Tangram Therapeutics Advances Novel RNAi Therapy TGM-312 to Clinical Trials for MASH Treatment
Key Insights
Tangram Therapeutics (search) has submitted a Clinical Trial Application to the MHRA for TGM-312 (search), a novel GalNAc-siRNA therapeutic targeting metabolic dysfunction-associated steatohepatitis (search) (MASH (search)).
The Phase 1/2 study will evaluate safety, tolerability, and efficacy in healthy volunteers and MASH (search) patients, with trial initiation expected in early 2026 and initial data anticipated in H2 2026.
Preclinical studies in the GAN-DIO mouse model demonstrated dramatic reductions in NAFLD (search) Activity Score, decreased hepatic inflammation, and slowed fibrosis progression.
Tangram Therapeutics (search) announced the submission of a Clinical Trial Application (CTA) to the Medicines and Healthcare products Regulatory Agency (MHRA) for TGM-312 (search), an investigational GalNAc-siRNA designed to treat metabolic dysfunction-associated steatohepatitis (search) (MASH (search)). The submission marks a significant milestone as the company transitions from preclinical development to becoming a clinical-stage biotechnology company.
Novel RNAi Approach Targets Hepatocyte Gene Silencing
TGM-312 (search) is a GalOmic GalNAc-conjugated small interfering RNA (GalNAc-siRNA) therapeutic candidate that specifically silences a novel gene in hepatocytes (search). The therapy is designed to address the substantial unmet medical need in MASH (search) treatment, offering a differentiated and patient-friendly therapeutic option.
"The submission of our first CTA is a significant milestone for Tangram. It is a testament to the power of combining AI and RNAi to discover novel medicines and the passion of our lean team," commented CEO Ali Mortazavi. "TGM-312 (search) has the potential to offer a differentiated and patient-friendly therapeutic option for people living with MASH (search), where substantial unmet need remains."
Phase 1/2 Trial Design and Timeline
The proposed Phase 1/2 study will evaluate TGM-312 (search) in both healthy adult volunteers and patients with MASH (search). The trial will assess multiple parameters including safety, tolerability, pharmacokinetics, and pharmacodynamics of the candidate. Additionally, the study will incorporate liver biopsies and exploratory imaging and biomarker endpoints specifically in MASH patients.
Pending regulatory clearance, the study is expected to commence in early 2026 in the United Kingdom, with initial data anticipated in the second half of 2026. The therapy has potential for a patient-friendly quarterly subcutaneous dosing regimen.
Promising Preclinical Results
In preclinical studies conducted in the highly translational Gubra-Amylin NASH diet-induced obese (GAN-DIO) mouse model, TGM-312 (search) demonstrated significant therapeutic effects. Administration of the therapy led to dramatic reductions in NAFLD (search) Activity Score (NAS), decreased hepatic inflammation, and slowed fibrosis progression. These benefits were observed both as monotherapy and in combination with approved and emerging MASH (search) therapies.
Platform Technology and Company Background
The CTA submission represents the advancement of Tangram's GalOmic RNAi platform into clinical development. Tangram Therapeutics (search) positions itself as a company committed to uniting computation and RNAi to accelerate medicine development. The company's innovative medicines are enabled by GalOmic, their proprietary RNAi chemistry platform designed to selectively silence disease-driving genes in hepatocytes (search).
Discovery efforts are powered by LLibra OS, the company's next-generation AI platform with agentic infrastructure. According to the company, the combination of these platforms forms the foundation of their approach to faster, smarter development of RNAi medicines designed for real-world impact.
Tangram is advancing a pipeline of GalOmic RNAi medicines targeting a broad range of diseases with high unmet medical need, with TGM-312 (search) serving as their lead pipeline program entering clinical development.