Sirus Therapeutics announced positive results from its Phase I clinical trial of SRSD107, a novel small interfering RNA (siRNA) therapeutic, at the 66th American Society of Hematology (ASH) Annual Meeting in San Diego. The study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneously administered SRSD107 in healthy volunteers, revealing promising signals for its potential in preventing and treating thromboembolic disorders.
Targeting Factor XI for Anticoagulation
SRSD107 is designed to inhibit Factor XI (FXI), a key component of the intrinsic coagulation pathway. By selectively targeting FXI, SRSD107 aims to reduce the risk of thrombosis without significantly increasing the risk of bleeding, a common side effect of current anticoagulant therapies. The rationale behind this approach is to offer a safer and more effective alternative for patients at risk of thromboembolic events such as myocardial infarction, ischemic stroke, and venous thromboembolism.
Phase I Trial Results: Safety and Efficacy Signals
The Phase I trial (NCT06116617) was a single-site, randomized, double-blind, placebo-controlled study involving 40 healthy subjects. Participants were divided into five cohorts, each receiving either a single dose of SRSD107 or a placebo. The results indicated that SRSD107 was safe and well-tolerated across all tested doses. Furthermore, the trial demonstrated significant changes in PD biomarkers, with maximal reductions in FXI antigen and activity exceeding 90% at the highest doses. Notably, the activated partial thromboplastin time (aPTT), a measure of blood clotting time, increased by over 100% at these doses, suggesting a potent anticoagulant effect.
Durable Pharmacodynamic Effects
A key finding of the study was the durability of SRSD107's effects. Activity levels of FXI remained suppressed for more than 16 weeks after a single dose, indicating the potential for less frequent administration. Sirus Therapeutics envisions SRSD107 as a twice-yearly treatment, which could significantly improve patient compliance and convenience compared to existing anticoagulants that require daily or more frequent dosing.
Implications for Future Development
"We are encouraged by the marked, prolonged reduction in FXI antigen and activity, and increase in clotting, or thromboplastin time, that are consistent potent anticoagulation over sustained periods and reduced bleeding risk respectively," said Patrick Yue, Chief Medical Officer at Sirus Therapeutics. "The trial provides a strong foundation for Phase II clinical studies."
The company plans to advance SRSD107 into Phase II trials to further evaluate its efficacy and safety in patients at risk of thromboembolic disorders. These studies will likely focus on specific patient populations, such as those undergoing surgery or with a history of venous thromboembolism, to assess the clinical benefit of SRSD107 in preventing thrombotic events.
