Tangram Therapeutics Advances TGM-312 to Patient Cohorts in Phase 1/2 RESTORE-MASH Trial for MASH Treatment

September 13, 2026

BioSpace USA

Overview

Tangram Therapeutics announced the progression of TGM-312, a novel GalNAc-siRNA therapeutic for MASH (Metabolic Dysfunction-Associated Steatohepatitis), to patient cohorts in its Phase 1/2 RESTORE-MASH trial. TGM-312 employs a differentiated dual mechanism of action by liver-specifically silencing the SLC25A5 gene, addressing both inflammation and steatosis, key drivers of MASH. This investigational drug, with its potential for quarterly subcutaneous dosing, could significantly reduce patient burden and set a new standard in MASH therapy.

In Depth

Key Findings

Tangram Therapeutics has announced the progression to patient cohorts in its Phase 1/2 RESTORE-MASH clinical trial for TGM-312, a novel GalNAc-siRNA therapy under development for Metabolic Dysfunction-Associated Steatohepatitis (MASH). This advancement follows promising preclinical and initial clinical safety and pharmacokinetic data, signaling a significant step forward in MASH treatment.

Technical and Clinical Details

TGM-312 is based on small interfering RNA (siRNA) technology, utilizing a liver-specific GalNAc (N-acetylgalactosamine) conjugate to enable targeted delivery to hepatocytes. The drug is engineered to silence the expression of the SLC25A5 gene, a critical driver in MASH pathophysiology. SLC25A5 is a protein that modulates mitochondrial function and influences hepatic fat accumulation and inflammation. TGM-312’s dual mechanism of action distinguishes it from existing and developing therapies by addressing both steatosis (fat accumulation in the liver) and inflammation, two primary facets of MASH. A key clinical advantage anticipated is a convenient, less burdensome quarterly subcutaneous dosing regimen, which could significantly improve patient adherence over the long term. The transition to patient cohorts in the Phase 1/2 study indicates successful completion of the initial safety assessment phase and ongoing evaluation of its pharmacological effects.

Background & Context

MASH is a severe and escalating chronic liver disease globally, with the potential to progress to cirrhosis, liver failure, and hepatocellular carcinoma. Currently, approved effective treatments for MASH are limited, representing a high unmet medical need. siRNA-based therapies are gaining traction as a promising approach for multifactorial diseases like MASH, given their ability to target and suppress specific gene expressions responsible for the root causes of disease. Tangram Therapeutics’ TGM-312 seeks to differentiate itself in the competitive MASH therapeutic market through its unique mechanism of action and convenient administration method. This development underscores the growing maturity of RNA-based therapeutics and their potential to address challenging diseases.

Strategic Significance & Outlook

The progression of TGM-312 into patient cohorts within the RESTORE-MASH trial signifies a crucial advancement in MASH drug development. If the drug demonstrates favorable efficacy and safety data through its dual mechanism of action and convenient dosing, it could substantially broaden treatment options for MASH patients. Specifically, a quarterly dosing schedule would improve patient quality of life (QOL) and establish a significant competitive advantage in the market. Should future clinical data meet expectations, Tangram Therapeutics is poised to become a key player in the MASH treatment landscape, potentially influencing the development of siRNA approaches for other liver diseases.

Source: https://www.biospace.com/press-releases/tangram-therapeutics-announces-progression-to-patient-cohorts-in-phase-1-2-restore-mash-trial-of-tgm-312-and-appointment-of-dr-sonya-montgomery-as-chief-development-officer

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