OrsoBio Validates New Pathway for Metabolic Disease in Major Study

MENLO PARK, CA – January 16, 2026 – OrsoBio, a clinical-stage biopharmaceutical company, has announced a significant scientific achievement with the publication of first-in-human clinical data for its drug candidate, TLC-2716, in the prestigious journal Nature Medicine. The paper provides critical validation for a novel therapeutic approach targeting serious metabolic diseases, including severe hypertriglyceridemia (SHTG) and metabolic dysfunction-associated steatotic liver disease (MASLD), conditions affecting over 80 million Americans.

The publication details positive results from a Phase 1 study, demonstrating that the oral, liver-targeted drug was safe and produced robust lipid-lowering effects in healthy volunteers. This milestone establishes the clinical and mechanistic potential of inhibiting Liver X Receptors (LXRs), a long-sought-after but historically challenging target in metabolic medicine.

A Scientific Leap in Liver-Targeted Therapy

At the heart of this development is a sophisticated new mechanism of action. TLC-2716 is a first-in-class inverse agonist of the Liver X Receptor (LXR). LXRs are nuclear receptors that play a pivotal role in regulating the body's cholesterol and triglyceride balance. For years, researchers attempted to develop LXR agonists—drugs that activate the receptor—to treat atherosclerosis. However, these attempts were consistently thwarted by a critical side effect: systemic LXR activation led to an undesirable buildup of fat in the liver (hepatic steatosis) and elevated blood triglycerides, the very conditions they aimed to treat.

OrsoBio’s approach circumvents this paradox. As an inverse agonist, TLC-2716 inhibits the baseline activity of the LXR. Furthermore, it is designed to be liver-targeted, concentrating its action in the liver and gut while having minimal exposure in the rest of the body. This precision pharmacology aims to harness the benefits of modulating LXR pathways without triggering the problematic systemic side effects.

The Nature Medicine publication powerfully supports this strategy. The Phase 1 trial, a randomized, double-blind, placebo-controlled study in 100 healthy volunteers, showed that 14 days of treatment led to clinically meaningful, dose-dependent reductions in multiple atherogenic lipids. Key results included:
* Up to a 39% reduction in triglycerides.
* Up to a 61% reduction in remnant cholesterol, a particularly dangerous type of cholesterol implicated in cardiovascular events.
* Up to a 17% reduction in LDL-C, often called "bad cholesterol."

Importantly, the drug was well tolerated, with no serious adverse events reported. The findings were remarkably consistent across preclinical models—including dysmetabolic rodents, non-human primates, and advanced human liver organoids—demonstrating a successful translation from the lab to human subjects.

“Our extensive analyses of human genetic data support liver-restricted LXR inhibition to treat lipids disorders and MASH,” said Johan Auwerx, MD, PhD, a professor at the École Polytechnique Fédérale de Lausanne (EPFL), Switzerland, and a co-author of the study. “These findings not only validate the underlying mechanism, they also demonstrate strong concordance with the safety and lipid-lowering effects of TLC-2716 observed across animal models, human organoids, and the Phase 1 clinical study.”

A New Hope for a Silent Epidemic

The clinical validation of TLC-2716 arrives at a critical time. SHTG and MASLD represent a massive and growing public health crisis. SHTG, characterized by fasting triglyceride levels over 500 mg/dL, significantly increases the risk of acute pancreatitis, a painful and potentially fatal condition. MASLD, a condition closely linked to obesity and type 2 diabetes, involves fat accumulation in the liver and can progress to a more severe form, MASH, leading to cirrhosis, liver failure, and cancer.

Current treatments for these conditions are limited. For SHTG, management relies on strict lifestyle changes, fibrates, and high-dose omega-3 fatty acids. While effective to a degree, many patients fail to reach their treatment goals. For MASLD, the first and only drug, Rezdiffra (resmetirom), was approved in 2024, but only for MASH with moderate-to-advanced fibrosis, leaving a large population of earlier-stage patients without a targeted therapy.

TLC-2716’s unique profile could position it as a vital new tool for physicians. By simultaneously lowering triglycerides, atherogenic cholesterol, and potentially reducing liver fat, it could address the interconnected pathologies that drive cardiovascular disease in this population.

“By improving key lipid parameters and reducing hepatic fat, TLC-2716 has the potential to address severe hypertriglyceridemia, elevated remnant cholesterol, and MASH—major contributors to cardiovascular morbidity and mortality,” stated Mani Subramanian, MD, PhD, Chief Executive Officer of OrsoBio.

OrsoBio’s Calculated Play in a Competitive Market

For OrsoBio, the Nature Medicine publication is more than a scientific victory; it is a major strategic validation that significantly de-risks its lead program. Founded in 2020, the privately held company has methodically built a robust pipeline focused on central pathways in energy metabolism.

The company's progress has attracted significant financial backing, with over $160 million raised to date. Notably, its investor syndicate includes major life science venture firms like Longitude Capital and Enavate Sciences, as well as the strategic corporate venture arm of pharmaceutical giant Eli Lilly and Company, a dominant player in the diabetes and obesity markets. This strong financial footing and high-profile backing provide the stability needed to advance its ambitious clinical programs.

Beyond TLC-2716, OrsoBio is developing a portfolio of other promising candidates, including mitochondrial protonophores for obesity and an ACC2 inhibitor for insulin resistance and diabetes. This multi-asset strategy positions the company as a serious contender in the highly competitive metabolic disease space, which has seen explosive growth with the success of GLP-1 agonists. The validation of its novel LXR platform strengthens its overall value proposition and could pave the way for future partnerships or an initial public offering.

The Path Forward to Pivotal Data

With the mechanism now validated in humans, all eyes are on the next critical step for TLC-2716. The drug is currently being evaluated in a Phase 2a clinical trial (NCT06564584), which is actively recruiting patients with both hypertriglyceridemia and MASLD.

This randomized, double-blind, placebo-controlled study is designed to confirm the efficacy and safety of TLC-2716 in the target patient population. The trial will measure changes in fasting triglycerides, liver fat content via MRI, and a host of other metabolic biomarkers.

OrsoBio anticipates reporting topline data from this pivotal study in the first half of 2026. The results will provide the first clear look at the drug's therapeutic potential in patients and will be a crucial determinant of its path toward regulatory approval and its ultimate role in managing these widespread and serious metabolic conditions.