OrsoBio, Inc. (“OrsoBio” or “the Company”), a clinical-stage biopharmaceutical company developing treatments for obesity and related metabolic disorders, today announced new clinical and preclinical data to be presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA), taking place June 5-8, 2026, in New Orleans, La. The findings underscore the potential multi-system benefits of the mitochondrial protonophore mechanism, with effects spanning weight loss, multi-tissue insulin sensitivity, exercise capacity, cardiovascular health, and obesity-associated cognitive decline.
OrsoBio will present clinical data from a Phase 2a study of TLC-6740 in combination with tirzepatide in people living with obesity without diabetes (NCT05822544). The randomized, double-blind, placebo-controlled study demonstrated significant improvements in weight loss, insulin sensitivity, liver health, and body composition compared with tirzepatide monotherapy. TLC-6740 was safe and well tolerated in combination with tirzepatide, consistent with prior clinical studies of TLC-6740.
The Company and collaborators from Yale School of Medicine will also present two abstracts featuring new preclinical data for TLC-1180, its novel second-generation mitochondrial protonophore. In diet-induced obese (DIO) mouse models, TLC-1180 improved insulin sensitivity across multiple tissues, enhanced exercise capacity, and mitigated obesity-associated cognitive impairment.
“These new data reinforce our belief that mitochondrial protonophores represent a differentiated therapeutic approach capable of addressing multiple manifestations of obesity-related disease,” said Mani Subramanian, MD, PhD, Chief Executive Officer of OrsoBio. “Much as advances in incretin biology transformed our understanding of obesity treatment, we believe targeting cellular energy expenditure through mitochondrial protonophores may unlock broad benefits across metabolic, cardiovascular, and neurocognitive health in people living with obesity. The consistency of these findings across clinical and preclinical studies strengthens our confidence in the promise of mitochondrial protonophores as a potential new therapeutic class.”
“Our clinical findings further support the potential of mitochondrial protonophores as complementary therapies that increase energy expenditure while incretin-based medicines primarily target energy intake,” said Rob Myers, MD, Chief Medical Officer of OrsoBio. “The additive metabolic benefits and favorable safety profile observed with TLC-6740 and tirzepatide validate findings previously seen in preclinical studies and reinforce the potential of this mechanism as both a combination partner and a standalone therapeutic approach in obesity.”
TLC-1180 is currently being evaluated in a Phase 1 clinical trial (NCT07300189) assessing the safety, tolerability, and pharmacokinetics of OrsoBio’s novel, oral, second-generation mitochondrial protonophore, designed to provide greater potency and broader systemic distribution than TLC-6740.
Conference Presentation Details:
Increasing Energy Expenditure with the Liver-Targeted Mitochondrial Protonophore TLC-6740 Enhances Weight Loss and Metabolic Benefits in Combination with Tirzepatide in Obesity: A Phase 2a Study
Poster #2869-LB | Sunday, June 7, 2026 (12:30 p.m. – 1:30 p.m.)
This 24-week, proof-of-concept Phase 2a study assessed the safety and efficacy of once-daily oral TLC-6740 180 mg combined with the GLP-1/GIP receptor agonist tirzepatide (5 mg by weekly subcutaneous injection) in people living with obesity without diabetes (NCT05822544). At week 24, participants receiving TLC-6740 plus tirzepatide achieved an additional 4.5% mean weight loss compared to those treated with tirzepatide alone, and showed significant improvements in insulin sensitivity, liver health, and body composition. TLC-6740 was safe and well tolerated in combination with tirzepatide. Adverse event rates, including gastrointestinal events typical of incretin therapy, were similar between groups, and no Grade 3 or severe adverse events, treatment discontinuations, or signs of excessive systemic uncoupling (e.g., fevers) were observed in participants receiving TLC-6740.
TLC-1180 Enhances Liver, Muscle, WAT and Myocardial Insulin Sensitivity and Increases Exercise Capacity in DIO Mice
Poster #1790-P | Sunday, June 7, 2026 (12:30 p.m. – 1:30 p.m.)
This preclinical study evaluated the effects of TLC-1180 on energy expenditure, insulin sensitivity, and exercise capacity in DIO mice. TLC-1180 increased energy expenditure, promoted fat-selective weight loss while preserving lean mass, and improved insulin sensitivity across the liver, skeletal muscle, heart, and adipose tissue, resulting in a 140% improvement in whole-body insulin sensitivity. TLC-1180 also improved cardiac metabolic function and enhanced exercise performance, as demonstrated by longer exercise duration and faster running speed. These findings suggest that TLC-1180 may have therapeutic potential across a range of obesity-related metabolic and cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF).
Mitochondrial Protonophore TLC-1180 Mitigates Cognitive Decline in Diet-Induced Obese Mice
Poster #3064-LB | Sunday, June 7, 2026 (12:30 p.m. – 1:30 p.m.)
This preclinical study investigated the impact of chronic high-fat/high-sucrose feeding on cognition and whether treatment with TLC-1180 could reverse obesity-associated metabolic and neurological deficits. In DIO mice, TLC-1180 reduced body weight, improved glucose tolerance and hyperinsulinemia, and partially restored exploratory behavior and recognition memory. These behavioral improvements were accompanied by restoration of neuronal activation in thalamic brain regions involved in cognition, with neuronal activity returning to levels comparable to lean control animals. These findings suggest that improving metabolic health through mitochondrial protonophore treatment may help mitigate obesity-associated cognitive decline.
About TLC-6740
TLC-6740 is a novel, oral, liver-targeted mitochondrial protonophore in development for obesity and related metabolic diseases, including diabetes and MASH. By increasing energy expenditure through targeted hepatic activity, TLC-6740 is designed to drive weight loss and improve metabolic health, including insulin sensitivity and lipid metabolism. In a Phase 2a trial in individuals with obesity, TLC-6740 combined with tirzepatide resulted in an average of 4.5% greater weight loss compared with tirzepatide alone, with no additional safety concerns, discontinuations, or weight loss plateau at 24 weeks, and improvements across multiple metabolic measures (NCT05822544).
About TLC-1180
TLC-1180 is a novel, potent, oral, mitochondrial protonophore with liver-biased distribution that increases energy expenditure and promotes fat-selective weight loss. In preclinical studies of obese mice and non-human primates, TLC-1180 reduced fat mass, improved glucose control and insulin sensitivity, increased exercise capacity, and mitigated cognitive decline associated with obesity, while also enhancing the efficacy of GLP-1 receptor agonists. TLC-1180 is currently being evaluated in a first-in-human, Phase 1 study (NCT07300189).
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.
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