CRISPR Therapeutics Expands into siRNA Therapies with $95M Sirius Partnership for Thromboembolic Disorders
核心洞察
CRISPR Therapeutics is diversifying beyond gene editing through a strategic $95 million partnership with Sirius Therapeutics (搜索) to develop SRSD107, a long-acting siRNA therapy targeting Factor XI (搜索) for thromboembolic disorders (搜索).
In Phase 1 trials, SRSD107 demonstrated impressive efficacy with over 93% reduction in Factor XI (搜索) levels and doubled blood clotting time, with effects lasting up to six months from a single dose.
The collaboration includes a 50-50 cost and profit-sharing structure for SRSD107 development, with CRISPR leading U.S. commercialization and retaining rights to license two additional siRNA targets.
CRISPR Therapeutics has announced a strategic partnership with Sirius Therapeutics (搜索) to co-develop and co-commercialize SRSD107, a next-generation small interfering RNA (siRNA) therapy targeting Factor XI (搜索) for thromboembolic disorders (搜索). The deal, announced Monday, includes a $25 million upfront cash payment and a $70 million equity investment in Sirius.
This collaboration marks a significant expansion of CRISPR's therapeutic approach beyond its core gene-editing technology, as the company looks to develop a broader range of transformative gene-based medicines.
Promising Clinical Data for SRSD107
SRSD107 has already shown compelling results in Phase 1 clinical trials. The investigational therapy demonstrated peak reductions in Factor XI (搜索) activity exceeding 93% and more than doubled activated partial thromboplastin time (aPTT), a measure of how long blood takes to clot. Importantly, these effects were maintained for up to six months after a single dose.
"SRSD107 offers the potential for a therapy with lower bleeding risk, infrequent dosing for better compliance, without concerns for renal clearance or drug interactions, and reversibility to further mitigate bleeding risks that could be differentiated from currently available therapies and other Factor XI (搜索) modalities," said Christian T. Ruff, M.D., M.P.H., senior investigator of TIMI Group and director of General Cardiology at Brigham and Women's Hospital.
The therapy's mechanism of action targets Factor XI (搜索), a key driver of pathological thrombosis that has minimal impact on normal hemostasis. This approach aims to reduce thrombotic events while minimizing bleeding risk—a significant advantage over current Factor Xa inhibitors.
Expanding Therapeutic Applications
The potential applications for SRSD107 extend beyond its initial focus. The addressable patient population includes those with:
- Atrial fibrillation
- Venous thromboembolism (VTE)
- Cancer-associated thrombosis
- Chronic coronary artery disease
- Chronic peripheral vascular disease
- End-stage renal disease requiring hemodialysis
- Patients undergoing major orthopedic surgery
A Phase 2 clinical trial is now being initiated to evaluate SRSD107's safety and efficacy for preventing VTE in patients undergoing total knee arthroplasty.
Strategic Significance for CRISPR Therapeutics
For CRISPR Therapeutics, this partnership represents a strategic diversification beyond its flagship CRISPR/Cas9 gene-editing platform, which led to the historic approval of CASGEVY (exagamglogene autotemcel) for sickle cell disease (搜索) and transfusion-dependent beta thalassemia (搜索).
"We are excited to partner with Sirius, and broaden our cardiovascular medicine portfolio, on the heels of promising top-line data that we recently shared for CTX310, which targets ANGPTL3 (搜索)," said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. "Sirius' siRNA platform complements our existing capabilities and expands our therapeutic toolkit, enabling us to develop a broader range of transformative gene-based medicines."
Analysts at William Blair viewed the collaboration positively, noting that it "provides additional synergies for CRISPR's cardiovascular pipeline" and expands the company's offerings "beyond 'one and done' therapies" like CASGEVY.
Collaboration Structure
Under the agreement, CRISPR Therapeutics and Sirius will jointly develop SRSD107 with a 50-50 cost and profit-sharing structure. CRISPR will lead commercialization efforts in the United States, while Sirius will be responsible for the Greater China region.
Additionally, CRISPR has the option to nominate up to two additional siRNA targets for research and development. For these programs, CRISPR will fund research activities and retain opt-in rights to lead clinical development and commercialization, with Sirius eligible to receive milestone payments and tiered royalties ranging from high single to low-double digits.
Addressing a Significant Global Health Burden
Thromboembolic disorders (搜索) represent a substantial unmet medical need globally. According to data cited from The Lancet, these conditions are estimated to cause as many as one in four deaths worldwide.
"Thrombotic diseases represent a significant unmet need, and our promising Phase 1 data highlights the potential of SRSD107 as a best-in-class Factor XI (搜索)-targeted therapy," said Qunsheng Ji, MD, Ph.D., Chief Executive Officer of Sirius Therapeutics (搜索).
The semi-annual subcutaneous injection schedule proposed for SRSD107 could also address compliance challenges associated with current daily oral anticoagulants, potentially improving long-term patient outcomes.
Looking Ahead
This partnership comes as CRISPR Therapeutics anticipates several key milestones in 2025. In its cardiovascular portfolio, the company awaits data for its in vivo therapy CTX320, which is being studied in patients with elevated lipoprotein(a) levels, with results expected in the second quarter.
As the collaboration progresses, the companies will work to advance SRSD107 through clinical development, with the Phase 2 trial results likely to inform dose selection for future pivotal studies and potentially establish this therapy as a significant new option for patients at risk of thromboembolic events.