First-in-Class ERAP1 Inhibitor Enters Clinical Development

Study to Evaluate GRWD5769 as Monotherapy, as well as in Combination with PD-1 Inhibitor Libtayo® (cemiplimab)

OXFORD, UK and MELBOURNE, Australia I March 28, 2023 I Grey Wolf Therapeutics, a biotechnology company focused on generating entirely novel anti-tumour immune responses through targeted cancer neoantigen creation, today announced dosing of the first patient in the initial monotherapy module of an adaptive Phase 1/2 clinical trial evaluating GRWD5769, the company’s investigational first-in-class ERAP1 inhibitor. The trial, named EMITT-1 (ERAP Mediated Immunopeptide Targeting Trial – 1), is a modular multi-part, multi-arm open-label study designed to evaluate the safety, tolerability, preliminary efficacy and pharmacokinetics of GRWD5769 alone and in combination with Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) in patients with advanced solid tumours.

While the potential for ERAP1 inhibition is broad and the study will include patients across different solid tumours in both the GRWD5769 monotherapy and GRWD5769/Libtayo®   combination modules of the trial, a particular focus will be on patients with virally associated solid tumours, such as head and neck squamous cell carcinoma, cervical cancer, and hepatocellular carcinoma, as Grey Wolf’s analysis of publicly available patient data suggests these could be particularly sensitive to ERAP1 inhibition. Regeneron is providing Libtayo® for the trial as part of a clinical supply agreement.

“We are proud to announce our advancement of GRWD5769 into the clinic as this reflects a critical first step in our evaluation of this first-in-class ERAP1 inhibitor. We have strategically designed this initial clinical study with an adaptive, modular framework to assist in the generation of the most informative data set possible,” said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. 

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.

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 elicits a powerful and differentiated immune response against the tumour pre-clinically.

Further information about the initial Phase 1/2 clinical trial of GRWD5769 can be found by searching trial registration number ACTRN12623000108617 on the Australian New Zealand Clinical Trial Registry ( 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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SOURCE: Grey Wolf Therapeutics