Iovance Biotherapeutics (IOVA) risk factors, FY2024 10-K

Risks Related to Our Financial Position and Need for Additional Capital

1. 01We have a history of operating losses; we expect to continue to incur losses, and we may never be profitable
2. 02Significant judgement is required in estimating GTN adjustments considering legal interpretations of applicable laws and regulations, historical experience, payer channel mix, current contract prices under applicable programs, processing time lags, and inventory levels in the distribution channel
3. 03The use of our net operating loss carryforwards and research tax credits may be limited
4. 04In recent years, various tax legislations were signed into law. On December 22, 2017, the Tax Cuts and Jobs Act of 2017, or the Tax Act, was signed into law, making significant changes to the Internal Revenue Code

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

1. 05Even though our lead product Amtagvi® is approved and commercialized, we may not become profitable
2. 06Because our current products represent, and our other potential product candidates will represent novel approaches to the treatment of disease, there are many uncertainties regarding the development, the market acceptance, third-party reimbursement coverage, and the commercial potential of our product candidates
3. 07No assurance can be given that the Gen 2 manufacturing process or other processes we have selected will be FDA compliant or more efficient and will lower the cost to manufacture TIL products
4. 08Our business entails a significant risk of product liability. If product liability lawsuits are brought against us, whether or not meritorious, we may incur substantial liabilities and may be required to limit or halt commercialization of our products and/or product candidates
5. 09We face significant competition from other biotechnology and pharmaceutical companies and from non-profit institutions
6. 10Our projections regarding the market opportunities for our products and product candidates may not be accurate, and the actual market for our products and product candidates may be smaller than we estimate
7. 11If our products or product candidates do not achieve broad market acceptance, the revenues that we generate from their sales will be limited
8. 12Our products and product candidates may face competition sooner than anticipated
9. 13We will need to obtain approval of any proposed proprietary branded product names, and any failure or delay associated with such approval may adversely affect our business
10. 14As a condition of approval, the FDA and foreign regulatory authorities may require that we implement various post-marketing requirements and conduct post-marketing studies, any of which would require a substantial investment of time, effort, and money, and which may limit our commercial prospects
11. 15We will need to grow the size and capabilities of our organization, and we may experience difficulties in managing this growth
12. 16We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products
13. 17indications. As a result, we may need to discontinue use of the WuXi manufacturing capacity and instead use the iCTC facility or other manufacturers to supply our therapies

Risks Related to the Development of Our Product Candidates

1. 18We depend on the success of our product candidates and cannot guarantee that these product candidates will successfully complete development, receive regulatory approval, or be successfully commercialized
2. 19Development of a product candidate intended for use in combination with an already approved product may present more or different challenges than development of a product candidate for use as a single agent

Risks Related to Clinical Trials

1. 20We may face risks due to the need to rely on third parties, including clinical trial sites
2. 21We may encounter substantial delays in our clinical trials, not be able to conduct our clinical trials on the timelines we expect, and be required to conduct additional clinical trials or modify current or future clinical trials based on feedback we receive from the FDA and foreign regulatory authorities
3. 22Clinical trial delays could shorten any periods during which our products have patent protection and may allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates and may harm our business and results of operations
4. 23It may take longer and cost more to complete our clinical trials than we project, or we may not be able to complete them at all
5. 24conducted them entirely on our own. If we fail to commence or complete, or experience delays in, any of our planned clinical trials, our stock price and our ability to conduct our business as currently planned could be harmed
6. 25Clinical trials are expensive, time-consuming and difficult to design and implement, and our clinical trial costs may be higher than for more conventional therapeutic technologies or drug products
7. 26Our clinical trials may fail to demonstrate adequately the safety and efficacy of our product candidates, which would prevent or delay regulatory approval and commercialization
8. 27If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected
9. 28Our commercial product and product candidates may cause 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
10. 29We will be unable to commercialize our products if our trials are not successful

Risks Related to Third Parties

1. 30We may not be able to license new technology from third parties
2. 31We are required to pay substantial royalties and lump sum benchmark payments under our license or acquisition agreements with the NIH, Novartis, Clinigen, and Cellectis, and we must meet certain milestones to maintain our license rights
3. 32We are dependent on third parties to support our research, development, and supplement our internal manufacturing activities and, therefore, are subject to the efforts of these parties and our ability to successfully collaborate with these third parties
4. 33Our current line of business, and the biotechnology industry in which we operate, makes it difficult to evaluate our business plan and our prospects
5. 34Our internal computer systems, or those used by our CROs or other contractors or consultants, may fail or suffer security breaches
6. 35We are dependent on information technology, systems, infrastructure and data
7. 36Our failure to comply with international data protection laws and regulations could lead to government enforcement actions and significant penalties against us, and adversely impact our operating results
8. 37confidentiality of the personal data, data breach notification and the use of third-party processors in connection with the processing of personal data
9. 38Our failure to comply with state and/or national data protection laws and regulations could lead to government enforcement actions and significant penalties against us, and adversely impact our operating results
10. 39If we engage in future acquisitions or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities, and subject us to other risks
11. 40We have global operations, which expose us to additional risks, and any adverse event could have a material adverse effect on our results of operations and financial condition
12. 41goods. Russian military actions and the resulting sanctions could continue to adversely affect the global economy and financial markets and lead to instability and lack of liquidity in capital markets, potentially making it more difficult for us to obtain additional funds
13. 42We are exposed to fluctuations in currency exchange rates that could negatively impact our financial results and cash flows
14. 43Climate change or legal, regulatory, or market measures to address climate change may negatively affect our business, results of operations, cash flows and prospects
15. 44Environmental, social, and governance matters may impact our business and reputation

Risks Related to Government Regulation

1. 45The FDA and foreign regulatory approval process is lengthy and time-consuming, and we may experience significant delays in the clinical development and regulatory approval of our product candidates
2. 46Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not mean that we will be successful in obtaining or maintaining regulatory approval of our product candidates in other jurisdictions
3. 47Any of these events could further have other material and adverse effects on our operations and business and could adversely impact our stock price and could significantly harm our business, financial condition, results of operations, and prospects
4. 48If we fail to comply with applicable healthcare and promotional laws, including fraud and abuse and information privacy and security laws, we could face substantial penalties and our business, financial condition, results of operations, and prospects could be adversely affected
5. 49litigation and, if we do not successfully defend against such actions, those actions may have a material adverse effect on our business, financial condition, results of operations and prospects
6. 50Coverage and reimbursement may be limited or unavailable in certain market segments for our product candidates, which could make it difficult for us to sell our product candidates profitably
7. 51Patients who are provided medical treatment for their conditions often rely on third-party payors to reimburse all or part of the costs associated with their treatment. Obtaining coverage and adequate reimbursement from payors is critical to new product acceptance
8. 52We are subject to new legislation, regulatory proposals, and healthcare payor initiatives that may increase our costs of compliance and adversely affect our ability to market our products, obtain collaborators, and raise capital
9. 53judicial deference to administrative action by agencies in the executive branch. Furthermore, the Supreme Court’s decision in Corner Post may result in challenges to FDA decisions by new litigants long into the future
10. 54Political uncertainty may have an adverse impact on our operating performance and results of operations, and uncertainty surrounding the potential legal, regulatory, and policy changes by a new U.S. presidential administration may directly affect us and the global economy
11. 55We are subject to a variety of U.S. and international laws and regulations
12. 56Governments outside the U.S. tend to impose strict price controls, which may adversely affect our revenues, if any
13. 57Our employees, independent contractors, consultants, commercial partners and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements

Risks Related to Our Intellectual Property

1. 58We may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, or lawsuits accusing our products of patent infringement, which could be expensive, time-consuming and unsuccessful
2. 59We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights
3. 60Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or the USPTO
4. 61If we are unable to protect our proprietary rights, we may not be able to compete effectively or operate profitably
5. 62We cannot prevent other companies from licensing most of the same intellectual properties that we have licensed or from otherwise duplicating our business model and operations
6. 63The use of our technologies could potentially conflict with the rights of others
7. 64Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products
8. 65We have limited foreign intellectual property rights and may not be able to protect our intellectual property rights throughout the world
9. 66We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties

Risks Related to Our Securities

1. 67Our officers, directors and principal stockholders own a substantial percentage of our stock and will be able to exert significant control over matters subject to stockholder approval
2. 68Our stock price may be volatile, and our stockholders’ investment in our stock could decline in value
3. 69You may experience future dilution as a result of future equity offerings or other equity issuances
4. 70Future sales of our common stock in the public market could cause our stock price to fall
5. 71If equities or industry analysts do not publish research or reports about our company, or if they issue adverse or misleading opinions regarding us or our stock, our stock price and trading volume could decline
6. 72We are, and in the future may be, subject to federal or state securities or related legal actions that could adversely affect our results of operations and our business
7. 73Our Board of Directors could issue one or more additional series of preferred stock without stockholder approval with the effect of diluting existing stockholders and impairing their voting and other rights
8. 74Provisions in our corporate charter documents and under Delaware law may prevent or frustrate attempts by our stockholders to change our management and hinder efforts to acquire a controlling interest in us, and the market price of our common stock may be lower as a result
9. 75Provisions in our amended and restated bylaws could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers or employees