CRISPR Therapeutics and Sirius Therapeutics Announce Multi-Target Collaboration to Develop Novel siRNA Therapies

CRISPR Therapeutics, a Swiss biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, and Sirius Therapeutics, a sino-american clinical stage biotech company developing innovative small interfering RNA (siRNA) therapies for global markets, have concluded a strategic partnership to develop and commercialize siRNA therapies. Collaboration brings together complementary capabilities to co-develop and co-commercialize SRSD107, a next generation, long-acting Factor XI (FXI) siRNA for the treatment of thromboembolic disorders. SRSD107 is a next generation, long-acting siRNA designed to selectively inhibit FXI, a key driver of pathological thrombosis with minimal impact on normal hemostasis.
SRSD107 specifically targets the human coagulation FXI mRNA and inhibits FXI protein expression, thereby blocking the intrinsic coagulation pathway and promoting anticoagulant/anti-thrombotic effects. SRSD107 has been engineered for the potential to enable twice-a-year dosing. By targeting FXI, SRSD107 aims to reduce thrombotic events while minimizing the risk of bleeding – representing a differentiated approach compared to Factor Xa inhibitors. In addition, SRSD107 may offer the potential for reversibility not observed with other anti-Factor XI modalities. The addressable population includes patients with atrial fibrillation, venous thromboembolism, cancer-associated thrombosis, chronic Coronary Artery Disease, chronic Peripheral Vascular Disease, end-stage renal disease requiring hemodialysis, and patients undergoing major orthopedic surgery, where bleeding risk limits existing therapies.

The clinical program for SRSD107 includes two Phase 1 clinical trials, where single doses of SRSD107 were found to be safe and well tolerated. In addition, SRSD107 demonstrated robust pharmacodynamic effects, including reductions of over 93% in FXI levels and FXI activity, along with more than a twofold increase in activated partial thromboplastin time relative to baseline. These effects were sustained, with responses maintained for up to 6 months post-dosing. SRSD107 has the potential to be a best-in-class FXI inhibitor, showing deep reductions in FXI via semi-annual subcutaneous injection. Results from the Phase 1 trials were presented at both the 2025 Annual Scientific Sessions of the American College of Cardiology and the 2024 Annual Meeting of the American Society of Hematology.

Figure 1. SRSD107 Phase 1 Clinical Results: Sustained, dose-dependent pharmacodynamic response to therapy

A Phase 2 clinical trial of SRSD107 is being initiated to evaluate its safety and efficacy for the prevention of VTE in patients undergoing total knee arthroplasty. The trial aims to confirm the anticoagulant benefits of SRSD107 and to inform dose selection for future pivotal trials.

Collaboration Details
Under the terms of the agreement, CRISPR Therapeutics will make an upfront payment of $25 million in cash and $70 million in equity to Sirius Therapeutics. The companies will jointly develop SRSD107 under a 50-50 cost and profit-sharing structure. CRISPR Therapeutics will lead commercialization in the U.S., while Sirius will be responsible for commercialization in Greater China. Additionally, CRISPR Therapeutics will have the option to nominate up to two siRNA targets for research and development. For each target, CRISPR Therapeutics will fund research and retain opt-in rights to lead clinical development and commercialization. Sirius will be eligible to receive milestone payments, as well as tiered royalties ranging from high single to low-double digits.

21/05/2025