MENLO PARK, Calif. — OrsoBio, a clinical-stage biopharmaceutical company developing treatments for obesity and related metabolic disorders, today announced positive topline results from a Phase 2a proof-of-concept study (NCT06564584) evaluating TLC-2716, the Company’s oral, liver-targeted liver X receptor (LXR) inverse agonist, in patients with severe hypertriglyceridemia (SHTG) and metabolic dysfunction–associated steatotic liver disease (MASLD). The study met its primary efficacy endpoint, demonstrating reductions in fasting triglycerides at week four, and showed clinically meaningful improvements in remnant cholesterol and hepatic fat.
In the randomized, double-blind, placebo-controlled Phase 2a study, once-daily oral treatment with TLC-2716 (6 mg or 12 mg) for four weeks resulted in clinically meaningful and statistically significant reductions in fasting triglycerides and remnant cholesterol, along with improvements in liver fat as assessed by MRI-PDFF, compared with placebo. Lipid reductions were observed at both doses and were particularly pronounced in patients with more severe baseline hypertriglyceridemia (triglycerides ≥500 mg/dL). TLC-2716 was generally well tolerated, with no Grade ≥3 or serious adverse events reported.
“These Phase 2a data provide compelling clinical validation of LXR inverse agonism as a differentiated therapeutic strategy for severe metabolic disorders,” said Rob Myers, MD, Chief Medical Officer and Head of Development for OrsoBio. “The substantial reductions in triglycerides, remnant cholesterol, and other atherogenic lipids—along with improvements in liver fat and a favorable safety profile—support the potential of TLC-2716 to become a meaningful therapeutic option for patients with diseases driven by excessive lipid production, including SHTG, MASH, and elevated remnant cholesterol.”
The study enrolled 30 overweight adults with fasting triglycerides ≥350 mg/dL and evidence of MASLD (via imaging or biopsy). Across the trial population, TLC-2716 demonstrated consistent improvements across multiple atherogenic lipid parameters, including total cholesterol, non-HDL cholesterol, and VLDL cholesterol, supporting continued evaluation of this differentiated mechanism for modulating hepatic lipid metabolism.
“We look forward to presenting a comprehensive dataset at a future scientific conference to provide a more detailed characterization of the therapeutic profile of TLC-2716,” added Dr. Myers. “These results support continued development of TLC-2716 across multiple severe metabolic disorders, which collectively affect millions of patients worldwide.”
Liver X receptors are oxysterol-activated nuclear hormone receptors that play a central role in triglyceride and cholesterol homeostasis. TLC-2716 is an oral, liver-targeted LXR inverse agonist designed to modulate plasma triglycerides and cholesterol through multiple complementary mechanisms, including suppression of hepatic de novo lipogenesis, enhanced clearance of triglyceride- and cholesterol-rich lipoproteins, and reduced intestinal lipid absorption.
These results follow the recent publication in Nature Medicine of preclinical and first-in-human Phase 1 clinical data, which established clinical and mechanistic validation of TLC-2716 across human genetics, organoid systems, and preclinical murine and non-human primate models.
About TLC-2716
TLC-2716 is a potent, oral, small-molecule, liver-targeted, inverse agonist of the Liver X Receptor (LXR). By modulating key pathways involved in lipid homeostasis—including de novo lipogenesis, lipoprotein clearance, and intestinal lipid absorption—TLC-2716 has the potential to treat a range of serious metabolic diseases. Topline data from a Phase 2a study of TLC-2716 (NCT06564584) in patients with hypertriglyceridemia and MASLD demonstrated clinically meaningful improvements in plasma lipids and liver fat with a favorable safety profile. Additional study data will be presented at a future scientific conference.
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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