UNITED STATES
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FORM
Current Report
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| Item 8.01 | Other Events. |
On August 8, 2024, 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. |
(d) Exhibits.
| Exhibit No. |
Description | |
| 99.1 | Iovance Biotherapeutics, Inc., Corporate Presentation – August 8, 2024 | |
| 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 9, 2024 | Iovance Biotherapeutics, Inc. | ||
| By: | /s/ Frederick G. Vogt | ||
| Name: | Frederick G. Vogt, Ph.D., J.D. | ||
| Title: | Interim CEO and President, and General Counsel | ||
Exhibit 99.1
1 © 2024, Iovance Biotherapeutics, Inc. © 2024, Iovance Biotherapeutics, Inc. Corporate Overview August 2024 1
2 © 2024, Iovance Biotherapeutics, Inc. Forward - Looking Statements Certain matters discussed in this press release are “forward - looking statements” of Iovance Biotherapeutics, Inc. (hereinafter r eferred to as the “Company,” “we,” “us,” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). Without limiting the foregoing, we may, in some cases, us e terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “forecast,” “guidance,” “outlook,” “may,” “can,” “could,” “might,” “w ill,” “should,” or other words that convey uncertainty of future events or outcomes and are intended to identify forward - looking statements. Forward - looking statements are based on assumptions and ass essments made in light of management’s experience and perception of historical trends, current conditions, expected future developments, and other factors believed to be appropria te. Forward - looking statements in this press release are made as of the date of this press release, and we undertake no duty to update or revise any such statements, whether as a result of new info rma tion, future events or otherwise. Forward - looking statements are not guarantees of future performance and are subject to risks, uncertainties, and other factors, many of which are outside of our co ntrol, that may cause actual results, levels of activity, 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 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 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, th e following substantial known and unknown risks and uncertainties inherent in our business: the risks related to our ability to successfully commercialize our products, including Amtagvi, for wh ich we have obtained U.S. Food and 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 authorities may not approve or may delay approval for our marketing authorization application submission for lifileucel in metastatic melanoma; the acceptance by the mar ket of our products, 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 int ernational markets and whether such acceptance is sufficient to support continued commercialization or development of our products, including Amtagvi and Proleukin, or product candidates, respectiv ely ; future 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 u sin g third party 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 l aun ch; 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 re cen t 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, a nd 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 a uth ority 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 auth ori ties 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 may not supp ort 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 of ou r o ngoing 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 FDA and oth er 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 conduct addit ion al 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 clinical tri als 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 from our prior mee tin gs 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 ongoing or planned cl ini cal trials or may not support regulatory approval or renewal of authorization; the risk that unanticipated expenses may decrease our estimated cash balances and forecasts and increase our estimated capita l r equirements; 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 indicator for Amtagvi revenues; the ri sks regarding our anticipated operating and financial performance, including our financial guidance and projections; the effects of global pandemic; the effects of global and domestic geopolit ica l factors; and other factors, including general economic conditions and regulatory developments, not within our control. Financial guidance as stated above in this press release assumes the follow ing : no material change in our ability to manufacture our products; no material change in payor coverage; no material change in revenue recognition policies; no new business development transactio ns not completed as of the period covered by this press release; and no material fluctuation in exchange rates.
3 © 2024, Iovance Biotherapeutics, Inc. Global Leadership in Innovating, Developing and Delivering TIL Therapy for Patients with Cancer 3 Approved Products Commercial Launch People & Assets 51 >225M >55 ~$ 450M Cash Position as of 7/24 /24 1 $31.1M First Launch Quarter Revenue (2Q24) ~7 00 Employees 3 1 1 DESIGNATIONS: Fast Track BTD RMAT Authorized Treatment Centers as of 8/8/24 Amtagvi Patients Treated as of 8/8/24 2 U.S. patient lives covered under payer policies Amtagvi Global Addressable Population >20K Pipeline Clinical Trials in 7 Tumor Types 8 Registrational Clinical Trials 2 Global Regulatory Submissions (US, EMA) 2 $160 - $165M FY24 Product Revenue Guidance © 2024, Iovance Biotherapeutics, Inc. 1. I ncludes net proceeds of approximately $200.0 million raised from an at - the market (ATM) equity financing facility during the sec ond and third quarter of 2024 Abbreviations: BTD=Breakthrough Therapy Designation; FDA=U.S. Food and Drug Administration; RMAT=Regenerative Medicine Advanc ed Therapy Designation
4 © 2024, Iovance Biotherapeutics, Inc. Iovance Solid Tumor Portfolio Highlights *Enrollment complete 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 Label Expansion Opportunities INDICATIONS PHASE 1 PHASE 2 PHASE 3 APPROVED Commercial Post - anti - PD - 1 advanced melanoma (U.S.) Planned submissions: EU (2Q24), U.K. & Canada (2H24) Amtagvi treatment regimen (U.S.) Advanced melanoma, renal cell carcinoma (U.S., ex - U.S.) Registration - Directed Lifileucel + pembrolizumab Frontline advanced melanoma TILVANCE - 301 Phase 3 (FTD, Confirmatory) Lifileucel Post - chemo & anti - PD - 1 advanced NSCLC IOV - LUN - 202: Cohorts 1&2 Lifileucel Pipeline Lifileucel Post - chemo & anti - PD - 1 endometrial cancer IOV - END - 201: Cohorts 1&2 Lifileucel, Lifileucel + ICI 1 - 4L incl. post - anti - PD - 1 advanced NSCLC IOV - COM - 202: Cohorts 3A, 3B*, 3C Lifileucel + ICI ICI - naïve advanced melanoma IOV - COM - 202: Cohorts 1A, 1D Lifileucel core biopsy 2L post - chemo & post - anti - PD - 1 advanced NSCLC IOV - LUN - 202: Cohort 3 Next - Generation Products PD - 1 Inactivated TIL (IOV - 4001) Post anti - PD1 advanced melanoma IOV - GM1 - 201: Cohort 1 PD - 1 Inactivated TIL (IOV - 4001) 2 - 4L incl. post - anti - PD - 1 advanced NSCLC IOV - GM1 - 201: Cohort 2 IL - 2 analog (IOV - 3001) TIL Treatment Regimen (planned IND in 3Q 2024) Planned IL - 12 tethered TIL (IOV - 5001) Basket trial (planned IND in 2025) Planned
5 © 2024, Iovance Biotherapeutics, Inc. Tumor Infiltrating Lymphocytes (TIL): Leading Cell Therapy Platform for Solid Tumors TIL – Unique Proposed Mechanism of Action • Individualized • One - time therapy • Deploys the patient’s own T cells to fight cancer Tumor Tissue Collection Patient - specific T Cells Grown into the Billions 1 TIL Treatment Regimen 1. Amtagvi USPI
6 © 2024, Iovance Biotherapeutics, Inc. 1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2024 Estimates. https://seer.cancer.g ov (accessed May 2024) 2. World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2022 U.S. Deaths 1 Global Deaths 2 Melanoma 8K 59K Lung & Bronchus 125K 1.8M Endometrial 13K 97K 91% of all cancer cases are solid tumors 1 1 .8 M New cases of solid tumors in the U.S. 1 Expand into other indications Significant Market Potential in Solid Tumors and our Key Programs
7 © 2024, Iovance Biotherapeutics, Inc. 1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2024 Estimates. https://seer.cancer.gov (accessed May 2024) 2. World Health Organization International Agency for Research on Cancer (IARC). GLOBOCAN 2022 3. Data on file as of July 31, 2024 >20K Advanced Melanoma Treatment Expansion Opportunities 3 Significant Opportunity to Expand Advanced Melanoma Market >60K Annual Addressable Opportunity in Previously Treated Advanced Melanoma 3 Annual Deaths 1,2 Frontline Addressable Patients 3 U.S. 8K 14K Ex - U.S. Anticipated Markets 22K 27K Total 30K 41K Geographic Footprint Earlier Treatment Settings UK: 2H 2024 Canada: 2H 2024 EU : 2 Q 2024 Australia: 1H 2025 1H 2H 1H 2H Initial Ex - U.S. Planned Regulatory Submissions: Switzerland: 2025
8 © 2024, Iovance Biotherapeutics, Inc. 8 First one - time, individualized T cell therapy approved by FDA for a solid tumor cancer
9 © 2024, Iovance Biotherapeutics, Inc. 1. National Comprehensive Cancer Network® Guidelines, Melanoma: Cutaneous, Version 2.24 Preferred second - line+ therapy in NCCN guidelines 1
10 © 2024, Iovance Biotherapeutics, Inc. Amtagvi ¯ Delivered Deep and Durable Responses (95% CI: 21.1, 43.4) mDOR Not Reached ORR 31.4 % (95% CI: 24.1, 39.4) (Range: 1.4+, 45.0+) (Range: 1.4+, 26.3+; 95% CI: 4.1, NR) 18.6 months follow up 21.5 months follow up 2 1. C - 144 - 01 Clinical Trial, Amtagvi USPI 2. Data on file. Abbreviations: CI=confidence interval; mDOR = median duration of response; NR = not reached; ORR=objective response rate Cohort 4 Pivotal 1 (n=73) Supportive Pooled Data 1 (n=153) mDOR Not Reached ORR 31. 5 %
11 © 2024, Iovance Biotherapeutics, Inc. Amtagvi ¯ Durability at 4 - Years Median DOR not reached at 4 - year follow - up 4 - year Follow - up of Pooled Analysis (n=153) 31.4% (95% CI: 24.1, 39.4) ORR Not Reached (95% CI: 8.3, NR) mDOR 48.1 months follow - up 21.9% of patients were alive at 4 - year follow - up 1. Medina et al, ESMO IO 2023 Abbreviations: CI=confidence interval; mDOR = median duration of response; NR = not reached; ORR=objective response rate
12 © 2024, Iovance Biotherapeutics, Inc. Amtagvi ¯ Patient Journey Amtagvi Autologous T Cell Therapy Lymphodepletion Enrollment Process Treatment Regimen Reimbursement Approval ~3 Weeks Manufacturing & Release Testing Time to treatment decreasing over time driven by faster reimbursement and scheduling, earlier lymphodepletion ~34 days Short - Course Proleukin® Scheduling Tumor Procurement Goal <2 weeks 7 Days Amtagvi 3 - 4 Weeks 22 - Day Process
13 © 2024, Iovance Biotherapeutics, Inc. Iovance Cell Therapy Center: i CTC • Built - to - suit custom facility in Navy Yard Philadelphia • Commercial and clinical TIL therapy supply • Expanding headcount in alignment with expected growth in demand • Control to optimize capacity, quality & COGS FDA - Approved Cell Therapy Manufacturing Facility Dedicated to Commercial and Clinical TIL Cell Therapies
14 © 2024, Iovance Biotherapeutics, Inc. Iovance Cell Therapy Center ( i CTC): Capacity Expansion Plans i CTC Campus Expansion 10,000+ patients/year i CTC building expansion 3 Automation 14 © 2024, Iovance Biotherapeutics, Inc. Today (as built) up to 2,000 + patients/year 1 12 core suites for commercial 4 separate flex suites for clinical Site Expansion (in progress) 2 5,000+ patients/year 24 core suites for commercial 4 separate flex suites for clinical 1. Ongoing staffing, CDMO provides flexibility for incremental additional capacity 2. Expansion within existing shell 3. Option to build on adjacent parcel Pre - Approval (Complete) 100s of patients/year Launch Prep in core suites for commercial 4 separate flex suites for clinical
15 © 2024, Iovance Biotherapeutics, Inc. 15 Authorized Treatment Centers (ATCs) 1. Amtagvi.com Note: There are at least 50 authorized treatment centers; Not all authorized treatment centers may be listed on the locator tool (Last accessed August 7, 2024) . Abbreviations: ATC=Authorized Treatment Centers Goal to ensure patients have geographic accessibility to ATCs Amtagvi ¯ Authorized Treatment Centers 1 51 ATCs in August 2024 70 ATCs by Year End 90% Of Addressable Patients within 200 miles of an ATC
16 © 2024, Iovance Biotherapeutics, Inc. Broad Market Access Data on file, as of July 31, 2024. Data on file. Abbreviations: NCCN = National Comprehensive Cancer Network Initial payer medical coverage policies consistent with Amtagvi label, clinical trials and NCCN guidelines >225 Million Patient Lives Covered, Majority of Patients have private coverage ~75% of Amtagvi patients covered by private payers ~3 Weeks Time to financial clearance
17 © 2024, Iovance Biotherapeutics, Inc. 17 Amtagvi ¯ Expansion Plans in Advanced Melanoma
18 © 2024, Iovance Biotherapeutics, Inc. Unprecedented Rate, Depth & Durability of Responses in Frontline Advanced Melanoma 1 • Median PFS not reached at nearly 2 years of median follow - up • mDOR Not Reached (median follow - up 21.7 months) • All response - evaluable patients demonstrated regression of target lesions • Safety consistent with underlying disease and known safety profiles of pembrolizumab, NMA - LD, lifileucel, and IL - 2 LIFILEUCEL + PEMBROLIZUMAB IN FRONTLINE ADVANCED MELANOMA: IOV - COM - 202 COHORT 1A 1. Thomas et al, ASCO 2024 *CR confirmed following data cut. a One patient without a postdose tumor response assessment was not included. b Target lesion lymph node at baseline decreased by 50% is no longer pathological, and thus is shown here as - 100% representing uCR. CI, confidence interval; CR, complete response; ORR, objective r esponse rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; SD, stable disease; SOD, sum of diameters; AE, adverse event; IL - 2, interleukin - 2; NMA - LD, nonmyeloablative lymphodepletion Data supports rationale for TILVANCE frontline study: 65.2% ORR via RESCIST v 1.1 30.4% CR 64% PFS at 6 & 12 months Best Percentage Change from Baseline in Target Lesion SOD Time to Response and Time of Efficacy Assessment for Confirmed Responders (PR or Better)
19 © 2024, Iovance Biotherapeutics, Inc. 1:1 Randomization TILVANCE - 301 Global Phase 3 and Confirmatory Trial LIFILEUCEL + PEMBROLIZUMAB IN FRONTLINE ADVANCED MELANOMA Abbreviations: BIRC=blinded independent review committee; ORR=objective response rate; PD=progressive disease; PD - 1=programmed cell death protein - 1; PFS=progression free survival Arm A: lifileucel plus pembrolizumab Long - term follow up Patient Population Unresectable or metastatic melanoma; no prior therapy for metastatic disease N=670 >40 active sites in U.S., Europe, Australia, Canada A dditional 60 sites committed Arm B: pembrolizumab alone Study Design with FDA Agreement • Dual Primary Endpoints: ORR & PFS • Interim analysis on ORR • Final analysis on PFS • Registrational for frontline melanoma • Confirmatory for full approval of Amtagvi ¯ in post - anti - PD - 1 melanoma • First patient randomized 2Q23 Option to crossover to lifileucel after BIRC - confirmed PD Randomized, multicenter study with optional crossover to Iifileucel (NCT05727904)
20 © 2024, Iovance Biotherapeutics, Inc. 20 TIL Therapy Pipeline
21 © 2024, Iovance Biotherapeutics, Inc. 1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2024 Estimates. https://seer.cancer.gov (accessed May 2024) 2. American Cancer Society, Lung Cancer. https://www.cancer.org/cancer/types/lung - cancer/about.html (accessed May 2024) 3. National Cancer Database, NSCLC survival from >1 million patients assessed. Lou Y et al. Survival trends among non - small cell lu ng cancer patients over a decade: impact of initial therapy at academic centers. Cancer Med. 2018. 4. Clarivate DRG Disease Landscape (2021) Abbreviations: EU5=France, Germany, Italy, Spain and U.K.; 1L=first line therapy; 2L=second line therapy; 3L=third line thera py; NSCLC=non - small cell lung cancer Potential Market for Advanced Non - Small Cell Lung Cancer (NSCLC) Addressing a Substantial Unmet Need in Metastatic NSCLC Iovance TIL clinical program: • 6 cohorts across 3 trials • Multiple treatment regimens • Various populations and stages of disease 125K annual deaths in U.S. 1 107K 51.6K 19.0K 116K 46.2K 12.3K 1L 2L 3L US EU5 NSCLC Drug - Treated Population in 2022 Stage IV (U.S. and EU5) 4 Leading cause of U.S. cancer deaths, accounting for ~1 in 5 cancer - related deaths 2 9% 5 - year survival rate 2 and real - world overall survival <6 months 3 in U.S.
22 © 2024, Iovance Biotherapeutics, Inc. IOV - LUN - 202 Registrational Trial Design Phase 2 Multicenter Study of Lifileucel † in Patients Post - Anti - PD - 1 NSCLC (NCT04614103) Endpoints • Primary: ORR by IRC • Secondary: Safety † Gen 2 TIL product † † Cohort 3 patients unable to undergo surgical harvest, TIL grown from core biopsy 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 Iovance TIL Therapy Lifileucel in NSCLC IOV - LUN - 202 is designed to enroll patients with advanced NSCLC with a high unmet medical need, post anti - PD - 1 treatment Patient Population Unresectable or metastatic NSCLC with progression on or after prior anti - PD - 1 treatment and chemotherapy ~35 sites and expanding in U.S., Canada, Europe, APAC Cohort 1: < 1% or unknown TPS Cohort 2: ≥ 1% TPS Cohort 3: Core Biopsy and Gen3 †† Cohort 4 : P re - progression tumor harvest Retreatment Cohort Exploratory Cohorts Registrational Cohorts Enrollment completion and topline data for registrational cohorts anticipated in 2025
23 © 2024, Iovance Biotherapeutics, Inc. All responses remain ongoing at time of data cut Strong Preliminary Clinical Results in Second - Line mNSCLC IOV - LUN - 202 COHORTS 1 AND 2, POST - ANTI - PD - 1 NSCLC % Change from Baseline (n=23) Patients Data cut: July 6, 2023. 21 evaluable patients for response. Responses were assessed by investigator 1 . Patients who have progressed on or after chemotherapy and anti - PD - 1 therapy for advanced (unresectable or metastatic) NSCLC wi thout 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. 2. A bar is presented for each patient starting from date of Lifileucel infusion up to date of new anti - cancer therapy, end of asse ssment, death, or data cutoff date, whichever occurs earlier. 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; NSCLC, non - small cell lung cancer; ORR, objective response rate; PD, progressive disease; PR, partial response; SD, stable disea se; SOD, sum of diameters; TEAE, treatment - emergent AE ; TPS, tumor proportion score. Tumor Reduction and Deep, Durable Responses in Previously Treated NSCLC, Regardless of PD - L1 Status 1 Best Percentage Change from Baseline in Target Lesion SOD 26.1% ORR by RECIST 1.1, Regardless of PD - L1 Status 2
24 © 2024, Iovance Biotherapeutics, Inc. 1. National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2024 Estimates. https://seer.cancer.gov (ac cessed May 2024); 2. NCCN Guidelines Version 2.2024 Endometrial Carcinoma; 3. Kang et al, Nature Portfolio, Scientific Reports, 2022; 4. Makker V, et al. N Engl J Med. 2022; 5. McMeekin S, et al. Gyne col Oncol. 2015. Abbreviations: Anti - PD - 1 = anti - programmed cell death inhibitor; pMMR = proficient DNA mismatch repair; dMMR = deficient DNA mismatch repair; TMB - H = tumor mutational burden high; ORR = objective response rate Changing Treatment Landscape for Endometrial Cancer, an Immunosensitive Tumor Type Unmet Need after Progression on/after Standard of Care (SoC) Chemotherapy and ICI Anti - PD - (L)1 moving into front - line therapy setting: • 1L chemotherapy plus anti - PD - (L)1 now considered SoC for both dMMR and pMMR tumors 2 • After frontline chemotherapy (no ICI): ‒ dMMR tumors: anti - PD - (L)1 monotherapy ‒ pMMR tumors: lenvatinib/pembrolizumab • No SoC for 2L+ post - anti - PD - 1 ‒ Molecularly defined subgroups with available targeted therapies are small ‒ ORR with mono - chemotherapy after front - line chemo doublet: ~ 15% 4,5 ‒ Currently no data on treatments after anti - PD - (L)1 13.3K Uterine cancer is the most common gynecologic cancer and the fourth most frequent cancer in women in the U.S. 1 67.8K Prevalence of biomarkers in endometrial cancer 3 dMMR: 27% (i.e., pMMR accounts for ~3/4 of endometrial cancer) TMB - H: 43% annual deaths from Uterine Cancer in U.S. 1 >90% of Uterine Cancers are Endometrial Cancers 5 - yr survival of women with distant metastases 1 estimated new cases in U.S. 1 18.9% LIFILEUCEL IN ADVANCED ENDOMETRIAL CANCER
25 © 2024, Iovance Biotherapeutics, Inc. IOV - END - 201 Phase 2 Proof of Concept Study Endpoints • Primary : ORR per RECIST v1.1 by investigator • Secondary : CR rate , DOR, DCR, PFS, OS, safety and tolerability • Interim data, including subgroup analyses, specified in the protocol. • Potentially registrational pMMR Subgroup dMMR Subgroup Endometrial Cancer Patient Population * Recurrent, metastatic or primary unresectable disease after chemo and anti - PD - 1 therapy <= 3 lines of prior systemic therapy with no more than 1 line of chemotherapy *Sample size and study population of registrational ph2 study will be determined after PoC final analysis Abbreviations: Anti - PD - 1, anti - programmed cell death inhibitor; CR, complete response; dMMR, mismatch repair deficient; pMMR, mi smatch repair proficient; DCR, disease control rate; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression free survival LIFILEUCEL IN ADVANCED ENDOMETRIAL CANCER Proof - of - Concept Trial in Patients with Mismatch Repair Proficient and Deficient Tumors (NCT06481592)
26 © 2024, Iovance Biotherapeutics, Inc. 26 © 2024, Iovance Biotherapeutics, Inc. IOV - 4001 - PD - 1 Inactivated TIL Therapy APC Tumor cell T cell PD - L1 TCR TCR pMHCI pMHCI CD80 PD - L1 PD - L2 PD - L2 PD1 PD1 • Persistent antigen encounter in the tumor leads to upregulation of PD1 on antigen - specific T cells 1 • PD1 engagement by its cognate ligands, PD - L1 and PD - L2, and downstream signaling negatively regulates the function of neo - antigen reactive T cells • Deletion of PD1 in IOV - 4001 serves to obviate the deleterious impact of PD1 engagement with signaling partners • Exhibited superior antitumor activity in preclinical PDX model 2 • Iovance continues to utilize TALEN® technology 3 to develop other investigational gene - edited TIL cell therapies with multiple knockout targets to potentially improve efficacy 1. Sharpe AH, Pauken KE, Nat Rev Immunol 2018, 18:153 - 167 2. Natarajan A, Cubas R et.al. AACR 2022 3. Licensed from Cellectis
27 © 2024, Iovance Biotherapeutics, Inc. Phase 1/2 Open - Label First - in - Human Study: IOV - GM1 - 201 Endpoints • Phase 1: Safety (Complete) • Phase 2 Primary: ORR per RECIST v1.1 by investigator • Secondary : CR rate , DOR, DCR, PFS, OS, safety and tolerability Cohort 1: Unresectable or metastatic melanoma Post - anti - PD - 1/L1, post - BRAF/MEK inhibitor in patients with BRAF mutations Cohort 2: Stage III or IV NSCLC Post - anti - PD - 1/L1 or post targeted therapy and either chemotherapy or anti - PD - 1/L1 Patient Population Adults with unresectable or metastatic melanoma or advanced NSCLC N=53 Genetically Modified, PD - 1 Inactivated TIL Therapy IOV - 4001 in Previously Treated Metastatic Melanoma and NSCLC (NCT05361174) NEXT - GENERATION TIL THERAPY: IOV - 4001 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
28 © 2024, Iovance Biotherapeutics, Inc. 28 © 2024, Iovance Biotherapeutics, Inc. IOV - 3001 – Next Generation IL - 2 for TIL Supportive Regimen • IOV - 3001 is a recombinant fusion protein in which a modified copy of the coding sequence for aldesleukin (mdIL - 2) is incorporated into a humanized monoclonal immunoglobulin (Ig)G1 κ antibody • The mdIL - 2 moiety of IOV - 3001 binds to the IL - 2 - receptor (IL - 2R) with subsequent phosphorylation of signal transducer and activator of transcription 5 (STAT5), resulting in an enhancement in T cell survival and cellular proliferation Mitra S, Leonard WJ, Journal of Leukocyte Biology 2018 103(4 ): 643 - 655 Simpson - Abelson MR, Johnson S et al, ASCO 2024. Gene Expression: • Survival • Proliferation mdIL - 2 IL - 2R JAK1 P JAK3 STAT5 dimer Cytosol Nucleus P IOV - 3001 IOV - 3001 Heavy chain Light chain IOV - 3001 Modified IL - 2 (mdIL - 2) TIL
29 © 2024, Iovance Biotherapeutics, Inc. IOV - 5001 - IL - 12 TIL Therapy to Increase Efficacy • Tethered IL - 12 TILs can improve efficacy by remodeling the suppressive tumor microenvironment into an immuno - supportive state – In advanced melanoma patients, an ORR of 63% (n=16) was observed using IL - 12 TIL doses 10 - to 100 - fold lower than current TIL products 1 • IL - 12 shows independent clinical efficacy over many modes of administration, 1,2 with safe delivery to the tumor being the primary challenge • Expression of IL - 12 by IOV - 5001 is induced upon antigen encounter in the tumor microenvironment 1,2 • IOV - 5001’s expressed IL - 12 is tethered on the membrane surface of TIL to avoid release into circulation 2 • Avoidance of IL - 12 shedding is expected to allow increased cells doses with IOV - 5001 for better persistence, and improved TIL efficacy for use in solid tumor cancers 1. Zhang L, Rosenberg SA, et al, Clin Cancer Res 2015;21(10):2278 – 2288 2. Zhang L, Davis JS, et al, J Immunother Cancer 2020;8:e000210 3. Kobayashi M, Fitz L, et al, J Exp Med 1989;170:827 – 845. 4. Zeh HJ, Hurd S et al, J Immunother 1993;14:155 – 61. 5. Tugues S, Burkhard SH, et al, Cell Death and Differentiation 2015;22:237 – 246. 6. Cao X, Leonard K, et al, Cancer Res 2009;69:8700 – 9. 7. Steding CE, Wu S, et al, Immunology 2011;133:221 – 38. IL=12 = interleukin 12; MDSC = myeloid derived suppressor cell; NK = natural killer cell; NKT = natural killer T cell; ORR = obj ective response rate; T reg = regulatory T cell NK and NK - T cell activation and proliferation 3 CD8 + T cell activation and proliferation 4 CD4 + T cell differentiation to Th1 5 T reg and MDSC downregulation 6,7 29 © 2024, Iovance Biotherapeutics, Inc. IFN γ Cytosol Nucleus TIL NFAT - TeIL - 12 Lentivirus IL - 12 IL - 12R TCR
30 © 2024, Iovance Biotherapeutics, Inc. 30 Corporate Summary & Milestones
31 © 2024, Iovance Biotherapeutics, Inc. 31 June 30, 2024 (in millions) Unaudited cash position (July 24, 2024) ~$449.6 1 Common shares outstanding 297.3 Preferred shares outstanding 2.9 2 Stock options and restricted stock units outstanding 30.7 1. Includes net proceeds of approximately $200.0 million raised from an at - the market (ATM) equity financing facility during the se cond and third quarter of 2024 2. Preferred shares are shown on an as - converted basis 3. Includes anticipated revenue from Amtagvi ¯ and Proleukin® Well - Capitalized in Pursuit of TIL Commercialization Cash runway is sufficient into early 2026 3
32 © 2024, Iovance Biotherapeutics, Inc. REGULATORY □ Obtain FDA approval for lifileucel in advanced melanoma (approved on Feb. 16, 2024) □ Submit EMA regulatory dossier (1H24) □ Submit additional ex - U.S. dossiers (2H24) □ Meet with FDA to discuss NSCLC registrational path/frontline study PIPELINE □ Report clinical and pre - clinical data □ Resume enrollment in IOV - LUN - 202 □ Initiate Phase 2 trial in endometrial cancer □ Continue to enroll patients in clinical trials for advanced melanoma, NSCLC and gynecological cancers □ Advance new products toward clinic, including additional genetically - modified TIL therapies MANUFACTURING □ Fulfill patient demand for commercial launch and clinical trials □ Further expand capacity to meet U.S. and ex - U.S. demand COMMERCIAL □ Execute commercial launch (1Q24) □ On - board 50 ATCs within 90 days of PDUFA date □ On - board 70 ATCs by end of 2024 Anticipated 2024 Milestones Abbreviations: ATC=Authorized Treatment Centers; EMA=European Medicines Agency; FDA=U.S. Food and Drug Association; NSCLC=non - sm all cell lung cancer; PDUFA=Prescription Drug User Fee Act
33 © 2024, Iovance Biotherapeutics, Inc. Corporate Highlights Pioneering a Transformational Approach to Cure Cancer Large Market Opportunity in High Unmet Need Cancers First FDA Approved T Cell Therapy for a Solid Tumor Cancer Efficient and Scalable Proprietary Manufacturing Facility Fully - Integrated for Commercial Success • Initial focus in post - ICI solid tumors • Expansion into combinations, new tumor types, earlier lines of therapy and genetic modifications • Key late - stage trials in melanoma, NSCLC • First - in - human trial of genetically modified PD - 1 inactivated TIL • FDA accelerated approval for Amtagvi ¯ in advanced melanoma • TILVANCE - 301 Phase 3 confirmatory trial in frontline advanced melanoma (FTD) • Defined registration strategy in NSCLC • Iovance Cell Therapy Center ( i CTC) in - house manufacturing • Ample capacity for U.S. launch and global clinical trials • Additional capacity with contract manufacturer • Experienced cross - functional cell therapy team • TIL service - line capabilities established with leading U.S. cancer centers • IovanceCares ¯ proprietary platform 33 © 2024, Iovance Biotherapeutics, Inc. Abbreviations: FTD, fast track designation; ICI, immune checkpoint inhibitor; NSCLC, non - small cell lung cancer; PD - 1, programme d cell death protein - 1
34 © 2024, Iovance Biotherapeutics, Inc. © 2024, Iovance Biotherapeutics, Inc. Thank You