8-K
IOVANCE BIOTHERAPEUTICS, INC. (IOVA)
8-K
2025-08-29
For: 2025-08-29
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April 07, 2026
UNITED STATESSECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
Current Report
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (date of earliest event
reported): August 29, 2025
IOVANCE BIOTHERAPEUTICS, INC.
(Exact Name of Registrant as Specified in Charter)
| Delaware | |
|---|---|
| (State of Incorporation) | |
| 001-36860 | 75-3254381 |
| Commission File Number | (I.R.S. Employer Identification No.) |
| 825 Industrial Road, Suite 100 | |
| San Carlos, California | 94070 |
| (Address of Principal Executive Offices) | (Zip Code) |
| (650) 260-7120 | |
| (Registrant’s Telephone Number, Including Area Code) |
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425). |
|---|---|
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12). |
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| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)). |
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| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)). |
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Indicate by check mark whether the registrant is an emerging growth company as defined in as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). 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 13(a) of the Exchange Act. ¨
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading <br><br>Symbol(s) | Name of each exchange on which<br><br> registered |
|---|---|---|
| Common stock, par value $0.000041666 per value | IOVA | The<br> Nasdaq Stock Market, LLC |
| Item 8.01 | Other Events. | |
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On August 29, 2025, Iovance Biotherapeutics, Inc. (the “Company”) updated its corporate presentation that it uses for presentations at healthcare conferences and to analysts, current stockholders, and others. A copy of the Company’s presentation that it intends to use at such events is attached as Exhibit 99.1 and is incorporated herein by reference.
| Item 9.01 | Financial Statements and Exhibits. |
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(d) Exhibits.
| Exhibit No. | Description |
|---|---|
| 99.1 | Iovance Biotherapeutics, Inc., Corporate Presentation – August 2025 |
| 104 | Cover Page Interactive Data File (embedded as Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this Report to be signed on its behalf by the undersigned hereunto duly authorized.
| Date: August 29, 2025 | Iovance Biotherapeutics, Inc. | ||
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| By: | /s/ Frederick G. Vogt | ||
| Name: | Frederick G. Vogt, Ph.D., J.D. | ||
| Title: | Interim CEO, President, and General Counsel |
Exhibit 99.1
| 1<br> © 2025, Iovance Biotherapeutics, Inc.<br> © 2025, Iovance Biotherapeutics, Inc.<br>Corporate Overview<br>August 2025<br>1 |
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| 2<br> © 2025, Iovance Biotherapeutics, Inc.<br>Forward-Looking Statements<br>Certain matters discussed in this presentation are “forward-looking statements” of Iovance Biotherapeutics, Inc. (hereinafter referred to as the “Company,” “we,” “us,” or “our”) within the meaning<br>of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). Without limiting the foregoing, we may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,”<br> “estimates,” “anticipates,” “expects,” “plans,” “intends,” “forecast,” “guidance,” “outlook,” “may,” “can,” “could,” “might,” “will,” “should,” or other words that convey uncertainty of future<br>events or outcomes and are intended to identify forward-looking statements. Forward-looking statements are based on assumptions and assessments made in light of management’s experience<br>and perception of historical trends, current conditions, expected future developments, and other factors believed to be appropriate. Forward-looking statements in this presentation are made as of<br>the date of this presentation, and we undertake no duty to update or revise any such statements, whether as a result of new information, future events or otherwise. Forward-looking statements are<br>not guarantees of future performance and are subject to risks, uncertainties, and other factors, many of which are outside of our control, that may cause actual results, levels of activity,<br>performance, achievements, and developments to be materially different from those expressed in or implied by these forward-looking statements. Important factors that could cause actual<br>results, developments, and business decisions to differ materially from forward-looking statements are described in the sections titled "Risk Factors" in our filings with the U.S. Securities and<br>Exchange Commission, including our most recent Annual Report on Form 10-K and Quarterly Reports on Form 10-Q, and include, but are not limited to, the following substantial known and<br>unknown risks and uncertainties inherent in our business: the risks related to our ability to successfully commercialize our products, including Amtagvi, for which we have obtained U.S. Food and<br>Drug Administration (“FDA”) approval, and Proleukin, for which we have obtained FDA and European Medicines Agency (“EMA”) approval; the risk that the EMA or other ex-U.S. regulatory<br>authorities may not approve or may delay approval for our marketing authorization application submission for lifileucel in metastatic melanoma; the acceptance by the market of our products,<br>including Amtagvi and Proleukin, and their potential pricing and/or reimbursement by payors, if approved (in the case of our product candidates), in the U.S. and other international markets and<br>whether such acceptance is sufficient to support continued commercialization or development of our products, including Amtagvi and Proleukin, or product candidates, respectively; future<br>competitive or other market factors may adversely affect the commercial potential for Amtagvi or Proleukin; the risk regarding our ability or inability to manufacture our therapies using third party<br>manufacturers or at our own facility, including our ability to increase manufacturing capacity at such third party manufacturers and our own facility, may adversely affect our commercial launch;<br>the results of clinical trials with collaborators using different manufacturing processes may not be reflected in our sponsored trials; the risk regarding the successful integration of the recent<br>Proleukin acquisition; the risk that the successful development or commercialization of our products, including Amtagvi and Proleukin, may not generate sufficient revenue from product sales, and<br>we may not become profitable in the near term, or at all; the risks related to the timing of and our ability to successfully develop, submit, obtain, or maintain FDA, EMA, or other regulatory authority<br>approval of, or other action with respect to, our product candidates; whether clinical trial results from our pivotal studies and cohorts, and meetings with the FDA, EMA, or other regulatory<br>authorities may support registrational studies and subsequent approvals by the FDA, EMA, or other regulatory authorities, including the risk that the planned single arm Phase 2 IOV-LUN-202 trial<br>may not support registration; preliminary and interim clinical results, which may include efficacy and safety results, from ongoing clinical trials or cohorts may not be reflected in the final analyses<br>of our ongoing clinical trials or subgroups within these trials or in other prior trials or cohorts; the risk that enrollment may need to be adjusted for our trials and cohorts within those trials based on<br>FDA and other regulatory agency input; the risk that the changing landscape of care for cervical cancer patients may impact our clinical trials in this indication; the risk that we may be required to<br>conduct additional clinical trials or modify ongoing or future clinical trials based on feedback from the FDA, EMA, or other regulatory authorities; the risk that our interpretation of the results of our<br>clinical trials or communications with the FDA, EMA, or other regulatory authorities may differ from the interpretation of such results or communications by such regulatory authorities (including<br>from our prior meetings with the FDA regarding our non-small cell lung cancer clinical trials); the risk that clinical data from ongoing clinical trials of Amtagvi will not continue or be repeated in<br>ongoing or planned clinical trials or may not support regulatory approval or renewal of authorization; the risk that unanticipated expenses may decrease our estimated cash balances and forecasts<br>and increase our estimated capital requirements; the risk that we may not be able to recognize revenue for our products; the risk that Proleukin revenues may not continue to serve as a leading<br>indicator for Amtagvi revenues; the risks regarding our anticipated operating and financial performance, including our financial guidance and projections; the effects of global pandemic; the effects<br>of global and domestic geopolitical factors; and other factors, including general economic conditions and regulatory developments, not within our control. Any financial guidance provided in this<br>presentation assumes the following: no material change in our ability to manufacture our products; no material change in payor coverage; no material change in revenue recognition policies; no<br>new business development transactions not completed as of the period covered by this presentation; and no material fluctuation in exchange rates. |
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| 3<br> © 2025, Iovance Biotherapeutics, Inc.<br>Global Leadership in Innovating, Developing and<br>Delivering TIL Therapy for Patients with Cancer<br>Approved<br>Products<br>Commercial Launch People & Assets<br> >80<br> >250M<br>~$307<br>Cash as of 6/30/25<br>M<br>~1K<br>Employees<br>3 1 1<br>FDA Designations<br>Fast<br>Track BTD RMAT<br>Treatment Centers<br>as of 6/30/25*<br>2<br>U.S. patient lives<br>covered under payer<br>policies/plans<br>Global Advanced<br>Melanoma Patient >70K Treatment Opportunity<br>Pipeline<br>Planned clinical data<br>updates in 2025 3 2<br>Ex-U.S. Regulatory 2 Filings in Review1<br> >240M<br>Prior 12 Month Product Revenue3<br> © 2025, Iovance Biotherapeutics, Inc.<br>1. UK & Australia. 2. Iovance sponsored clinical trials, does not include expanded access or investigator sponsored studies. 3. Includes Amtagvi & Proleukin revenue for period 7/1/24-6/30/25<br>*Includes centers in final stages of readiness, soon to be authorized or planned.<br>Abbreviations: BTD=Breakthrough Therapy Designation; FDA=U.S. Food and Drug Administration; RMAT=Regenerative Medicine Advanced Therapy Designation<br> >1,000 Commercial & clinical patients<br>treated with Iovance TIL products<br>U.S. & Canada<br>Multiple Markets Globally |
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| 4<br> © 2025, Iovance Biotherapeutics, Inc.<br>Iovance Solid Tumor Portfolio Highlights<br>*Enrollment complete in IOV-COM-202 Cohorts 1A, 3A & 3B; Enrollment paused in Cohorts 3D & 3E.<br>Abbreviations: 1L=first line; 2L=second line; 4L=fourth line; FTD=Fast Track Designation; ICI=immune checkpoint inhibitor; IL-2=interleukin 2; IL-12=interleukin 12; IND=investigational new drug application; NSCLC=non-small cell lung cancer; PD-1=programmed cell death protein-1; TIL=tumor infiltrating lymphocytes<br>Label Expansion<br>Opportunities<br>INDICATION & TREATMENT SETTING PHASE 1 PHASE 2 PHASE 3 APPROVED<br>Commercial<br>Post-anti-PD-1 advanced melanoma (U.S., Canada)<br>EMA , UK & Australia submitted<br>Amtagvi treatment regimen (U.S., Canada)<br>Advanced melanoma, renal cell carcinoma (U.S., ex-U.S.)<br>Registration-Directed<br>Lifileucel + pembrolizumab Frontline advanced melanoma TILVANCE-301 Phase 3 (FTD, Confirmatory)<br>Lifileucel Post-chemo & anti-PD-1 advanced NSCLC IOV-LUN-202: Cohorts 1&2<br>Lifileucel<br>Pipeline<br>Lifileucel Post-chemo & anti-PD-1 endometrial cancer IOV-END-201: Cohorts 1&2<br>Lifileucel; + ICI; +ICI & chemo 1-4L ICI-naïve & post-anti-PD1 advanced NSCLC IOV-COM-202: Cohorts 3A-3E*<br>Lifileucel + ICI ICI-naïve advanced melanoma IOV-COM-202: Cohorts 1A,* 1D<br>Lifileucel core biopsy 2L post-chemo & post-anti-PD-1 advanced NSCLC IOV-LUN-202: Cohort 3<br>Next-Generation<br>Products<br>PD-1 Inactivated TIL (IOV-4001) Post anti-PD1 advanced melanoma IOV-GM1-201: Cohort 1<br>PD-1 Inactivated TIL (IOV-4001) 2-4L incl. post-anti-PD-1 advanced NSCLC IOV-GM1-201: Cohort 2<br>IL-2 analog (IOV-3001) TIL treatmentregimen IOV-IL2-101<br>IL-12 tethered TIL (IOV-5001) Basket trial Planned |
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| 5<br> © 2025, Iovance Biotherapeutics, Inc.<br>Tumor Infiltrating Lymphocytes (TIL):<br>Leading Cell Therapy Platform for Solid Tumors<br>TIL –Unique<br>Mechanism of Action<br> • Individualized<br> • One-time therapy<br> • Deploys the patient’s own<br>T cells to fight cancer<br>Tumor Tissue<br>Collection<br>Patient-specific T Cells<br>Grown into the Billions1<br>TIL Treatment Regimen<br>1. Amtagvi USPI |
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| 6<br> © 2025, Iovance Biotherapeutics, Inc.<br>U.S. Deaths1 Global Deaths2<br>Melanoma 8K 59K<br>Lung & Bronchus 125K 1.8M<br>Endometrial 13K 97K<br>1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2025 Estimates. https://seer.cancer.gov (accessed August 2025)<br>2. World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2022<br>91% of all cancer cases are solid tumors1<br>Significant Market Potential in Solid Tumors Programs<br>1 Expand into other indications: 2 Expand into additional markets:<br>Approved Markets<br>for Previously<br>Treated Advanced<br>Melanoma<br>Near-Term<br>Planned Markets |
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| 7<br> © 2025, Iovance Biotherapeutics, Inc.<br>Significant unmet need in frontline and beyond1<br>Opportunity to Expand<br>Advanced Melanoma Market<br>2L+ Advanced Melanoma<br>Patient Population2,3<br>US:<br>8K<br>Potential<br>ex-US Markets:<br>22K<br>Overall (1L+):<br>70K<br>Prognosis for patients who progress on front-line PD-1 therapy7<br>BRAF wild-type<br>(prior treatment with ICI)<br>~5 months<br>BRAF mutated<br>(prior treatment with ICI<br>and targeted therapy)<br>~3 months<br>Abbreviations: 1L, first line; ICI, immune checkpoint inhibitors; mOS, median overall survival; mPFS, median progression-free survival; PD-(L)1, programmed death receptor-1 or programmed death-ligand<br>1. Chesney J, et al. J Immunother Cancer. 2022; 2. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2025 Estimates. https://seer.cancer.gov (accessed August 2025); World Health Organization International Agency for Research on Cancer (IARC).<br>GLOBOCAN 2022;3. Data on file as of July 2025. Includes more than 20,000 patients initial target markets plus additional potential markets; 4. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. NEJM. 5. Robert C, et al.. Lancet 6. Tawbi HA, Schadendorf D, Lipson EJ, et al. NEJM 7. Patrinely<br>JR et al.Cancer.2020<br>More than half of patients progress<br>within 12 months on current 1L<br>checkpoint inhibitor treatment options,<br>regardless of BRAF mutation status4-6<br>mOS After<br>Disease Progression:<br>2L Patients |
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| 8<br> © 2025, Iovance Biotherapeutics, Inc.<br>First FDA-approved One-time, Individualized<br>T cell Therapy for a Solid Tumor Cancer |
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| 9<br> © 2025, Iovance Biotherapeutics, Inc.<br>Amtagvi Addresses High Unmet Need for Patients Who Progress<br>After Immune Checkpoint Inhibitors1<br>Preferred second-line+ therapy in NCCN guidelines2<br>Deep & durable responses at 5-year follow up1<br>1. Medina et al, ASCO 2025. Pooled Analysis (n=153), Heavily Pre-Treated Patient Population 2. National Comprehensive Cancer Network® Guidelines, Melanoma: Cutaneous, Version 2.24<br>Abbreviations: mDOR=median duration of response; mOS=media overall survival; NR=not reached; ORR=objective response rate; OS=overall survival<br>5yr OS<br>19.7%<br>(57.8 months median follow up)<br>mDOR<br>36.5 Months<br>ORR<br>31.4%<br>mOS<br>13.9 Months |
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| 10<br> © 2025, Iovance Biotherapeutics, Inc.<br>Higher response rates observed in<br>third-line or earlier patients<br>Physician-assessed responses<br>reinforce Amtagvi clinical benefit<br>60.9% ORR (14/23)<br>Nearly Half of Patients Responded to Amtagvi in Real-World Analysis1<br>1. All evaluable patients received commercial Amtagvi according to the U.S. prescribing information and completed at least one follow-up physician assessment. Data on file.<br>2. Three Prior Lines of Therapy (1L-3L): 1L ipilimumab + nivolumab; 2L dabrafenib + trametinib; 3L nivolumab + relatlimab. 86% reduction in target lesions. Response ongoing at 260-day follow up. Photo Credit and Permission: H. Lee Moffitt Cancer Center<br>Abbreviations: ORR=objective response rate<br>48.8% ORR (20/41)<br>Preliminary analysis of patients treated in real-world clinical setting<br>33.3% ORR (6/18)<br>Before Lifileucel Post-Lifileucel (Week 6)<br>Real-World Patient: Durable Ongoing Partial Response (PR)2<br>PR with significant tumor burden reduction at Week 6<br> ≤ 2 prior lines of therapy<br> ≥ 3 prior lines of therapy |
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| *Earlier time to treatment driven by faster reimbursement and scheduling, earlier lymphodepletion,<br>and shorter turnaround for manufacturing/release as the launch continues<br>11<br> © 2025, Iovance Biotherapeutics, Inc.<br>Amtagvi® Patient Journey<br>Lymphodepletion<br>Reimbursement<br>Approval<br>~3 Weeks<br>Manufacturing,<br>Release & Shipment<br>Turnaround times will be reduced*<br>Short-Course<br>Scheduling Tumor<br>Procurement<br>Goal: <2 weeks<br>Primary<br>Oncologist<br>ATC Medical<br>Oncologist<br>Patient<br>Post-Regimen Follow-Up &<br>Return to Primary Oncologist<br>ENROLLMENT<br>TREATMENT<br>3-4 WEEKS<br>~33 DAYS<br>7 DAYS<br>Community<br>Practice |
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| 12<br> © 2025, Iovance Biotherapeutics, Inc.<br>Philadelphia, PA<br> • Flex facility with<br>capacity for up to<br>5K patients/year<br> • Supplies<br>commercial and<br>clinical TIL cell<br>therapies globally<br> • Control to optimize<br>capacity, quality &<br>COGS<br>FDA-Approved Cell Therapy Manufacturing Facility<br>Dedicated to Commercial and Clinical TIL Cell Therapies<br>COGS= cost of goods sold |
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| 13<br> © 2025, Iovance Biotherapeutics, Inc.<br>Amtagvi® Authorized Treatment Centers (ATC)<br> >90%<br>of Addressable<br>Patients<br>within 200 miles<br>of ATCs1,2<br> ≤100 10K+<br>Population2<br>1. Not all authorized treatment centers are listed, Includes onboarded ATCs as well as in-process ATCs.<br>2. U.S. Census Bureau, 2024 Annual Estimates. SEER annual estimated death rate from melanoma: 2 deaths per 100K people: https://seer.cancer.gov/ (accessed April 2025)<br>3. Internal data |
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| 14<br> © 2025, Iovance Biotherapeutics, Inc.<br>Broad Market Access<br>Data on file as of July 2025.<br>*Plans or policies that cover Amtagvi, including pharmacy benefit managers (PBMs)<br>Abbreviations: NCCN = National Comprehensive Cancer Network<br>Payer medical coverage policies consistent with Amtagvi label, clinical trials and NCCN guidelines<br>Patient lives covered;<br>Majority of patients<br>have private<br>coverage*<br>Typical time to financial<br>clearance<br>250+<br>Million<br>~3<br>Weeks<br> >75%<br>of Amtagvi patients<br>covered by private<br>payers |
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| 15<br> © 2025, Iovance Biotherapeutics, Inc.<br>Amtagvi® Expansion Plans in Advanced Melanoma |
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| 16<br> © 2025, Iovance Biotherapeutics, Inc.<br>Unprecedented Rate, Depth &<br>Durability of Responses in<br>Frontline Advanced Melanoma<br> • Median PFS and median DOR not reached at nearly 2 years of median<br>follow-up (median follow-up 21.7 months)<br> • All response-evaluable patients demonstrated regression of target lesions<br> • Safety consistent with underlying disease and known safety profiles of<br>pembrolizumab, NMA-LD, lifileucel, and IL-2<br> • Late AEs consistent with anti-PD-1 monotherapy, differentiated from ICI<br>combination therapies<br>L I F I L E U C E L + P E M B R O L I Z U M A B I N F R O N T L I N E A D V A N C E D<br>M E L A N O M A : I O V - C O M- 2 0 2 C O H O R T 1 A<br>1. Thomas et al, ASCO 2024; Data on file as of May 31, 2024.<br>* Unconfirmed CRs, confirmed following data cut.<br>A One patient without a postdose tumor response assessment was not included. bTarget lesion lymph node at baseline decreased by 50% is no longer<br>pathological, and thus is shown here as -100% representing uCR. CI, confidence interval; CR, complete response; DOR, duration of response; ICI,<br>immune checkpoint inhibitor; ORR, objective response rate; PD, progressive disease; PFS, progression free survival; PR, partial response; RECIST,<br>Response Evaluation Criteria in Solid Tumors; SD, stable disease; SOD, sum of diameters; AE, adverse event; IL-2, interleukin-2; NMA-LD,<br>nonmyeloablative lymphodepletion<br>Data support rationale for TILVANCE frontline study:1<br>65.2%<br>ORR via RECIST v 1.1<br>30.4%<br>CR<br>64.7%<br>PFS at 6 & 12 months<br>Best Percentage Change from Baseline in Target Lesion SOD<br>Time to Response and Time of Efficacy Assessment for<br>Confirmed Responders (PR or Better) |
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| 17<br> © 2025, Iovance Biotherapeutics, Inc.<br>Option to crossover to<br>lifileucel after BIRC-confirmed PD<br>1:1<br>Randomization<br>TILVANCE-301 Global Phase 3 and Confirmatory Trial<br>L I F I L E U C E L + P E M B R O L I Z U M A B I N F R O N T L I N E A D V A N C E D M E L A N O M A<br>*Pembrolizumab in both arms is started at the same time after randomization.<br>Abbreviations: BIRC=blinded independent review committee; ORR=objective response rate; PD=progressive disease; PD-1=programmed cell death protein-1; PFS=progression free survival<br>Arm A:<br>lifileucel plus<br>pembrolizumab*<br>Long-term<br>follow up<br>Patient<br>Population<br>Unresectable or<br>metastatic melanoma;<br>no prior therapy for<br>metastatic disease<br>N=670<br>70+ sites in U.S.,<br>Canada, Europe, APAC Arm B:<br>pembrolizumab<br>alone*<br>Study Design<br>with FDA Agreement<br> • Dual primary endpoints: ORR & PFS<br> • Interim analysis on ORR<br> • Final analysis on PFS<br> • Registrational for frontline melanoma<br> • Confirmatory for full approval of<br>Amtagvi in post-anti-PD-1 melanoma<br> • Enrollment on track with internal<br>projections<br>Randomized, multicenter study with optional crossover to Iifileucel (NCT05727904) |
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| 18<br> © 2025, Iovance Biotherapeutics, Inc.<br>TIL Therapy Pipeline |
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| 19<br> © 2025, Iovance Biotherapeutics, Inc.<br>Cohorts investigating multiple treatment regimens and patient<br>populations in three Iovance clinical trials<br>Large Domestic and Global Addressable Market<br>in Non-Small Cell Lung Cancer (NSCLC)<br>1. Clarivate DRG Disease Landscape (2021), figures approximate<br>2. Data on file as of September 30, 2024, figures approximate<br>3. American Cancer Society, Lung Cancer. https://www.cancer.org/cancer/types/lung-cancer/about.html accessed July 2023<br>4. National Cancer Database, NSCLC survival from >1 million patients assessed. Lou Y et al. Survival trends among non-small-cell lung cancer patients over a decade: impact of initial therapy at academic centers. Cancer Med. 2018.<br>2L+ NSCLC Addressable<br>Patient Population1,2<br>Frontline NSCLC<br>addressable patient<br>population in U.S.<br>and globally<br>210K+<br>1,2<br>US:<br>50K<br>Target<br>EU Markets:<br>50K<br>Globally (2L+):<br>100K<br>of U.S. cancer deaths, accounting for approx.<br>cancer-related deaths 1 3<br>in 5<br>Leading cause<br>Real-world overall<br>survival (US) 4<br>6 month 9%<br>5-yr<br>survival rate3<br>Less than |
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| 20<br> © 2025, Iovance Biotherapeutics, Inc.<br>IOV-LUN-202 Registrational Trial Design<br>Phase 2 Multicenter Study of Lifileucel†<br>in Patients Post-Anti-PD-1 NSCLC (NCT04614103)<br> †Gen 2 TIL product † † Cohort 3 patients unable to undergo surgical harvest, TIL grown from core biopsy<br>Abbreviations: Anti-PD-1=anti-programmed cell death inhibitor; IRC=independent review committee; NSCLC=non-small cell lung cancer; ORR=objective response rate; TPS=tumor proportion score<br>Iovance TIL Therapy Lifileucel in NSCLC<br>IOV-LUN-202 is designed<br>to enroll patients with<br>advanced NSCLC with a<br>high unmet medical need,<br>post anti-PD-1 treatment<br>Endpoints<br> • Primary: ORR by IRC<br> • Secondary: Safety<br>Patient<br>Population<br>Unresectable or<br>metastatic NSCLC with<br>progression on or after<br>prior anti-PD-1<br>treatment and<br>chemotherapy<br>40+ sites in U.S.,<br>Canada, Europe, APAC<br>Cohort 1: < 1% or unknown TPS<br>Cohort 2: ≥ 1% TPS<br>Cohort 3: Core Biopsy and Gen3††<br>Cohort 4: Pre-progression tumor<br>harvest<br>Retreatment Cohort<br>Exploratory Cohorts<br>Registrational Cohorts<br>Updated interim data for registrational cohorts anticipated in 2025 |
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| 21<br> © 2025, Iovance Biotherapeutics, Inc.<br>Strong Preliminary Clinical Results in Second-Line mNSCLC<br>I O V- L U N- 2 0 2 C O H O R T S 1 A N D 2 , P O S T -A N T I-P D-1 N S C L C<br>% Change from Baseline<br>(n=23)<br>Patients<br>*Data cut: July 6, 2023. 21 evaluable patients for response. Responses were assessed by investigator; **Updated analysis in November 2023 showed additional ongoing responses (not indicated in above charts)<br>1. Patients who have progressed on or after chemotherapy and anti-PD-1 therapy for advanced (unresectable or metastatic) NSCLC without EGFR, ROS or ALK genomic mutations and had received at least one line of an FDA-approved targeted therapy if indicated by other actionable tumor mutations.<br>2. A bar is presented for each patient starting from date of Lifileucel infusion up to date of new anti-cancer therapy, end of assessment, death, or data cutoff date, whichever occurs earlier.<br>Abbreviations: AE, adverse event; CI, confidence interval; CR, complete response; DOR, duration of response; ICI, immune checkpoint inhibitor; NE, not evaluable; NMA-LD, non-myeloablative lymphodepletion;<br>NSCLC, non-small cell lung cancer; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disease; SOD, sum of diameters; TEAE, treatment-emergent AE; TPS, tumor proportion score.<br>Tumor Reduction and Deep, Durable Responses in Previously Treated NSCLC, Regardless of PD-L1 Status1<br>Best Percentage Change from<br>Baseline in Target Lesion SOD<br>26.1% ORR<br>by RECIST 1.1, Regardless of PD-L1 Status*<br>2<br>Duration of response >6 months for 71% of<br>confirmed responders in the trial** |
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| 22<br> © 2025, Iovance Biotherapeutics, Inc.<br>Cohort 3A Results Support Adding TIL Therapy to Frontline NSCLC1<br>I O V- C O M- 2 0 2 C O H O R T 3 A , I C I- N A Ï V E N S C L C<br>% Change from Baseline<br>Time (Months) Since TIL Infusion<br>Patients<br>PD-L1 negative, EGFRWT subgroup has a high unmet need2<br>Best Percentage Change from Baseline in Target Lesion SOD<br>64.3% ORR EGFRWT<br>Time to Response for Confirmed Responders (PR or Better, EGFRWT Patients)<br>mDOR not reached (median follow-up 26.5 months)<br> • Safety consistent with Iovance TIL combination studies<br> • Supports adding TIL therapy to pembrolizumab plus chemotherapy<br>for frontline NSCLC in IOV-COM-202 cohorts 3D/3E<br>1. Creelan et al,SITC 2024<br>2. KEYTRUDA USPI; OPDIVO USPI<br>*PR response based on target lesion reduction of 100% with the persistence of nontarget lesions.<br>Abbreviations: CR, complete response; EGFR, epidermal growth factor receptor; ICI, immune checkpoint inhibitor; NSCLC, non-small-cell lung cancer; ORR, objective response rate; PD, progressive disease;<br>PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SOD, sum of diameter; TPS, tumor proportion score; WT, wild-type<br>54.5% ORR EGFR WT PD-L1 Negative<br>by RECIST 1.1<br>Anti-PD-1 ORR Benchmarks2<br>Treatment-naïve<br>(mono)<br>27% (TPS ≥ 1%);<br>39 - 45% (TPS ≥ 50%)<br>Post-chemotherapy<br>(mono)<br>18 - 20%<br>Frontline (anti-PD-1 +<br>chemo)<br>48-58%<br>2<br>60<br>40<br>20<br>0<br> –20<br> –40<br> –60<br> –80<br> –100<br>a<br>3A-03 3A-16 3A-08 3A-22 3A-15 3A-09 3A-04 3A-02 3A-PD-L1 TPS <1 <1 <1 <1 ≥50 <1 <1 <1 <1<br>3A-10<br> ≥50<br>3A-17<br> ≥50<br>3A-11<br> <1<br>3A-13<br> <1<br>80<br>100 PD SD PR CR |
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| 23<br> © 2025, Iovance Biotherapeutics, Inc.<br>1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2025 Estimates. https://seer.cancer.gov (accessed August 2025); 2. World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2022<br>3. NCCN Guidelines Version 2.2024 Endometrial Carcinoma; 4. Kang et al, Nature Portfolio, Scientific Reports, 2022; 5. Makker V, et al. N Engl J Med. 2022; 6. McMeekin S, et al. Gynecol Oncol. 2015.<br>Abbreviations: Anti-PD-1=anti-programmed cell death inhibitor; pMMR = proficient DNA mismatch repair; dMMR = deficient DNA mismatch repair; SOC=standard of care; TMB-H = tumor mutational burden high; ORR = objective response rate<br>Potential Market for Advanced Endometrial Cancer<br>L I F I L E U C E L I N A D V A N C E D E N D O M E T R I A L C A N C E R<br>Immunosensitive Tumor Type with Significant Unmet Need in 2L+<br>Anti-PD-(L)1 moving into front-line therapy<br>setting3<br>No standard of care for 2L+ post-anti-PD-1<br> • Molecularly defined subgroups with available<br>targeted therapies are small<br> • ORR with mono-chemotherapy after front-line<br>chemo doublet: ~15%5,6<br> • Limited data on treatments after anti-PD-(L)1<br>~14K<br>~98K<br>US annual uterine<br>cancer deaths 1<br>5-yr survival<br>(distant metastases)1<br>Global deaths2<br>19.5%<br>Endometrial<br>Cancer<br>Biomarkers4<br>dMMR: 27%<br>pMMR: 73%<br> >90%<br>of Uterine Cancers<br>are Endometrial |
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| 24<br> © 2025, Iovance Biotherapeutics, Inc.<br>pMMR<br>Subgroup<br>dMMR<br>Subgroup<br>Endpoints<br> • Primary: ORR per RECIST v1.1 by<br>investigator<br> • Secondary: CR rate, DOR, DCR, PFS,<br>OS, safety and tolerability<br> • Subgroup analyses specified in protocol<br> • Potential to expand / convert to<br>registrational trial<br> • First patient enrolled Q4 2024<br>IOV-END-201 Phase 2 Proof of Concept Study<br>Endometrial Cancer<br>Patient Population*<br>Recurrent, metastatic<br>or primary unresectable<br>disease after chemo and<br>anti-PD-1 therapy<br> ≤3 lines of prior systemic<br>therapy with no more than<br>1 line of chemotherapy<br>*Sample size and study population of registrational ph2 study will be determined after PoC final analysis<br>Abbreviations: Anti-PD-1, anti-programmed cell death inhibitor; CR, complete response; dMMR, mismatch repair deficient; pMMR, mismatch repair proficient; DCR, disease control rate; DOR, duration of response; ORR,<br>objective response rate; OS, overall survival; PFS, progression free survival<br>L I F I L E U C E L I N A D V A N C E D E N D O M E T R I A L C A N C E R<br>Proof-of-Concept Trial in Patients with Mismatch Repair (MMR) Proficient and Deficient Tumors (NCT06481592) |
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| 25<br> © 2025, Iovance Biotherapeutics, Inc. © 2025, Iovance Biotherapeutics, Inc.<br>IOV-4001: PD-1 Inactivated TIL Therapy 2<br>T cell<br>PD-1<br>PD-1 inhibits the ability<br>of T cells to fight cancer:<br>T cells, upon encountering<br>cancer cells, produce PD-1, a<br>checkpoint receptor that is<br>activated by proteins (PD-L1<br>and PD-L2) found on cancer<br>and other immune cells.1<br>PD-L2<br>PD-L1<br>PD-1<br>TCR<br>pMHCI<br>PD-L1 PD-L2<br>Tumor cell<br>Antigen-presenting<br>cell<br>1. Sharpe AH, Pauken KE, Nat Rev Immunol 2018, 18:153-167<br>2. Natarajan A et.al. AACR 2022<br>3. Licensed from Cellectis<br>1<br>IOV-4001<br>TCR<br>pMHCI<br>PD-L2<br>PD-L1<br>Tumor cell<br>PD-1 Inactivated T Cells<br>Avoid Checkpoint Signals:<br>PD-1 is inactivated using TALEN, restoring<br>the ability of TIL cells to kill cancer cells.2,3<br>Cognate<br>Antigen<br>Cognate<br>Antigen |
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| 26<br> © 2025, Iovance Biotherapeutics, Inc.<br>Phase 1/2 Open-Label First-in-Human Study: IOV-GM1-201<br>Endpoints<br> • Phase 1: Safety (Complete)<br> • Phase 2 Primary: ORR per<br>RECIST v1.1 by investigator<br> • Secondary: CR rate, DOR,<br>DCR, PFS, OS, safety and<br>tolerability<br>Genetically Modified, PD-1 Inactivated TIL Therapy IOV-4001 in Previously Treated<br>Metastatic Melanoma and NSCLC (NCT05361174)<br>Cohort 1: Unresectable or<br>metastatic melanoma<br>Post-anti-PD-1/L1, post-BRAF/MEK<br>inhibitor in patients with BRAF<br>mutations<br>Cohort 2: Stage III or IV NSCLC<br>Post-anti-PD-1/L1 or post targeted<br>therapy and either chemotherapy or<br>anti-PD-1/L1<br>Patient<br>Population<br>Adults with<br>unresectable or<br>metastatic<br>melanoma or<br>advanced NSCLC<br>N=53<br>N E X T - G E N E R A T I O N T I L T H E R A P Y : I O V - 4 0 0 1<br>Abbreviations: Anti-PD-1=anti-programmed cell death inhibitor; CR=complete response;; DCR=disease control rate; DOR=duration of response; NSCLC=non-small cell lung cancer; ORR=objective response rate; OS=overall survival; PFS= progression free survival |
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| 27<br> © 2025, Iovance Biotherapeutics, Inc. © 2025, Iovance Biotherapeutics, Inc.<br>IOV-3001: Next Generation IL-2 for TIL Supportive Regimen1,2<br>Phase 1/2 trial enrolling patients<br>Recombinant fusion protein designed<br>to enhance TIL survival and cellular<br>proliferation<br> • A modified copy of the coding sequence for<br>aldesleukin (mdIL-2) is fused to a<br>humanized monoclonal immunoglobulin<br>(Ig)G1κ antibody<br> • The mdIL-2 moiety of IOV-3001 binds to the<br>IL-2-receptor (IL-2R) with subsequent<br>phosphorylation of signal transducer and<br>activator of transcription 5 (STAT5),<br>resulting in enhanced performance<br>1. Mitra S, Leonard WJ, Journal of Leukocyte Biology 2018 103(4): 643-655<br>2. Simpson-Abelson M et al, ASCO 2024<br>Gene Expression:<br> • Survival<br> • Proliferation<br>mdIL-2<br>IL-2R<br>JAK1<br>P<br>JAK3<br>STAT5<br>dimer<br>Cytosol<br>Nucleus<br>P<br>IOV-3001<br>IOV-3001<br>Heavy chain<br>Light chain<br>IOV-3001<br>Modified IL-2<br>(mdIL-2)<br>TIL<br>Antibody<br>Preclinical data suggest IOV-3001 may have a better safety<br>profile and require less frequent dosing compared to Proleukin |
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| 28<br> © 2025, Iovance Biotherapeutics, Inc.<br>IOV-5001: IL-12 TIL Therapy<br>to Increase Efficacy<br>1. Zhang L, Rosenberg SA, et al, Clin Cancer Res 2015;21(10):2278–2288<br>2. Zhang L, Davis JS, et al, J Immunother Cancer 2020;8:e000210<br>3. Kobayashi M, Fitz L, et al, J Exp Med 1989;170:827–845.<br>4. Zeh HJ, Hurd S et al, J Immunother 1993;14:155–61.<br>5. Tugues S, Burkhard SH, et al, Cell Death and Differentiation 2015;22:237–246.<br>6. Cao X, Leonard K, et al, Cancer Res 2009;69:8700–9.<br>7. Steding CE, Wu S, et al, Immunology 2011;133:221–38.<br> • Tethered IL-12 TIL cells can improve efficacy by<br>remodeling the suppressive TME into an immuno-supportive state<br> – In advanced melanoma patients, an ORR of 63% (n=16) was<br>observed with prior generation IL-12 secreting TIL product at doses<br>10- to 100-fold lower than conventional TIL products1<br> • IL-12 shows independent clinical efficacy, with safe<br>delivery to the TME being the primary challenge1,2<br> • Expression of IL-12 on IOV-5001 is induced upon<br>antigen encounter in the TME1,2<br> • IOV-5001’s expressed IL-12 is tethered to the<br>membrane surface of TIL to avoid release into<br>circulation (shedding) 2<br> • Inducible IL-12 expression in the TME and lack of IL-12 shedding are expected to allow increased IOV-5001 cell doses and improved TIL efficacy in solid<br>tumor cancers<br>IL=12 = interleukin 12; MDSC = myeloid derived suppressor cell; NK = natural killer cell; NKT = natural killer T cell; ORR = objective response rate; TME = tumor<br>microenvironment; Treg = regulatory T cell<br>NK and NK-T cell<br>activation and<br>proliferation3<br>CD8+ T cell<br>activation and<br>proliferation4<br>CD4+ T cell<br>differentiation<br>to Th15<br>Treg and MDSC<br>downregulation6,7<br>28<br>Direct Action<br>IFNγ<br>Cytosol<br>Nucleus<br>TIL<br>NFAT-TeIL-12<br>IL-12 IL-12R<br>TCR<br>Antigen<br> © 2025, Iovance Biotherapeutics, Inc. |
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| 29<br> © 2025, Iovance Biotherapeutics, Inc.<br>Corporate Summary<br> & Milestones |
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| 30<br> © 2025, Iovance Biotherapeutics, Inc.<br>1. Includes anticipated revenue from Amtagvi and Proleukin® and anticipated savings from strategic restructuring announced on August 7, 2025<br>2. Iovance is implementing a strategic restructuring to optimize business performance, resulting in more than $100 million in annual cost savings starting in the fourth quarter of 2025<br>3. Preferred shares are shown on an as-converted basis.<br>Financial Position & Outlook<br>Guidance<br>Cash runway into<br>Q4 20261<br>Cash burn<br> <$245M2<br>(3Q25 - 3Q26)<br>FY 2025 revenue<br>$250M - $300M<br>Targeting significant<br>gross margin<br>expansion<br>over next several years<br>June 30, 2025 (in millions)<br>Cash position $307.1<br>Common shares outstanding 341.9<br>Preferred shares outstanding 2.03<br>Stock options and restricted stock<br>units outstanding 30.4 |
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| 31<br> © 2025, Iovance Biotherapeutics, Inc.<br>Corporate Highlights<br>Pioneering a Transformational Approach to Cure Cancer<br>Abbreviations: FTD, fast track designation; ICI, immune checkpoint inhibitor; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein-1<br>Large Market<br>Opportunity in High<br>Unmet Need Cancers<br>First FDA Approved T<br>Cell Therapy for a Solid<br>Tumor Cancer<br>Efficient & Scalable<br>Manufacturing<br>Fully-Integrated for<br>Commercial Success<br> • Initial focus in post-ICI<br>solid tumors<br> • Expansion into<br>combinations, new tumor<br>types, earlier lines of<br>therapy and genetic<br>modifications<br> • Key late-stage trials in<br>melanoma, NSCLC<br> • First-in-human trial of<br>genetically modified PD-1<br>inactivated TIL<br> • U.S. FDA & Health Canada<br>approval for Amtagvi® in<br>advanced melanoma<br> • Global TILVANCE-301<br>Phase 3 confirmatory trial<br>in frontline advanced<br>melanoma<br> • Defined registration<br>strategy in NSCLC<br> • Regulatory dossiers under<br>review or planned across<br>multiple global markets<br> • Iovance Cell Therapy<br>Center (iCTC) in-house<br>manufacturing<br> • Ample capacity for U.S.<br>launch, global clinical trials<br>and planned commercial<br>expansion to ex-U.S.<br>markets<br> • Additional capacity with<br>U.S.-owned contract<br>manufacturer<br> • Experienced cross-functional cell<br>therapy team<br> • TIL service-line capabilities<br>established with leading<br>U.S. cancer centers<br> • IovanceCares<br>proprietary platform for<br>end-to-end patient<br>management |
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| 32<br> © 2025, Iovance Biotherapeutics, Inc.<br> © 2025, Iovance Biotherapeutics, Inc.<br>Thank You |
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