CRISPR Therapeutics and Sirius Therapeutics have achieved a significant milestone in their collaborative effort to develop next-generation anticoagulant therapies, announcing that the first patient has been dosed in a Phase 2 clinical trial of SRSD107 in Europe. The novel small interfering RNA (siRNA) therapy targets Factor XI (FXI) for the prevention of venous thromboembolism (VTE) in patients undergoing total knee arthroplasty (TKA).
Addressing Limitations of Current Anticoagulant Options
"Until now, existing anticoagulant options have been limited by bleeding risk, frequent dosing, and complex management challenges for patients with high thrombotic risk," said Naimish Patel, M.D., Chief Medical Officer of CRISPR Therapeutics. "SRSD107 offers the potential to reduce pathological thrombosis while minimizing bleeding risk, with sustained but reversible pharmacodynamic effects and the possibility of infrequent dosing."
The ongoing Phase 2 clinical trial is a randomized, multicenter, global study evaluating the safety and efficacy of SRSD107 for VTE prevention in TKA patients. The trial will assess the anticoagulant effects and pharmacological profile of SRSD107 to inform dose selection for future pivotal studies.
Strong Phase 1 Results Support Advancement
SRSD107 has demonstrated promising results in prior Phase 1 clinical trials conducted in Australia and China. Single doses of the siRNA therapy were well tolerated and showed strong, sustained pharmacodynamic effects, including reductions of over 93% in FXI levels, along with more than a twofold increase in activated partial thromboplastin time (aPTT) relative to baseline. These effects were sustained for up to six months post-dosing.
"This study will evaluate clinical efficacy as proof of concept for Factor XI inhibition using our siRNA approach, building on the positive results from our Phase 1 trials," said Patrick Yue, M.D., Chief Medical Officer of Sirius Therapeutics.
Mechanism and Therapeutic Potential
SRSD107 is designed to selectively inhibit FXI, a key driver of pathological thrombosis, with minimal impact on normal hemostasis. The double-stranded siRNA targets human coagulation factor XI mRNA and inhibits FXI protein expression, modulating the intrinsic coagulation pathway to provide anticoagulant and antithrombotic effects.
The therapy has the potential to be a best-in-class FXI inhibitor, achieving deep reductions in FXI with the possibility of infrequent, semi-annual subcutaneous administration and offering reversibility not observed with other anti-FXI modalities.
Broad Addressable Patient Population
The addressable population for SRSD107 extends well beyond orthopedic surgery patients. The therapy is projected to have utility in patients with atrial fibrillation, VTE, cancer-associated thrombosis, chronic Coronary Artery Disease (CAD), chronic Peripheral Vascular Disease (PVD), end-stage renal disease requiring hemodialysis, and patients undergoing major orthopedic surgery, where bleeding risk limits existing therapies.
Significant Medical Need
Thromboembolic disorders represent a substantial global health burden. Published data in The Lancet estimate that thromboembolic disorders account for approximately one in four deaths worldwide. Thrombosis, or blood clot formation, is the common underlying mechanism of most cases of myocardial infarction, ischemic stroke, and venous thromboembolism.
Strategic Collaboration
CRISPR Therapeutics and Sirius Therapeutics entered into a strategic collaboration in 2025 to develop and commercialize novel siRNA therapies for thromboembolic disorders and other serious diseases. Under the agreement, the companies will co-develop SRSD107 and share costs and profits equally, with CRISPR Therapeutics leading commercialization in the U.S. and Sirius leading in Greater China.
The collaboration expands CRISPR Therapeutics' therapeutic portfolio into RNA-based medicines, complementing its ongoing efforts in gene editing and broadening its impact across serious and chronic diseases. For Sirius, the collaboration marks a major milestone in its mission to deliver innovative RNA-based therapies globally.
