Sirius Therapeutics Announces First Patient Dosed in Phase 1/2a Trial of SRSD384, a Novel INHBE-Targeting siRNA for Obesity

First-in-human study evaluates SRSD384 as a non‑hormonal, muscle‑sparing approach to obesity and metabolic health

San Diego, U.S. and Shanghai, China – Sirius Therapeutics today announced that the first patient has been dosed in a Phase 1/2a clinical trial of SRSD384, a novel small interfering RNA (siRNA) candidate designed to target Inhibin Subunit Beta E (INHBE) for the treatment of obesity. SRSD384 represents a genetically validated, non‑incretin approach to addressing the global obesity epidemic, with the potential to promote fat reduction while preserving lean muscle mass.

The Phase 1/2a study is a two‑part, first‑in‑human trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SRSD384 in overweight or obese participants. Part A will assess single ascending doses of SRSD384 as monotherapy; Part B will explore SRSD384 in combination with tirzepatide in overweight or obese participants with type 2 diabetes mellitus (T2DM). The study is being conducted at clinical sites in Australia, and the company expects to report interim data in the first half of 2027.

“Dosing the first patient in the Phase 1/2a trial of SRSD384 marks a significant milestone for Sirius Therapeutics and for patients living with obesity,” said Dr. Patrick Yue, Chief Medical Officer of Sirius Therapeutics. “By targeting INHBE, a genetically validated regulator of metabolic homeostasis, we aim to recapitulate the naturally protective metabolic traits observed in individuals with loss‑of‑function INHBE variants—including lower abdominal fat, reduced triglycerides, and a lower risk of type 2 diabetes and coronary heart disease. SRSD384 offers a differentiated, non‑incretin mechanism that promotes fat loss while sparing muscle, addressing a key limitation of current GLP-1‑based therapies and providing a new option for the millions of patients who struggle with chronic weight management.”

About Obesity

Obesity is a complex, chronic metabolic disease that affects nearly one billion people worldwide. It is a major driver of non‑communicable diseases, including cardiovascular disease, type 2 diabetes, certain cancers, and metabolic dysfunction‑associated steatotic liver disease (MASLD). Despite advances in GLP‑1‑based therapies, significant unmet need remains, including GI intolerance, loss of lean muscle mass during weight reduction, and high discontinuation rates. Novel mechanisms that promote healthy, muscle‑sparing weight loss is a strong unmet medical need.

About SRSD384

SRSD384 is a novel, double‑stranded GalNAc‑conjugated siRNA therapeutic designed to silence the INHBE gene in the liver. INHBE encodes Activin E, a hepatokine that regulates adipose tissue function via the ALK7 receptor. By silencing INHBE, SRSD384 reduces Activin E levels, promoting fat breakdown while preserving lean muscle. The candidate has demonstrated potent, durable target suppression in preclinical models and has advanced into a first‑in‑human Phase 1/2a study in overweight or obese participants. SRSD384 is being developed both as a monotherapy and in combination with established incretin‑based agents to enhance metabolic outcomes.

About Sirius Therapeutics

Sirius is a global, clinical-stage biotech company developing innovative siRNA therapies focusing on the treatment of chronic diseases. The Company's pipeline is centered around three key franchises with mega blockbuster potential: coagulation disorders, cardiometabolic diseases, and obesity. Sirius' most advanced investigational programs include SRSD107, a FXI inhibitor targeting the anticoagulation market, SRSD216, an inhibitor of Lp(a) synthesis intended to address atherosclerotic cardiovascular disease, and SRSD384, an INHBE inhibitor for managing obesity.

Founded in 2021 by a world-class leadership team and investors, Sirius has established an innovation center in the United States and a translational medicine center in China. Sirius has raised nearly US$150 million in funding to date from OrbiMed, Creacion Ventures, Hankang Capital, Delos Capital, and BioTrack Capital.

Forward‑Looking Statements

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Contact:

ir@siriusrna.com