Slide 1: Primary Analysis of the IGNYTE Registrational Cohort in Anti-PD1 Failed Melanoma
IGNYTE Investor Event (6/6/24) 1 Primary Analysis of the IGNYTE Registrational Cohort in Anti-PD1 Failed Melanoma June 6, 2024
Slide 2: Safe Harbor
IGNYTE Investor Event (6/6/24) 2 Safe Harbor Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934,
Slide 3: Today's Speakers/Q&A Panel
IGNYTE Investor Event (6/6/24) 3 Today’s Speakers/Q&A Panel CAROLINE ROBERT Professor Head of Dermatology Unit, Institute Gustave Roussy and Co-Director Melanoma Research Unit INSERM, Paris-Sud University. MICHAEL WONG Professor Melanoma Medical Oncology, University of Texas MD Anderson Cancer Cente
Slide 4: Today's Agenda
IGNYTE Investor Event (6/6/24) 4 Today’s Agenda • Data Summary • ASCO 2024 Recap: IGNYTE 12-month Investigator-assessed Data • Topline IGNYTE Primary Analysis by Independent Central Review • Progress to BLA • Q&A
Slide 5: Data Summary
IGNYTE Investor Event (6/6/24) 5 Data Summary • Strong primary analysis data: ORR of 33.6% (mRECIST 1.1) and 32.9% (RECIST 1.1) by independent central review • Improvement versus investigator-assessed ORR of 32.1% (mRECIST 1.1) • Median DOR >35 months; 100% of responses last >6 months (from baseline
Slide 6: ASCO Recap: Anti-PD1 Failed Melanoma Patients from the IGNYTE Clinical Trial
IGNYTE Investor Event (6/6/24) 6 ASCO Recap: Anti-PD1 Failed Melanoma Patients from the IGNYTE Clinical Trial
Slide 7: Options are Limited in Melanoma Following Progression on Anti-PD1 Therapy
IGNYTE Investor Event (6/6/24) 7 Options are Limited in Melanoma Following Progression on Anti-PD1 Therapy • Further single agent anti-PD1 for patients having confirmed PD on prior anti-PD1 gives a response rate of 6-7%1,2 • Nivolumab + ipilimumab is a potential option3, but toxicity is high4-5 • An
Slide 8: IGNYTE Study Design Anti-PD1 Failed Melanoma Cohort
IGNYTE Investor Event (6/6/24) 8 IGNYTE Study Design Anti-PD1 Failed Melanoma Cohort Key eligibility criteria Confirmed progression while on prior anti-PD1 therapyc At least 8 weeks of prior anti–PD1, confirmed progression while on anti– PD1; anti–PD1 must be the last therapy before clinical trial.
Slide 9: Baseline Clinical Characteristics
IGNYTE Investor Event (6/6/24) 9 Baseline Clinical Characteristics A ‘real world’ anti-PD1 failed melanoma population was enrolled • Good representation of each of the sub-groups of patients who progress on prior anti-PD1 therapy Median follow up is 15.4 months (range 0.5-55.5) Patients, n (%) All p
Slide 10: Efficacy
IGNYTE Investor Event (6/6/24) 10 Efficacy Investigator assessed data with all patients having at least 12 months follow up Data cutoff: March 8th 2024. BOR, best overall response; CR, complete response; CTLA-4, cytotoxic T-lymphocyte an6gen 4; PD-1, programmed cell death protein 1; PD, progressive
Slide 11: Depth of Response
IGNYTE Investor Event (6/6/24) 11 Depth of Response • Target lesions were reduced in >50% of patients • Responses were seen across disease stages, including CRs in patients with stage IVM1b/c disease Patients Data cutoff: March 8th 2024. The target lesion response is shown for pa6ents with at least
Slide 12: Responses are Systemic
IGNYTE Investor Event (6/6/24) 12 • 70.4% of responding patients had non-injected lesions • Injected and non-injected lesions responded with similar duration and kinetics • Depth of response independent of injection status Responses in non-injected lesions demonstrate systemic benefit Responses are
Slide 13: Duration of Response
IGNYTE Investor Event (6/6/24) 13 Duration of Response From baseline • Responses are durable, with a median DOR of 36.6 months Probability (%) >6 months >12 months >18 months >24 months 100% 84.2% 74.9% 65.2% Data cutoff: March 8th 2024. Dura6on of response defined as 6me from baseline to end of res
Slide 14: Safety: Treatment-related AEs (N = 156)
IGNYTE Investor Event (6/6/24) 14 Safety: Treatment-related AEs (N = 156) RP1 combined with nivolumab continues to be a generally well tolerated regimen • Predominantly grade 1 and 2 constitutional-type side effects • Low incidence of grade 3 and 4 events • No grade 5 events Additional grade 3 and 4
Slide 15: Conclusions
IGNYTE Investor Event (6/6/24) 15 Conclusions • RP1 combined with nivolumab in melanoma patients who had confirmed progression on prior anti-PD1 continues to show: • Deep and durable, systemic responses • A favorable safety profile, with generally ‘on target’ and transient grade 1–2 side effects ind
Slide 16: Topline Data for the IGNYTE Registrational Cohort Assessed by Independent Central Review
IGNYTE Investor Event (6/6/24) 16 Topline Data for the IGNYTE Registrational Cohort in Anti-PD1 Failed Melanoma Assessed by Independent Central Review
Slide 17: Strong IGNYTE Primary Analysis Data by Independent Central Review
IGNYTE Investor Event (6/6/24) 17 Strong IGNYTE Primary Analysis Data by Independent Central Review Overall Response Rate (registration-intended cohort: n=140) (%) Investigator Assessment Independent Central Review1 Modified* RECIST 1.1 32.1% Primary Endpoint Modified* RECIST 1.1 33.6% RECIST 1.1**
Slide 18: Patient Example
IGNYTE Investor Event (6/6/24) 18 Patient Example Prior atezolizumab+cobimetinib, ipilimumab, SX682 (CXCR-inhibitor)+ atezolizumab, ipilimumab+nivolumab Baseline 9 Months Baseline 9 Months Responses in uninjected distant and visceral tumors including healing of lytic bone lesions (increasing scleros
Slide 19: Patient Example
IGNYTE Investor Event (6/6/24) 19 Patient Example Prior pembrolizumab (1L), encorafenib+binimetinib (2L), and nivolumab+relatlimab (3L) Baseline 4 months 15 months
Slide 20: IGNYTE Data Shows Clinically Meaningful Benefit
IGNYTE Investor Event (6/6/24) 20 IGNYTE Data Shows Clinically Meaningful Benefit • One third of patients respond (ORR: 33.6%) • Responses are durable • 100% last >6 months, median DOR >35 months (from baseline) • RP1 combined with nivolumab continues to be a generally well tolerated regimen • Predo
Slide 21: Progress to BLA
IGNYTE Investor Event (6/6/24) 21 Progress to BLA
Slide 22: IGNYTE Data and Phase 3 Confirmatory Trial Incorporates FDA Feedback
IGNYTE Investor Event (6/6/24) 22 IGNYTE Data and Phase 3 Confirmatory Trial Incorporates FDA Feedback Type B meeting in 2021 A real-world population, representative of the IO progressed landscape should be enrolled Patients should have confirmed progression while on anti-PD1 therapy, with minimum 8
Slide 23: IGNYTE-3: Confirmatory Phase 3 Trial Design
IGNYTE Investor Event (6/6/24) 23 Advanced cutaneous melanoma Progressed on anti-PD1 AND anti-CTLA-4 OR not candidates for anti-CTLA-4 Up to 2 prior lines of systemic therapy for advanced disease BRAF mutant patients must have been treated with BRAF/MEK-directed therapy1 N=~400 Randomized 1:1 3-year
Slide 24: Manufacturing on Track to Support RP1 BLA and Commercialization
IGNYTE Investor Event (6/6/24) 24 Manufacturing on Track to Support RP1 BLA and Commercialization • Type C meeting with FDA confirmed alignment on Chemistry, Manufacturing and Controls (CMC) plans to support RP1 BLA submission • 63,000 square foot state-of-the-art facility for GMP manufacturing in F
Slide 25: U.S. Melanoma RP1 Patient Opportunity
IGNYTE Investor Event (6/6/24) 25 U.S. Melanoma RP1 Patient Opportunity Compelling potential option for a broad range of anti-PD1 failed patients ~13K patients1 Addresses a high unmet need in anti-PD1 failed settings 1L prior adjuvant 2L+ BRAF WT 2L+ BRAF MT An#-PD1 failed melanoma Source: 1Melanoma
Slide 26: RP1 Well Positioned for BLA Submission and Commercialization
IGNYTE Investor Event (6/6/24) 26 RP1 Well Positioned for BLA Submission and Commercialization • Strong IGNYTE primary endpoint ORR data by independent central review of 33.6% (mRECIST 1.1) • Durable responses: 100% last >6 months, median DOR >35 months (from baseline) • Manufacturing on track to su
Slide 27: Thank You
IGNYTE Investor Event (6/6/24) 27 Thank You