PRAME Phase 1
of brenetafusp (IMC F106C) in cutaneous melanoma
May 31, 2024
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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 other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements, other than statements of historical facts, included in this presentation are forward-looking statements. These statements include, but are not limited to, statements regarding Immunocore's ImmTAC platform, including its ability to predict clinical benefit; statements regarding the expected clinical benefits of KIMMTRAK, brenetafusp (IMC-F106C) and Immunocore's other product candidates, including overall response rate and progression free survival and extended overall survival benefit, tumor reduction, ctDNA molecular response and extended overall survival benefit; the expected safety, efficacy and tolerability of Immunocore's products and product candidates, including brenetafusp and tebentafusp, alone and in combination with other therapies; and the Company's expectations regarding the design, progress, timing, scope and results of Immunocore's existing and planned clinical trials, including the
Phase 1/2 dose escalation trial with brenetafusp in patients with multiple solid tumor cancers including non-small cell lung cancer, small-cell lung cancer, endometrial, ovarian, cutaneous melanoma, and breast cancers, the Phase 3 PRISM-MEL301 trial with brenetafusp plus nivolumab and the converted Phase 3 trial evaluating KIMMTRAK for previously treated advanced cutaneous melanoma.. Any forward-looking statements are based on management's current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual events or results to differ materially and adversely from those set forth in or implied by such forward-looking statements, many of which are beyond Immunocore's control. These risks and uncertainties include, but are not limited to, that interim data, data from any interim analysis of ongoing clinical trials and data from completed clinical trials may not be predictive of future trial results, the impact of worsening macroeconomic conditions on Immunocore's business, financial position, strategy and anticipated milestones, including Immunocore's ability to conduct ongoing and planned clinical trials; Immunocore's ability to obtain a clinical supp ly of current or future product candidates or commercial supply of KIMMTRAK or any future approved products, including as a result of health epidemics or pandemics, war in Ukraine, the conflict between Hamas and Israel, the broader risk of a regional conflict in the Middle East, or global geopolitical tension; Immunocore's ability to obtain and maintain regulatory approval of its product candidates, including KIMMTRAK; Immunocore's ability and plans in continuing to establish and expand a commercial infrastructure and to successfully launch, market and sell KIMMTRAK and any future approved products; Immunocore's ability to successfully expand the approved indications for KIMMTRAK or obtain marketing approval for KIMMTRAK in additional geographies in the future; the delay of any current or planned clinical trials, whether due to patient enrollment delays or otherwise; Immunocore's ability to successfully demonstrate the safety and efficacy of its product candidates and gain approval of its product candidates on a timely basis, if at all; competition with respect to market opportunities; unexpected safety or efficacy data observed during preclinical studies or clinical trials; actions of regulatory agencies, which may affect the initiation, timing and progress of clinical trials or future regulatory approval; Immunocore's need for and ability to obtain additional funding, on favorable terms or at all, including as a result of worsening macroeconomic conditions, including changes inflation and interest rates and unfavorable general market conditions, and the impacts thereon of the war in Ukraine, the broader risk of a regional conflict in the Middle East, the conflict between Hamas and Israel, and global geopolitical tension; Immunocore's ability to obtain, maintain and enforce intellectual property protection for KIMMTRAK or any product candidates it or its collaborators are developing; and the success of Immunocore's current and future collaborations, partnerships or licensing arrangements, including the risk that Immunocore may not realize the anticipated benefits of its collaboration with Bristol Myers Squibb. These and other risks and uncertainties are described in greater detail in the section titled "Risk Factors" in Immunocore's filings with the Securities and Exchange Commission, including Immunocore's most recent Annual Report on Form 10-K for the year ended December 31, 2023 filed with the Securities and Exchange Commission on February 28, 2024, as well as discussions of potential risks, uncertainties, and other important factors in Immunocore's subsequent filings with the Securities and Exchange Commission.
All forward looking statements contained in this presentation speak only as of the date on which they were made and should not be relied upon as representing its views as of any subsequent date. Except to the extent required by law, Immunocore undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Certain information contained in this presentation relates to or is based on studies, publications, surveys, and other data obtained from third party sources and Immunocore's own internal estimates and research. While Immunocore believes these third party sources to be reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy, or completeness of, any information obtained from third party sources.
KIMMTRAK™ is a trademark owned or licensed to Immunocore.
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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
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Pioneering a new class of immunotherapy
Cell | |||
Antibody-Drug | Therapy | ||
Checkpoint | Conjugate | ||
Targeted | Therapy | ||
Therapy | |||
Chemotherapy | |||
2013 | 2017 | ||
2011 | |||
1997 | |||
1949 |
T Cell Receptor (TCR) Therapy
2022
4
KIMMTRAK: OS and PFS benefit with unique mechanism of action
T cell infiltration into tumors
Baseline | Day 16 | |
CD3
CD8
CD4
T cells
Blood
ImmTAC | |||
Effector | CD3 | ||
domain | |||
receptor | |||
Targeting | |||
domain | |||
Peptide
HLA-A*02:01
Interferon-γ
Granzyme B
Perforin
In pre-clinical studies...
Distinct mechanism of action than checkpoints
In tumor biopsies…
More robust T cell infiltration and activation than checkpoints1
In Phase 1-3…
Measuring full clinical benefit different than checkpoints
Tumor
5 | 1 Hamid O J Trans Med 2011; 9: 204; Higgs et al., Clin Can Res 2018; 24: 3857; Postel-Vinay, JITC 2023; 11:e005301. ImmTAC: immune mobilizing monoclonal TCR against cancer |
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 |
InflammationNecrosis
6 | 1 Middleton M Clinical Cancer Research 2020 |
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
-1% to -29%
reduction
-30% to -99%
reduction
SD with tumor reduction*
11 months
median duration reduction
PR/CR
11 months
median duration response
SD patients with tumor reduction have same durability as PR (both 11 months)
Similar observation in 2L+ mUM, ASCO 2024 poster #9529
7 | *Phase 3 KIMMTRAK Trial (IMCgp100-202); *Defined as: any tumor reduction that is confirmed during at least one subsequent scan without intervening progression |
Disease control rate, strong predictor of significant PFS
DCR mostly of stable disease (SD) | Both PR and SD very durable | |
Disease | 46% | |
control rate |
Drives PFS benefit
SD
PR/CR
27%
22%
5%
35%
11%
PFS
HR 0.73
Control KIMMTRAK
OS (HR 0.51) best endpoint to capture allbenefit
8 | *Hassel JC, et al. NEJM 2023 (Phase 3 KIMMTRAK Trial (IMCgp100-202)); The duration of tumor reduction was based on principles of RECISTv1.1 duration of response (DoR) |
KIMMTRAK activity higher in early lines of therapy vs 2L+
1L KIMMTRAK1 | 2L+ KIMMTRAK2 |
N=128 | N=94 |
Clearance | 13% | ||||
37% | |||||
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., et. al. Nat Med 28, 2364-2373 (2022); |
T cell fitness in blood important parameter of ImmTAC benefit
T cells
Blood
Interferon-γ
Granzyme B
Perforin
Tumor
T cell fitness defined by Naïve and
T stem cell (Tscm) blood signature more data
this year
Naïve/Tscm
Effector
Exhausted
Similar association between T cell
fitness and CAR-T and TILs1
10 | 1 Gattinoni, et al. Nature Rev Cancer 2012; 12:671-684; Kishton, et al. Curr Opin Imm 2022; 74:39-45; Mehta, et al. Front Immunol 2021; 12:780442; Arcangeli, et al. J Clin Invest 2022; 123:e150807; Rosenberg, et al. |
Clin Cancer Res 2011; 17:4550-4557 |
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Immunocore Holdings plc published this content on 31 May 2024 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 19 June 2024 05:11:02 UTC.