Tangram Therapeutics Initiates First-in-Human Trial of TGM-312 for MASH Treatment
Key Insights
Tangram Therapeutics (search) has dosed the first participant in its Phase 1/2 RESTORE-MASH (search) trial evaluating TGM-312 (search), marking the first clinical trial of a GalOmic medicine.
TGM-312 (search) is a novel GalNAc-siRNA designed to silence a target gene in hepatocytes (search) for treating MASH (search), a serious liver disease affecting over 250 million people globally.
The trial will assess safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers and MASH (search) patients, with initial data expected in H2 2026.
Tangram Therapeutics (search) announced the dosing of the first participant in its Phase 1/2 RESTORE-MASH (search) trial evaluating TGM-312 (search), a novel GalOmic medicine, in healthy volunteers and people living with metabolic dysfunction-associated steatohepatitis (search) (MASH). This milestone marks the first clinical trial of a GalOmic medicine and represents a significant step forward in addressing a serious liver disease that affects more than 250 million people globally.
Novel RNAi Approach Targets MASH
TGM-312 (search) is a GalNAc-conjugated small interfering RNA (GalNAc-siRNA) designed to selectively silence a gene target in the liver for the treatment of steatotic liver diseases, including MASH (search). The investigational therapy has the potential for quarterly subcutaneous administration and features a differentiated mechanism of action that tackles multiple key drivers of MASH.
MASH (search) is characterized by fat accumulation in the liver which can progress to cirrhosis (search), liver failure (search), liver cancer (search), need for liver transplantation, and premature mortality if left untreated. The disease represents a significant unmet medical need with limited treatment options currently available.
Clinical Trial Design and Objectives
The Phase 1/2 RESTORE-MASH (search) trial aims to evaluate TGM-312 (search) in healthy adult volunteers and people with MASH, assessing the safety, tolerability, pharmacokinetics, and pharmacodynamics of the candidate. The MASH cohorts will incorporate liver biopsies alongside exploratory imaging and biomarker assessments to comprehensively evaluate the therapy's effects.
Initial safety data are anticipated in the second half of 2026, providing the first clinical insights into this novel therapeutic approach.
Promising Preclinical Results
In preclinical studies conducted in the highly translational Gubra-Amylin NASH diet-induced obese (GAN-DIO) mouse model, administration of TGM-312 (search) led to dramatic reductions in NAFLD (search) Activity Score (NAS), decreased hepatic inflammation and slowed fibrosis progression. These effects were observed both as monotherapy and in combination with approved and emerging MASH (search) therapies, suggesting potential for broad therapeutic application.
Company Leadership Perspective
"Initiating RESTORE-MASH (search) dosing is a defining moment for Tangram and an important step towards bringing our GalOmic medicines to patients," said Ali Mortazavi, Chief Executive Officer. "Having generated outstanding preclinical data, we're excited to now evaluate TGM-312 (search) in clinical trials. We believe TGM-312 could serve as a differentiated backbone therapy across MASH segments, both as monotherapy and in combination with approved and emerging treatments."
Mortazavi emphasized that TGM-312 (search) has the potential to offer a patient-friendly treatment option to support liver health in a rapidly evolving therapeutic landscape.
GalOmic Platform Technology
TGM-312 (search) is complementary to approved and emerging therapies, supporting potential use both as monotherapy and in combination across a broad range of disease stages. The therapy is enabled by Tangram's proprietary GalOmic RNAi chemistry platform, which is designed to selectively silence disease-driving genes in hepatocytes (search).
Tangram Therapeutics (search) is a clinical-stage biotech company that combines computation, RNAi, and unconventional approaches to accelerate medicine development. The company's discovery efforts are powered by LLibra OS, a next-generation AI platform with agentic infrastructure, which together with the GalOmic platform forms the foundation of their drug development approach.