PTT-4256

Pathios Therapeutics日前宣布完成2500万美元的B轮融资，这笔融资包括来自新投资者百时美施贵宝（Bristol Myers Squibb），以及包括Canaan和Brandon Capital在内现有投资者的支持。融资所获得的款项将主要用于支持其潜在“first-in-class”GPR65抑制剂PTT-4256的开发。 Pathios正在研究一种潜在能够逆转酸性肿瘤微环境（TME）所引发免疫细胞（例如，肿瘤相关巨噬细胞）极化而造成免疫抑制现象的新型免疫肿瘤学癌症治疗方法。该公司打算开发靶向一种称为GPR65的酸性感应G蛋白偶联受体来攻击常见的癌症免疫逃逸途径。GPR65已被证明能促进免疫细胞的免疫抑制极化。在2023年美国癌症研究协会（AACR）年会上公布的PTT-4256临床前数据显示，该化合物具有出色的类药物特性和强大的单药抗肿瘤活性。值得一提的是，PTT-4256被证明能有效抵消低pH值（即高酸度）所导致人类和小鼠巨噬细胞极化至免疫抑制状态的作用。 此次融资所得将用于支持Pathios继续开发其GPR65靶向抗癌疗法。该公司预计将在2024年底前将其内部发现的口服GPR65小分子抑制剂PTT-4256推进到晚期实体瘤的人体临床试验。此外，Pathios将利用融资所得扩大其团队，包括高管领导层，以配合其公司继续发展成为临床阶段公司。 参考资料：[1] Pathios Therapeutics Raises $25M in FirstClose of Series B Financing to Advance First-in-Class Immunotherapy Approach into Clinic. Retrieved April 19, 2024 from https://pathiostherapeutics.com/pathios-series-b-bms/ 内容来源于网络，如有侵权，请联系删除。

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