New Data Demonstrate Ability of ERAP1 Inhibition to Generate and Upregulate Cancer Antigens to be Targeted by MHC Class I Directed T Cell Receptor Bispecific Therapies
First-in-Class ERAP1 Inhibitor Drives Improved Potency and Magnitude of Anti-Tumour Activity of an Immunocore TCR Bispecific ImmTAC® Therapy
OXFORD, UK – April 18, 2023 – Grey Wolf Therapeutics, a biotechnology company focused on generating entirely novel anti-tumour immune responses through targeted cancer neoantigen creation, today announced the presentation of new preclinical data on the company’s potential first-in-class inhibitors of ERAP1 at the American Association of Cancer Research (AACR) Annual Meeting 2023. Presented data highlighted the ability of the company’s ERAP1 inhibitors to generate and upregulate cancer antigens, creating novel therapeutic targets for combination with MHC Class I directed therapies, including an investigational T cell receptor (TCR) bispecific therapy. The study results were featured in an oral presentation (#3467) entitled, “First-in-class inhibitors of ERAP1: Generating antigens as novel targets for MHC1-directed therapies,” at the AACR annual meeting, being held April 14-19, 2023, in Orlando, Florida.
Grey Wolf Therapeutics’ unique therapeutic strategy is centered on generating entirely novel immune responses against tumours thereby overcoming key resistance mechanisms to current immuno-oncology therapy such as poor tumour recognition by T cells and T cell exhaustion. This is achieved through targeted inhibition of the endoplasmic reticulum aminopeptidases (ERAP1 or ERAP2), which drives the generation and presentation of novel and potent cancer antigens to the surface of tumour cells, in turn eliciting a de novo T cell response against tumours.
The presented findings included results from a preclinical research collaboration between Grey Wolf Therapeutics and Immunocore (Nasdaq: IMCR) which evaluated the combination of ERAP1 inhibition, a potential first-in-class mechanism, and an investigational MHC Class I directed TCR bispecific therapy (ImmTAC®). Data showed that ERAP1 inhibition upregulated, across multiple cancer types, the surface presentation of the ACTL8 cancer peptide that is targeted by the ImmTAC therapy. This drove an improvement in the potency and magnitude of cancer cell line killing of the ACTL8-targeted ImmTAC in translationally relevant primary human co-culture assay systems. This preclinical research lays the foundation for broadening the potential of ERAP inhibition, demonstrating that upregulated and new cancer antigens created with ERAP1 inhibition can generate novel targets for MHC Class I directed therapies.
“Grey Wolf continues to generate compelling preclinical data that support the therapeutic potential of ERAP1 inhibition in the treatment of cancer. These latest research findings reported at AACR are notable as they offer a promising glimpse into the potential of our clinical stage ERAP1 inhibitor, GRWD5769, to significantly enhance the therapeutic activity of MHC Class I directed therapies such as TCR bispecifics like Immunocore’s ImmTAC therapy used in the research collaboration. This is just the latest anti-tumour therapeutic modality, joining immune checkpoint inhibitors, that we have shown the ability to enhance with our novel approach to immuno-oncology,” said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. “Our growing data collection, which consistently spotlights the impact of ERAP1 inhibition on neoantigen generation, differentiated T cell response and tumour growth inhibition, provides us with great optimism for our recently initiated first-in-human clinical trial of GRWD5769. Furthermore, we are leveraging these latest preclinical findings to drive further research into the ability of our ERAP1 inhibition platform to identify entirely novel therapeutic cancer antigens, which has the potential to support new internal and collaborative drug discovery and development efforts.”
About Grey Wolf Therapeutics
Grey Wolf Therapeutics is a UK- and Australian-based drug discovery and development biotechnology company spearheading a new therapeutic approach in immuno-oncology. The company’s first-of-its-kind immuno-oncology approach is centered on inhibiting the endoplasmic reticulum aminopeptidases (ERAP1 or ERAP2), which play a key role in the antigen presentation pathway. Inhibiting ERAP1 or ERAP2 generates novel cancer antigens and upregulates certain other neoantigens, resulting in the mobilisation of an entirely novel T cell response against the tumour that increases tumour visibility where current therapies are ineffective, and bypasses the challenge faced by current immunotherapy when once anti-tumourigenic T cells become irreversibly exhausted and hence ineffective. Based on this approach, the company is developing a portfolio of potentially first-in-class small molecules that inhibit ERAP1 or ERAP2. The company’s clinical candidate, GRWD5769, is a potent and selective ERAP1 inhibitor that is currently being evaluated in a Phase 1/2 clinical trial. A second program, focused on ERAP2 inhibition, is advancing through the discovery process. The company is also leveraging its leadership in neoantigen creation to unlock entirely novel cancer antigens that can be targeted with MHC Class I directed therapies, such as soluble T cell receptor (TCR) and TCR mimic bispecifics.
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Grey Wolf Therapeutics
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