Immunocore Holdings Plc · NASDAQ:IMCR
Immunocore — 41st Annual J.P. Morgan Healthcare Conference (January 2023)
45 slides from Immunocore's conference presentation, Jan 9, 2023
Slide 1: Transformative Medicines for Patients January 2023
Transformative Medicines for Patients January 2023
Slide 2: 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,” “potential” and similar expressions (as well as other words or expressions referencing futu
Slide 3: We have written the next chapter in cancer treatment
We have written the next chapter in cancer treatment 3 T Cell Receptor (TCR) Therapy Off-the-shelf bispecific T cell engagers Chemotherapy 1949 Targeted Therapy 1997 Immunotherapy 2011 Antibody-DrugConjugate 2013 Cell Therapy 2017 2022
Slide 4: Harnessing the immune system with off-the-shelf bispecific soluble TCRs
4 Harnessing the immune system to fight disease with targeted, off-the-shelf, bispecific, soluble T cell receptors (TCRs)
Slide 5: Delivering leading bispecific TCR pipeline
5 Multiple candidates in oncology and infectious diseases Delivering leading bispecific TCR pipeline Candidate Target Indication IND-enabling Phase 1 Phase 2 Phase 3 Approved gp100 Uveal melanoma Tebentafusp Advanced melanoma IMC-F106C PRAME-A02 Multiple solid tumors Multiple solid tumors 2L+ cutane
Slide 6: Technology platform
Technology platform
Slide 7: Converting membrane-bound TCRs into soluble bispecific therapeutics (ImmTAX)
7 …into soluble, off-the-shelf, bispecific therapeutics (ImmTAX) We pioneered converting membrane-bound T cell receptors… Natural TCR ImmTAX
Slide 8: TCR therapeutics target >90% of the human proteome
8 TCR therapeutics target >90% of the human proteome
Slide 9: Our platform is modular
Our platform is modular Applicable across 3 therapeutic areas 9 Oncology Infectious Diseases Autoimmune Conditions UPREGULATION OF THE IMMUNE SYSTEM DOWNREGULATION OF THE IMMUNE SYSTEM
Slide 10: KIMMTRAK in metastatic melanoma
KIMMTRAK® in metastatic melanoma
Slide 11: Using TCR technology to target gp100 in melanoma
11 We are using our TCR technology to target gp100 protein in melanoma Metastatic Uveal Melanoma (mUM): is an ultra-rare and aggressive tumor ~1,000 Until KIMMTRAK, no approved treatment3 Originates from melanocytes within the uveal tract of the eye Median age at diagnosis is 62 years1 HLA-02 mUM pt
Slide 12: KIMMTRAK: First-in-class, off-the-shelf, bispecific TCR
Nathan, P. et. al. New England Journal of Medicine 2021; 385:1196-1206 12 KIMMTRAK®: First-in-class, off-the-shelf, bispecific TCR Primary endpoint: Overall Survival (OS) statistically significant Overall Survival benefit in patients treated with KIMMTRAK or investigator’s choice in first-line KIMMT
Slide 13: Safety profile of KIMMTRAK was predictable and manageable
Safety profile of KIMMTRAK was predictable and manageable 13 Key KIMMTRAK findings No treatment related deaths 378 previously untreated mUM patients randomized 2:1 KIMMTRAK vs. Investigator’s Choice (pembrolizumab 82%, ipilimumab 13%, dacarbazine 6%) Majority of ARs in first 3 weeks Low discontinuat
Slide 14: Time since last anti-PD(L)1 does not impact OS
Time since last dose of prior anti-PD(L)1 does not impact OS 14 OS by whether prior anti-PD(L)1 therapy was remote or most recent therapy Tebentafusp active in cutaneous melanoma Time from prior anti-PD(L)1 1-yr OS 2-yr OS Remote 75% 22% Immediately prior 75% 23% Benchmark 55% N/A Median time from l
Slide 15: Randomization to real world treatment as control arm
15 Randomization to ‘real world’ treatment as a control arm Phase 2/3 trial for previously treated, advanced melanoma patients Phase Primary endpoint Per arm size 2 ctDNA and OS 40 3 OS 170 Optionality to review Phase 2 data to inform changes to Phase 3, including line of prior therapy, dropping an
Slide 16: PRAME Franchise: A02, A24, A02-HLE
PRAME Franchise:A02, A24, A02-HLE
Slide 17: PRAME heavily expressed in multiple solid tumor types
PRAME heavily expressed in multiple solid tumor types LOW HIGH Tumor gp100 expression PRAME expression MAGE-A4 expression Cutaneous melanoma Renal Cell Carcinoma (RCC) Bladder Non-Small Cell Lung Cancer (NSCLC) Hepatocellular carcinoma (HCC) Gastric Esophageal SCCHN1 Small Cell Lung Cancer (SCLC) Tr
Slide 18: Most broadly expressed cancer-testis antigen with minimal normal tissue expression
18 Most broadly expressed cancer-testis antigen in several tumor types but with minimal normal tissue expression IMC-F106C: ImmTAC targeting HLA-A2-presented peptide from PRAME Squamous NSCLC Adeno NSCLC Ovarian serous carcinoma Cutaneous melanoma Endometrial adenocarcinoma
Slide 19: IMC-F106C-101 PRAME Phase 1 study design
IMC-F106C-101 PRAME Phase 1 study design 19 Screening Treatment Follow-up Weekly IV infusion with intra-patient dose escalation (over 3 weeks) Tumor assessment every 9 weeks HLA-A*02:01 (central testing) Select advanced solid tumors Tumor PRAME by immunohistochemistry High PRAME prevalence: enroll a
Slide 20: T cell activation and re-direction into tumor
20 T cell activation and re-direction into tumor seen across ImmTAC platform Strong and consistent pharmacodynamic activity at ≥20 mcg IMC-F106C Interferon induction T cell trafficking Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355.
Slide 21: Baseline patient characteristics
Baseline patient characteristics 21 Characteristic Safety Population N=55 Efficacy Population N=31† Age – Mean (range) 60 (26, 79) 61 (36, 79) ECOG status 0 – n (%) 30 (55%) 19 (61%) PRAME status (IHC) Positive 49 (89%) 28 (90%) Negative 2 (4%) 0 Not evaluable 4 (7%) 3 (10%) Median H-score 195 188 T
Slide 22: Most frequent related AE was Grade 1/2 CRS
Most frequent related AE was Grade 1/2 CRS, consistent with proposed mechanism IMC-F106C was well tolerated MTD not reached CRS events were all manageable Majority (77%) within first 3 doses 71% Grade 1 29% Grade 2 No Grade ≥ 3 CRS No treatment-related discontinuation or Grade 5 related AEs Adverse
Slide 23: IMC-F106C responses observed in multiple tumor types
* Two patients (1 with NSCLC, 1 serous ovarian) discontinued treatment due to PD with scan data not available at DCO ; † This serous ovarian patient (H-score 39) had an unconfirmed partial response (uPR) at the time of the ESMO Congress September 2022 presentation, that was subsequently confirmed.;
Slide 24: Majority of patients have durable tumor response or stabilization
NSCLC, non small cell lung carcinoma Hamid, O., et. al, Annals of Oncology (ESMO 2022) 33 (suppl_7): S331-S355. 24 IMC-F106C ESMO 2022 Majority of patients have durable tumor response or stabilization
Slide 25: Two PRs ongoing for 7+ months
25 IMC-F106C ESMO 2022 | Two PRs ongoing for 7+ months Responses are durable, 6 of 7 PRs still ongoing * 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;
Slide 26: Reduction in circulating tumor DNA observed across tumor types
† 20 of 31 efficacy evaluable patients had paired ctDNA. Data not yet available for 9 patients, including 3 PRs. Two patients did not have baseline detectable ctDNA. B, triple-negative breast cancer; C, cutaneous melanoma; ctDNA, circulating tumor DNA; E, endometrial carcinoma; LA, non small cell lu
Slide 27: Expanding clinical trial footprint
Monotherapy activity provides optionality to develop in single arm and randomized trials 27 Expanding clinical trial footprint | Aim to understand breadth of clinical activity in solid tumors Enrolling patients globally in adaptive trial with multiple arms P Endometrial Monotherapy expansion Monothe
Slide 28: PRAME-A02 has potential to benefit a large number of patients
Total ~150,000 PRAME+, HLA-A2 patients/year PRAME-A02 has the potential to benefit a large number of patients Tumor type Prevalence of PRAME expression1 HLA*02:01+, PRAME+ metastatic patients (G7)2 70-100% Endometrial >10K Melanoma >10K Ovarian >15K NSCLC-squamous >30K 50-70% NSCLC-adeno >40K SCLC >
Slide 29: Consistency of RECIST responses enriched at higher H scores
Consistency of RECIST responses enriched at higher H scoresKIMMTRAK demonstrated ctDNA reduction and OS benefit at high and low H score 29 PRAME MAGE-A4 KIMMTRAK Phase 1/2 Study IMCgp100-1021 Phase 1 Study IMC-C103C-1012,5,6 Phase 1 Study IMC-F106C-1013,4 Non-PR PR Best overall response 1. Carvajal
Slide 30: Consistency of ImmTAC platform beyond gp100
30 Consistency of ImmTAC platform beyond gp100 T cell activation Durable tumor shrinkage Activity even in low target expression ctDNA reduction Overall survival benefit KIMMTRAK® gp100 IMC-F106C PRAME IMC-C103C MAGE-A4
Slide 31: Expansion of ImmTAC franchise targeting PRAME
HLE, Half-life extension Building on enthusiasm for IMC-F106C targeting PRAME HLA-A02 Expansion of ImmTAC franchise targeting PRAME IMC-F106C PRAME HLA-A02 TCRxCD3 Clinically validated Focus on expanding clinical program IMC-T119C PRAME HLA-A24 TCRxCD3 Expands potential addressable population by ~30
Slide 32: IMC-P115C: Half-Life Extended ImmTAC targeting PRAME-A02
32 IND enabling studies ongoing IMC-P115C: Half-Life Extended (HLE) ImmTAC targeting PRAME-A02 * Half-life estimated using a research tool version of IMC-P115C Same PRAME peptide Same CD3 end Less frequent dosing Same TCR specificity Half-life ~ 7 days in mouse PK study* Highly potent in vitro
Slide 33: IMC-T119C: ImmTAC targeting PRAME-A24
Prevalence of individual HLA subtypes 2. 5EU: France, Germany, Italy, Spain, and the United Kingdom 33 IND enabling studies ongoing IMC-T119C: ImmTAC targeting PRAME-A24 Patient diversity, including Japan Expands beyond PRAME-A02 by ~30% in non-overlapping patients PRAME-A02 development as a bluepri
Slide 34: Novel ImmTAC Candidate for GI cancers from our discovery engine
Novel ImmTAC Candidate for GI cancers from our discovery engine
Slide 35: PIWIL1: promising target in colorectal cancer
PIWIL1, piwi-like protein1, MSS, ^ including mutant & wildtype RAS and BRAF; microsatellite stable (MSS) and Microsatellite instability (MSI)-high 35 CRC is historically insensitive to immune checkpoints PIWIL1: promising target in colorectal cancer (CRC) PIWIL1 RNA in situ hybridization Colon adeno
Slide 36: IMC-R117C: First-in-class immunotherapy targeting PIWIL1
ImmTAC, Immune mobilizing T cell receptor Against Cancer; PIWIL, piwi-like protein 1 36 IND planned Q4 2023 IMC-R117C: First-in-class immunotherapy targeting PIWIL1 (PIWIL1 x CD3) Tumor type Prevalence of PIWIL1 expression HLA*02:01+, PIWIL1+ metastatic patients (G7) 20-30% Colorectal >20K Esophagea
Slide 37: Pursuing a functional cure in infectious diseases
Pursuing a functional cure in infectious diseases
Slide 38: Our unique approach for functional cure of chronic Hepatitis B
Our unique approach for functional cure of chronic Hepatitis B Key advantages of redirecting non-exhausted T cells Same CD3 MoA validated in oncology Independent of natural T cell reactivity to Hep B Goal is functional cure with finite treatment Mass-spectrometry antigen discovery engine for HBV Pip
Slide 39: IMC-I109V: Encouraging signs of activity observed in HBV
IMC-I109V: Encouraging signs of activity observed in HBV 39 Induction of IL-6 in all 3 patients1 Transient decrease in HBsAg transiently coincided with transient increase in ALT 1 Patient #1 Patient #2 Patient #3 1. Bourgeois, et al. EASL 2022 Initial results from single 0.8 mcg dose presented at EA
Slide 40: Functional cure program for HIV
40 Functional cure program for HIV with goal of eliminating HIV reservoirs Same MoA as tebentafusp, but optimized for low target viral peptide presentation Bypasses exhausted T cells Targets highly conserved & functionally constrained viral epitopes Active in ex vivo assays of infected CD4+ T cells
Slide 41: KIMMTRAK commercial performance
KIMMTRAK commercial performance
Slide 42: Preliminary 2022 Financial Results
~$400M *Preliminary financial results are approximated and unaudited. 1. “Net sales” refers to total net product and net pre-product revenue of KIMMTRAK and tebentafusp. 2. Dollar amounts based on conversion rate of approximately 1.21. 42 ~$50M Q4 preliminary net sales of KIMMTRAK / tebentafusp1,2 P
Slide 43: Delivering on our promise – Consistent execution
Delivering on our promise – Consistent execution
Slide 44: Looking ahead
41st Annual J.P. Morgan Healthcare Conference 44 Continuing to write the next chapter of cancer and infectious diseases treatment Looking ahead Continue responsible management of resources Sustain and grow Deliver IND for 3 new ImmTAC candidates Global site expansion for PRAME-A02 trial (data by 1H
Slide 45: S O > < = <x a3 _
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Immunocore Holdings — 41st Annual J.P. Morgan Healthcare Conference (January 2023) on 6ix