TLC-2716 / OrsoBio - LARVOL DELTA

The Liver X Receptor Inverse Agonist TLC-2716 Reduces Triglycerides, Remnant Cholesterol, and Liver Fat in Patients with Severe Hypertriglyceridemia and Metabolic Dysfunction-Associated Steatotic Liver Disease (ENDO 2026) - P2 | "In this 4-week, proof-of-concept study in patients with SHTG and MASLD, the liver-targeted LXR inverse agonist TLC-2716 produced clinically meaningful improvements in TGs, RC, and hepatic fat. Comparable activity at both doses supports evaluation of lower doses to optimize benefit-risk."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Pancreatitis • Severe Hypertriglyceridemia

OrsoBio hits target in midstage study for metabolic conditions but stays silent on details (FierceBiotech) - "OrsoBio’s phase 2a trial recruited 30 adults who were overweight, had fasting triglycerides equal to or higher than 350 mg/dL and showed evidence of MASLD per imaging tests. The study tested out once-daily TLC-2716 at two different dose levels, examining the drug’s ability to change fasting triglycerides—a measure of lipids in the blood—and treatment-emergent adverse events...At four weeks, the biotech’s oral drug was tied to reductions in fasting triglycerides compared to baseline, while also demonstrating clinically meaningful improvements in remnant cholesterol and hepatic fat, according to OrsoBio. The company did not disclose any data, with more details expected to be shared at an upcoming scientific conference."

P2a data • Metabolic Dysfunction-Associated Steatotic Liver Disease • Severe Hypertriglyceridemia

OrsoBio Announces Nature Medicine Publication Establishing Clinical and Mechanistic Validation of First-in-Class LXR Inverse Agonist TLC-2716 for the Treatment of Serious Metabolic Diseases (Businesswire) - "Treatment with TLC-2716 reduced plasma and hepatic triglycerides, lowered plasma cholesterol, and improved glucose tolerance in dysmetabolic rodents, with findings observed in human liver organoids (HLOs)...Treatment for up to 14 days resulted in clinically meaningful, dose-dependent reductions versus placebo across multiple atherogenic lipid parameters, including triglycerides (up to 39%), remnant cholesterol (up to 61%), VLDL-C (up to 34%), LDL-C (up 17%), and LDL particles (up to 37%), along with decreases in apolipoprotein C3 and ANGPTL3, key regulators of lipoprotein clearance."

P1 data • Preclinical • Cardiovascular • Metabolic Disorders

TLC-2716 is currently being evaluated in a Phase 2a clinical trial in patients with severe hypertriglyceridemia (SHTG) and metabolic dysfunction-associated steatotic liver disease (MASLD) (NCT06564584), with topline data expected in the first half of 2026. (Businesswire)

P2a data • Metabolic Dysfunction-Associated Steatotic Liver Disease • Severe Hypertriglyceridemia

An oral, liver-restricted LXR inverse agonist for dyslipidemia: preclinical development and phase 1 trial. (PubMed, Nat Med) - P1 | "In conclusion, these results highlight the tolerability and therapeutic potential of TLC-2716 as a treatment for managing dyslipidemia and reducing residual atherosclerotic cardiovascular disease risk in humans. ClinicalTrials.gov identifier: NCT05483998 ."

Journal • P1 data • Preclinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Inflammation • Metabolic Disorders

Phase 2a Study of Safety, Tolerability, and Efficacy of TLC-2716 in Subjects With Hypertriglyceridemia and NAFLD (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: OrsoBio, Inc | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Dysfunction-Associated Steatotic Liver Disease

Phase 2a Study of Safety, Tolerability, and Efficacy of TLC-2716 in Subjects With Hypertriglyceridemia and NAFLD (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: OrsoBio, Inc

New P2 trial • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants (clinicaltrials.gov) - P1 | N=100 | Completed | Sponsor: OrsoBio, Inc | Active, not recruiting ➔ Completed | N=150 ➔ 100

Enrollment change • Trial completion

Safety, Pharmacokinetics, and Lipid Lowering Effects of the Oral, Liver-Targeted Liver X Receptor (LXR) Inverse Agonist TLC-2716 in Healthy Volunteers (AHA 2023) - P1 | "The liver-targeted LXR inverse agonist TLC-2716 was well tolerated and caused significant lipid lowering in healthy subjects, supporting its evaluation in patients with SHTG and NASH."

Clinical • PK/PD data • Dyslipidemia • Hepatology • Hypertriglyceridemia • Non-alcoholic Steatohepatitis • ABCA1 • ABCG1

A Study to Evaluate Single and Multiple Doses of TLC-2716 in Healthy Participants (clinicaltrials.gov) - P1 | N=150 | Active, not recruiting | Sponsor: OrsoBio, Inc | Recruiting ➔ Active, not recruiting

Enrollment closed