On March 30, 2023 ThirtyFiveBio, a biotechnology company developing first-in-class small molecule inhibitors of G protein-coupled receptor 35 (GPR35) for the treatment of gastrointestinal (GI) disease, emerged from stealth and reported that it will present the first data from its GPR35 antagonist program at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 (Press release, ThirtyFiveBio, MAR 30, 2023, View Source [SID1234629633]). The presentation will include a suite of preclinical data highlighting the biological role of GPR35 in GI disease and cancers, outlining the hypothesis that GPR35 activity has the potential to drive pro-oncogenic growth biology in digestive tract cancers, and spotlighting the company’s discovery of potent GPR35 inhibitors that demonstrate the ability to prevent GPR35 signaling and tumour growth in a patient-derived cancer model. The AACR (Free AACR Whitepaper) conference is being held April 14-19, 2023, in Orlando, Florida.
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ThirtyFiveBio, which has raised $20 million in seed financing to date, was created in 2021 by M:M Bio Limited (M:M Bio) in partnership with Canaan Partners. The company was formed to advance foundational research on the biology of GPR35 and the role that the target plays in a range of GI diseases, including cancers of the digestive tract. In less than two years since its founding, ThirtyFiveBio has built a fully enabled drug discovery platform and is advancing multiple unique families of first-in-class small-molecule inhibitors of GPR35 through lead optimization activities.
"We are excited to unveil ThirtyFiveBio, the third innovative biotechnology company that we have created in collaboration with Canaan Partners, a group with who we share the goal of supporting efficient development of first-in-class medicines with clear benefit to patients and payers," said Tom McCarthy, Ph.D., chairman of M:M Bio and co-founder and executive chair of ThirtyFiveBio. "ThirtyFiveBio has the key elements that we look for when starting a company, namely thought leadership on the biology of a genetically validated target in an area of high unmet clinical need, paired with the drug discovery know-how required for the creation of first-in-class small molecules. As with Grey Wolf Therapeutics and Pathios Therapeutics, our other ecosystem companies, ThirtyFiveBio benefits from M:M Bio’s hubs of excellence, which span a wide range of drug discovery and development services, as well as complete and agile operational support."
The role of GPR35 in GI diseases is genetically validated with several drug developers advancing programs designed to address the target. To date, virtually all these efforts have been focused on increasing the activity of GPR35 with targeted agonists. However, important recent scientific findings, including key insights from the ThirtyFiveBio team, support the hypothesis that GPR35 antagonism may represent a more appropriate therapeutic approach by blocking unwanted GPR35 signaling. Based on this evolved scientific perspective, supported by the company’s work with several world-leading, academic GPR35 specialists, ThirtyFiveBio is uniquely pursuing antagonism of the target with first-in-class small molecule GPR35 inhibitors.
Supporting the company’s focus on GPR35 inhibition is a collection of pre-clinical data generated by its scientists that highlights the association between GPR35 mutations and GI diseases. This includes research showing that GPR35 variants are linked to irritable bowel disease, and that GPR35 expression is upregulated in GI cancers. The company has also shown that pathogenic mutations of GPR35 drive its increased expression and function. Furthermore, study results have demonstrated that commonly dysregulated GI-cancer genes can be reversed by knocking out GPR35 in cancer cells. Taken together, these findings provide compelling evidence that hyperactive genetic mutations within GPR35 contribute to a range of GI disease processes, and that inhibiting GPR35 activity may have therapeutic utility in these diseases.
"Our evolving understanding of GPR35 biology and its relevance to GI diseases has guided our unique focus on target antagonism and positioned the company with the unique opportunity to discover and advance multiple families of first-in-class small molecule inhibitors," said James Westcott, Ph.D., chief executive officer of ThirtyFiveBio. "We’re excited to unveil the first data from our GPR35 inhibition program, which will spotlight the extensive work our scientists and bioinformaticians have undertaken illuminating the way GPR35 impacts digestive tract cancers, how these findings support our rationale of pursuing GPR35 inhibition as a potential anti-tumour therapy, and our identification of various novel GPR35 antagonists suitable for advancement."
The AACR (Free AACR Whitepaper) presentation (#454/18), entitled "Validation of GPR35 as a Novel Cancer Target in Digestive Tract Cancers and Discovery of Potent, Selective GPR35 Inverse Agonists," will take place on Sunday, April 16, 2023, at 1:30 p.m. Eastern in the "New Drug Targets" poster session (PO.ET02.08) located in Section 16 within the Orange County Convention Center. The abstract for the poster presentation can be found here: View Source!/10828/presentation/2492