Grey Wolf Therapeutics Presents First Clinical Data for GRWD5769, a First-in-Class ERAP1 Inhibitor, at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting

Preliminary data from ongoing Phase 1/2 trial show dose dependent target engagement and provide clinical proof-of-mechanism for GRWD5769, demonstrating ability to modulate the human immunopeptidome with therapeutic intent for first time

Company's lead immuno-oncology candidate shown to be well tolerated with predictable pharmacokinetics following oral administration

OXFORD, UK – June 3, 2024 – Grey Wolf Therapeutics, a clinical-stage biotechnology company leveraging first-of-its-kind antigen modulation therapies to address the source of immune dysfunction in oncology and autoimmunity, today announced that initial data from the company's ongoing adaptive Phase 1/2 clinical trial of GRWD5769, an investigational first-in-class ERAP1 inhibitor, were reported in a poster presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The presented data consisted of preliminary findings from the initial repeat dosing monotherapy module of the study and demonstrated well-tolerated dose dependent target engagement following administration of escalating oral doses of GRWD5769.  Importantly, the observed modulation of the human immunopeptidome with GRWD5769 provides clinical proof-of-mechanism for the novel immuno-oncology candidate and its foundational antigen modulation technology.

"We are highly encouraged by the initial data from our ongoing study, highlighted by the achievement of success in the first known attempt to modulate the immunopeptidome for specific therapeutic purposes. These clear signs of target engagement provide compelling support for our antigen modulation strategy in immuno-oncology, which is designed to allow T cells to recognize new targets on tumour cells and drive de novo anti-tumour responses," said Tom Lillie, M.D., Ph.D., chief medical officer of Grey Wolf Therapeutics. "The presented data demonstrate a promising tolerability profile for GRWD5759 across all four dose levels administered to date, along with achievement of stable disease for a number of patients, some of whom have remained on treatment for nearly a year. These findings strongly support our recent initiation of combination dosing with GRWD5769 and cemiplimab, and our plans for further expansion cohorts in the near future."

Grey Wolf has developed and is advancing a unique immuno-oncology therapeutic strategy utilizing a proprietary antigen modulation strategy to reveal novel and potent cancer antigens on the surface of tumour cells. This is achieved through oral delivery of a targeted inhibitor of the endoplasmic reticulum aminopeptidases (ERAP1 or ERAP2), key proteins in the antigen presentation pathway. The targeted inhibition of ERAP is designed to elicit a de novo T cell response against tumours and to avoid T-cell exhaustion, thereby overcoming two key resistance mechanisms to current immuno-oncology therapy.

The company is evaluating this novel immuno-oncology approach through the EMITT-1 (ERAP Mediated Immunopeptide Targeting Trial – 1) Phase 1/2 clinical trial.  The modular multi-part, multi-arm open-label study is 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 a range of solid tumour types.

Key takeaways from the EMITT-1 trial presented at ASCO include:

• GRWD5769 was well tolerated, with predictable pharmacokinetics following repeat oral administration in all dose cohorts (up to 200 mg BID).
• Dose-dependent target engagement as evidenced by modulation of the immunopeptidome.
• Clinical proof-of-mechanism, confirming the expected mechanistic effects of ERAP1 inhibition and consistent with those seen in preclinical models.
• Initial, early efficacy assessments demonstrating stable disease achieved by a number of patients, some of whom have remained on treatment for nearly a year.

The dose escalation portion of the trial continues as the company seeks to identify the recommended Phase 2 dose for GRWD5769. The company has also recently initiated dosing in the study's first cohort combining GRWD5769 with immune checkpoint inhibition. Grey Wolf recently reported that it is expanding the scope of the study, allowing for the enrolment of patients with additional tumour types.

Further information about the EMITT-1 Phase 1/2 clinical trial can be found by searching trial registration number ACTRN12623000108617 on the Australian New Zealand Clinical Trial Registry (www.anzctr.org.au).

About Grey Wolf Therapeutics

Grey Wolf Therapeutics is a clinical-stage, UK- and Australian-based drug discovery and development biotechnology company spearheading a new therapeutic approach based on a first-of-its-kind antigen modulation platform. The company’s lead clinical development candidate, GRWD5769, is a potent and selective oral ERAP1 inhibitor that has shown the potential to elicit a powerful and differentiated immune response against tumours. A second ERAP1 inhibitor, GRWD0715, is advancing through preclinical development as a potential treatment for autoimmune disease. The company is also leveraging its leadership in neoantigen creation with an ERAP2 drug discovery program and by therapeutically targeting novel ERAP1 inhibitor generated cancer antigens with MHC Class I directed therapies, such as soluble T cell receptor (TCR) and TCR mimic bispecifics.

For more information, please visit: www.gwt.bio