the timing and likelihood of such payments are not known. Potential milestone and royalty payments are described below under "-Milestone and Royalty Payments."
(2) Amounts due, net of prepayments. Real property lease obligations are described below under "-Real Property Leases."

Name

Age

Director Since

Position

Audit Committee

Compensation Committee

Nominating and Corporate Governance Committee

Frank Torti, M.D.

42

2018

Chairperson

Atul Pande, M.D.

66

2015

Lead Independent Director

ü

ü

ü*

Pavan Cheruvu, M.D.

39

2018

Chief Executive Officer and Director

Berndt Modig

62

2015

Director

ü

ü*

Senthil Sundaram

42

2019

Director

ü*

ü

Eric Venker, M.D., Pharm.D.

34

2020

Director

Kristiina Vuori, M.D., Ph.D.

53

2020

Director

ü

Name

Age

Position(1)

Executive Officers

Pavan Cheruvu, M.D.

39

Chief Executive Officer

David Nassif, J.D.

67

Chief Financial Officer and Chief Accounting Officer, General Counsel

Gavin Corcoran, M.D.

58

Chief R&D Officer

•recommending and retaining an independent registered public accounting firm to serve as our independent auditors, for purposes of the Companies Act, overseeing our independent auditors’ work and determining our independent auditors’ compensation;

•evaluating the performance of and assessing the qualifications of our independent auditors;

•approving in advance all audit services and non-audit services to be provided to us by our independent auditors;

•monitoring the rotation of partners of the independent auditors on our audit engagement team as required by law;

•assessing and taking other appropriate action to oversee the independence of our independent auditors, including reviewing written disclosures from the independent auditors delineating all relationships between the auditors, or their affiliates, and us, or persons in financial oversight roles at Sio, that may reasonably be thought to bear on independence (at least annually, consistent with the Public Company Accounting Oversight Board, or PCAOB, Rule 3526);

•reviewing the financial statements proposed to be included in our Annual Report on Form 10-K to be filed with the SEC and recommending to the Board whether such financial statements should be so included;

•reviewing and discussing with management and our independent auditors the results of the annual audit and the independent auditor’s review of our quarterly financial statements, including, as appropriate, a review of our disclosures under “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our periodic reports filed with the SEC;

•reviewing and discussing with management and our independent auditors, as appropriate, our guidelines and policies with respect to risk assessment and management, including risks related to our accounting matters, financial reporting and legal and regulatory compliance; and reviewing and discussing with management, as appropriate, insurance programs;

•conferring with management and our independent auditors, as appropriate, regarding the scope, adequacy and effectiveness of our internal control over financial reporting;

•coordinating the Board’s oversight of the performance of our internal audit function;

•reviewing and approving or rejecting transactions between us and any related persons; and

•establishing procedures for the receipt, retention and treatment of complaints received by us regarding accounting, internal accounting controls, auditing or compliance matters and the confidential and anonymous submission by our employees of concerns regarding questionable accounting or auditing matters.

* The material in this report is not deemed "filed" with the SEC, and is not to be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.

•reviewing, modifying and approving our overall compensation strategy and policies, including: (1) reviewing and approving corporate goals and objectives relevant to the compensation of our executive officers and other senior management, as appropriate; (2) evaluating and approving, or recommending to the Board for approval, compensation plans and programs advisable for us, including modifications and terminations to those plans and programs; (3) establishing policies with respect to equity compensation arrangements; (4) assessing the adequacy and competitiveness of our executive compensation programs among comparable companies in our industry; (5) reviewing and approving the terms of any employment agreements, severance arrangements, change-of-control protections and any other compensatory arrangement for our executive officers and other senior management, as appropriate; (6) reviewing our practices and policies of employee compensation as they relate to risk management and risk-taking incentives; (7) considering and establishing share ownership guidelines for our executive officers and directors, if deemed appropriate; and (8) evaluating the efficacy of our compensation policy and strategy in achieving expected benefits to us and otherwise furthering our policies;

•establishing and approving individual and corporate goals and objectives of our Chief Executive Officer and our other executive officers and senior management and evaluating performance of the Chief Executive Officer and our other executive officers and senior management, as appropriate, in light of these stated objectives;

•reviewing and approving the type and amount of compensation to be paid or awarded to Board members;

•selecting and retaining compensation consultants, legal counsel and other advisers; and

•adopting, amending, administering, and terminating our equity compensation plans, pension and profit sharing plans, bonus plans, deferred compensation plans and similar programs.

•identifying, reviewing and evaluating candidates to serve as directors, consistent with criteria approved by the Board;

•reviewing, evaluating and considering the recommendation for nomination of incumbent directors for re-election to the Board;

•reviewing, discussing and assessing the performance of the Board, including Board committees, such assessment to include evaluation of the Board’s contribution as a whole and effectiveness in serving the best interests of Sio and its shareholders, specific areas in which the Board and/or management believe contributions could be improved, overall Board composition and makeup, including the reelection of current Board members, and the independence of directors;

•overseeing the Board’s committee structure and operations, evaluating the performance of the members of the committees of the Board, reviewing the composition of such committees, and recommending to the Board the membership of each such committee;

•reviewing, discussing and assessing our corporate governance principles;

•reviewing our policy statements to determine adherence to our Code of Business Ethics and Conduct; and

•overseeing and reviewing the processes and procedures we use to provide accurate, relevant and appropriately detailed information to the Board and its committees on a timely basis.

The Board has adopted a formal process by which shareholders may communicate with the Board or any of its directors. Shareholders who wish to communicate with the Board or an individual director may do so by sending written communications to the Board or such director at Sio Gene Therapies Inc., Attn: Corporate Secretary, at 130 West 42nd Street, 26th Floor, New York, New York 10036. The Corporate Secretary will forward each communication to the Legal Department of Sio Gene Therapies Inc., and the communication will be further forwarded to the Board or individual directors to whom the communication is addressed unless the communication contains advertisements or solicitations or is unduly hostile, threatening or similarly inappropriate, in which case the communication will be discarded.

In addition to shareholder communications with directors, any interested person may communicate directly with the presiding director of the Board’s executive sessions or the independent or non-management directors as a group. Persons interested in communicating directly with the independent or non-management directors regarding their concerns or issues may do so by addressing correspondence to a particular director, or to the independent or non-management directors generally, in care of Sio Gene Therapies Inc., Attn: Corporate Secretary, at 130 West 42nd Street, 26th Floor, New York, New York 10036. If no particular director is named, letters will be forwarded, depending upon the subject matter, to the Chairperson of the Audit, Compensation, or Nominating and Corporate Governance Committee.

Name and Principal Position			Fiscal Year			Salary			Stock Awards (1)			Option Awards(1)			Non-Equity Incentive Plan Compensation(2)			Other						Total
Pavan Cheruvu, M.D.			2020			$	517,500		$	388,815		$	483,113		$	298,080		$	19,191		(3)			$	1,706,699
Chief Executive Officer			2019			500,000			351,056			1,784,077			225,000			8,616			(4)			2,868,749
David Nassif, J.D. (5)			2020			414,000			181,470			225,415			213,728			43,485			(6)			1,078,098
Chief Financial Officer and Chief Accounting Officer, General Counsel			2019			300,000			234,032			970,828			175,000			81,350			(7)			1,761,210
Gavin Corcoran, M.D. (7)			2020			433,500			146,280			181,989			204,769			17,410			(8)			983,948
Chief R&D Officer			2019			425,000			248,663			628,885			146,094			8,616						1,457,258

(1) Amounts reported in this column do not reflect the amounts actually received by our named executive officers. Instead, these amounts reflect the aggregate grant date fair value of each stock option and stock award granted to the named executive officers during the indicated fiscal year, as computed in accordance with Financial Accounting Standards Board ("FASB") Accounting Standards Codification ("ASC") 718. Assumptions used in the calculation of these amounts are included in Note 10 to our consolidated financial statements included in this Annual Report on Form 10-K for the year ended March 31, 2021. As required by SEC rules, the amounts shown exclude the impact of estimated forfeitures related to service-based vesting conditions. In March 2020, RSL forfeited all of Dr. Cheruvu’s RSL restricted stock units ("RSL RSUs") and granted him newly issued RSL equity instruments: RSL performance options and RSL capped value appreciation rights ("RSL CVARs"). The vesting of the RSL performance options and RSL CVARs is not deemed probable as of March 31, 2021. These two instruments will vest only to the extent certain RSL liquidity conditions and vesting requirements (a mix of time-based and market conditions) are achieved by a specified date in the future, and provided, for the time-based vesting requirements, that Dr. Cheruvu has provided continued service to RSL or an affiliate of RSL, such as Sio. As a result, as of the grant date the RSL performance options and RSL CVARs performance criteria were deemed not probable of occurring, therefore no stock-based compensation expense has been recorded related to these newly awarded RSL instruments and no value has been ascribed to such instruments in the table above. Assuming that the vesting conditions to the RSL performance options and RSL CVARs were met and the performance criteria was deemed probable, the value of such awards as of the grant date would have been $7.7 million.

(2) See "—Annual Cash Bonus".

(3) Amount includes (a) $18,975 in 401(k) matching contributions.

(4) Amount excludes $1,011,993 in stock-based compensation expense allocated to Sio from RSL for RSL equity instruments granted to Dr. Cheruvu.

(5) Mr. Nassif joined Sio in July 2019.

(6) Amount includes (a) $25,173 for reimbursed temporary housing expenses, as a result of the Company requiring Mr. Nassif to reside in New York City for one year as a condition to his employment; and (b) $18,172 in 401(k) matching contributions.

(7) Amount includes (a) $78,206 for reimbursed temporary housing expenses.

(8) Amount includes (a) $17,194 in 401(k) matching contributions.