Iovance Biotherapeutics (IOVA) risk factors, FY2025 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 channel38% rewritten
3. 03We may be unable to realize the expected benefits from restructuring activities, including workforce reductions, and our business might be adversely affectedNew
4. 04Subject to various spending levels approved by our Board of Directors, our management will have broad discretion in the use of the net proceeds from our capital raises, including proceeds from sales pursuant to our “at-the-market” sale agreement with Jefferies LLC, and may not use them effectivelyNew
5. 05The use of our net operating loss carryforwards and research tax credits may be limited30% rewritten
6. 06Recently enacted tax reform legislation in the U.S., changes to existing tax laws, or challenges to our tax positions could adversely affect our business and financial conditionNew

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

1. 07Even though our lead product Amtagvi® is approved and commercialized, we may not become profitable32% rewritten
2. 08able to successfully pass all aspects of surveillance or pre-approval inspections by the FDA or other foreign regulatory authorities for Amtagvi® or future product candidatesNew
3. 09Because 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 candidates23% rewritten
4. 10inadequate coverage and reimbursement for our products. Seeking prior authorization and negotiating the single-case agreement may take anywhere from days to months to obtain, if at all, and may cause ATCs, clinics and patients to decline to use our productsNew
5. 11No 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
6. 12Our 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
7. 13We face significant competition from other biotechnology and pharmaceutical companies and from non-profit institutions
8. 14Our 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
9. 15If our products or product candidates do not achieve broad market acceptance, the revenues that we generate from their sales will be limited
10. 16Our products and product candidates may face competition sooner than anticipated
11. 17We 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
12. 18As 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
13. 19We will need to grow the size and capabilities of our organization, and we may experience difficulties in managing this growth
14. 20We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products and product candidates96% rewritten

Risks Related to the Development of Our Product Candidates

1. 21We 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 commercialized82% rewritten
2. 22therapies provided to the patient during the treatment process. Supportive therapies may impact costs and patient viability and may potentially limit availabilityNew
3. 23Development 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. 24We may face risks due to the need to rely on third parties, including clinical trial sites
2. 25We 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. 26Clinical 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. 27It 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. 28Clinical 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
6. 29Our clinical trials may fail to demonstrate adequately the safety and efficacy of our product candidates, which would prevent or delay regulatory approval and commercialization58% rewritten
7. 30may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies and initial clinical trials. Preclinical studies may also reveal unfavorable product candidate characteristics, including safety concernsNew
8. 31If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected
9. 32Our 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. 33We will be unable to commercialize our products if our trials are not successful

Risks Related to Third Parties

1. 34We may not be able to license new technology from third parties
2. 35We 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. 36We 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. 37Our current line of business, and the biotechnology industry in which we operate, makes it difficult to evaluate our business plan and our prospects
5. 38Our internal computer systems, or those used by our CROs or other contractors or consultants, may fail or suffer security breaches
6. 39We are dependent on information technology, systems, infrastructure and data86% rewritten
7. 40Our business could be adversely affected by the effects of health epidemics and pandemics, in regions where we or third parties on which we rely have significant manufacturing facilities, concentrations of clinical trial sites or other business operationsNew
8. 41Our 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 results79% rewritten
9. 42Our 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 results54% rewritten
10. 43If 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. 44We 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 condition70% rewritten
12. 45We are exposed to fluctuations in currency exchange rates that could negatively impact our financial results and cash flows
13. 46Climate change or legal, regulatory, or market measures to address climate change may negatively affect our business, results of operations, cash flows and prospects
14. 47Environmental, social, and governance matters may impact our business and reputation

Risks Related to Government Regulation

1. 48The 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 candidates36% rewritten
2. 49Obtaining 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. 50Any 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. 51If 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 affected93% rewritten
5. 52business. If we do not comply with all applicable laws, we may be subject to enforcement by both the federal government and the states in which we conduct our business as well as by other third parties, such as patientsNew
6. 53generally do not restrict or regulate the behavior of physicians in their choice of treatment within the practice of medicine. Regulatory authorities do, however, restrict communications by biopharmaceutical companies concerning off-label useNew
7. 54Coverage and reimbursement may be limited or unavailable in certain market segments for our products or product candidates, which could make it difficult for us to sell our product candidates profitably
8. 55Patients 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
9. 56We 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 capital62% rewritten
10. 57Political 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 economy84% rewritten
11. 58We are subject to a variety of U.S. and international laws and regulations
12. 59Governments outside the U.S. tend to impose strict price controls, which may adversely affect our revenues, if any
13. 60Our 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. 61We 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. 62We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights61% rewritten
3. 63Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or the USPTO
4. 64If we are unable to protect our proprietary rights, we may not be able to compete effectively or operate profitably
5. 65We 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. 66The use of our technologies could potentially conflict with the rights of others
7. 67Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products
8. 68We have limited foreign intellectual property rights and may not be able to protect our intellectual property rights throughout the world
9. 69We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties29% rewritten

Risks Related to Our Securities

1. 70Our 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. 71Our stock price may be volatile, and our stockholders’ investment in our stock could decline in value
3. 72You may experience future dilution as a result of future equity offerings or other equity issuances
4. 73Future sales of our common stock in the public market could cause our stock price to fall27% rewritten
5. 74If 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. 75We 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 business49% rewritten
7. 76Our 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. 77Provisions 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. 78Provisions 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