Tangram Therapeutics has advanced its experimental MASH treatment TGM-312 into patient cohorts in the Phase 1/2 RESTORE-MASH trial, a key step in the clinical development of the company’s RNAi platform.
The biotech also appointed Sonya Montgomery as Chief Development Officer, bringing more than 25 years of drug development experience to the company as it expands its clinical pipeline.
MASH, a common and potentially serious liver disease, affects an estimated 250 million people globally. Despite recent treatment advances, Tangram says significant unmet need remains for effective therapies that offer improved tolerability and lower treatment burden.
TGM-312 is an investigational GalOmic siRNA designed to target SLC25A5, a gene the company says plays a role in inflammation and steatosis — two key drivers of MASH and other chronic liver diseases.
The program has now moved from single ascending dose testing in healthy volunteers to multiple ascending dose testing in patients with MASH following a favorable review by an independent Data Monitoring Committee.
Tangram said TGM-312 has so far been administered across four healthy-volunteer cohorts without serious or severe adverse events. The company expects to report interim data from MASH patients in 2027.
“The progression of TGM-312 into MASH patient cohorts marks an important step forward for Tangram and reflects the strength of our GalOmic platform and the dedication of our team.” said Laura Roca-Alonso, Interim Chief Executive Officer.
“Sonya's appointment comes at exactly the right time to build on this momentum, and her broad experience will be invaluable as we continue to advance our programs towards and through the clinic."
Montgomery joins Tangram after senior leadership roles across pharma and biotech, including positions at Pfizer, ProQR, Gyroscope Therapeutics and Evox Therapeutics. Most recently, she served as Chief Development Officer at OSE Immunotherapeutics.
“I am pleased to join Tangram at this pivotal moment for the company”, added Sonya Montgomery, “TGM-312 has the potential to make a meaningful difference for people living with MASH, and I'm looking forward to helping drive its development, as well as progressing Tangram’s broader innovative pipeline, including TGM-148 for bleeding disorders.”
Tangram is positioning TGM-312 as a potentially differentiated treatment because of its liver-directed mechanism and dual mode of action. The company says the therapy is designed to selectively silence SLC25A5 in liver cells, potentially allowing infrequent dosing while limiting systemic exposure.
Preclinical studies in the GAN-DIO mouse model showed reductions in NAFLD Activity Score, hepatic inflammation and fibrosis progression, according to the company. Tangram also reported synergistic effects when TGM-312 was combined with approved and emerging MASH therapies.
The company says the drug could ultimately be developed both as a standalone treatment and in combination with other therapies across different stages of disease.
TGM-312 is part of Tangram’s broader RNAi pipeline, which is built around its proprietary GalOmic chemistry platform for selectively silencing disease-driving genes in hepatocytes. The company is also developing TGM-148 for bleeding disorders.
