MENLO PARK, Calif.– OrsoBio, Inc., a clinical-stage biopharmaceutical company developing treatments for severe metabolic disorders, today announced preliminary safety and pharmacokinetic (PK) data from the single ascending dose (SAD) portion of an ongoing Phase 1 trial of TLC-6740, a liver-targeted, mitochondrial protonophore. This study is exploring the safety and efficacy of TLC-6740 as an oral, first-in-class treatment for obesity and obesity-associated diseases, including diabetes and nonalcoholic steatohepatitis (NASH).
Increasing cellular energy expenditure by mitochondrial uncoupling is a validated approach to weight loss, however, toxicity due to systemic uncoupling (e.g., increased body temperature) has restricted its clinical use. To circumvent these potential toxicities, TLC-6740 was developed to be actively taken up by hepatocytes (liver cells), thereby avoiding high plasma exposures. In addition, by targeting the liver—a key organ governing whole body energy metabolism—TLC-6740 has multiple potential metabolic benefits, including weight loss and improvements in NASH, insulin resistance, lipids, and cardiovascular risk.
“Preliminary results from this Phase 1 study are very promising and support the safety of liver-targeted mitochondrial uncoupling with TLC-6740,” said Rob Myers, MD, Chief Medical Officer of OrsoBio. “Modeling of plasma and liver concentrations upon multiple dosing suggests that high systemic exposures of TLC-6740 will be avoided, providing large safety margins compared with thermogenic exposures in preclinical studies, while efficacious exposures will be achieved at low doses. We look forward to confirming these findings in the multiple ascending dose (MAD) cohorts of this study, and to generating additional data to support the potential of TLC-6740 to treat obesity and its comorbidities.”
