OrsoBio’s experimental oral drug lowered fasting triglyceride levels at four weeks of treatment, hitting the primary efficacy goal in a midstage study of metabolic conditions.
The California company is evaluating TLC-2716, a liver X receptor (LXR) inverse agonist, among patients with severe hypertriglyceridemia (SHTG) and metabolic dysfunction–associated steatotic liver disease (MASLD), the latter of which is a common condition tied to risk factors like obesity, diabetes and high blood pressure.
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.
The proof-of-concept study was also examining the safety of TLC-2716, which the California biotech said was “generally well tolerated,” with zero grade 3 or higher adverse events occurring.
OrsoBio is now “exploring financing options to move this compound into the next phase of development, which will be a phase 2b study,“ a company spokesperson told Fierce, adding that the biotech is open to a partnership but is currently pursuing a path to move forward independently.
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“These phase 2a data provide compelling clinical validation of LXR inverse agonism as a differentiated therapeutic strategy for severe metabolic disorders,” OrsoBio’s chief medical officer and development head, Rob Myers, M.D., said in a Feb. 10 release.
“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,” Myers said.
MASH, or metabolic dysfunction-associated steatohepatitis, is a more severe form of MASLD, which currently affects about 30% of the world’s population.
OrsoBio debuted near the end of 2022 with its sights set on several metabolic diseases. Both CMO Myers and CEO Mani Subramanian, M.D., are alums of Gilead Sciences, where they worked on liver diseases.
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The company even licensed a liver-targeted mitochondrial protonophore called TLC-6740 from Gilead. At the end of 2025, the asset was tied to an additional 4.5% mean weight loss when paired with tirzepatide versus tirzepatide alone in a phase 1b/2a obesity trial. OrsoBio is planning a phase 2b trial for the asset for this year.
As for the liver-targeting TLC-2716, OrsoBio snagged the program from Phenex Pharmaceuticals.
