Slide 1: Phase 1 dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific
Phase 1 dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors September 9, 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “may,” “can”, “will,” “believe,” “expect,” “plan,” “anticipate,” “project” and similar expressions (as well as other words or e
Slide 3: Overview & ImmTAC Platform; agenda
Overview & ImmTAC Platform Bahija Jallal, PhD – Chief Executive Officer Phase 1 study of IMC-F106C Targeting PRAME Omid Hamid, MD – Cedars-Sinai Cancer, the Angeles Clinic & Research Institute Next steps for IMC-F106C David Berman, MD, PhD – Head of R&D Concluding Remarks Bahija Jallal, PhD – Chief
Slide 4: We are defining a new frontier of cancer treatment
We are defining a new frontier of cancer treatment 2022 2017 2013 2011 T Cell Receptor Cell Therapy (TCR) Therapy 1997 Antibody-Drug Conjugate Off-the-shelf bispecific T cell engagers Immunotherapy 1949 Targeted Therapy Chemotherapy 4
Slide 5: Omid Hamid, MD
Omid Hamid, MD Chief, Translational Research and Immunotherapy and Co-Director, Melanoma Therapeutics Internationally recognized leader in immuno-oncology drug development and melanoma therapeutics Investigator in the initial trials with ipilimumab, pembrolizumab, nivolumab, atezolizumab and vemuraf
Slide 6: Phase 1 dose escalation of IMC-F106C (ESMO #728O)
#728O Phase 1 dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors Omid Hamid,1 Takami Sato,2 Diwakar Davar,3 Margaret Callahan,4 Fiona Thistlethwaite,5 Raid Aljumaily,6 Melissa Johnson,7 Hendrik-Tobias Arkenau,8 Ecaterina Dumbrava,9 Benjamin Izar,10 Hui Amy
Slide 7: Declaration of Interests
DECLARATION OF INTERESTS Dr Omid Hamid Advisory/Consulting: Aduro Biotech, Akeso Biopharma, Alkermes, Amgen, BeiGene, BioAtla, BMS, Genentech, GlaxoSmithKline, Idera, Immunocore, Incyte, Iovance Biotherapeutics, Janssen, Merck, NextCure, Novartis, Pfizer, Regeneron, Roche, Sanofi, Seattle Genetics,
Slide 8: IMC-F106C: ImmTAC targeting HLA-A2-presented peptide from PRAME
IMC-F106C: ImmTAC targeting HLA-A2-presented peptide from PRAME (PRAME × CD3) PRAME: most broadly expressed cancer-testis antigen in several tumor types but with minimal normal tissue expression Adeno NSCLC Prevalence of Tumor PRAME expression Melanoma, endometrial, NSCLC, TNBC, SCLC, ovarian RCC, e
Slide 9: Phase 1 Study Design Dose escalation
Phase 1 Study Design Dose escalation Tumor assessment every 9 weeks Target Dose, Starting Day 15 Cohorts 6 Screening Treatment Follow-up 320 mcg and above Weekly IV infusion with intra-patient dose Efficacy escalation (over 3 weeks) 160 mcg population n=31* Key eligibility criteria Key objectives 80
Slide 10: Strong and Consistent Pharmacodynamic Activity at ≥20 mcg IMC-F106C
Strong and Consistent Pharmacodynamic Activity at ≥20 mcg IMC-F106C T cell activation and re-direction into tumor seen across ImmTAC platform Interferonγ induction T cell trafficking Peripheral blood Peripheral blood Tumor Pre-treatment Dose Dose CD3 Day 28 22-fold increase Results plotted as mean ±
Slide 11: Baseline patient characteristics
Baseline patient characteristics Safety Efficacy Characteristic Population Population N=55 N=31† Age — median yr (range) 60 (26, 79) 61 (36, 79) ECOG status 0 — n (%) 30 (55%) 19 (61%) PRAME status (IHC) Median PRAME H-score in efficacy population was high, Positive 49 (89%) 28 (90%) 188; most pat
Slide 12: IMC-F106C was well tolerated
IMC-F106C was well tolerated Most frequent related AE was Grade 1/2 CRS, consistent with proposed mechanism 0.3 – 10 mcg† 20 – 320 mcg† Total Preferred Term (MedDRA v23.1) (N=18) (N=37) (N=55) All Grades (events in ≥ 25% of patients), n (%) AT LEAST ONE EVENT 18 (100) 34 (92) 52 (95) Pyrexia* 10 (56
Slide 13: Responses observed in multiple tumor types
Responses observed in multiple tumor types PRAME expression‡ Positive Not evaluable * Two patients (1 with NSCLC, 1 serous ovarian) discontinued treatment due to PD with scan data not available at DCO † Ovarian cancer patient with unconfirmed PR (uPR) remains on treatment and eligible for confirmati
Slide 14: Majority of patients have durable tumor response or disease stabilization
Majority of patients have durable tumor response or disease stabilization NSCLC, non small cell lung carcinoma 9
Slide 15: Responses are durable, 6 of 7 PRs still ongoing
Responses are durable, 6 of 7 PRs still ongoing Two PRs ongoing for 7+ months * PRAME expression assessed by IHC H-score Endo, endometrial carcinoma; NSCLC, non small cell lung carcinoma; TNBC, triple-negative breast cancer; UM, uveal melanoma; ctDNA, circulating tumor DNA; ND, not yet determined (9
Slide 16: Reduction in circulating tumor DNA observed across tumor types
Reduction in circulating tumor DNA observed across tumor types (n=20)† Any reduction: 18 (90%) 50% reduction: 13 (65%) Cleared: 5 (25%) 0.0 Best log reduction Best % reduction 4 PR patients evaluated for 50 ctDNA had > 50% reduction, -0.5 including 3 with clearance 75 -2 Two patients had ctDNA -
Slide 17: Example responders: ovarian carcinoma and uveal melanoma
Example responders: ovarian carcinoma and uveal melanoma Baseline On treatment Patient #1 Ovarian Representative lesion cancer 5 prior lines, Unconfirmed PR platinum resistant Ongoing treatment; ctDNA pending Week 9 Patient #2 Uveal Confirmed PR Melanoma ctDNA cleared Ongoing treatment 1+ year Week
Slide 18: Example responder: cutaneous melanoma
Example responder: cutaneous melanoma Prior anti-CTLA4, multiple anti-PD1s and oncolytic virus Patient #3 Baseline 23 mm 63 mm 24 mm Confirmed PR ongoing treatment 5+ months 11 mm 47 mm 11 mm Week 9 Week 9 Week 9 Images courtesy of Dr. Omid Hamid (Angeles Clinic) 13
Slide 19: Example responder: serous ovarian carcinoma
Example responder: serous ovarian carcinoma 5 prior regimens including platinum, bevacizumab, anti-PD-1, investigational agents Patient #4 Baseline 19 mm 51 mm 29 mm Confirmed PR 9.7 mm 12 ctDNA 67% decrease 40 mm nontarget PD at Month 8 but ongoing treatment 1+ yr 16 mm Week 18 Week 18 Week 18 Imag
Slide 20: Conclusions
Conclusions IMC-F106C, first PRAME×CD3 ImmTAC, activates T cells and is well-tolerated CRS is mostly Grade 1, no Grade ≥3, and predominantly during initial 3 doses Treatment-related AEs are manageable; none have led to discontinuation or death Durable (up to 9+ months) RECIST PRs across mult
Slide 21: Thank you to all patients, families and caregivers
Thank you to all patients, their families and their caregivers who were involved in this global clinical trial & all investigators and their teams Omid Hamid The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate Takami Sato and Marlana Orloff Thomas Jefferson University Hospitals Diwak
Slide 22: IMC-F106C Clinical Development Plan
22 IMC-F106C Clinical Development Plan DAVID BERMAN Head of Research and Development
Slide 23: Insights from KIMMTRAK clinical development in mUM
Insights from KIMMTRAK clinical development in mUM MEDIAN OS: HAZARD RATIO: Overall Survival (OS) benefit 21.7 months 0.51 Redirects T cells Durable ctDNA Activity at high into tumor1 clinical activity2 reduction3 and low H score4 Best Overall Response Tumor Baseline Day 16 CD3 CD8 Best Overall Resp
Slide 24: RECIST responses enriched at higher H score for PRAME
RECIST responses enriched at higher H score for PRAME 300 250 200 IHC Score median median 150 100 50 median 0 KIMMTRAK (Phase 1/2) MAGE-A4 (Phase 1) PRAME (Phase 1) Study IMCgp100-1021,4 Study IMC-C103C-1012,4 Study IMC-F106C-1013,4 Best RECIST Response Non-PR PR 1. Carvajal RD, et al. J Clinical On
Slide 25: IMC-F106C-101 designed as an adaptive Phase 1/2 study
IMC-F106C-101 designed as an adaptive Phase 1/2 study Monotherapy All Combinations ongoing Monotherapy IV Checkpoint inhibitor dose escalation combinations Focus of today’s presentation Enables future Chemotherapy randomized trials into Cutaneous melanoma combinations earlier lines of therapy Monoth
Slide 26: PRAME, validated as TCR target, expressed in many solid tumors
PRAME, validated as TCR target, expressed in many solid tumors Prevalence of PRAME HLA*02:01+, PRAME+ Tumor type expression1 metastatic patients (G7)2 Endometrial >10K Melanoma >10K 70-100% Ovarian >15K NSCLC-squamous >30K NSCLC-adeno >40K 50-70% SCLC TNBC >15K >5K Total >150,000 PRAME+, HLA-A2 pati
Slide 27: Concluding Remarks
27 Concluding Remarks BAHIJA JALLAL Chief Executive Officer
Slide 28: Validation of ImmTAC platform in multiple solid tumors
Validation of ImmTAC platform in multiple solid tumors Durable tumor Activity even in low ctDNA Overall survival T cell activation shrinkage target expression reduction benefit KIMMTRAK® gp100 IMC-C103C MAGE-A4 To be presented IMC-F106C PRAME Promising rate of RECIST PRs enables broad development op
Slide 29: Q&A Session
7 Q&A Session OMID HAMID, MD BAHIJA JALLAL, PhD BRIAN DI DONATO DAVID BERMAN, MD, PhD MOHAMMED DAR, MD The Angeles Clinic Chief Executive Officer Chief Financial Officer Head of Research and Chief Medical Officer Chief, Translational Research and Head of Strategy Development and Immunotherapy and Co
Slide 30: Our pipeline
Our pipeline Leading bispecific TCR pipeline; FDA approval for KIMMTRAK® Candidate Target Indication Pre-clinical Phase 1 Phase 2 Phase 3 Approved Anticipated Milestones FDA, EC, MHRA approvals Uveal melanoma Commercial launch 1H 2022 KIMMTRAK® gp100 Advanced melanoma • Start Ph 2/3 study 4Q 202
Slide 31: Key portfolio milestones anticipated in 2022
Key portfolio milestones anticipated in 2022 1Q2022 2Q2022 3Q2022 4Q2022 KIMMTRAK Advanced Melanoma Commercial Launch Start Ph. 2/3 Randomized Trial FDA FDA Approval for mUM | 1Q Approval European Commission’s Approval for mUM | 2Q Oncology UK MHRA Approval for mUM | 2Q Australia and Canada