OrsoBio, Inc. (“OrsoBio” or “the Company”), a clinical-stage biopharmaceutical company developing treatments for obesity and related metabolic disorders, today presented results from its Phase 2a proof-of-concept study of TLC-2716 in patients with severe hypertriglyceridemia (SHTG) and metabolic dysfunction-associated steatotic liver disease (MASLD). The oral, liver-targeted LXR inverse agonist met its primary efficacy endpoint, producing rapid, substantial placebo-adjusted reductions in triglycerides of 57% and 46% at the 6 mg and 12 mg doses, respectively, after four weeks of treatment. Among patients with baseline triglycerides ≥500 mg/dL — the population at highest risk for acute pancreatitis — both doses produced consistent placebo-adjusted reductions of approximately 62%. TLC-2716 also reduced remnant cholesterol by over 50%, improved liver fat, and was generally well tolerated. Chief Medical Officer and Head of Development, Rob Myers, MD, presented study data at the Endocrine Society’s Annual Meeting (ENDO 2026) in Chicago, Ill.
“These Phase 2a data provide clinical validation of LXR inverse agonism as a differentiated therapeutic strategy for severe metabolic disorders driven by excessive lipogenesis,” said Rob Myers, MD, Chief Medical Officer and Head of Development at OrsoBio. “The significant reductions in triglycerides, remnant cholesterol, and other atherogenic lipids, together with improvements in liver fat, support TLC-2716’s potential across multiple diseases in this space, including SHTG and MASLD. The favorable safety profile and comparable activity across both dose levels suggest meaningful efficacy may be achievable at lower doses in Phase 2b.”
Liver X receptors (LXRs) are oxysterol-activated nuclear hormone receptors that play a central role in triglyceride and cholesterol homeostasis. TLC-2716 is an oral, once-daily, liver-targeted LXR inverse agonist that reduces plasma triglycerides, remnant cholesterol, and liver fat through suppression of hepatic de novo lipogenesis, enhanced clearance of triglyceride-rich lipoproteins, and reduced intestinal lipid absorption.
Study Summary
The double-blind, placebo-controlled Phase 2a study (NCT06564584) enrolled 30 overweight adults (BMI ≥28 kg/m²) with SHTG (fasting triglycerides ≥350 mg/dL) and MASLD confirmed by imaging and/or biopsy. Patients were randomized 1:1:1 to TLC-2716 6 mg (n=10), TLC-2716 12 mg (n=10), or placebo (n=10) once daily for four weeks. The primary efficacy endpoint was the percent change from baseline in fasting triglycerides at week four.
Key Results
The study population had markedly elevated baseline triglycerides (mean 701 mg/dL) and remnant cholesterol (mean 97 mg/dL), with 47% of patients having baseline triglycerides ≥500 mg/dL. Key findings included:
- Triglyceride reduction: TLC-2716 produced rapid, substantial placebo-adjusted reductions in fasting triglycerides at week four of 57% with the 6 mg dose (p=0.001) and 46% with the 12 mg dose (p=0.004) in the modified intention-to-treat population.1 Among patients with baseline triglycerides ≥500 mg/dL, both doses produced consistent placebo-adjusted reductions of approximately 62% (both p<0.05). Triglyceride normalization occurred in 22% of patients receiving 6 mg, 30% receiving 12 mg, and none receiving placebo.
- Remnant cholesterol reduction: Placebo-adjusted reductions in remnant cholesterol were 57% (p=0.005) with 6 mg and 51% (p=0.010) with 12 mg, representing clinically meaningful reductions in an increasingly recognized driver of residual cardiovascular risk.
- Broad lipid lowering: Pooled across both TLC-2716 doses, total cholesterol was reduced by 23% (p=0.005), non-HDL cholesterol by 31% (p=0.007), and VLDL cholesterol by 58% (p<0.001) versus placebo, with no change in LDL-C or HDL-C.
- Liver fat reduction: TLC-2716 reduced liver fat by approximately 30% versus placebo, as measured by MRI-PDFF. More than half of treated patients achieved a ≥30% relative reduction in liver fat — a threshold associated with histologic improvement — compared with 30% of placebo-treated patients, consistent with a meaningful treatment effect despite the small sample size.
- Safety: TLC-2716 was generally well tolerated at both doses, with no Grade ≥3 or serious adverse events reported.
Next Steps
Based on these results, OrsoBio plans to initiate a 12-week, dose-ranging Phase 2b study evaluating lower doses of TLC-2716 in patients with SHTG and elevated remnant cholesterol.
Prior Research
These results build on the recent publication in Nature Medicine of preclinical and first-in-human Phase 1 clinical data, which provided evidence validating the successful translation of TLC-2716 into humans from human genetics, organoid systems, and preclinical murine and non-human primate models.2
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 driven by excessive lipogenesis. Data from a Phase 2a study of TLC-2716 (NCT06564584) in patients with SHTG and MASLD, presented at ENDO 2026, demonstrated clinically meaningful improvements in plasma lipids and liver fat with a favorable safety profile.
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 SHTG. 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 Modified intention-to-treat population included participants who received ≥80% of scheduled doses of study medication. Baseline lipids defined as the mean of all pre-dose values during screening and on Day 1.
2 Li, X., Benegiamo, G., Vijayakumar, A. et al. An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial. Nat Med 32, 883–893 (2026). https://doi.org/10.1038/s41591-025-04169-6
View source version on businesswire.com: https://www.businesswire.com/news/home/20260614487129/en/
Media gallery
