GPR65

PRESS RELEASE OMass Therapeutics Selected by Fierce Biotech as a “Fierce 15” Winner for 2024 Oxford, United Kingdom – 5th August 2024 – OMass Therapeutics (‘OMass’ or ‘the Company’), a biotechnology company identifying medicines against highly validated target ecosystems such as membrane proteins or intracellular complexes, today announces that it has been named by Fierce Biotech as one of 2024’s ‘Fierce 15’ biotechnology companies. The annual Fierce 15 companies are selected for being the most innovative and promising biotechnology companies in the industry and highlights OMass as one of the most ambitious and successful next generation biopharma companies. Ros Deegan, Chief Executive Officer at OMass Therapeutics, commented: “OMass is redefining drug discovery for previously intractable targets by fundamentally innovating the process and it is an incredible honour to be recognised by Fierce Biotech as one of the Fierce 15. Over the past year OMass made significant progress in translating the outputs of our proprietary platform into an exciting pipeline of novel drugs including advancing the development of our lead program, an insurmountable antagonist of the MC2 receptor for Congenital Adrenal Hyperplasia towards the clinic. This recognition is a testament to the dedication and hard work of our team and underlines our progress so far as well as our ambition to become a fully integrated pharma company bringing to market medicines that meaningfully improve patient lives.” Originally spun out of Oxford University, OMass has industrialised the groundbreaking research by the highly-awarded Oxford-based scientist, Professor Dame Carol Robinson. The Company is a world leader in the application of native mass spectrometry (MS) to drug discovery and has selected a number of high-value targets and is developing potent small molecule drugs with high therapeutics potential against these. Its proprietary platform, OdyssION™, integrates novel biochemistry techniques, with next-generation native MS, and custom chemistry, to allow for the interrogation of protein interactions within their native ecosystem while avoiding the confounding complexity of the cell demonstrated in its in-house pipeline. OMass has already made significant progress with its portfolio of highly-validated, yet intractable or inadequately drugged targets. OMass’ lead programme is an insurmountable antagonist of the GPCR MC2 receptor for Congenital Adrenal Hyperplasia which is expected to complete IND-enabling studies in 2025. OMass additionally has a novel immunology portfolio including a SLC15A4 antagonist for lupus, a GPR65 agonist for the treatment of Inflammatory Bowel Disease, and inhibitors of cGAS for inflammatory disorders. OMass’s goal is to ultimately evolve into a fully integrated biopharma company that can take products to market whilst continuing to discover medicines in high unmet need indications within rare and immunological diseases. The Company will also explore collaborations and partnerships both in and outside of its core focus to ensure its platform is maximally exploited to the benefit of patients. OMass has recently expanded its facilities and team, moving into purpose designed facilities on Advance Research Cluster Oxford, recruiting key executives and team members bringing its headcount to 57, and, notably, attracting Boston-based Industry-leader James (Jim) Geraghty as independent chair of its Board of Directors, bringing US and international experience from Genzyme and as NED and chair of multiple listed biotechs. “For the past 22 years, we have evaluated hundreds of companies for inclusion in the ‘Fierce 15’ special report. Our selection process considers various factors, including technological robustness, strategic partnerships, venture support and market positioning,” said Ayla Ellison, Editor-in-Chief, Fierce Life Sciences and Healthcare. “This report highlights innovation and creativity amid intense competition.” -ENDS- For further information, please contact: OMass Therapeutics ICR Consilium Rosamond Deegan, Chief Executive OfficerPhone: +44 (0) 1235 527589Email: ros.deegan@omass.comSue Charles / Suki Virji / Kumail WaljeePhone: +44 (0)20 3709 5700 Email: omass@icrhealthcare.com About OMass Therapeutics OMass Therapeutics is a biotechnology company discovering medicines against highly- validated target ecosystems, such as membrane proteins or intracellular complexes. The company’s unique OdyssION™ technology platform comprises novel biochemistry techniques, next-generation native mass spectrometry, and custom chemistry. This allows OMass to interrogate not just the target, but also the interaction of the target with its native ecosystem, separate from the confounding complexity of the cell. The result is cell-system fidelity with cell-free precision. OMass is advancing a pipeline of small molecule therapeutics in rare diseases and immunological conditions, that target solute carriers, complex-bound proteins, and GPCRs. Headquartered in Oxford, UK, OMass has raised over $160M (£129M) from a top-tier international investor syndicate, including Syncona, Oxford Science Enterprises, GV, Northpond Ventures, Sanofi Ventures and British Patient Capital. To learn more, please visit www.omass.com. Follow us on LinkedIn and X. About Fierce Biotech Fierce Biotech is the biotech industry’s daily monitor, providing the latest news, articles, and resources related to clinical trials, drug discovery, FDA approval, FDA regulation, patent news, pharma news, biotech company news and more. More than 300,000 top biotech professionals rely on Fierce Biotech for an insider briefing on the day’s top stories.

Founding CEO, Stuart Hughes, Ph.D., to Transition to Chief Scientific Officer and Focus Efforts on Advancing Company's First-of-its-Kind GPR65 Inhibition Approach to Immuno-Oncology Company Continues Active Investor Engagement Following First Close of $25M Series B Financing in Q2 2024; On Target to Enter Clinic by End of Year OXFORD, England, July 9, 2024 /PRNewswire/ -- Pathios Therapeutics Limited ("Pathios"), a biotech company focused on the development of first-in-class therapies for cancer, today announced the appointment of experienced biotechnology industry executive, Paul G. Higham, as Chief Executive Officer (CEO). He brings over 20 years of C-level executive biotechnology company experience to Pathios, as the company prepares to enter clinical development with its first-in-class GPR65 antagonist. In conjunction with Mr. Higham's appointment, Pathios' founding CEO, Stuart Hughes, Ph.D., will transition to the role of Chief Scientific Officer (CSO), where he will continue to focus his efforts and deep scientific expertise on the company's first-of-its-kind GPR65 inhibition approach to cancer immunotherapy. This will include playing a key role on the team advancing PTT-4256, the company's lead internally discovered, oral, highly potent, and selective small molecule inhibitor of GPR65, into human clinical trials in advanced solid cancers by the end of 2024. "Following several years of excellent leadership under Stuart, Pathios is preparing to take a critical step forward and enter the clinic with its lead immuno-oncology program. As we transition from a company with preclinical assets to a full-fledged clinical-stage biotech, we will benefit greatly from Paul's deep operational and strategic expertise. We are thrilled to welcome Paul to the Pathios team and look forward to the successes he will drive, including ongoing fundraising efforts focused on completing our Series B round," said Tom McCarthy Ph.D., co-founder and Executive Chair of Pathios. "Importantly, Stuart will now be able to focus the full force of his scientific acumen on helping shepherd the company's unique therapeutic approach through development to unlock significant value for patients and shareholders alike." Paul most recently served as chief executive officer of Valo Therapeutics, an immuno-oncology company developing tumour antigen-coated oncolytic viruses. In this role, he led the company from pre-clinical stage into clinical development. Prior to his tenure with Valo Therapeutics, Paul held the position of CEO at two other immuno-oncology focused companies, Glycotope, and Immatics Biotechnologies. Earlier in his career, he built a strong foundation of strategic and operational expertise in roles that included commercial development at Ark Therapeutics Group, where he established the company's adenovirus gene-based medicine production facilities in Finland, Vice President, commercial development at GSK, and General Manager of Bayer Pharmaceuticals for Sweden and Denmark. "With an exciting first-in-class therapeutic candidate poised for advancement into first-in-human clinical studies and support from a top-tier investor syndicate of Bristol Myers Squibb, Canaan and Brandon Capital, Pathios is exceptionally well positioned for success. I am delighted to have the opportunity to bring my experience and energy to what is already an exceptional leadership team and help advance the exciting GPR65 antagonist approach at Pathios into much-needed additional therapeutic approaches for patients battling cancer," said Mr. Higham. "This is an exciting time for Pathios as we work diligently toward the initiation of clinical trials for PTT-4256. These studies will allow us to begin to test our scientific hypothesis around the therapeutic potential of inhibiting the immunosuppressive activity of GPR65 in patients with cancer, marking a key step forward for the development of this novel approach to immunotherapy," said Dr. Hughes. "I am looking forward to working alongside Paul to advance this science and support him in executing the strategic and operational initiatives that will best position Pathios for long-term success." Pathios is pursuing a novel immuno-oncology approach to the treatment of cancer focused on counteracting the immunosuppressive polarization of immune cells, including tumour associated macrophages (TAMs), that is triggered by an acidic tumour microenvironment (TME). It does so by attacking a ubiquitous cancer immune evasion pathway through the targeting of GPR65, an acid sensing G protein-coupled receptor that has been shown to foster immunosuppressive polarization of immune cells. GPR65 is exclusively expressed on immune cells and is associated with driving the immunosuppressive immune cell phenotype in the TME that prevents immune-mediated killing of cancer cells. Pathios' internal human genetic analysis demonstrates that reductions in GPR65 function are associated with significantly improved survival across a range of solid tumour types, positioning it as a unique immuno-oncology target for therapeutic intervention. Preclinical data for PTT-4256 have demonstrated that the compound possesses excellent drug-like properties and impressive monotherapy anti-tumour activity. In addition to cancer, there are strong genetic associations between GPR65 activity and a variety of other immunologically mediated diseases, offering Pathios the opportunity to expand its research and development into other high-value therapeutic areas with significant unmet need. About Pathios Therapeutics Pathios is a drug discovery and development company focused on translating innovative science into new medicines. Pathios was founded by a team of experienced biotech and pharmaceutical industry professionals, entrepreneurs, and clinicians. The company is focused on developing small molecule inhibitors of the pH-sensing G protein-coupled receptor GPR65 to counteract the GPR65 mediated immunosuppressive polarization of immune cells, including tumour associated macrophages, that is triggered by an acidic tumour microenvironment present in most cancers. To date, Pathios has raised a total of US$58M including support from the leading venture capital firms, Canaan and Brandon Capital, as well as a strategic investment from Bristol Myers Squibb. Pathios is headquartered at the Innovation Centre on Milton Park, a key science precinct south of Oxford, UK, where together with Grey Wolf Therapeutics and ThirtyFiveBio it is part of the unique M:M Bio drug discovery and development ecosystem. For more information, please visit . Contacts: Pathios Therapeutics Tom McCarthy, Executive Chair +44 1235 644 960 info@pathios.com Paul Higham, CEO +44 1235 644 960 info@pathios.com Vida Strategic Partners (on behalf of Pathios Therapeutics) Tim Brons +1 646 319 8981 tbrons@vidasp.com

Fundraising Includes New Strategic Investment by Bristol Myers Squibb along with Continued Support from Existing Investors including Canaan and Brandon Capital Proceeds to be Used to Advance Lead Candidate, PTT-4256, into the Clinic and Expand Leadership Team to Align with Pathios' Transition into a Clinical-Stage Company OXFORD, England, April 18, 2024 /PRNewswire/ -- Pathios Therapeutics Limited ("Pathios"), a biotech company focused on the development of first-in-class therapies for cancer, today announced that the company has raised $25 million in the first close of a Series B financing. The financing consists of a new strategic investment from Bristol Myers Squibb, as well as support from existing investors including Canaan and Brandon Capital. Proceeds from the raise will be used to support the continued development of Pathios' unique approach to cancer immunotherapy focused on the inhibition of GPR65, a novel target that has been genetically associated with a range of immunologically-mediated diseases. As part of these efforts, the company expects to advance PTT-4256, its lead internally discovered, oral, highly potent, and selective small molecule inhibitor of GPR65, into human clinical trials in advanced solid cancers by the end of 2024. Additionally, Pathios will leverage the proceeds from the financing to expand its team, including executive leadership, to align with its continued evolution into a clinical-stage company. "The support of a syndicate comprised of premier life science investors Canaan and Brandon Capital and a global leader in oncology in Bristol Myers Squibb adds both capital and expertise as we look to generate clinical evidence to support our conviction that GPR65 inhibition will open the door to an entirely new approach to immunotherapy," said Tom McCarthy Ph.D., co-founder and executive chair of Pathios. "It is particularly gratifying to know that our investors share our belief not only in the foundational science we are pursuing but also the significant range of potential therapeutic applications for the platform, both broadly across the field of cancer and into other immunologically mediated diseases. We are eager to leverage the proceeds from this raise to continue our work and successfully advance PTT-4256 into the clinic later this year." Pathios is pursuing a novel immuno-oncology approach to the treatment of cancer focused on counteracting the immunosuppressive polarization of immune cells, including tumor associated macrophages (TAMs), that is triggered by an acidic tumor microenvironment (TME). It does so by attacking a ubiquitous cancer immune evasion pathway through the targeting of GPR65, an acid sensing G protein-coupled receptor that has been shown to foster immunosuppressive polarization of immune cells. GPR65 is exclusively expressed on immune cells and is associated with driving the immunosuppressive immune cell phenotype in the TME that prevents immune-mediated killing of cancer cells. Pathios' internal human genetic analysis demonstrates that reductions in GPR65 function are associated with significantly improved survival across a range of solid tumor types, positioning it as a unique immuno-oncology target for therapeutic intervention. Furthermore, there are strong genetic associations between GPR65 activity and a variety of other immunologically-mediated diseases, offering the opportunity to expand its research and development into other high-value therapeutic areas with significant unmet need. "Our belief in the anti-tumor potential of our GPR65 inhibition platform is built upon two key pillars: the extensive validation of the target through human genetic analysis and the ubiquitous and fundamentally causal role that GPR65 plays in human cancer biology by creating a TME that is immunologically-favourable to tumor growth," said Stuart Hughes, Ph.D., chief executive officer of Pathios. "This funding will now enable us to evaluate our scientific hypothesis in the clinic, providing the opportunity to illuminate the activity of this novel target in humans for the first time. While our initial clinical study will have all the hallmarks of a first-in-human trial, it will also feature a biomarker-rich design that allows for the measurement of clinical target engagement." Preclinical data on PTT-4256 presented at the American Association for Cancer Research (AACR) Annual Meeting 2023 demonstrated that the compound possesses excellent drug-like properties and impressive monotherapy anti-tumor activity. Importantly, PTT-4256 was shown to be highly effective in counteracting the effects of low pH (i.e. high acidity) that polarize human and mouse macrophages toward an immunosuppressive state. This PTT-4256-induced relief of immune suppression was associated with dose-dependent increases in a range of pro-inflammatory genes that are consistent with an anti-tumor immune response, evidence of an infiltration of T cells and natural killer (NK) cells into the TME, and prevention of the activation of immunosuppressive cytokines. Together, this activity led to impressive monotherapy efficacy for PTT-4256 in syngeneic mouse cancer models following oral dosing. About Acidity in the Tumor Microenvironment The acidic tumor microenvironment, inherent to many cancers, causes a profound immunosuppression of infiltrating immune cells. This environment disarms the anti-cancer immune response and negates the effectiveness of current immunotherapies. This is particularly evident in TAMs, where acidity is sensed by the cell-surface receptor GPR65, leading to an induction of the transcriptional repressor ICER (inducible cAMP early repressor) and the widespread suppression of a host of pro-inflammatory mediators and anti-tumorigenic genes. About Pathios Therapeutics Launched in 2017, Pathios is a drug discovery and development company focused on translating innovative science into new medicines. Pathios was founded by a team of experienced biotech and pharmaceutical industry professionals, entrepreneurs, and clinicians. The company is focused on developing small molecule inhibitors of the pH-sensing G protein-coupled receptor GPR65 to counteract the GPR65 mediated immunosuppressive polarization of immune cells, including tumor associated macrophages, that is triggered by an acidic tumour microenvironment present in most cancers. To date, Pathios has raised a total of US$58M including support from the leading venture capital firms, Canaan Partners and Brandon Capital, as well as a strategic investment from Bristol Myers Squibb. Pathios is headquartered at the Innovation Centre on Milton Park, a key science precinct south of Oxford, UK where together with Grey Wolf Therapeutics and ThirtyFiveBio it is part of the unique M:M Bio drug discovery and development ecosystem. For more information, please visit . Contacts: Pathios Therapeutics Tom McCarthy, Executive Chair & Stuart Hughes, Chief Executive Officer/Chief Scientific Officer +44 1235 644 960 [email protected] Vida Strategic Partners (on behalf of Pathios Therapeutics) Tim Brons +1 646 319 8981 [email protected] SOURCE Pathios Therapeutics