TGM-148 enhances thrombin generation in impaired hemostasis
No thrombotic safety signals at repeat toxicology doses in healthy non-human primates
Phase 1 trial in healthy volunteers underway, with initial data anticipated in 2027
LONDON, Nov. 04, 2026 (GLOBE NEWSWIRE) -- Tangram Therapeutics ("Tangram"), a company committed to unlocking transformative RNAi medicines for meaningful patient impact, today announced that preclinical data from TGM-148, a novel GalOmic medicine for bleeding disorders, will be presented in an oral session at the 68th American Society of Hematology (ASH) Annual Meeting, taking place 12-15 December 2026 in New Orleans, Louisiana.
TGM-148 silences Protein Z-dependent Protease Inhibitor (ZPI), a natural regulator of coagulation. It is designed to combine robust hemostatic efficacy with low thrombotic risk and infrequent administration (four or fewer subcutaneous doses a year) to substantially reduce the burden of prophylaxis. In preclinical proof-of-concept studies, TGM-148 demonstrated efficacy in four distinct genetic disease models, including a model of von Willebrand disease (VWD), the planned entry indication.
Tangram's oral presentation at ASH will highlight TGM-148's unique, context-dependent mechanism of action. In non-human primate plasma depleted of factor VIII, modeling a deficiency that causes hemophilia A and is common in VWD, TGM-148 dose-dependently enhanced thrombin generation. In non-depleted plasma, TGM-148 had no effect on thrombin generation, consistent with ZPI's adaptive role in regulating coagulation. In addition, TGM-148 was well tolerated up to the highest dose tested in a repeat-dose toxicology study in healthy non-human primates, supporting a wide therapeutic window. Together, these findings demonstrate TGM-148's potential to restore hemostatic balance in people with bleeding disorders without increasing thrombotic risk.
"We are pleased to present data at ASH showcasing TGM-148's context-dependent mechanism of action, which was a key reason we chose to pursue this novel target. With this differentiated mechanism, and the prospect of quarterly or less frequent dosing, TGM-148 has the potential to offer effective, patient-friendly prophylaxis with a wide therapeutic window", said Alan Whitmore, BM BCh, FFPM, PhD, Chief Scientific Officer of Tangram.
"People living with bleeding disorders need more prophylactic options, and the data Tangram will be presenting highlight the potential of TGM-148 as a novel approach. I am excited to see it progress through clinical development to evaluate ZPI silencing as a viable mechanism for rebalancing hemostasis," added Robert F. Sidonio, Jr MD, MSc, Pediatric Hematologist at Hemophilia of Georgia Pediatric Center for Bleeding and Clotting Disorders, Emory University School of Medicine.
Presentation Details
Title: TGM-148, a Novel GalNAc-siRNA Targeting ZPI, Demonstrates Context-dependent Hemostatic Rebalancing in Cynomolgus Monkeys
Publication Number: 953
Session Name: 801. Gene Therapies: Beyond Transplant: The Expanding Role of Gene Therapy in Hematology
Session Date & Time: 14 December, 14:45-16:15
Location: MCCNO - 388-390
About TGM-148
TGM-148 is a first-on-target GalOmic GalNAc-conjugated small interfering RNA (GalNAc-siRNA) designed to selectively silence Protein Z-dependent Protease Inhibitor (ZPI) in the liver, where it is produced before circulating in the blood. Its context-dependent mechanism of action aims to enhance clotting in response to bleeding in those with bleeding disorders, while maintaining a favorable safety profile.
In preclinical studies, TGM-148 demonstrated efficacy in four genetic bleeding disorder models and was well tolerated at supratherapeutic doses in wildtype animals. Together, these findings support TGM-148's wide therapeutic window and provide a strong rationale for its development across a broad range of bleeding disorders, with VWD selected as the first indication. By offering the potential for quarterly or less frequent subcutaneous administration, TGM-148 is also designed to lower the barriers to prophylaxis, supporting broader uptake, better outcomes, and improved quality of life for patients.
About Tangram Therapeutics
Tangram Therapeutics is a clinical-stage biotech committed to unlocking transformative RNAi medicines for meaningful patient impact. Real progress in the treatment of diseases with high unmet need calls for drug discovery and development that goes beyond the obvious. Tangram pursues differentiated target genes, developing innovative medicines enabled by GalOmic, the Company's proprietary RNAi chemistry platform designed to selectively silence disease-associated genes in hepatocytes. Tangram is advancing a pipeline of investigational RNAi medicines for real-world patient benefit, including TGM-312 for the treatment of MASH and TGM-148 for the treatment of bleeding disorders.
Learn more at www.tangramtx.com.
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