TLC-1180

OrsoBio is conducting a Phase I trial of TLC-6740 in patients with obesity. Credit: New Africa/Shutterstock. Clinical-stage biopharmaceutical company OrsoBio has secured $67m in an oversubscribed Series B financing round to expedite the development of its mitochondrial protonophore portfolio for obesity and associated metabolic disorders. The funding round was led jointly by Ascenta Capital and Woodline Partners, with substantial contributions from current stakeholders including Samsara Biocapital, Enavate Sciences and Longitude Capital. Ascenta Capital co-founder and managing partner Evan Rachlin has joined the board of directors of OrsoBio. The capital injection will be channelled towards advancing the company’s mitochondrial protonophore portfolio for obesity which has shown promising results in preclinical studies. Mitochondrial protonophores have demonstrated the ability to directly increase energy expenditure, making them a potentially ideal complement to the metabolic benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs). See Also: Integrated Nanotherapeutics gains funds for new T1D treatment Moderna’s Laval facility gains Health Canada’s drug establishment licence Mitochondrial protonophores, developed by OrsoBio, have led to weight loss, preserved lean body mass and enhanced insulin sensitivity in preclinical trials. OrsoBio is conducting a 12-week Phase I clinical trial for TLC-6740, an oral, liver-targeted mitochondrial protonophore, in patients with obesity. The trial follows a successful Phase I study in healthy subjects, in which TLC-6740 was found to be safe and well-tolerated. It induced dose-dependent increases in energy expenditure and improvements in lipid profiles and insulin resistance markers. Phase Ib and Phase IIa studies for TLC-6740 are now set to begin targeting patients with obesity and type 2 diabetes, including those undergoing GLP-1 RA therapy. In 2025, OrsoBio plans to complete IND-enabling studies for two additional novel protonophores, TLC-1180 and TLC-1235. TLC-1180 is a potent mitochondrial protonophore suitable for weekly oral or subcutaneous administration, while TLC-1235 is a controlled-release mitochondrial protonophore that has demonstrated metabolic benefits across various models and species. OrsoBio founder and CEO Mani Subramanian stated: “We welcome Ascenta Capital and Woodline Partners to OrsoBio and appreciate their support and that of our existing investors. These resources enable us to continue advancing our portfolio of mitochondrial protonophores and other potential therapies to address the burden of obesity and obesity-associated diseases. “We believe that the future of obesity treatment will include GLP-1 RA-based combinations; this financing will enable us to build the scientific and clinical foundations to support our protonophores as components of these regimens.”

California biotech startup OrsoBio is betting the future of obesity drugs lies in combination approaches. To get there, OrsoBio told Endpoints News that it raised $67 million in a Series B, just 10 months after its $60 million Series A . Most large pharma companies are attempting to build a presence in the obesity R&D field, and a growing cohort of mid-size biopharmas and nimble upstarts are attracting the attention of potential acquirers , partners and investors with their varied takes on inducing weight loss. Ascenta Capital and Woodline Partners are new investors in OrsoBio. Existing backers that returned for the Series B include Samsara Biocapital, Longitude Capital, Enavate Sciences, NuevaBio and Eli Lilly. The investors want to see whether OrsoBio will successfully become one of the next-generation obesity biotechs that is looking to combine medicines with the landmark GLP-1 class from Novo Nordisk and Lilly. OrsoBio is an amalgamation of assets from Gilead, Shionogi, Phenex and Astellas, and it originally started as The Liver Company in 2020. Its two lead clinical programs are in Phase 2a trials for patients with type 2 diabetes and severe hypertriglyceridemia and MASH , but those projects are no longer the focus. Rather, OrsoBio’s Series B is dedicated to a portfolio of so-called mitochondrial protonophores, according to CEO Mani Subramanian. The experimental class of drugs aims to increase energy expenditure rather than suppress eating as GLP-1s do. In the lead is Gilead-derived TLC-6740, which is going through early-stage trials in New Zealand and recently received FDA clearance for clinical testing, Subramanian said. OrsoBio said it will start more Phase 1b and Phase 2a tests of the oral, liver-directed medicine in patients with obesity and type 2 diabetes in the coming months. “We definitely live in an incretin mimetic world. The advances with incretin therapies are incredible,” Subramanian said. “So the main opportunity is for complementary mechanisms of action that can address the unmet needs.” Behind TLC-6740 are two more mitochondrial protonophores. “The future is definitely in combinations and finding the best way to incorporate this into weight-management paradigms,” Subramanian said. That includes TLC-1180, a long-acting asset that OrsoBio may explore as a weekly oral treatment and/or an under-the-skin drug, Subramanian said, noting the route of delivery is yet to be determined. TLC-1235 is a controlled-released asset. Both will go through IND-enabling studies in the near term, with TLC-1180 expected to enter clinical studies around the middle of 2025. As for the type 2 diabetes and MASH/hypertriglyceridemia programs, Subramanian said their future depends on upcoming data readouts, given the large amount of resources required for those indications. The company expects data in November or December, the CEO said, and those assets could be advanced internally or partnered out. With investors and pharmas appearing to be interested in obesity for the long term, OrsoBio’s own future could go in multiple directions. The 15-employee company could go the IPO route as BioAge and other metabolic companies are pursuing. Or it could be swooped up like Carmot, Versanis and Inversago in the past year. “Based on both the quality, the magnitude, the level of interest in the data we generate, as well as what the market conditions are, we’re keeping all our options open,” Subramanian said. “The other question that comes up is, ‘Is there pharma interest?’ And clearly there is, given how complementary this is to the incretin space and the interest in both weight management as well as the comorbidities associated with obesity.”