Zevra Therapeutics (ZVRA) risk factors, FY2024 10-K

Other

1. 01Soon after approval of MIPLYFFA, the FDA approved a second therapy for NPC, AQNEURSA, which is approved for symptomatic treatment of ataxia in NPC patients, and is marketed by IntraBio, Inc. ("IntraBio")
2. 02Extensive clinical experience with favorable safety data. No significant safety findings have been reported with more than 600 patients treated in various clinical trials conducted for multiple indications and through our EAPs
3. 03OLPRUVA is differentiated from currently available forms of phenylbutyrate. OLPRUVA is formulated to improve palatability while providing patients with a portable and discrete pre-measured dose
4. 04Unique pharmacological profile. Mechanism of action in VEDS patients is thought to be through vascular dilatation and smooth muscle relaxation, the effect of which is to reduce the mechanical stress on collagen fibers in the arterial wall, and thereby potentially less incidence of vascular ruptures
5. 05Most AEs occurred during the titration period, were mild, and did not lead to early discontinuation
6. 06Mean total ESS scores decreased by approximately 9 points after 5 weeks of OL treatment
7. 07No drug-to-drug interactions observed to date. We have not observed drug-to-drug interactions in clinical drug-drug interaction studies
8. 08AZSTARYS (Partnered product)
9. 09Aquestive Termination Agreement
10. 10Relief Exclusive License Agreement
11. 11License Agreements Related to MIPLYFFA (arimoclomol)
12. 12Our Intellectual Property
13. 13OLPRUVA (sodium phenylbutyrate)
14. 14We also expect to benefit from potential commercial exclusivity afforded to the first drug approved after obtaining orphan drug designation for the treatment of MSUD. Orphan drug designation for OLPRUVA for the treatment of MSUD was granted by the FDA in August 2014
15. 15AZSTARYS and Serdexmethylphenidate (SDX)
16. 16In September 2024, the FDA approved the NDA for MIPLYFFA™ (arimoclomol), an orally-delivered treatment for NPC. MIPLYFFA has also been granted orphan designation for the treatment of NPC by the European Commission
17. 17Third-Party Payor Coverage and Reimbursement
18. 18In general, for purposes of NDA approval, human clinical trials are typically conducted in three sequential phases that may overlap
19. 19NDA Submission and Review by the FDA
20. 20Advertising and Promotion
21. 21Post-Approval Requirements
22. 22Orphan Drug Designation and Exclusivity
23. 23Rare Pediatric Disease Priority Review Voucher Program
24. 24abuse of the drug may lead to severe psychological or physical dependence
25. 25Other Healthcare Regulatory Frameworks
26. 26Data Privacy and Security Laws
27. 27Healthcare Reform Measures
28. 28The Foreign Corrupt Practices Act
29. 29Similarly to the United States, the various phases of non-clinical and clinical research in the EU are subject to significant regulatory controls
30. 30Data and Marketing Exclusivity
31. 31Orphan Medicinal Products
32. 32The aforementioned EU rules are generally applicable in the European Economic Area (“EEA”) which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland

Risks Related to Ownership of Our Common Stock and Our Status as a Public Company

1. 33Sales of a substantial number of shares of our common stock in the public market could cause the market price of our common stock to drop significantly, even if our business is doing well
2. 34We may be subject to securities litigation, class action and derivative lawsuits, which could result in substantial costs and could divert management attention away from other business concerns
3. 35If equity research analysts do not publish research or reports, or publish unfavorable research or reports, about us, our business or our market, our stock price and trading volume could decline
4. 36Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults, or non-performance by financial institutions, could adversely affect our business, financial conditions or results of operations
5. 102The trading price of the shares of our common stock is likely to be volatile, and purchasers of our common stock could incur substantial losses
6. 103Many of the factors described above are not within our control and we cannot guarantee that future instances of these influencing factors will not have effects on the trading price of our common stock
7. 104Future sales and issuances of equity and debt could result in additional dilution to our stockholders
8. 105The holders of any of the warrants described elsewhere in this Annual Report on Form 10-K may elect to exercise such warrants and receive shares of common stock
9. 106providing for a supermajority requirement to amend our amended and restated bylaws
10. 107If appropriate opportunities become available, we may seek to acquire businesses or assets to enhance our business. In connection with any acquisitions, we could issue additional equity securities, which would dilute our stockholders, incur substantial debt to fund the acquisitions or assume significant liabilities
11. 108We could be negatively affected as a result of the actions of activist stockholders, which could be disruptive and costly and may conflict with or disrupt the strategic direction of our business
12. 109Securities litigation against us could result in substantial costs and divert management’s attention from other business concerns, which could seriously harm our business
13. 110We might not be able to utilize a significant portion of our net operating loss carryforwards, which could adversely affect our profitability
14. 111Changes in tax laws or regulations that are applied adversely to us may have a material adverse effect on our business, cash flow, financial condition or results of operations
15. 112An active trading market for our common stock may not be sustained and you may not be able to resell your shares of our common stock for a profit, if at all
16. 113Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be your sole source of gains and you may never receive a return on your investment
17. 114The increasing focus on environmental sustainability and social initiatives could increase our costs, harm our reputation and adversely impact our financial results
18. 115Adverse developments affecting the financial services industry, including events or concerns involving liquidity, defaults, or non-performance by financial institutions, could adversely affect our business, financial condition or results of operations

Risks Related to the Commercialization of Our Approved Products and Product Candidates

1. 37If we are unable to establish effective sales, marketing and distribution capabilities for our approved products or product candidates, if approved, we may not be successful in commercializing any approved product candidate in the United States or any other jurisdictions
2. 38costs associated with maintaining compliance with the FDA’s marketing and promotional requirements, including ongoing training and monitoring, as well as unforeseen costs and expenses associated with creating an independent sales and marketing organization
3. 39Our approved products, or any of our product candidates that may receive marketing approval, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success
4. 40Because the target patient population for certain of our products is small, we must achieve significant market share and obtain relatively high per-patient prices for our products to achieve meaningful gross margins
5. 41We face substantial competition, which may result in others developing or commercializing products before or more successfully than we do
6. 42We may not be able to obtain either three-year FDA regulatory exclusivity or five-year FDA regulatory exclusivity as a new chemical entity
7. 43Even if we or our collaborators are able to commercialize our approved products, or any of our product candidates, if approved, they may be subject to unfavorable pricing regulations, third-party coverage and reimbursement policies
8. 44We may be subject to enforcement action if we engage in improper marketing or promotion of our products
9. 45Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of our approved products, or any of our product candidates that we may develop
10. 46the inability to successfully commercialize any of our approved products, or any of our product candidates that might be approved in the future
11. 47If commercialization of our approved products, or any of our product candidates, if approved, are not successful, or we experience significant delays in commercialization, our business will be harmed
12. 48maintaining a continued acceptable safety and efficacy profile of any of our products following approval
13. 49It is possible that none of our product candidates in clinical development or any of our future product candidates will ever obtain regulatory approval, even if we expend substantial time and resources seeking such approval

Risks Related to the Development of Our Product Candidates

1. 50If we are not able to obtain required regulatory approvals for any of our product candidates, or the approved labels are not sufficiently differentiated from other competing products, we will not be able to commercialize them and our ability to generate revenue or profits or to raise future capital could be limited
2. 51even if we obtain marketing approval in one or more countries, future safety or other issues could result in the suspension or withdrawal of regulatory approval in such countries
3. 52Any product candidates we develop may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude our obtaining regulatory approval or prevent or limit commercial use with respect to one or all intended indications
4. 53Clinical drug development involves a lengthy and expensive process, with an uncertain outcome. We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates
5. 54our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our investigators, regulators or IRBs to suspend or terminate the trials
6. 55have the product removed from the market after obtaining marketing approval
7. 56If we experience delays or difficulties in the enrollment of subjects in clinical trials, our receipt of necessary regulatory approvals could be delayed or prevented
8. 57Interim, topline, or 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
9. 58We may not be able to obtain or maintain orphan drug designations which we pursue for any of our product candidates, and we may be unable to maintain the benefits associated with orphan drug designation, including the potential for market exclusivity
10. 59Certain of our approved products and product candidates contain controlled substances, the manufacture, use, sale, importation, exportation, prescribing and distribution of which are subject to regulation by the DEA and other regulatory agencies
11. 60Our products and product candidates may be associated with serious adverse events, undesirable side effects or have other properties that could halt their clinical development, prevent their regulatory approval, limit their commercial potential or result in significant negative consequences
12. 61We 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
13. 62If the EAP is terminated prior to commercialization of arimoclomol in the EU, if approved, it will have a material adverse effect on our business, results of operations, cash flows, financial condition and/or prospects

Risks Related to Our Business, Our Financial Position and Our Capital Needs

1. 63Our future results will suffer if we do not effectively manage our expanded operations
2. 64A variety of risks associated with international operations could materially adversely affect our business
3. 65We may not be able to retain suppliers or distributors, or suppliers or distributors may seek to modify contractual relationships with us, which could have an adverse effect on our business and operations. Third parties may terminate or alter existing contracts or relationships with us
4. 66If we fail to maintain effective internal control over financial reporting and disclosure controls and procedures, we may not be able to accurately report our financial results or report them in a timely manner, which may adversely affect investor confidence in us and, as a result, the value of our common stock
5. 67We have incurred significant recurring negative net operating cash flows. We cannot predict if we will incur positive or negative net operating cash flows over the next several years, which may impact our ability to continue as a going concern, and we may never achieve or maintain profitability
6. 68add operational systems and personnel, if needed, to support any future commercialization efforts
7. 69We may need additional funding to pursue our business objectives. If we are unable to raise capital when needed, we could be forced to delay, reduce or altogether cease our development programs or commercialization efforts or cease operations altogether

Risks Related to Our Dependence on Third Parties

1. 70We rely on and expect to continue to rely on third parties to conduct our clinical trials for our product candidates, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials
2. 71carrier disruptions or increased costs that are beyond our control
3. 72Our approved products that we are commercializing, and product candidates that we are currently developing, or may develop in the future, may compete with other product candidates and drugs for access to manufacturing facilities, and we may be unable to obtain access to these facilities on favorable terms
4. 73If we enter into any future collaborations we will face similar risks with any future collaborators as well
5. 74If we are not able to establish collaborations for our product candidates, we may have to alter our development and commercialization plans
6. 75Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators

Risks Related to Our Intellectual Property

1. 76we may not develop additional proprietary technologies that are patentable
2. 77Any of these factors could hurt our ability to gain full patent protection for our products. Registered trademarks and trademark applications in the United States and other countries are subject to similar risks as described above for patents and patent applications, in addition to the risks described below
3. 78Changes in patent law in the United States and other jurisdictions could alter or diminish the value of patents in general, thereby impairing our ability to protect our products and technologies
4. 79We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful
5. 80Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could significantly harm our business
6. 81Even 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
7. 82We may need to license intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms
8. 83If we or our third-party licensors fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our business
9. 84The scope of our intellectual property may be reduced or may need to be reduced due to third-party intellectual property claims
10. 85We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property or claiming ownership of what we regard as our own intellectual property
11. 86Any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business
12. 87If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed
13. 88We may not be able to protect our intellectual property rights throughout the world
14. 89Our decision to seek approval of our product candidates under certain regulatory pathways, such as the 505(b)(2) NDA pathway for the FDA, may increase the risk that patent infringement suits are filed against us, which would delay FDA or comparable foreign regulatory authorities' approval of such product candidates

Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters

1. 90Failure to obtain marketing approval in international jurisdictions would prevent our approved products, and any of our other product candidates from being marketed abroad
2. 91A variety of risks associated with marketing our approved products and any of our product candidates, if approved, internationally, could affect our business
3. 92Our approved products are, and any of our product candidates for which we obtain marketing approval will remain subject to significant post-marketing regulatory requirements and oversight
4. 93injunctions or the imposition of civil or criminal penalties, including False Claims Act liability
5. 94Our employees, independent contractors, principal investigators, CROs, consultants, commercial collaborators, contract manufacturers, service providers and other vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements
6. 95These laws may affect our and our commercial partners' sales, marketing, and other promotional activities by imposing administrative and compliance burdens on us and our commercial partners
7. 96Recently enacted and future legislation may increase the difficulty and cost for us to obtain marketing approval of our product candidates and increase the cost to commercialize our approved products, and any of our product candidates that may be approved in the future and affect the prices thereof
8. 97a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research
9. 98Governments outside the United States tend to impose strict price controls, which may affect our revenue, if any
10. 99If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business
11. 100We are subject to complex and changing laws and regulations, which exposes us to potential liabilities, increased costs and other adverse effects on our business

Risks Related to Employee Matters and Managing Our Growth

1. 101Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel