Venous thromboembolism (VTE) is one of the complications that most often works against the benefit of surgery in ovarian cancer. SHR-2004, a factor XI (FXI)-blocking antibody developed by Hengrui Pharmaceuticals, was designed to lower that risk, and Prisys Biotech (浦灵生物) carried out part of the preclinical work that took the molecule from concept into a clinical trial.
Understanding the VTE Challenge in Ovarian Cancer
VTE is a common and potentially deadly complication in ovarian cancer patients, particularly after surgery. Reported rates in the postoperative period range from 10% to 30%, and the risk is higher again in advanced or recurrent disease, which is why prophylaxis belongs to the surgical plan itself. Tumor biology shifts the coagulation system toward clot formation, and surgery adds tissue factor exposure and immobility on top of it. An anticoagulant that limits clot growth without a matching rise in bleeding has been a long-standing gap in that setting.
SHR-2004 Clinical Trial: A Step Towards Safer Treatment
SHR-2004, originally developed as BJTJ-1837, has shown promising results in clinical trials. In the SHR-2004-202 Phase II trial, conducted with ovarian cancer patients, SHR-2004 produced a VTE rate of 12.6%, against 20.2% in the control group. No major bleeding events occurred in the SHR-2004 arm, and that is the observation which separates a factor XI approach from conventional anticoagulation.
Factor XI sits upstream in the contact pathway of coagulation. Blocking its activation is intended to limit pathological clot propagation while leaving the hemostatic response to injury largely intact, and the trial numbers above are the clinical test of that separation.
Prisys Biotech's Role in Development
Prisys Biotech worked on SHR-2004 as a contract research organization. The preclinical package drew on NHP Pharmacology capability and on the A-V Shunt, an arteriovenous shunt preparation in non-human primates in which clot growth on a foreign surface can be followed under controlled flow; work of this kind sits within the Coagulation/Hemostasis Nonhuman Primates Disease Model service area. The studies covered pharmacodynamics (Pharmacodynamics (PD)), pharmacokinetics (Pharmacokinetics (PK)), and the safety profile.
Imaging readouts through Clinical Imaging and the AI-based NHP Behavior Analysis System supported data collection, so the compound reached the clinic against a defined preclinical package, with endpoints chosen in advance.
Determination the function of BJTJ-1837 on FXI. (A) To test the effects of antibodies on FXIa activity directly, FXIa (1.7 μg/mL) was incubated with tested antibody (100 μg/mL) or negative control for 5 minute at 37 ◦C. FXIa substrate S-2366 was added to measure FXIa activity.
The same platforms, including real-time MRI for drug delivery and AI-powered behavioral analysis, gave a read on how SHR-2004 prevented thrombus formation without a significant bleeding risk. That body of work formed the basis on which the clinical program was designed.
Western blots of nonreducing SDS-PAGE of FXI (lane 1), tPA (lane 2), and FXI_Apple-tPA_PD (lane 3) were probed with BJTJ-1837, positive control (14E11-hFc, the variable domain of the murine precursor of AB023 fused to human IgG4/kappa constant domains), or negative control (NOV1090, a MAA868 precursor) respectively, and further probed with anti–hFc-HRP secondary antibody
The Future of VTE Prevention and SHR-2004
SHR-2004 addresses a patient group whose risk comes from both the tumor and its treatment: surgery and chemotherapy each raise the chance of a thrombotic event. A profile with no major bleeding events in the Phase II trial is what makes a factor XI antibody worth pursuing in oncology, where the margin between preventing clots and causing bleeding is narrow. As the clinical trials continue to evolve, SHR-2004 may soon become a standard in the management of VTE in oncology patients.
Prisys Biotech: Your Partner in Drug Development
Prisys Biotech provides preclinical research services, including drug efficacy evaluation and safety assessment, using non-human primate models and specialized research technologies. Our services support pharmaceutical and biotechnology companies in generating data to inform preclinical development and clinical translation.
If you are looking for preclinical research support for your drug development program, contact Prisys Biotech to learn more about our research capabilities and services.
SHR-2004 is being investigated for VTE prevention in patients with ovarian cancer. Prisys Biotech contributed to the preclinical research supporting its development. The research provided data to support further evaluation of SHR-2004 and its potential application in clinical development.
Ma T, Weng Z, Cao B, Dong Y,. The first-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the factor XI monoclonal antibody SHR-2004 in healthy subjects. Expert Opin Investig Drugs. 2024 Oct;33(10):1075-1082. doi: 10.1080/13543784.2024.2391837. Epub 2024 Aug 22. PMID: 39166425.
He X, Zhang J, Du Y, Liu X. BJTJ-1837, a novel FXI activation-blocking antibody. Res Pract Thromb Haemost. 2023 Feb 7;7(2):100067. doi: 10.1016/j.rpth.2023.100067. PMID: 36936858; PMCID: PMC10017418.
