Grey Wolf Therapeutics awarded £1.1M to accelerate ERAP1 inhibitor programme in collaboration with University of Oxford and University of Southampton

Grey Wolf Therapeutics will collaborate with The University of Oxford and the University of Southampton to accelerate and expand the therapeutic potential of ERAP1 inhibition.

OXFORD, UK, 12/05/2021 – Grey Wolf Therapeutics (“Grey Wolf”), a drug discovery company focused on developing first-in-class immuno-oncology agents, today announces that it has been awarded £1.1M ($1.5M) in grant funding following a successful application to the prestigious Innovate UK Biomedical Catalyst (BMC) competition. Peter Joyce, CEO of Grey Wolf, noted that the company was “Delighted to receive this grant from Innovate UK, which will allow Grey Wolf to work with The University of Oxford (“Oxford”) and the University of Southampton (“Southampton”) to expand the ERAP1 program and accelerate the company’s path through clinical development”. 
 
Over the past decade, immunotherapies have begun to transform cancer treatments, with significant impacts on clinical outcomes and survival rates. However, it has since become apparent that only a small subset of cancers and patient groups respond to these therapies. Clinical data suggests that one of the reasons behind this is due to low neoantigen expression at the cell surface. 
 
In response to the urgent need for new therapeutics, Grey Wolf are developing small molecule inhibitors that target ERAP1 and ERAP2; two key enzymes in the antigen presentation pathway. Rather than targeting the immune system, this approach aims to directly alter the tumour cells to improve neoantigen expression and therefore, immune visibility.  
 
The ERAP enzymes are responsible for trimming peptides prior to loading onto Major Histocompatibility Complex (MHC) Class I and presentation at the cell surface. These enzymes often over- or under-trim peptides in the endoplasmic reticulum, leading to a potential loss of immunogenic peptides and neoantigen presentation. Grey Wolf ERAP1 inhibitors significantly alter the neoantigen presentation on the surface of tumour cells, leading to greater recognition and destruction by the immune system. 
 
The investment awarded through Innovate UK will be focused on identifying patient subgroups where ERAP1 inhibition could be particularly efficacious based on either cancer type or genetic background, thus providing the foundation for future breakthrough designations and accelerated approval. Collaborating with the world leading capabilities of Nicola Ternette’s group in Oxford and Edd James’ group at the Centre for Cancer Immunology in Southampton will be vital to the success of the project. The Ternette Lab are recognised leaders in the field of immunopeptidomics and the study of antigen presentation by MHC. Nicola Ternette and her team will use the technique to characterise neoantigens that are expressed following ERAP1 inhibition. As experts in ERAP biology, the James’ lab will examine the mechanistic effects of ERAP1 inhibition on T cell and tumour biology using a number of bespoke pharmacological models.  
 
Peter Joyce, CEO at Grey Wolf: We are delighted to have been awarded this highly competitive funding from Innovate UK which will enable us to accelerate the development of our ERAP1 inhibitor program and broaden the potential utility of this first-in-class therapy for patients. The award allows Grey Wolf to also build on our strong associations with two world class research groups at the University of Oxford and Southampton and represents a great opportunity to demonstrate the UKs leading role in global biotechnology. 
 
 
Assoc. Prof. Nicola Ternette, The University of Oxford: The funding from Innovate UK will enable us to use Grey Wolf’s highly selective and potent ERAP1 inhibitors to mine their effects across the immunopeptidomes of different cancer types and genetic backgrounds. The truly exciting aspect of our research here will be gaining a fundamental understanding of the biology that can directly translate into clinical development of the therapy. 
 
Prof. Edd James, University of Southampton: We’re excited to build on our collaboration with Grey Wolf through this grant and apply our unique understanding of ERAP1 biology to exploit the translational potential of this approach.