Tangram's TGM-312 Advances to MASH Patient Cohorts in Phase 1/2 RESTORE-MASH Trial
核心洞察
Tangram Therapeutics (搜索) announced progression of its investigational GalNAc-siRNA TGM-312 (搜索) into Part B (multiple ascending dose) of the phase 1/2 RESTORE-MASH trial in MASH patients, following favorable independent Data Monitoring Committee review.
TGM-312 (搜索), a GalOmic siRNA targeting SLC25A5 (搜索), has been dosed across four healthy volunteer cohorts with no serious or severe adverse events, de-risking its novel mechanism and proprietary chemistry.
The company also appointed Dr Sonya Montgomery, a veteran with over 25 years of development experience, as chief development officer to lead its clinical pipeline.
Tangram Therapeutics (搜索) has advanced its investigational RNAi therapy TGM-312 (搜索) into Part B of the ongoing phase 1/2 RESTORE-MASH trial, marking the first dosing of the candidate in patients with metabolic dysfunction-associated steatohepatitis (搜索) (MASH). The progression follows a favorable independent Data Monitoring Committee review and moves the trial from single ascending dose (SAD) in healthy volunteers to multiple ascending dose (MAD) in MASH patients.
"The progression of TGM-312 (搜索) 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 Dr Laura Roca-Alonso, Interim Chief Executive Officer.
MASH is a common liver condition, affecting an estimated 250 million people globally and causing significant morbidity and mortality. Despite recent approvals in the space, substantial unmet need remains for efficacious treatments with good tolerability and lower patient burden.
A Dual Mode of Action Targeting Key MASH Drivers
TGM-312 (搜索) is a novel GalOmic GalNAc-conjugated small interfering RNA (GalNAc-siRNA) designed to selectively silence SLC25A5 (搜索) in the liver for the treatment of steatotic liver diseases, including MASH, with potential for quarterly subcutaneous administration. The candidate has a differentiated dual mode of action that directly impacts inflammation and steatosis, the key drivers of MASH and other chronic liver conditions.
The target was discovered in-house using Tangram's proprietary network biology approach in combination with MASH/MASLD population genetic data. TGM-312 (搜索)'s liver-directed mechanism is designed to minimize systemic side effects, offering a patient-friendly, infrequently dosed treatment option.
Preclinical Evidence and Combination Potential
In preclinical studies in the highly translational Gubra-Amylin NASH diet-induced obese (GAN-DIO) mouse model, administration of TGM-312 (搜索) led to dramatic reductions in NAFLD Activity Score (NAS), decreased hepatic inflammation and slowed fibrosis progression, both as monotherapy and in synergistic combination with approved and emerging MASH therapies.
TGM-312 (搜索)'s dual mode of action tackles multiple key drivers of MASH and is complementary to approved and emerging therapies, supporting potential use both as monotherapy and in combination across a broad range of disease stages.
Safety Profile and Clinical Timeline
TGM-312 (搜索) has been dosed across four cohorts of healthy volunteers to date with no serious or severe adverse events, de-risking both its novel mechanism of action and Tangram's proprietary GalOmic chemistry more broadly. Interim MASH patient data are anticipated during 2027.
Leadership Appointment
Tangram also announced the appointment of Dr Sonya Montgomery as chief development officer to lead the advancement of the company's clinical pipeline. Dr Montgomery brings over 25 years' experience designing and executing portfolio and development strategies, from translational research through registration, with work spanning a wide range of therapeutic areas and modalities, including genetic medicines.
Following her training in engineering and medicine in Canada, Dr Montgomery held global leadership positions at Pfizer and subsequently served as vice president clinical development at ProQR, vice president and head of clinical development at Gyroscope Therapeutics, chief medical officer at Evox Therapeutics, and, most recently, chief development officer at OSE Immunotherapeutics.
"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," said Dr Roca-Alonso.
"I am pleased to join Tangram at this pivotal moment for the company," added Dr Montgomery. "TGM-312 (搜索) 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 (搜索) for bleeding disorders."
Tangram Therapeutics (搜索) is a clinical-stage biotech committed to unlocking transformative RNAi medicines, developing innovative medicines enabled by GalOmic, its proprietary RNAi chemistry platform designed to selectively silence disease-driving genes in hepatocytes.