ERAP1

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, England, April 17, 2023 /PRNewswire/ -- 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. For more information, please visit: Contacts: Grey Wolf Therapeutics Peter Joyce Chief Executive Officer +44 (0) 01865 292 038 enquiries@gwt.bio Vida Strategic Partners (on behalf of Grey Wolf Therapeutics) Tim Brons (Media) 415-675-7402 tbrons@vidasp.com Company Codes: NASDAQ-NMS:IMCR

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, March 28, 2023 /PRNewswire/ -- 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. For more information, please visit: Contacts: Grey Wolf Therapeutics Pty Ltd Bio101, Suite 201/697 Burke Road Camberwell, VIC 3124 +61 8 6186 1875 [email protected] Grey Wolf Therapeutics Limited Peter Joyce Chief Executive Officer +44 1235 644970 [email protected] Vida Strategic Partners (on behalf of Grey Wolf Therapeutics) Tim Brons (Media) +1 415 675 7402 [email protected] SOURCE Grey Wolf Therapeutics

Premier Syndicate of Life Science Industry Investors led by Pfizer Ventures and Earlybird Venture Capital and including Canaan, Andera Partners, Oxford Science Enterprises and British Patient Capital Proceeds to Support Advancement of Lead Candidate, ERAP1 Inhibitor GRWD5769, into the Clinic in 1H 2023; Continued R&D for Follow-On ERAP Inhibition Strategies OXFORD, United Kingdom, Jan. 24, 2023 /PRNewswire/ -- Grey Wolf Therapeutics, a biotechnology company focused on generating entirely novel anti-tumour immune responses through targeted cancer neoantigen creation, today announced the closing of an oversubscribed $49 million Series B financing. The financing was co-led by Pfizer Ventures and Earlybird Venture Capital, and also included investment from new investors Oxford Science Enterprises and British Patient Capital and existing investors Canaan and Andera Partners. Proceeds will support the continued development of the company's first-of-its-kind immuno-oncology approaches designed to overcome key resistance mechanisms through the creation of novel cancer antigens. This includes the anticipated advancement of the company's lead asset, GRWD5769, into a Phase 1/2 clinical trial in the first half of 2023. 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 ground-breaking research and development activities conducted by the Grey Wolf team have generated a pipeline of novel ERAP inhibition programs, led by GRWD5769, a potentially first-in-class ERAP1 inhibitor. During the first half of 2023, the company intends to initiate an adaptive Phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of GRWD5769, including a planned combination with the PD-1 inhibitor Libtayo® (cemiplimab), in a range of solid tumour types. Additionally, the company will direct a portion of the Series B proceeds to follow-on programs including efforts focused on ERAP2 inhibition and the identification of 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. "This syndicate of leading life science industry investors brings a wealth of relevant expertise and resources to Grey Wolf at a critical time in our evolution as we prepare to enter the clinic," said Peter Joyce, Ph.D., chief executive officer of Grey Wolf Therapeutics. "The funding these groups have committed to Grey Wolf will not only support our efforts to demonstrate clinical proof-of-concept for ERAP inhibition with our lead program, but it will also drive our continued scientific exploration in this area as we aim to further advance and broaden our pipeline of first-of-their-kind therapeutics." "The scientific ground being pursued by the Grey Wolf team is fertile with potential solutions for overcoming two of the most significant resistance mechanisms limiting current immune-oncology therapies – poor tumour visibility and T cell exhaustion," said Marie-Claire Peakman, Ph.D., principal with Pfizer Ventures. "We look forward to supporting the company as it enters the clinical setting and works to develop an actionable and completely novel therapeutic approach." "We believe Grey Wolf is establishing the next essential pillar in oncology treatment, with the potential to overcome treatment resistance and change the game for attacking cancer," said Rabab Nasrallah, Ph.D., principal, Earlybird Venture Capital. "Importantly, preclinical research suggests that the company's elegant treatment approach holds great promise as a monotherapy, as well as the potential to synergistically improve outcomes when used in rational combination with other anti-cancer agents including immune checkpoint inhibitors. This flexibility further amplifies the potential breadth of impact these investigational therapeutics may have in treating patients." In conjunction with the financing, Grey Wolf Therapeutics has announced several new appointees to its board of directors including: Sally Dewhurst, senior associate, Oxford Science Enterprises Emma Johnson, investment manager, British Patient Capital Rabab Nasrallah, principal, Earlybird Venture Capital Marie-Claire Peakman, principal, Pfizer Ventures 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 lead development candidate, GRWD5769, is a potent and selective ERAP1 inhibitor that elicits a powerful and differentiated immune response against the tumour and is entering the clinic in the first half of 2023. A second program, focused on ERAP2 inhibition, is advancing through the discovery process. The company is 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. For more information, please visit: Contacts: Grey Wolf Therapeutics Peter Joyce Chief Executive Officer +44 (0) 01865 292 038 [email protected] Vida Strategic Partners (on behalf of Grey Wolf Therapeutics) Tim Brons (Media) 415-675-7402 [email protected] SOURCE Grey Wolf Therapeutics