On September 10, 2022 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported a comprehensive preclinical data set for its T cell engaging receptor (TCER) product candidate IMA402 at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 held in Paris, France, from September 9 to 13, 2022 (Press release, Immatics, SEP 10, 2022, View Source [SID1234619356]). IMA402 is the company’s second program in its TCR Bispecifics pipeline and is directed against an HLA-A*02:01-presented peptide derived from PRAME, a cancer target broadly expressed in many solid tumors. The data are available as an ePoster on the ESMO (Free ESMO Whitepaper) platform at 9 AM on Saturday, September 10, and will be presented during the poster session from noon to 1 PM CEST on Monday, September 12.
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Immatics TCER molecules are "off-the-shelf" TCR Bispecifics engineered with two binding regions: a TCR domain and a T cell recruiter domain.
1) Clinical Trial Application (CTA) is the equivalent of an Investigational New Drug (IND) application in Europe
Data Highlights:
TCER format is optimized for efficacy and safety
The IMA402 TCER utilizes a high-affinity TCR designed to specifically bind to an HLA-A*02:01-presented peptide derived from PRAME on tumor cells
The T cell recruiter domain is a proprietary low-affinity T cell recruiter against the TCR/CD3 complex that demonstrates superior in vivo tumor control compared to analogous TCER molecules designed with higher-affinity variants of a widely used antibody recruiter
The IMA402 TCER is optimized to reduce T cell engager-associated toxicities in patients, which is demonstrated by reduced recruiter-mediated cytokine release in vitro
Compelling preclinical data
IMA402 showed potent and selective activity against PRAME-positive tumor cell lines in vitro
In vivo studies in mice demonstrated dose-dependent anti-tumor activity of IMA402. Sufficiently high drug doses were key to achieving the desired anti-tumor effects over a prolonged period
In vitro safety assessment including toxicity screening against 20 normal tissue types, whole blood cytokine release assessment and alloreactivity evaluation confirmed favorable safety profile for IMA402
The half-life extended format of IMA402 confers a serum half-life of >1 week in mice suggesting a favorable dosing regimen and prolonged drug exposure at therapeutic levels when compared to TCR Bispecifics lacking half-life extension strategies
Clinical trial evaluating IMA402 in patients with solid tumors to start in 2023
IMA402 is designed to allow high dosing not limited by toxicities with the goal of reaching relevant therapeutic doses in tumor tissue and achieve a meaningful clinical benefit in patients
"Improving drug safety, efficacy and dosing schedule are key considerations in the field of bispecific T cell engaging molecules. The promising preclinical results for our next-generation, half-life extended TCER IMA402 reflect the potential of our TCR Bispecific approach for patients with solid tumors," commented Carsten Reinhardt, M.D., Ph.D., Chief Development Officer at Immatics. "We look forward to initiating the IMA402 Phase 1/2 clinical trial in 2023 as part of our strategy to tackle PRAME with two distinct therapeutic modalities. We believe PRAME is the most promising, clinically validated T cell target for solid cancers to date and with our cell therapy and bispecific approaches, we are well positioned to provide innovative treatment options for a variety of cancer patient populations with different medical needs."
To enable the start of the Phase 1/2 trial in 2023, Immatics has completed the manufacturing process development for IMA402 and manufacturing of the clinical batch is on track for 2H 2022. The Phase 1 part of the trial will start with a minimal anticipated biological effect level (MABEL) dose of IMA402 and will have an adaptive design aimed at accelerating dose escalation to determine the recommended Phase 2 dose (RP2D). HLA-A*02:01-positive patients with different solid tumors expressing PRAME will initially receive weekly infusions of IMA402. Pharmacokinetics data will be assessed throughout the trial and might provide an opportunity to adapt the treatment interval. The Phase 2a dose expansion part of the trial will be designed to comprise several cohorts to further evaluate IMA402 in specific indications and combination therapies. Submission of the IND1 application is planned for Q2 2023.
The ESMO (Free ESMO Whitepaper) Congress 2022 poster presentation is available on Immatics’ website using this link.
About TCER
Immatics’ half-life extended TCER molecules are next-generation, antibody-like "off-the-shelf" biologics that leverage the body’s immune system by redirecting and activating T cells towards cancer cells expressing a specific tumor target. The design of the TCER molecules enables the activation of any T cell in the body to attack the tumor, regardless of the T cells’ intrinsic specificity. Immatics proprietary biologics are engineered with two binding regions: a TCR domain and a T cell recruiter domain. The TCER format is designed to maximize efficacy while minimizing toxicities in patients. It contains a high-affinity TCR domain that is designed to bind specifically to the cancer target peptide on the cell surface presented by an HLA molecule. The antibody-derived, low-affinity T cell recruiter domain is directed against the TCR/CD3 complex and recruits a patient’s T cells to the tumor to attack the cancer cells. With a low-affinity recruiter aiming for optimized biodistribution and enrichment of the molecule at the tumor site instead of the periphery, TCER are engineered to reduce the occurrence of immune-related adverse events, such as cytokine release syndrome. In addition, the TCER format consists of an Fc-part conferring half-life extension, stability, and manufacturability. TCER are "off-the-shelf" biologics and thus immediately available for patient treatment. They can be distributed through standard pharmaceutical supply chains and provide the opportunity to reach a large patient population without the need of specialized medical centers.