Iovance Biotherapeutics

Commercial Manufacturing Facility Agreement

On May 28, 2019, we entered into a lease agreement, or the Commercial Manufacturing Facility Lease, for a build-to-suit commercial manufacturing facility, laboratories, and offices located in Philadelphia, Pennsylvania. Under the Commercial Manufacturing Facility Lease, we lease approximately 136,000 rentable square feet of space in a building located at 300 Rouse Boulevard, Philadelphia, Pennsylvania known as the Iovance Cell Therapy Center, or the iCTC. The construction of the iCTC began in July 2019 and in the third quarter of 2021 we completed the commissioning activities as well as certain tenant improvements. The Commercial Manufacturing Facility Lease includes an option to extend the term of the lease by giving the landlord prior written notice thereof at least 18 months in advance of expiration date, exercisable under certain conditions as described in the Commercial Manufacturing Facility Lease, such that the overall term, when added to the initial term, shall be 359 months.

Our monthly base rent under the Commercial Manufacturing Facility Lease is approximately $0.3 million, subject to an annual increase of 2% for the first ten years. Commencing on the first day of each lease year thereafter, for the remainder of the lease term, monthly rent is subject to an annual increase of the greater of 2% or 75% of the average ten-year consumer price index. We are also responsible for paying operating expenses, such as common area maintenance.

Tampa Lease

Our research and development facilities consist of 8,673 square feet in a facility located at the University of South Florida Research Park in Tampa, Florida. These facilities are leased under an agreement with a lease term through December 2024 for approximately $20,500 a month. In June 2020, we amended the lease agreement to further increase the rentable space to 13,139 square feet and extend the lease term to June 5, 2025, for approximately $34,500 a month. On December 22, 2021, we entered into a second

amendment to lease an additional 2,731 square feet of space through June 5, 2025, co-terminus with the existing leased space. Upon completion of tenant improvements of the premises, lease payments will be approximately $45,000 per month. On July 28, 2025, we entered into a third amendment, to extend the lease term through January 2028. Lease payments are approximately $50,000 per month.

Former Philadelphia Office Lease

On May 2, 2019, we entered into an agreement to lease approximately 1,500 square feet of office space in Philadelphia, Pennsylvania until July 1, 2019, for a rate of $2,000 a month, and then approximately 4,500 square feet of office space for the remainder of a three-year term at an initial rate of $11,063 per month, subject to annual increases of 2.5%. On September 1, 2021, we entered into an agreement to extend the lease term for an additional three years to July 31, 2025, for approximately $11,900 a month, effective as of June 1, 2022, subject to annual increases of 2.5%. The lease agreement expired at the end of July 2025 and was not further extended.

American National Red Cross Lease

On February 1, 2022, we entered into an agreement to lease approximately 4,500 square feet of rentable area located in Pennsylvania, consisting of laboratories, clean room and office space, for a three-year term at a rate of approximately $17,000 a month subject to an annual increase of 2.5%. We have since entered into various lease amendments to expand the rentable square feet of office space and lab space. Most recently, in May 2025, we amended the lease agreement to extend the lease term to July 31, 2029, with the option to subsequently extend for an additional two years. The lease payments are approximately $41,000, subject to annual increases of 3.75%.

Netherlands Office Lease

On July 28, 2023, we entered into an agreement to lease satellite office space in Amsterdam, Netherlands for a twelve-month term at a rate of approximately €5,400 per month, which was renewed in 2025 to extend the lease term through July 28, 2026. Such agreement automatically renews for successive periods unless cancelled with no less than three months’ notice prior to the end of the current term.

We believe that our existing facilities are adequate to meet our current needs, and that suitable additional alternative spaces will be available in the future on commercially reasonable terms.

• Because 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.
• No 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.
• Our 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.
• We face significant competition from other biotechnology and pharmaceutical companies and from non-profit institutions.
• Our 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.
• We have limited commercial experience and may be unable to establish effective marketing and sales capabilities or enter into agreements with third parties to market and sell our products and product candidates, if they are approved, and as a result, we may be unable to generate significant product awareness, and the lack of awareness may limit the revenues that we generate.
• If our products or product candidates do not achieve broad market acceptance, the revenues that we generate from their sales will be limited.
• Our products and product candidates may face competition sooner than anticipated.
• We 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.
• As 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.
• We will need to grow the size and capabilities of our organization, and we may experience difficulties in managing this growth.
• We may rely on third parties to perform many essential services for any products that we commercialize, including services related to distribution, government price reporting, customer service, accounts receivable management, cash collection, and adverse event reporting. If these third parties fail to perform as expected or to comply with legal and regulatory requirements, our ability to commercialize our current or future products will be significantly impacted and we may be subject to regulatory sanctions.
• We may be unable to successfully or sufficiently expand our manufacturing capacity to meet demand for our products and product candidates.
• Risks Related to the Development of Our Product Candidates
• We 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.
• Development 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.
• A Fast Track, breakthrough therapy, or regenerative medicines advanced therapy product designations, or other designation to facilitate product candidate development may not lead to faster development or a faster regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
• While lifileucel has received orphan drug designation for melanoma stages IIB-IV and for cervical cancer patients with tumors greater than 2 cm, there is no guarantee that we will be able to maintain this designation, receive these designations for any of our other product candidates, or receive or maintain any corresponding benefits, including periods of exclusivity.
• Risks Related to Clinical Trials
• We may face risks due to the need to rely on third parties, including clinical trial sites.
• We 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.
• It 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.
• Clinical 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.
• Our clinical trials may fail to demonstrate adequately the safety and efficacy of our product candidates, which would prevent or delay regulatory approval and commercialization.
• If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected.
• Our 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.
• We will be unable to commercialize our products if our trials are not successful.
• Risks Related to Third Parties
• We may not be able to license new technology from third parties.
• We 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.
• We 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.
• We rely on and collaborate with governmental, academic, and corporate partners or agencies to approve, improve, and develop TIL cell therapies for new indications for use in combination with other therapies and to evaluate new TIL manufacturing methods, the results of which, because the manufacturing processes are not within our control, may be incorrect or unreliable.
• Other Risks Related to Our Business
• Our current line of business, and the biotechnology industry in which we operate, makes it difficult to evaluate our business plan and our prospects.
• Our internal computer systems, or those used by our CROs or other contractors or consultants, may fail or suffer security breaches.
• We are dependent on information technology, systems, infrastructure and data.
• We, directly or through our third-party service providers, may adopt, use or incorporate artificial intelligence, or AI, technology and capabilities into the information technology systems or software that we use in our business and operations. Defects in such AI technology or related security breaches, loss of data and other disruptions as well as changes in implementation standards and enforcement practices under a rapidly evolving regulatory framework for AI technology may adversely affect our business and operations and potentially expose us to increasing liability.
• Our 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 operations.
• Our 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.
• Our 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.
• If 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.
• We 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.
• We are currently operating in a period of economic uncertainty and capital markets disruption, which has been significantly impacted by geopolitical instability, ongoing military conflicts, and inflation. Our business, financial condition and results of operations could be materially adversely affected by any negative impact on the global economy and capital markets resulting from the conflicts in Ukraine, the Middle East and other global conflicts, geopolitical tensions, or inflation.
• We are exposed to fluctuations in currency exchange rates that could negatively impact our financial results and cash flows.
• Climate change or legal, regulatory, or market measures to address climate change may negatively affect our business, results of operations, cash flows and prospects.
• Environmental, social, and governance matters may impact our business and reputation.
• Risks Related to Government Regulation
• We are subject to extensive regulation, which can be costly and time consuming and can subject us to unanticipated delays in obtaining regulatory approvals for our products and/or product candidates, and even after obtaining regulatory approval for some of our products and/or product candidates, those products and/or product candidates may still face regulatory difficulties.
• The 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.
• Obtaining 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.
• We are, and if we receive regulatory approval of our product candidates, will continue to be subject to ongoing regulatory obligations and continued regulatory review, which may result in significant additional expense, and we may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with our product candidates.
• If 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.
• Coverage 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.
• We 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.
• Political 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.
• We are subject to a variety of U.S. and international laws and regulations.
• Governments outside the U.S. tend to impose strict price controls, which may adversely affect our revenues, if any.
• Our 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
• We 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.
• We may incur substantial costs as a result of litigation or other proceedings relating to patent and other intellectual property rights.
• Issued patents covering our product candidates could be found invalid or unenforceable if challenged in court or the USPTO.
• If we are unable to protect our proprietary rights, we may not be able to compete effectively or operate profitably.
• We 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.
• The use of our technologies could potentially conflict with the rights of others.
• Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.
• We have limited foreign intellectual property rights and may not be able to protect our intellectual property rights throughout the world.
• We may be subject to claims that our employees, consultants or independent contractors have wrongfully used or disclosed confidential information of third parties.