PALO ALTO, Calif.–(BUSINESS WIRE)– OrsoBio, Inc., a clinical-stage biopharmaceutical company developing treatments for severe metabolic disorders, today announced completion of the second cohort of subjects in an ongoing Phase 1 trial of TLC-6740, a liver-targeted mitochondrial protonophore. The first-in-human, Phase 1 study is exploring the safety and efficacy of TLC-6740 as an oral, first-in-class, liver-targeted mitochondrial protonophore for the treatment of obesity and obesity-associated diseases, including diabetes and nonalcoholic steatohepatitis (NASH).
Today, over 40% of adults and 20% of children in the United States — approximately 100 million and 14.7 million, respectively — have obesity.1 Obesity drives a range of complications, including cardiovascular diseases, diabetes, liver disease, and some cancers, which are increasing in prevalence due to the obesity epidemic.2
“With the growing burden of obesity and obesity-associated diseases, development of effective and safe oral therapies that are complementary to existing therapies, such as GLP-1 receptor agonists, is vital. In rodent models of obesity and insulin resistance, TLC-6740 led to weight loss, reduced liver and plasma triglycerides, and improved insulin sensitivity, without evidence of excessive systemic mitochondrial uncoupling,” said Rob Myers, MD, Chief Medical Officer of OrsoBio. “This first-in-human study is an important milestone for OrsoBio as we continue to advance our pipeline with this third program progressing to the clinic. TLC-6740 has been well tolerated in the first two single-dose cohorts and preliminary pharmacokinetic (PK) data support once-daily dosing.”
The randomized, double-blind Phase 1 trial (NCT05822544) is designed to evaluate the safety, tolerability, PK, and pharmacodynamics of single and multiple ascending doses of TLC-6740 for up to 10 days in healthy subjects. Preliminary evidence of the activity of TLC-6740 will be determined based on changes in body weight, plasma lipids, biomarkers of fatty acid oxidation and de novo lipogenesis, and energy expenditure. Data from the trial will be available by the end of 2023.
“We are optimistic about the potential of TLC-6740 to be a highly effective and safe mitochondrial protonophore based on the novel approach of liver targeting and available preclinical toxicology and efficacy data,” said Gerald Shulman, MD, PhD, MACP, MACE, FRCP, the George R. Cowgill Professor of Medicine and Professor of Cellular and Molecular Physiology at Yale School of Medicine, Co-Director of the Yale Diabetes Research Center, and scientific advisor to OrsoBio. “By increasing energy expenditure, TLC-6740 is a promising complement to GLP-1 receptor agonists for obesity and offers the potential to improve obesity-associated comorbidities, including diabetes and NASH.”
TLC-6740 is a novel, oral, liver-targeted mitochondrial protonophore in development for the treatment of obesity and obesity-associated diseases, including diabetes and NASH. Based on active hepatic uptake and mitochondrial protonophoric activity, TLC-6740 increases energy expenditure in hepatocytes, and is expected to have broad, systemic metabolic and cardiovascular benefits, including weight loss, and improved insulin sensitivity, NASH, and dyslipidemia. Preclinical data presented at AASLD’s The Liver Meeting® in 2022 showed that dysmetabolic rodents treated with TLC-6740 achieved dose-dependent reductions in body weight and improvements in glucose tolerance and liver and plasma triglycerides. Moreover, due to active hepatic uptake, plasma exposures of TLC-6740 are limited, serving to enhance its therapeutic safety.
About OrsoBio, Inc.
OrsoBio, Inc. is a privately held, clinical-stage biopharmaceutical company dedicated to developing therapies to treat severe metabolic disorders, including type 2 diabetes, obesity, NASH, and severe dyslipidemias. The company was co-founded by Mani Subramanian, MD, PhD, former Therapeutic Area Head for Liver Diseases at Gilead Sciences, and Samsara BioCapital. 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 Centers for Disease Control and Prevention, Adult obesity facts. Available: https://www.cdc.gov/obesity/data/adult.html.
Centers for Disease Control and Prevention, Childhood obesity facts. Available: https://www.cdc.gov/obesity/data/childhood.html.
2 World Health Organization, Obesity and overweight fact sheet. Available: