Grey Wolf Therapeutics secures funding for cancer therapies development

Grey Wolf target ERAP enzymes to modulate antigen presentation and elevate tumour visibility.

The company targets ERAP antigen presentation pathways with the aim of ‘illuminating’ non-responsive tumours for attack and destruction by the immune system.

The new funding will allow the company to accelerate development of therapies targeting endoplasmic reticulum aminopeptidase 2 (ERAP2), following many positive signals of its potential. Funds will also be used to continue to drive the lead endoplasmic reticulum aminopeptidase 1 (ERAP1) modulator program.

For context, both of Grey Wolf’s novel ERAP approaches are aimed at directly altering tumour cells, illuminating them for attack and destruction by the immune system. The goal is to exploit this increased tumour visibility in monotherapy and to extend the therapeutic benefit of already approved immunotherapies to many more cancers. The company is developing small molecule modulators of ERAP1 and ERAP2, two key proteins in the antigen presentation pathway, to change the antigen repertoire of tumours and thereby increase the number and range of cancer-related antigens, including neoantigens, presented on tumor cells available to engage an immune response.

“We are delighted to have the continued support of Andera and Canaan.” said Peter Joyce, CEO and Co-Founder. “The financing reflects growing potential in both our ERAP1 and ERAP2 approaches. We continue to see momentum, both in our own work and in the broader scientific community. These funds will allow us to further capitalize on this opportunity and expand our leadership position in the discovery and development of both ERAP1 and ERAP2 modulators.”

Grey Wolf is expanding efforts around ERAP2 for two reasons. First, clinical data continue to demonstrate that tumours that are more visible to the immune system show improved responses to checkpoint inhibitors. One such example is the recent November 2019 paper published in Nature Medicine by the Chan group at MSKCC. The results are consistent across patients that have either a higher tumour mutational burden, heterozygosity of the Class I HLA locus or greater structural/sequence divergence at the Class I HLA locus. Second, the company has developed unique insight into the targeting of the ERAP enzymes through the lead program ERAP1 and validated the role for ERAP inhibition in modulating the cancer-related antigen repertoire. These in-house data provide compelling evidence that the therapies could have a real impact on the treatment of oncology.

“We have continued to generate data showing that modulation of both ERAP pathways drives change to the cancer-related antigen repertoire,” said Tom McCarthy, Executive Chairman and Co-Founder of Grey Wolf Therapeutics. “Data clearly demonstrate that modulation of ERAP2 drives an altogether different change to the antigen repertoire when compared with ERAP1 modulation, due to ERAP2’s clearly differentiated peptide substrate specificities. With this investment and the prior knowledge base within Grey Wolf, we will be able to accelerate the ERAP2 program quickly through optimization, building on our leading position in ERAP disease-related biology.”

The additional funds represent further confidence from investors. “Grey Wolf has already provided compelling insight into the potential of ERAP1 modulation,” said Raphaël Wisniewski, Partner at Andera Partners. “This timely investment further underlines our excitement in these approaches. Grey Wolf is fast becoming true experts in modulation of ERAP biology for treatment of cancer.”

Brent Ahrens, General Partner at Canaan, added: “Canaan continues to be excited by the potential of targeting the ERAP pathway and are impressed with the progress the team has made in such a short space of time since closing Series A. The additional A2 investment enables the Company to push forward ERAP2 whilst maintaining the momentum on the lead ERAP1 program.”