Immunocore Holdings Plc · NASDAQ:IMCR
Immunocore — ASCO 2024
36 slides from Immunocore's conference presentation, May 31, 2024
Slide 1: PRAME Phase 1 study of brenetafusp (IMC-F106C) in cutaneous melanoma
PRAME Phase 1 study of brenetafusp (IMC- F106C) in cutaneous melanoma May 31, 2024 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Words such as “may”, “will”, “believe”, “expect”, “plan”, “anticipate” and similar expressions (as well as othe
Slide 3: Agenda
Agenda Welcome Bahija Jallal, CEO Insights from KIMMTRAK David Berman, Head of R&D Phase 1/2 study of brenetafusp targeting PRAME Dr. Diwakar Davar, UPMC Q&A Session 3
Slide 4: Pioneering a new class of immunotherapy
Pioneering a new class of immunotherapy T Cell Receptor Cell (TCR) Therapy Antibody-Drug Therapy Conjugate Checkpoint Targeted Therapy Therapy Chemotherapy 2022 2017 2013 2011 1997 1949 4
Slide 5: KIMMTRAK: OS and PFS benefit with unique mechanism of action
KIMMTRAK: OS and PFS benefit with unique mechanism of action T cells In pre-clinical studies... T cell infiltration into tumors Blood Distinct mechanism of Baseline Day 16 action than CD3 checkpoints In tumor biopsies… Week 12 (CD3 T cell) More robust T cell CD8 Interferon-g infiltration and Granzym
Slide 6: Case Study: clinical benefit in patient with SD and tumor reduction
Case Study: clinical benefit in patient with SD and tumor reduction (-7%) due to necrosis and inflammation Cutaneous melanoma patient1 KIMMTRAK monotherapy Ph 1 Day 1 Day 8 Day 30 Inflammation Necrosis 6 1 Middleton M Clinical Cancer Research 2020
Slide 7: Definition of KIMMTRAK benefit broader than RECIST ORR
Definition of KIMMTRAK benefit broader than RECIST ORR 24% patients (11% PR + 13% SD with confirmed tumor reduction)- durable with median 11 mo. Durability of response SD with tumor reduction* -1% to -29% 11 months reduction median duration reduction PR/CR -30% to -99% reduction 11 months median dur
Slide 8: Disease control rate, strong predictor of significant PFS
Disease control rate, strong predictor of significant PFS DCR mostly of stable disease (SD) Both PR and SD very durable Drives PFS benefit Disease control rate 46% SD PR/CR 27% 35% PFS HR 0.73 22% 11% 5% Control KIMMTRAK OS (HR 0.51) best endpoint to capture all benefit 8 *Hassel JC, et al. NEJM 202
Slide 9: KIMMTRAK activity higher in early lines of therapy vs 2L+
KIMMTRAK activity higher in early lines of therapy vs 2L+ 1L KIMMTRAK1 2L+ KIMMTRAK2 N=128 N=94 Clearance 37% 13% Molecular response 81% 42% ctDNA reduction is early surrogate of OS benefit and independent of CT/MRI 9 1 Sullivan R, et. Al. Cancer Res (2023) 83 (7_Supplement): 1035.; 2 Carvajal, R.D.
Slide 10: T cell fitness in blood important parameter of ImmTAC benefit
T cell fitness in blood important parameter of ImmTAC benefit T cell fitness defined by Naïve and more data T cells T stem cell (Tscm) blood signature this year Blood Naïve/Tscm Interferon-g Granzyme B Effector Perforin Exhausted Similar association between T cell fitness and CAR-T and TILs1 Tumor 1
Slide 11: Insights from KIMMTRAK that can be applied to ImmTAC platform
Insights from KIMMTRAK that can be applied to ImmTAC platform Distinct MoA with more robust T cell infiltration and activation than checkpoints • Distinct measures of benefit required - broader than RECIST ORR Disease control, including durable tumor reduction, is a hallmark of platform • High DCR p
Slide 12: Diwakar Davar, MD, MS
Diwakar Davar, MD, MS Clinical Director of the Melanoma and Skin Cancer Program, University of Pittsburgh Medical Center (UPMC) Hillman Board-certified in internal medicine and medical oncology and completed both his residency and fellowship at UPMC Clinical interests include management of advanced
Slide 13: Phase 1 safety and efficacy of brenetafusp in post-checkpoint cutaneous melanoma
#9507 Phase 1 safety and efficacy of brenetafusp (IMC-F106C), a PRAME × CD3 ImmTAC bispecific, in post-checkpoint cutaneous melanoma (CM) Omid Hamid1, Anja Williams2, Juanita Lopez3, Daniel Olson4, Takami Sato5, Heather Shaw6, Claire F. Friedman7, Fiona Thistlethwaite8, Mark R. Middleton9, Celeste L
Slide 14: Disclosures and Disclaimer
14 Disclosures Consulting: ACM Bio, Ascendis, Castle, Clinical Care Options (CCO), Gerson Lehrman Group (GLG), Immunitas, Medical Learning Group (MLG), Replimmune, Trisalus, Xilio Therapeutics; Contracted Research for Institution: Arcus, Immunocore, Merck, Regeneron Pharmaceuticals Inc., Tesaro/GSK;
Slide 15: Brenetafusp: ImmTAC bispecific T cell engager targeting PRAME
Brenetafusp: ImmTAC bispecific T cell engager targeting HLA-A2-presented peptide from PRAME Blood Any T cell T cell • TCR bispecific ImmTAC molecules redirect polyclonal T trafficking to cells to target cancer cells by recognizing intra-/extra- tumor Brenetafusp CD3 cellular cancer proteins receptor
Slide 16: Brenetafusp Phase 1/2 Study Design
Brenetafusp Phase 1/2 Study Design Key objectives: Key eligibility criteria for CM: Dose escalation Expansion Primary Results • Unresectable or metastatic Cutaneous • Safety from • MTD/expansion dose • HLA-A*02:01 (central testing) melanoma N=47* • Efficacy (in expansion only) • Previously treated w
Slide 17: CM Demographics and baseline characteristics
17 CM Demographics and baseline characteristics Brenetafusp monotherapy and in combination with pembrolizumab Monotherapy + Pembro Characteristic N=47 N=9 Patients were heavily pre-treated Age, yr – median (range) 64 (31-79) 65 (24-78) • All received prior checkpoint inhibitors (CPI) Female – n (%)
Slide 18: Brenetafusp monotherapy was well tolerated
18 Brenetafusp monotherapy was well tolerated TRAE in ≥ 15% of patients (N=47) Incidence of selected TRAEs Preferred Term (%) Any grade Grade 3 / 4 ANY 43 (92%) 19 (40%) Cytokine release 24 (51%) - syndrome* Rash (composite)† 23 (49%) 1 (2%) Pyrexia 17 (36%) 1 (2%) Chills 13 (28%) - Lymphocyte decre
Slide 19: Clinical benefit characterized by durable disease control
Clinical benefit characterized by durable disease control 19 Brenetafusp monotherapy (n= 36 evaluable*) PRAME positive group for efficacy analysis includes H-score ≥1 and pts with unknown PRAME IHC results * 36/47 patients had baseline and at least one tumor assessment on treatment; 10 patients had
Slide 20: Clinical benefit characterized by disease control
20 Clinical benefit characterized by disease control PR + SD with DCR N confirmed tumor ORR (PR+SD) reduction* All mono 36 56% 28% 11% PRAME+ 31 58% 32% 13% PRAME- 5 40% 0% 0% Reduction in tumor burden is associated with clinical benefit across ImmTAC platform Nathan NEJM1; Middleton CCR2; see ASCO
Slide 21: Tumor reduction observed only in PRAME+ pts
Tumor reduction observed only in PRAME+ pts 21 Brenetafusp monotherapy (n= 36 evaluable) PRAME positive group for efficacy analysis includes H-score ≥1 and pts with unknown PRAME IHC results PRESENTED BY: Dr. Omid Hamid
Slide 22: Tumor reduction observed in patients with high tumor burden
Tumor reduction observed in patients with high tumor burden 22 Brenetafusp monotherapy (n= 36 evaluable) PRESENTED BY: Dr. Omid Hamid
Slide 23: Tumor reduction observed in patients with liver and brain mets
Tumor reduction observed in patients with liver and brain mets 23 Brenetafusp monotherapy (n= 36 evaluable) PRESENTED BY: Dr. Omid Hamid
Slide 24: ctDNA molecular response in 42% of PRAME+ patients
ctDNA molecular response in 42% of PRAME+ patients Brenetafusp monotherapy (n=28 ctDNA evaluable*) 100 PRAME+ PRAME- 50 • Trend for longer PFS (HR 0.5) and OS % reduction (HR 0.3) in molecular responders 0 • Molecular response in patients with -50 PR, SD and PD 0.5 log reduction (molecular response†
Slide 25: Promising initial PFS and OS, enriched in PRAME+ pts
Promising initial PFS and OS, enriched in PRAME+ pts Brenetafusp monotherapy (n= 47) Progression free survival Overall survival mPFS mo (95% CI) 6-mo OS rate All mono 3.3 (2.1-5.6) All mono 87% PRAME+ 4.2 (2.1-6.1) PRAME+ 95% PRAME- 2.1 (1.3-NC) PRAME- 40% Median follow up 7.8 mos PRAME positive gro
Slide 26: Initial data for anti-PD1 combination shows well tolerated profile
26 Initial data for anti-PD1 combination shows well tolerated profile Brenetafusp + pembrolizumab dose escalation safety cohort (n=9 CM patients) brenetafusp + pembrolizumab • Primary goal to demonstrate safety in combination Any grade Grade 3 / 4 • Safety profile similar to each agent alone Preferr
Slide 27: Phenotype of peripheral blood T cells may be important for clinical activity
Phenotype of peripheral blood T cells, which are recruited by brenetafusp, 27 may be important for clinical activity Brenetafusp recruits peripheral Hypothesis: blood T cells into the tumor Specific T cell subsets in the blood may be associated with brenetafusp benefit Baseline (CD3 T cell) Blood Me
Slide 28: Novel T cell fitness signature associated with brenetafusp benefit
28 Novel T cell fitness (TCF) signature associated with brenetafusp benefit TCF higher in earlier lines of therapy and highly correlated with naïve/Tscm cells Monotherapy benefit by TCF signature TCF signature, by line of therapy N=48‡ High* Low N=41† n=21 n=20 Higher mPFS 6 mo 2 mo ORR 19% 0% media
Slide 29: Conclusions
29 Conclusions ▪ Brenetafusp is well tolerated ▪ Most frequent TRAE is reversible and manageable CRS (Grade 1-2) ▪ Brenetafusp can be safely combined with anti-PD1 ▪ Promising monotherapy activity in heavily pretreated CM supports a PFS endpoint ▪ Enriched in PRAME+: DCR (58%), confirmed tumor reduc
Slide 30: PRISM-MEL301: First-line advanced CM Phase 3
30 PRISM-MEL301: First-line advanced CM Phase 3 Randomization Treatment phase Follow-up Key inclusion criteria • Previously untreated, advanced Nivolumab (q4w) or N~325 melanoma Nivolumab + relatlimab (q4w)* Key endpoints • HLA-A*02:01 Primary: PFS by BICR • No prospective PRAME testing R Secondary:
Slide 31: Thank you to all patients, families and caregivers
Thank you to all patients, their families and their caregivers who were 31 involved in this global clinical trial & all investigators and their teams Omid Hamid The Angeles Clinic and Research Institute, A Peter Lau Linear Clinical Research, Harry Perkins Institute for Cedars-Sinai Affiliate Georgin
Slide 32: Multiple lines of evidence supports 1L Ph3 combo (nivo + brene)
Multiple lines of evidence supports 1L Ph3 combo (nivo + brene) High monotherapy DCR in 2L+ | ImmTAC activity higher in 1L | Combination with nivolumab in 1L 2L+ 1L mPFS 3.7m 3.1m 3.2m 3.3m 4.2m 4.6m 10.2m ? 56% 58% 60% 47% 11% 13% 13% 49% DCR 40% 38% PR/CR 43% 27% 9% SD 10% 8% 33% 44% 45% 45% 28% 3
Slide 33: Melanoma franchise
Melanoma franchise IMMUNOCORE
Slide 34: TEBE-AM trial now conducted as a Ph3
TEBE-AM trial now conducted as a Ph3 All patients randomized to date included in ITT following FDA consultation Original Design (Ph2/3) Updated Design (Ph3) Phase 2 Phase 3 Phase 3 • Leverages recent rapid accrual KIMMTRAK KIMMTRAK KIMMTRAK or • More robust evaluation of KIMMTRAK + anti-PD-1 two KIM
Slide 35: Building ImmTAC melanoma franchise with three Phase 3 trials
Building ImmTAC melanoma franchise with three Phase 3 trials Uveal Melanoma Cutaneous Melanoma KIMMTRAK® Adjuvant Phase 3 ATOM To start 2H’24 Brenetafusp + Nivolumab 1L Phase 3 PRISM-MEL-301 Enrolling KIMMTRAK® ± Pembrolizumab Approved TEBE-AM 2L+ Phase 3 Enrolling 35
Slide 36: Q&A Session
Q&A Session Bahija Jallal Brian Di Donato David Berman PhD MD, PhD Chief Executive Officer Chief Financial Officer EVP, Research and and Head of Strategy Development Ralph Torbay Mohammed Dar Koustubh Ranade MD PhD Head of SVP, Clinical Development SVP, Translational Medicine Commercial and Chief Me