Data Readout

CRISPR's FXI siRNA CTX611 heads toward H2 2026 data versus enoxaparin in TKA

A four-arm Phase 2 trial testing whether subcutaneous SRSD107 can cut VTE after knee replacement without a validated Factor XI precedent to lean on.

By AppliedXLJuly 13, 2026Trial NCT07140523

Executive Summary

CRISPR Therapeutics and its siRNA partner Sirius Therapeutics are testing whether a Factor XI-targeting siRNA can prevent blood clots after knee replacement surgery, measured head-to-head against the standard injectable anticoagulant.
No Factor XI-directed therapy has yet produced a comparative readout in this surgical population, so the trial's result will be an early test of whether inhibiting this clotting factor translates into a clinical benefit without added bleeding risk.
The study has moved through its early conduct without enrollment target changes or endpoint amendments, and the sponsor has repeated the same second-half 2026 data guidance across two separate disclosures.
The trial sits in a Factor XI landscape still dominated by Phase 3 programs from Regeneron testing an antibody against a different clotting stage, leaving CTX611 as one of a small number of siRNA entrants without a resolved same-mechanism precedent in this exact surgical setting.

The trial

The Phase 2 study, registered as NCT07140523, is randomizing 450 adults aged 60 to 80 undergoing elective unilateral total knee arthroplasty across four arms: three experimental dosing cohorts of SRSD107 and one active comparator arm of enoxaparin. Patients take the study drug subcutaneously starting at least 28 days before surgery, and the trial checks for clots with venography 10 to 14 days after the procedure. CRISPR Therapeutics said it expects top-line data from the study in the second half of 2026, first disclosed in a January 12, 2026 strategic-priorities release and repeated in its fourth-quarter and full-year 2025 business update. NCT07140523+1

Probability of Success

Endpoint Met49%

Completes96%

Clinical Significance9%

Regulatory60%

The endpoint bar

The registered primary endpoint is the incidence of total venous thromboembolism events, measured against enoxaparin, the guideline-standard low-molecular-weight heparin used for VTE prophylaxis after joint replacement. Eight secondary endpoints track bleeding, including major bleeding, clinically relevant non-major bleeding, and the composite of both against VTE incidence, so the trial is built to weigh efficacy against a bleeding trade-off rather than efficacy alone. That structure matters for a Factor XI mechanism specifically: the biological rationale for targeting Factor XI, rather than the more established Factor Xa or thrombin pathways used by rivaroxaban, apixaban, and enoxaparin, is that it may lower clot risk without the bleeding penalty those older mechanisms carry. NCT07140523

Operational stability

The trial has recorded only two registry events since its August 2025 filing: its initial submission and a January 15, 2026 status change from Not yet recruiting to Recruiting. Its enrollment target has held flat at 450 patients with no amendment to eligibility criteria, endpoints, or population, a pattern the underlying operational model reads as a typical, unremarkable trajectory for a trial at this stage. The sponsor's guidance window itself has not moved either: both the January and February 2026 disclosures point to the same second-half 2026 readout. NCT07140523+1

The competitive frame

No other Factor XI-targeted program has produced a comparative readout in total knee arthroplasty prophylaxis. The closest mechanism neighbor identified is Suzhou Alphamab's KN060, also targeting Factor XI in the same TKA prophylaxis setting, which has moved to Active, not recruiting status ahead of a mid-December 2025 primary completion date. The broader Factor XI competitive field is dominated by Regeneron's cenvacibart, an FXIa-targeted antibody advancing through Phase 3 trials in atrial fibrillation, peripheral artery disease, cancer-associated thrombosis, and venous thromboembolism, and by REGN7508, a related Regeneron Factor XI asset now in a head-to-head Phase 3 against apixaban and enoxaparin for the same TKA prophylaxis indication with a February 2027 primary completion date. Against that backdrop, CTX611's siRNA approach to lowering Factor XI production, rather than blocking the activated enzyme with an antibody, is one of the few entrants testing a distinct delivery mechanism for this target ahead of its Phase 3 competitors' own data.

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.