Company eyes GLP-1 combination potential for ‘mitochondrial protonophore’ technology designed to combat obesity and associated diseases.
Silicon Valley biotech OrsoBio has secured $67 million in an “oversubscribed” Series B financing round. The funding will support the ongoing development of the Menlo Park-based company’s therapeutic approach, which aims to restore energy homeostasis to address obesity and metabolic disorders.
OrsoBio’s core objective is to tackle obesity and associated conditions such as type 2 diabetes, metabolic dysfunction-associated steatohepatitis (MASH) and severe dyslipidemias. The company cites the recent success of GLP-1 receptor agonists like semaglutide (Ozempic/Wegovy), which it says have shown effectiveness in reducing caloric intake but come with potential downsides, including loss of lean mass and a decrease in energy expenditure.
Leveraging a technology called “mitochondrial protonophores”, OrsoBio is aiming to increase energy expenditure, a function that it believes could enhance the benefits of GLP-1 s without those associated drawbacks. Protonophores are compounds that enable the transport of protons across membranes, which, in mitochondria, leads to the production of heat and other effects to meet energy demands.
OrsoBio’s lead candidate, TLC-6740, is currently being evaluated in a Phase 1b clinical trial for obesity. The liver-targeted mitochondrial protonophore has already demonstrated safety, tolerability and positive metabolic effects, such as increased energy expenditure and improved lipid profiles in earlier studies. The company plans to extend the development of TLC-6740 into additional trials, focusing on patients with obesity and Type 2 diabetes, with a particular interest in combining it with GLP-1 therapies to boost fat loss and preserve muscle mass. Further studies are expected to launch soon.
“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,” said Dr Mani Subramanian, CEO of OrsoBio.
OrsoBio has two other protonophore candidates, TLC-1180 and TLC-1235, currently going through IND-enabling studies. These compounds are designed for different approaches, such as broader systemic distribution and extended activity. Both are expected to complete preclinical studies in 2025.
In addition to its mitochondrial protonophore portfolio, OrsoBio is developing TLC-3595, an ACC2 inhibitor, which is undergoing a Phase 2a study for type 2 diabetes, and TLC-2716, a liver X receptor inverse agonist, which is being studied for severe hypertriglyceridemia and MASH.
The latest funding round was co-led by Ascenta Capital and Woodline Partners LP and follows a $60 million Series A in November last year. Existing investors including Samsara Biocapital, Longitude Capital and Eli Lilly also participated.
“OrsoBio’s novel mechanisms hold promise to enhance weight loss, improve metabolic function, and preserve lean muscle mass,” said Ascenta Capital’s Evan Rachlin. “These medicines could one day complement GLP-1 RA-based approaches and expand the long-term health benefits of these treatments.”
