TLC-6740

MENLO PARK, Calif.--( BUSINESS WIRE )--OrsoBio, Inc. ("OrsoBio” or “the Company”), a clinical-stage biopharmaceutical company developing treatments for obesity and obesity-associated disorders, today announced the close of an oversubscribed $67 million Series B financing. The financing was co-led by new investors Ascenta Capital and Woodline Partners LP, with significant participation from existing investors Samsara Biocapital, Longitude Capital, Enavate Sciences, NuevaBio, and Eli Lilly and Company. In conjunction with the financing, Evan Rachlin, MD, Co-Founder and Managing Partner of Ascenta Capital, has joined the OrsoBio Board of Directors. Proceeds from the financing will be used to accelerate development of the Company’s mitochondrial protonophore portfolio for the treatment of obesity and associated metabolic disorders. Obesity affects more than 40% of U.S. adults and leads to a range of adverse health outcomes including type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatohepatitis (MASH). Obesity is caused by an imbalance between energy intake and energy expenditure that leads to excess adiposity. Although glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized weight management by reducing caloric intake, they may cause loss of lean mass and metabolic adaptations that reduce energy expenditure. Mitochondrial protonophores directly increase energy expenditure and may represent the ideal means to complement the metabolic benefits of GLP-1 RAs. In preclinical studies, mitochondrial protonophores developed by OrsoBio led to weight loss, preserved lean mass, and improved insulin sensitivity. Further, when these potential therapies were used in combination with a GLP-1 RA, additional weight and fat mass loss were observed, without significant effects on lean mass. These benefits were sustained with continued protonophore therapy following GLP-1 RA discontinuation. 1 TLC-6740 is a novel, oral, liver-targeted mitochondrial protonophore under evaluation in a 12-week, Phase 1b clinical trial in patients living with obesity ( NCT05822544 ). In a prior Phase 1 study in healthy subjects, TLC-6740 was safe, well tolerated, and caused dose-dependent increases in energy expenditure and improvements in lipids and markers of insulin resistance. Additional Phase 1b and Phase 2a studies of TLC-6740 in patients with obesity and type 2 diabetes, including those on a GLP-1 RA, will initiate in the coming months. IND-enabling studies for two additional novel protonophores (TLC-1180 and TLC-1235) with unique attributes compared to TLC-6740, including greater systemic distribution, are expected to be completed in 2025. TLC-1180 is a potent, long-acting mitochondrial protonophore that is suitable for weekly oral or subcutaneous administration. TLC-1235 is a controlled-release mitochondrial protonophore (CRMP) that has shown metabolic benefits across a range of models and species. 2 "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,” said Mani Subramanian, MD, PhD, CEO and Founder of OrsoBio. “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.” "OrsoBio’s novel mechanisms hold promise to enhance weight loss, improve metabolic function, and preserve lean muscle mass,” said Evan Rachlin, MD, Co-Founder and Managing Partner of Ascenta Capital. “These medicines could one day complement GLP-1 RA-based approaches and expand the long-term health benefits of these treatments. We look forward to partnering with the world-class team at OrsoBio to help bring these extraordinary medicines to patients.” OrsoBio’s portfolio of compounds in clinical development also includes TLC-3595, an ACC2 inhibitor, currently in a Phase 2a study for the treatment of type 2 diabetes, and TLC-2716, a liver X receptor (LXR) inverse agonist currently in a Phase 2a study for severe hypertriglyceridemia and MASH. About OrsoBio, Inc. OrsoBio, Inc. is a privately held, clinical-stage biopharmaceutical company dedicated to developing therapies to treat obesity and obesity-associated disorders, including type 2 diabetes, MASH, and severe dyslipidemias. OrsoBio currently has four programs in clinical and preclinical development with first-in-class compounds that address central pathways in energy metabolism. For more information, please visit www.orsobio.com . ____________________________ 1 Data accepted for presentation at ObesityWeek® 2024. 2 Perry RJ, et al. Science 2015 ( PMID: 25721504 ); Goedeke L, et al. Mol Metab 2021 ( PMID: 33545391 ).

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.”