| 1 © 2023, Iovance Biotherapeutics, Inc. © 2023, Iovance Biotherapeutics, Inc. Corporate OverviewJanuary 20231 |
| 2 © 2023, Iovance Biotherapeutics, Inc. Forward-Looking StatementsCertain matters discussed in this press release are “forward-looking statements” of Iovance Biotherapeutics, Inc. (hereinafter referred to as the “Company,” “we,” “us,” or “our”) within the meaning of the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). All such written or oral statementsmade in this press release, other than statements of historical fact, are forward-looking statements and are intended to be covered by the safe harbor for forward-looking statementsprovided by the PSLRA. Without limiting the foregoing, we may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,”“expects,” “plans,” “intends,” “forecast,” “guidance,” “outlook,” “may,” “could,” “might,” “will,” “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 assessments made in light of management’s experience and perception of historical trends, current conditions, expected future developments and other factors believed to be appropriate. 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 information, future eventsor 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 ourcontrol, 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 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, the following substantial known and unknown risks and uncertainties inherent in our business: the effects of the COVID-19 pandemic; risks related to the timing of and our ability to successfully develop, submit, obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, our product candidates, and our ability to successfully commercialize any product candidates for which we obtain FDA approval; whether clinical trial results from our pivotal studies and cohorts may support registration and approval by the FDA; 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 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 FDA and other regulatory agency input; 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 additional clinical trials or modify ongoing or future clinical trials based on feedback from the FDA or other regulatory authorities; the risk that our interpretation of the results of our clinical trialsor communications with the FDA may differ from the interpretation of such results or communications by the FDA (including from the recent pre-BLA meeting with the FDA); the risk that the rolling BLA submission for lifileucel inmetastatic melanoma may take longer than expected; the acceptance by the market of our product candidates and their potentialreimbursement by payors, if approved; our ability or inability to manufacture our therapies using third party manufacturers or our own facility may adversely affect our potential commercial launch; the results of clinical trials with collaborators using different manufacturing processes may not be reflected in our sponsored trials; the risk thatunanticipated expenses may decrease our estimated cash balances and forecasts and increase our estimated capital requirements; and other factors, including general economic conditions and regulatory developments, not within our control. |
| 3 © 2023, Iovance Biotherapeutics, Inc. Global Leadership in Innovating, Developing and Delivering TIL Therapy for Patients with Cancer Active Clinical TrialsPlatformPipelinePeople & AssetsPartners & CollaboratorsAbbreviations: BLA=Biologics License Application; BTD=Breakthrough Therapy Designation; RMAT=Regenerative Medicine Advanced Therapy Designation*Anticipated cash runway, inclusive of proceeds from equity sold through at-the-market (ATM) facility in 4Q22, is sufficient well into 2024 22-dayProprietary Manufacturing Process~$367M*Cash as of 9/30/2290%+Manufacturing Success Rate500+Patients Treated with Iovance TIL3 1 160+US and International Patents500+Employees6Tumor Types in Clinic5Designations The University of TexasMD Anderson Cancer Center 3 © 2023, Iovance Biotherapeutics, Inc.Rolling BLA Submission in Progress1 Rolling BLA Submission in Progress1Fast TrackBTDRMAT |
| 4 © 2023, Iovance Biotherapeutics, Inc. 2022 Accomplishments REGULATORY•BLA: Commenced rolling BLA submission in August 2022PIPELINE•Advanced melanoma (post-anti-PD-1): Cohort 4 data at SITC 2022 and in JITC•Frontline advanced melanoma: began Phase 3 trial•NSCLC: enrolled additional patients in IOV-LUN-202 and IOV-COM-202 trials •Cervical: expanded Cohort 2 to support regulatory submissions•TIL combinations: continued ongoing solid tumor cohorts of TIL + pembrolizumab•Genetically-modified TIL: initiated IOV-GM1-201 first-in-human trial of IOV-4001•Research: advanced new products toward clinicMANUFACTURING•Executed GMP commercial readiness activities, scaled up production at iCTCCOMMERCIAL•Executed ATConboarding activities and payer engagement |
| 5 © 2023, Iovance Biotherapeutics, Inc. *Enrollment completeAbbreviations: 1L=first line; 2L=second line; 4L=fourth line; BTD=breakthrough therapy designation; FTD=fast track designation; ipi/nivo=ipilimumab/nivolumab; NSCLC=non-small cell lung cancer; ODD=orphan drug designation; PD-1=programmed cell death protein-1; RMAT=Regenerative Medicines Advanced Therapy; TIL=tumor infiltrating lymphocytesIovance Solid Tumor Pipeline Highlights Confirmatory, FTDRolling BLA In Progress, RMATBTD, ODD PRODUCT CANDIDATEINDICATION(S)PHASE 1PHASE 2PIVOTAL Advanced Melanoma (Metastatic or Unresectable) Next Generation Lifileucel + pembroFrontlineTILVANCE-301 Phase 3TIL (Lifileucel/LN-144)Post-anti-PD-1C-144-01, Cohorts 2 & 4Lifileucel + pembroAnti-PD-1naïve IOV-COM-202, Cohort 1APD-1 Inactivated TIL (IOV-4001)Post-anti-PD-1IOV-GM1-201, Cohort 1 Metastatic NSCLC Next Generation N-1452 post-cemo post-anti-D-1O-N-202 Coorts 1 2N-145 pembroAnti-D-1 naeO-CO-202 Coort 3AN-1452-4 incl post-anti-D-1O-CO-202 Coort 3N-145 ipinioost-anti-D-1 O-CO-202 Coort 3CN-145 Gen 3 core biops2 post-cemo post-anti-D-1O-N-202 Coort 3D-1 nactiated O-40012-4 incl post-anti-D-1O-G1-201 Coort 2 Cervical Lifileucel Post-chemo & post-anti-PD-1C-145-04, Cohort 2 LN-145 + pembro1L –chemo and anti-PD-1 naïve C-145-04, Cohort 3* |
| 6 © 2023, Iovance Biotherapeutics, Inc. Potential market for early lines in combo with standard of care Potential to address unmet need in late lines of treatment1. https://seer.cancer.gov accessed May 2022 Deaths1New Cases1 Melanoma 7,65099,780 Cervical 4,28014,100 Lung & Bronchus 130,180236,740 Oral Cavity, Pharynx & Larynx 15,05066,470 Breast 43,780290,560 Pancreatic 49,83062,210 Brain & Other Nervous System 18,28025,05090%of all cancer casesare solid tumors11.7MNew cases of solid tumors in the U.S.1Expand into other indicationsMove into earlier line of therapySignificant Market Potential in Solid Tumors |
| 7 © 2023, Iovance Biotherapeutics, Inc. Tumor Infiltrating Lymphocytes (TIL): Leading Platform for Treatment of Solid TumorsTIL –Unique Mechanism of Action•Individualized•Patient’s own immune system amplified and rejuvenated•One-time therapy Remove Tumor Sample Expand & Rejuvenate Patient-specific T Cells1Lymphodepletion& Infusion1. Simpson-Abelson et al., ESMO 2020 |
| 8 © 2023, Iovance Biotherapeutics, Inc. Tumor TIL Mechanism of Action TILPeripheralbloodBloodvesselTumorcellTILTILTumorbedTIL Lysingtumorcell T-cellreceptorTumorneoantigenpeptidesMHC-I/II ChemokinereceptorCirculationMigrationPeptide Antigen RecognitionLysis(Tumor Killing)Chemokine TIL IFN γ |
| 9 © 2023, Iovance Biotherapeutics, Inc. Iovance Streamlined 22-Day GMP Manufacturing Process 1 2Patient IntakeTumor SampleProcurement 3 4NMA-LDTIL 5 6IL-2Recovery/Discharge 4 2 Gen 2 Process: 22 Days 9 © 2023, Iovance Biotherapeutics, Inc. |
| 10 © 2023, Iovance Biotherapeutics, Inc. Iovance Cell Therapy Center: iCTCBuilt-to-suit custom facility in Navy Yard Philadelphia136,000 ft2, $85M investmentLEED gold certification for core and shell buildingHonorable Mention Winner: 2022 ISPE Facility of the Year AwardsClinical supply initiated 3Q21 Commercial manufacturing expected with BLA approvalControl to optimize capacity, quality & COGS Leading Cell Therapy Manufacturing Facility |
| 11 © 2023, Iovance Biotherapeutics, Inc. Iovance Cell Therapy Center (iCTC): Building Annual Capacity for Thousands of Cancer Patients Phase 1 iCTCToday100sof patients/yearBLA Prepin core suites for commercial4separate flex suites for clinical Phase 2iCTC Ongoing Staffing2,000+patients/year12core suites for commercial4separate flex suites for clinical Phase 3iCTC Expansion15,000+patients/year24core suites for commercial4separate flex suites for clinical Phase 4 iCTC+Additional Site(s)10,000+ patients/yeariCTCAdjacentand new sites2Automation 11 © 2023, Iovance Biotherapeutics, Inc. 1. Expansion within existing shell2. Option to build on adjacent parcel |
| 12© 2023, Iovance Biotherapeutics, Inc. 12 Iovance TIL Therapy in Advanced Melanoma |
| 13 © 2023, Iovance Biotherapeutics, Inc. 1.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA Cancer J Clin., May 2021 2.https://seer.cancer.gov accessed May 20223.Clarivate DRG Disease Landscape (2021)4.Keytruda USPI accessed Mar 20225.Keytruda USPI accessed Mar 2022 (4%) and Weber et al., Lancet Oncol 2015 (ICC 10%)6.Kirchburger et al., Eur J Cancer 2016 and Goldinger et al., J Clin Oncol 2018Unmet Medical Need for Metastatic Melanoma TherapyNo FDA Approved Treatment Options After Progression on ICI (Anti-PD-1) Therapy and BRAF/MEK inhibitorsBRAF/MEK inhibitors if BRAF mutation +Chemotherapy ORR 4-10%5mOS ~7-8 months6Anti-PD-1 Immunotherapy21%-33% ORR4Available Care: 9.9K6.3K4.8K8.9K5.2K3.5K 1L 2L 3L-4L US EU5Melanoma Drug-Treated Population in 20213Unresectable / Metastatic (US and EU5) Annual new cases worldwide1325k100kAnnual new cases in U.S.257k7.7kAnnual deaths worldwide1Annual deaths in U.S.21L2L+ Abbreviations: EU5=France, Germany, Italy, Spain and United Kingdom; 1L=first line therapy, 2L=second line therapy, 3L=third line therapy, 4L=fourth line therapy; ICI=immune checkpoint inhibitor; ORR=objective response rate; mOS=median overall survival; PD-1=programmed cell death protein-1 |
| 14 © 2023, Iovance Biotherapeutics, Inc. Estimated total incidence and incidence of unresectable or metastatic melanoma by initial disease stage (US) 5%34%4%24%4%5%14%16%73%21%Est. US Incidence of Melanoma(All Stage -2021)1Est. US Incidence of Unresectable or Metastatic Melanoma (2021)2~100K~15K Stage IStage IIStage III -unresectableStage III -resectableStage IV1.Estimate of US incidence from Epiphany Health with stage III resectability status informed by market research 2.Estimate of US incidence of unresectable or metastatic melanoma based on secondary and primary market researchInitial disease stage |
| 15 © 2023, Iovance Biotherapeutics, Inc. C-144-01 Phase 2 Study DesignAbbreviations: DOR=duration of response; ECOG=Eastern Cooperative Oncology Group; IL-2=interleukin 2; IRC=Independent Review Committee; NMA-LD=nonmyeloablative lymphodepletion; ORR=objective response rate; OS=overall survival; PD-1=programmed cell death protein 1; RECIST=Response evaluation Criteria in Solid Tumors; TEAE=treatment-emergent adverse events; TIL=tumor-infiltrating lymphocytes Cohort 1:Non-cryopreserved TIL product (Gen 1)N=30Closed to enrollment Cohort 2: Cryopreservedlifileucel (Gen 2)N=66Enrollment:Apr 2017 to Jan 2019 Cohort 3: TIL re-treatment N=~10 PatientPopulationUnresectable or metastatic melanoma treated with ≥1 prior systemic therapy including a PD-1–blocking antibody and, if BRAF V600 mutation positive, a BRAF inhibitor ±MEK inhibitor Cohort 4:PivotalCryopreservedlifileucel (Gen 2)N=75Enrollment:Feb 2019 to Dec 2019 Key Endpoints•Primary: ORR (IRC-assessed using RECIST v1.1)•Secondary: DOR, PFS, OS, TEAE incidence and severityKey Eligibility Criteria•Tumor lesion/s for TIL generation and response assessment•No limit on number of prior therapies or markers of tumor burden (including size or LDH)Treatment Regimen (Cohorts 2 and 4)•22-day Gen2 manufacturing process•All patients received NMA-LD, a single lifileucel infusion, and up to 6 doses of high-dose IL-2Data cutoff date:July 15, 2022 Identical Eligibility and TreatmentforCohorts 2 and 4Phase 2, multicenter study to assess the efficacy and safety of autologous TIL (lifileucel) for treatment of patients with metastatic melanoma (NCT02360579) |
| 16 © 2023, Iovance Biotherapeutics, Inc. 64.4%Cohort 4 (n=87)Disease burden (>3 lesions)40.9%Cohort 2 (n=66)Highlighted Prior Therapy and Baseline Disease Characteristics* *Refer to SITC 2022 presentation for full baseline characteristics1. All patients received prior anti-PD1 therapyAbbreviations: CTLA-4=cytotoxic T-lymphocyte antigen 4; ICI=immune checkpoint inhibitor; LDH=lactate dehydrogenase; PD-1=programmed cell death protein 1; ULN=upper limit of normal83.9%Cohort 4 (n=87)65.2%Cohort 2 (n=66)Elevated LDH (>ULN), a negative prognostic factor •Median of 3 lines of therapy (range, 1-9)1•Median of 2lines (range, 1-7) of ICI‐containing therapy•113 (73.9%)retreated with ICI-containing therapy•125 (81.7%) received anti–CTLA-4•82 (53.6%) received anti–PD-1 + anti–CTLA-4 combinationCohorts 2 and 4 Heavily Pre-Treated and Mostly Similar; Cohort 4 had Higher Disease Burden and LDH ElevationBaseline Disease CharacteristicsPrior Therapy Experience (Cohorts 2+4)SITC 2022 C-144-01 COHORTS 2 + 4 POOLED ANALYSIS ASSESSED BY IRCUSING RECIST 1.1 |
| 17 © 2023, Iovance Biotherapeutics, Inc. Safety Non-Hematologic TEAEs in ≥30% of Patients*,†*Per CTCAE v4.03; Safety Analysis Set (N=156).†Grade 5 TEAEs included pneumonia (n=1), acute respiratory failure (n=1), arrhythmia (n=1), and intra-abdominal hemorrhage (n=1).All occurrences of AEs were counted if a patient experienced a new onset of the same AE at different timepoints. If multiple records were reported on the electronic case report form because of toxicity grade decrease of the same AE that had not resolved, then the event was counted once with the highest grade reported.15 events were reported after Month 12 (Grade 1, n=7; Grade 2, n=6; Grade 3, n=1; Grade 5, n=1).AE=adverse event; D=day; IL-2=interleukin 2; M, month; NMA-LD=nonmyeloablative lymphodepletion; TEAE=treatment-emergent adverse event •Median of 6 IL-2 doses administered •All patients experienced ≥1 TEAE (any grade); 94.9% experienced ≥1 Grade 3/4 TEAE•TEAEs were consistent with known safety profiles of NMA‐LD and IL-2 and in line with previous reports•Incidence of TEAEs decreased rapidly within the first 2 weeks after lifileucel infusion Preferred Term, n (%)Any GradeGrade 3/4Chills117 (75.0)8 (5.1)Pyrexia81 (51.9)17 (10.9)Febrile neutropenia65 (41.7)65 (41.7)Hypophosphatemia58 (37.2)41 (26.3)Hypotension52 (33.3)17 (10.9)Fatigue51 (32.7)6 (3.8)Diarrhea48 (30.8)2 (1.3) Preferred Term, n (%)Grade 3/4Leukopenia156 (100.0)Lymphopenia156 (100.0)Neutropenia156 (100.0)Thrombocytopenia147 (94.2)Anemia111 (71.2)Grade 3/4 Hematologic Lab Abnormalities* Grade 1 2 3 4 5 222 1441 2 4 G 11Transient and Manageable Nature of AEs Support the Potential Benefit of One-Time Treatment with Lifileucel |
| 18 © 2023, Iovance Biotherapeutics, Inc. Objective Response Rate (ORR) of 31.4% by IRC91% Concordance Rate between IRC-and Investigator-assessed ORR *Patient did not have acceptable target lesions and had best overall response of non-CR/non-PD per IRC assessment. †Six patients were nonevaluable for response (5 due to early death; 1 due to new anticancer therapy). CR,=complete response; IRC=independent review committee; ORR=objective response rate; PD=progressive disease; PR=partial response; SD=stable disease Cohort 2(n=66)Cohort 4(n=87)Cohort 2+4(N=153)ORR, n (%)23 (34.8)25 (28.7)48 (31.4)(95% CI)(23.5, 47.6)(19.5, 39.4)(24.1, 39.4)Best overall response, n (%)CR5 (7.6)4 (4.6)9 (5.9)PR18 (27.3)21 (24.1)39 (25.5)SD24 (36.4)47 (54.0)71 (46.4)Non-CR/Non-PD*1 (1.5)01 (0.7)PD15 (22.7)12 (13.8)27 (17.6)Nonevaluable†3 (4.5)3 (3.4)6 (3.9)SITC 2022 C-144-01 COHORTS 2 + 4 POOLED ANALYSIS ASSESSED BY IRCUSING RECIST 1.1•33 days median time from resection to lifileucel infusion •Lifileucel manufactured within specification in 94.7% of patients•Median number of TIL cells infused was 21.1 ×109(range, 1.2 ×109to 99.5 ×109) |
| 19 © 2023, Iovance Biotherapeutics, Inc. Tumor Burden Reduction and Best Response to Lifileucel13patients in the full analysis set are not included (9 had no post lifileucel target lesion SOD measurements, and 4 had no acceptable target lesions by IRC).*-100% change from baseline is presented for CR assessment that includes lymph node lesions.Best Percentage Change From Baseline in Target Lesion SOD (Cohort 2+4) SITC 2022 C-144-01 COHORTS 2 + 4 POOLED ANALYSIS ASSESSED BY IRCUSING RECIST 1.1Reduction of Tumor Burden in 79.3% (111/140) of PatientsCR=complete response; PD=progressive disease; PR=partial response; SD=stable disease; SOD=sum of diameters % Change from Baseline Patient |
| 20 © 2023, Iovance Biotherapeutics, Inc. Time to Response, Duration of Response, and Time on Efficacy Assessment for Confirmed Responders (PR or Better)•Median time from lifileucel infusion to best response was 1.5months•Responses deepened over time–7 patients (14.6%) initially assessed as PR were later confirmed CR–4 patients (8.3%) converted to CR >1 year post-lifileucel infusion; 2 (4.2%) of 4 patients converted after 2 years–10 patients (20.8%) improved from best response of SD to PR•35.4% of responses ongoing as of data cutoffAbbreviations: CR=complete response; PD=progressive disease; PR=partial response; SD=stable disease SITC 2022 C-144-01 COHORTS 2 + 4 POOLED ANALYSIS ASSESSED BY IRCUSING RECIST 1.1 |
| 21 © 2023, Iovance Biotherapeutics, Inc. Cohort 2(n=23)Cohort 4(n=25)Cohort 2+4(N=48)Median follow-up, months45.133.036.595% CI(44.2, 51.4)(30.4, 35.2)(34.7, 44.2)Median DOR†, monthsNR10.4NR95% CI(NR, NR)(4.1, NR)(8.3, NR)Min, max (months)1.4+, 54.1+1.4+, 34.3+1.4+, 54.1+DOR ≥12 months, n (%)15 (65.2)11 (44.0)26 (54.2)DOR ≥24 months, n (%)11 (47.8)9 (36.0)20 (41.7)Duration of Response**Patients not experiencing PD or who did not die prior to the time of data cut had their event times censored at the last adequate tumor assessment. For patients who received new anticancer therapies, DOR was censored at the date of last tumor response assessment prior to the start of new anticancer therapies. For patients with PD or death immediately after ≥2 consecutive missing tumor assessment visits, DOR was censored at the last adequate tumor assessment prior to the missing tumorassessments.†Based on Kaplan-Meier estimate.Shaded area indicates 95% CI DOR=duration of response; NR=not reached; PD=progressive diseaseSITC 2022 C-144-01 COHORTS 2 + 4 POOLED ANALYSIS ASSESSED BY IRCUSING RECIST 1.1Median DOR Not Reached at Median Study Follow Up of 36.5 Months 41.7%of responses continued for ≥24 months |
| 22 © 2023, Iovance Biotherapeutics, Inc. Lifileucel in combination with anti-PD-1/PD-L1 therapy in ICI-naïve patients (IOV-COM-202 Cohort 1A, N=12)1Iovance TIL Clinical Highlights in Combination with Pembrolizumab in Metastatic Melanoma•8 / 12 patients had a confirmed objective response per RECIST 1.1 (3 CRs & 5 PRs)•6 / 8 responders had ongoing response at the time of the last data cut•5 responders had a duration of response >1 year•FDA Fast Track Designation66.7%ORR IOV-COM-202 COHORT 1A MELANOMA COMBINATION (TIL+PEMBROLIZUMAB) 1.As assessed by investigator using RECIST 1.1 (January 20, 2022data cutoff). 2.Each bar is presented for each patient starting from date of TIL infusion up to date of new anti-cancer therapy, end of assessment, death, or data cutoff date, whichever occurs earlier. Abbreviations: CR=complete response; ICI=immune checkpoint inhibitor; ORR=objective response rate; PR=partial response; SD=stable disease; pembro=pembrolizumab; RECIST=Response Evaluation Criteria in Solid TumorsPatient IDTime (months) since TIL Infusion 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 Pembro Infusion Progression Ongoing on Study PR Start CR Start Time (months) since TIL Infusion 1A-031A-011A-051A-061A-071A-041A-111A-12 Patient ID Time to Response for Responders2Patient ID -30 1A091A021A081A011A111A121A041A051A031A061A07 -100 -80 -60 -40 -20 0 20 N=0N=11Cohort 1A % Change from Baseline SD PRCR 1A-09 1A-02 1A-08 1A-01 1A-11 1A-12 1A-04 1A-05 1A-03 1A-06 1A-07 Patient ID Best Overall Response for Evaluable Patients |
| 23© 2023, Iovance Biotherapeutics, Inc. 23 LaunchPreparation |
| 24 © 2023, Iovance Biotherapeutics, Inc. •Core suites: TIL commercial manufacturing•Flexible suites: clinical supply, pipeline expansion and advanced manufacturing, including IOV-4001 and Gen 3•Integrated quality control, supply chain and IT systems•100+ employees with additional staffing into launch and beyond•iCTCsupplemented with external CDMO manufacturing capacityiCTC Designed for High-Volume TIL Manufacturing and Flexibility |
| 25 © 2023, Iovance Biotherapeutics, Inc. Targeting Potential Authorized Treatment Centers (ATCs) Potential ATCIovance Clinical Trial Site1 1. ClinicalTrials.govAbbreviations:NCCN=National Comprehensive Cancer Network;KOL=Key Opinion Leaders;BMT=Bone Marrow Transplant Targeting Considerations•Patient volume•NCCN status, KOLs•Existing cell therapy / BMT•Inpatient capacity•Iovance clinical trial(s)Drive Demand •Top account prioritization•Community referrals |
| 26 © 2023, Iovance Biotherapeutics, Inc. Supporting Providers & Patients: IovanceCares™Abbreviations: COI=Chain of Identity; COC=Chain of Custody Customer-Centric •Patient management ecosystem •Proprietary COI/COC•Treatment center quality program Patient-Centric•Dedicated case managers•Reimbursement support•Patient support Quality SystemDedicated Case ManagersReimbursement & Patient Support Order Submission &Tumor ProcurementOrder Management& COI / COCManufacturing TIL Patient |
| 27 © 2023, Iovance Biotherapeutics, Inc. 55%Commercial29%MedicareMetastatic Melanoma Payer MixAll Treatment Settings and Lines of TherapyEnabling Market Access1. Metastatic Melanoma Insurance Claims Analysis, TIL-eligible patients treated in the ATC setting(1/1/2018 –6/30/2021)Abbreviations: ICD-10 PCS=International Classification of Diseases, 10thRevision, Procedure Coding System; IPPS=In-patient Prospective Payment System High Unmet Need in Metastatic Melanoma and Clinical Value of Lifileucel Payer Engagement•Unmet need•Clinical data•Educational presentations and tools•Engagement with commercial and Medicarepayers responsible for ~90% of covered livesCoding, Coverage and Payment•ICD-10 PCS codes issued•Medicare expanded DRG-018 to other immunotherapies, including lifileucel, in IPPS FY 2022 final rule19%Other7%Medicaid |
| 28© 2023, Iovance Biotherapeutics, Inc. 28 TIL Therapy Clinical Program Highlights |
| 29 © 2023, Iovance Biotherapeutics, Inc. 1.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CA Cancer J Clin., May 2021 2.https://seer.cancer.gov accessed May 20223.Brahmer et al., NEJM 2015; Borghaei et al., NEJM 2015; Herbst et al., Lancet 2016; Rittmeyer et al., Lancet 2017 Potential Market for Non-Small Cell Lung Cancer (NSCLC) Addressing a Defined Unmet Need in Second Line NSCLC The clinical data for LN-145 in heavily treated patients with metastatic non-small cell lung cancer is exciting. It represents the first experience for TIL monotherapy to show clinical benefit in metastatic non-small cell lung cancer.”Adam J. Schoenfeld, MDMedical OncologistMemorial Sloan Kettering Cancer Center New cases WW each year12.2M237kNew cases in U.S. each year21.8M Available Care:130kDeaths WW each year1 Deaths in U.S. each year29-13% ORR for docetaxel in 2ndline NSCLC following progression on chemo3Checkpoint Inhibitor + Chemo as 1stline option |
| 30 © 2023, Iovance Biotherapeutics, Inc. Single-Agent LN-145 Following Progression on Anti-PD-1 Therapy (IOV-COM-202 Cohort 3B, N=28)Iovance IOV-COM-202 Efficacy: NSCLC Cohort 3B (post ICI)Best Overall Response for Evaluable Patients (n=24) 60 ― ― ― ― ― ― ― ― ― •All received prior anti-PD-1 / anti-PD-L1 therapy •24/28 patients (85.7%), including all responders, received ≥2 prior lines of systemic therapyHeavily Pre-Treated Patient PopulationLong Lasting Responseswith Durations of 18 and 37+ (ongoing) Months21%ORR 37+months ongoing CR Pt ID# of Lines of Prior TherapyPD-L1 TPS (%)2*3<117**2702530 26** 340222528390Time to Response for Confirmed Responders (PR or Better; n=6)Time (months) since TIL Infusion % Change from BaselineN=5 -30 Cohort 3B N=19 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 Death Progression Ongoing on Study PR Start CR Start Response in Pt. 2 Remains Ongoing37.3+ months18.2 months IOV-COM-202 COHORT 3B, POST-ANTI-PD-1 NSCLC, NOVEMBER 2022 |
| 31 © 2023, Iovance Biotherapeutics, Inc. Phase 2, Multicenter Study of LN-145 in Patients with Metastatic NSCLC (NCT04614103)IOV-LUN-202Endpoints •Primary: Efficacy defined as ORR by IRC•Secondary: Safety and efficacyStudy Updates•2Q21: first patients treated•40+ sites are active in U.S., Canada, Europe Cohort 1: NSCLCPatients with < 1% or unknown TPSLN-145N=40 Cohort 2: NSCLCPatients with ≥1% TPSLN-145N= 40 Cohort 3: Core Biopsy and Gen 3*LN-145N=15*Cohort 3 patients unable to undergo surgical harvest, TIL grown from core biopsyAbbreviations: ICI=immune checkpoint inhibitor; IRC=independent review committee; NSCLC=non-small-cell lung cancer; ORR=objective response rate; TPS=tumor proportion score Iovance TIL Therapy LN-145 in NSCLCIOV-LUN-202 (NCT04614103) is designed to enroll patients with NSCLC with an unmet medical need but with fewer prior lines of therapy to maximize the potential for more sustained responses Patient PopulationUnresectable or metastatic, NSCLC with progression on prior ICI + chemotherapy, N=95 Cohort 4: Retreatment |
| 32 © 2023, Iovance Biotherapeutics, Inc. Phase 1/2 Open-Label First-in-Human Study: IOV-GM1-201Endpoints•Phase 1: Safety •Phase 2: Objective Response Rate (ORR) per RECIST v1.1 as assessed by the investigator•Secondary endpoints include complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), safety and tolerability, feasibilityStudy Updates•1Q22: Investigational New Drug (IND) Allowance •3Q22: first patient treated Cohort 1: Unresectable or metastatic melanomaPost-anti-PD-1/L1, post-BRAF/MEK inhibitor in patients with BRAF mutations Cohort 2: Stage III or IV NSCLCPost -anti-PD-1/L1 orpost targeted therapy and either chemotherapy or anti-PD-1/L1 Patient PopulationAdults with unresectable or metastatic melanoma or advanced NSCLCN=53 Genetically Modified, PD-1 Inactivated TIL Therapy IOV-4001 in Previously Treated Metastatic Melanoma and NSCLC (NCT05361174) NEXT GENERATION TIL THERAPY IOV-4001NSCLC=non-small-cell lung cancer |
| 33 © 2023, Iovance Biotherapeutics, Inc. 1L Therapy2L Therapy3L Therapy4L TherapySOCIOVA TrialSOCIOVA TrialSOCIOVA TrialSOCIOVA TrialAnti-PD-1 MonoORR 39-45%1COM-202Cohort 3AChemo DoubletCOM-202Cohort 3CDocetaxel or Docetaxel +RamucirumabORR 9-23%2LUN-202Cohorts 1-3GM1-201Cohort 2*GM1-201Cohort 2*Anti-PD-1 + ChemoORR 48-58%1Docetaxel or Docetaxel + RamucirumabORR 9-23%2LUN-202Cohorts 1-3GM1-201Cohort2*TKIAnti-PD-1+ChemoORR 48-58%1COM-202Cohort 3ADocetaxel or Docetaxel + RamucirumabORR 9-23%21(-3) L TKIChemoORR 17-32%3COM-202Cohort 3A* GM1-201 Cohort 2 population is comparable to completed COM-202 Cohort 3BMoving TIL Therapy into Relevant Lines of Therapy in NSCLC COM-202 Cohort 3A (TIL+pembrolizumab) LUN-202 Cohorts 1-3(TIL mono) COM-202 Cohort 3C (TIL+nivolumab/ipilimumab) GM1-201 Cohort 2IOV-4001 (PD1-KO TIL) Current Standard of Care Patient Populations Advanced or metastatic NSCLC, no prior systemic therapy Driver mutation (-)PD-L1 ≥50%PD-L1 0-49%Driver mutation (+)Other actionable mutationsEGFRALKROSAbbreviations: L=line; NSCLC=non-small cell lung cancer PD-1=programmed cell death protein-1; TIL=tumor infiltrating lymphocytes; TKI=tyrosine kinase inhibitor1. KEYTRUDA USPI;2. CYRAMZA USPI; Brahmer et al., NEJM 2015; Borghaei et al., NEJM 2015; Herbst et al., Lancet 2016;Rittmeyer et al., Lancet 2017 3. Park et al., Cancer Res Treat 2015; Yoshida et al., Lung Cancer 2017 |
| 34 © 2023, Iovance Biotherapeutics, Inc. Potential Market for Cervical Cancer1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, CACancer J Clin., May 2021; 2. https://seer.cancer.gov accessed May 2022; 3. Tewari, et al., NEJM 2014 4. Colombo et al., NEJM 2021; 5. Keytruda USPI; 6. Coleman et al., Lancet Oncol 2021; 7. McLachlan et al., Clin Oncol 2017; 8. Miller et al., Gynecol Oncol 2008 New cases WW each year1604k14kDiagnoses in U.S. each year2342k4kDeaths WW each year1Deaths in U.S. each year2 Available CareORRMedian DORFrontline:Combination chemotherapy + bevacizumab348%Not Reportedpembrolizumab + chemo + bevacizumab (PD-L1+ patients)468.1%18 monthsSecond Line/Third Line:pembrolizumab post-chemo (PD-L1+ patients)514.3%Not Reachedtisotumab vedotin-tftv post-chemo624%8.3 monthsChemotherapy in second line/third line7,83.4%–15%4.4 months8Addressing a Defined Unmet Need in Cervical Cancer Following Chemo and Anti-PD-1 |
| 35 © 2023, Iovance Biotherapeutics, Inc. Pivotal Phase 2 Study of Lifileucel (Formerly LN-145) in Recurrent, Metastatic or Persistent Cervical Carcinoma (NCT03108495)Endpoints (Pivotal Cohort 2)•Primary: ORR as determined by IRC•Secondary: safety and efficacyStudy Updates•4Q21: Initial Cohort 3 data at SITC1•3Q22: regulatory strategy updated with Cohort 2 to be pivotal•Expanded Cohort 2 to support regulatory submissions Cohort 1 TILClosed to Enrollment Cohort 2Lifileucel Cohort 3 Lifileucel + pembroClosed to Enrollment Cohort 4LN-145, previously enrolled pts e.g., Gen 1 TIL Cohort 5 LN-145Retreatment Cervical Cancer progressed on at least 1 prior systemic therapy excluding checkpoint Cervical Cancer progressed on prior therapy including anti-PD-1/PD-L1 Cervical Cancer with no prior systemic therapy 1. O’Malley et al., SITC 2021 Regulatory Strategy Focused on Significant Unmet Need in Cervical Cancer Following Chemo and Anti-PD-1 Therapy |
| 36© 2023, Iovance Biotherapeutics, Inc. 36 Next Generation Research Programs |
| 37 © 2023, Iovance Biotherapeutics, Inc. Genetically modify TILDevelop more potent TILOptimize processExpand TIL into new regimensCellectis gene-editing TALEN®collaboration1,2PD-1 and other immune checkpoint targetsDouble knockoutsCytokine tethered TILsPD-1+ selected TILCD39/69 double negative TILs3Gen 3 (16-day) process Core biopsy IOV-3001 IL-2 analog licensed from Novartis: IND enabling studiesWhat’s Next 1.Ritthipichai et al., ESMO 20202.Natarajan, et al., AACR 20223.Cubas et al., ESMO IO 2021 37 © 2023, Iovance Biotherapeutics, Inc. |
| 38© 2023, Iovance Biotherapeutics, Inc. 38 Corporate Summary & Milestones |
| 39 © 2023, Iovance Biotherapeutics, Inc. September 30, 2022In millions (unaudited)Common sharesoutstanding157.8Preferred shares outstanding2.91Stock options and restricted stock units outstanding17.3Cash, cash equivalents, investments, restricted cash$366.62Anticipated cash runway, inclusive of proceeds from equity sold through at-the-market (ATM) facility in 4Q22, is sufficient well into 20241. Preferred shares are shown on an as-converted basis2. Includes Restricted Cash of $6.4 million as of September 30, 2022Well-Capitalized in Pursuit of TIL Commercialization |
| 40 © 2023, Iovance Biotherapeutics, Inc. Broad, Iovance-Owned IP Around TIL Therapy TIL products and compositions: Gen 2, Gen 3, use of co-stimulants, selection of TIL,stable and transient genetic modifications, cryopreservation 1Tumor SampleProcurement 3 4NMA-LDTIL Infusion 5IL-2 Infusions60+ granted or allowed US and international patentsCompositions of matter for TIL productsMethods of treatment in a broad range of cancersManufacturing processes 4 2 TIL from: •Tumor•Marrow infiltrating lymphocytes•Peripheral blood lymphocytes•Frozen tumor technologies•Remnant TIL and digest processes •Combination of TIL and ICIs including PD-1 antibodies •Patient subpopulations IL-2 variants and regimens |
| 41 © 2023, Iovance Biotherapeutics, Inc. Investment HighlightsPioneering a Transformational Approach to Cure Cancer Large market opportunity & strong unmet need Potential to be first one - time cell therapy approved for solid tumors Efficient & scalable proprietary manufacturing Infrastructure for commercial success •Initial focus in post-ICI solid tumors•Expansion into combinations, earlier lines of therapy, and genetic modification(s)•Keylate-stagetrials in melanoma, cervical, and NSCLC•First-in-human trial of genetically modified TIL (PD-1 inactivated)•BLA submission on track to complete in 1Q23•Phase 3 frontline advanced melanoma confirmatory trial (FTD)•Accelerated path toapproval in melanoma (RMAT)andcervical cancer (BTD)•Defined registration strategy in cervical cancer•Iovance Cell Therapy Center (iCTC) in-house manufacturing•Additional capacity with contract manufacturers•Rapid 22-day Gen 2 manufacturing with 90%+ success rate•>500 patients treated with Iovance proprietary process•Fully integrated•Experienced cross-functional cell therapy team•Partnering with leading U.S. Cancer Centers to develop TIL service-line capabilities•IovanceCares™proprietary platform 41 © 2023, Iovance Biotherapeutics, Inc.Abbreviations: BLA=Biologics License Application; BTD=breakthrough therapy designation; FTD=fast track designation; ; ICI=immunecheckpoint inhibitor; NSCLC=non-small cell lung cancer; PD-1=programmed cell death protein-1; RMAT=Regenerative Medicines Advanced Therapy; TIL=tumor infiltrating lymphocytes |
| 42 © 2023, Iovance Biotherapeutics, Inc. Anticipated 2023 Milestones REGULATORY•BLA: Complete rolling BLA submission in Q1 2023•BLA: FDA approvalPIPELINE•Melanoma: enroll frontline advanced melanoma Phase 3 confirmatory trial•NSCLC: report data and continue to enroll IOV-LUN-202, IOV-COM-202, IOV-GM1-201 trials•Cervical: enroll additional patients in registrational Cohort 2•PD-1 inactivated TIL (IOV-4001): complete Phase 1 safety portion and proceed to Phase 2 portion of IOV-GM1-201 trial•Research: advance new products toward clinic, including additional genetically-modified TIL therapiesMANUFACTURING•Execute GMP commercial readiness activities to support BLA approval and supply lifileucel at launchCOMMERCIAL•Prepare for and execute commercial launch |
| 43 © 2023, Iovance Biotherapeutics, Inc. © 2023, Iovance Biotherapeutics, Inc. Thank You |
