OrsoBio Announces First Patient Dosed in Phase 2 Clinical Trial of the ACC2 Inhibitor TLC-3595, a Potential Treatment for Type 2 Diabetes

— Trial will evaluate the insulin-sensitizing effects of TLC-3595, alone and in combination with approved diabetes therapies —

PALO ALTO, Calif.–(BUSINESS WIRE)–OrsoBio, Inc., a clinical-stage biopharmaceutical company developing treatments for severe metabolic disorders, today announced that the first patient has been dosed in a Phase 2a clinical trial evaluating TLC-3595, a selective inhibitor of acetyl-CoA carboxylase 2 (ACC2). The trial aims to demonstrate the safety and insulin-sensitizing effects of TLC-3595 in patients with insulin resistance, including those with type 2 diabetes on approved glucose-lowering therapies. Proof-of-concept data supporting the safety and efficacy of TLC-3595 will be available by the end of 2023.

Today, 537 million adults are living with diabetes, a number projected to grow to over 640 million by 2030 and approximately 780 million by 2045.1 Insulin resistance is pathogenic across the spectrum of diabetes—from patients with prediabetes to advanced diabetes requiring insulin—and drives a range of complications, including cardiovascular disease, renal disease, and cancer.

“With the growing global burden of type 2 diabetes, the need for novel, well-tolerated therapies that enhance insulin sensitivity has never been greater,” said Rob Myers, MD, Chief Medical Officer of OrsoBio. “Dosing our first patient in this Phase 2a trial is an important milestone for OrsoBio as we continue to advance our four programs to address unmet needs in patients with severe metabolic disorders, including diabetes, obesity, nonalcoholic steatohepatitis (NASH), and dyslipidemias.”

The Phase 2a, multicenter, randomized, double-blind, placebo-controlled trial (NCT05665751) is designed to evaluate the safety, tolerability, and efficacy of two doses of TLC-3595 in patients with insulin resistance. The study will enroll 50 overweight or obese subjects with insulin resistance, including type 2 diabetes treated with glucose-lowering therapies. The trial’s primary endpoint is improvement in insulin sensitivity based on results from an oral glucose tolerance test (OGTT) after 4 weeks of therapy. Additional exploratory endpoints include biomarkers of glycemic control (e.g., HbA1c, glucose, glycated albumin), fatty acid oxidation (FAO), lipids, and MRI/magnetic resonance spectroscopy (MRS)-based assessments of muscle and liver fat, key drivers of insulin resistance.

“ACC2 inhibition is a novel mechanism of action that holds great potential to address insulin resistance in patients with type 2 diabetes, including those being treated with other complementary therapies,” 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. “It’s critical that we identify novel therapies that are safe, well tolerated, and effective in improving insulin sensitivity, both as standalone medicines and to enhance the effectiveness of existing treatments for diabetes.”

OrsoBio previously presented data from a successful Phase 1 trial of TLC-3595 in a poster (Abstract #3677) entitled “Evaluation of the safety and pharmacokinetic effects of the oral, acetyl-CoA carboxylase-2 (ACC2) inhibitor TLC-3595 in healthy volunteers” at AASLD’s The Liver Meeting® in November 2022. This single and 14-day, multiple ascending dose trial showed that TLC-3595 was well tolerated, led to improvements in LDL and total cholesterol, and had pharmacokinetic parameters supporting once daily oral administration.

About TLC-3595 and ACC2 Inhibition

TLC-3595 is a novel and selective ACC2 inhibitor designed to treat type 2 diabetes by increasing FAO, reducing ectopic lipid accumulation, and improving insulin sensitivity in skeletal muscle and liver. The compound may also have potential as a treatment for other conditions characterized by impaired FAO, including cirrhosis with myosteatosis-associated sarcopenia and NASH. In 2022, OrsoBio acquired exclusive worldwide rights to an ACC2 inhibitor program with lead compound TLC-3595 (formerly S-723595) from Shionogi & Co., Ltd.

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, nonalcoholic steatohepatitis, severe dyslipidemias, and lipodystrophies. 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 International Diabetes Federation Diabetes Atlas 2022. Available: https://diabetesatlas.org.

Recent News

OrsoBio team members collaborated with Professor Takebe in his pioneering study in Cell on the first use of en masse human liver organoids to define the genetic basis of metabolic liver disease and potential for tailored therapeutic development.