A New Model for Preventing Life-Threatening Blood Clots

Episode Summary

Executive Summary: The episode examines the limitations of current anticoagulants, which reduce clotting but also increase bleeding and lead to underuse. Anthos Therapeutics CEO John Glaspool discusses an experimental monoclonal antibody targeting factor XI/ XIa, designed to prevent thrombosis while preserving hemostasis. He outlines early efficacy, ongoing phase 3 trials in cancer-associated thrombosis, and the company’s financing and commercialization strategy.

Main Topics: The clinical problem with current anticoagulants: Existing therapies such as warfarin and DOACs prevent thrombosis but also interfere with normal hemostasis, causing bleeding and discouraging use by patients and clinicians. Hemostasis vs. thrombosis as a therapeutic target: Glaspool distinguishes physiological hemostasis (needed to stop bleeding after injury) from pathological thrombosis (harmful clot formation causing stroke or MI), framing the goal as separating the two. Why anticoagulants are underutilized: Bleeding fears, real-world bleeding rates, clinician caution in fragile patients, daily injections for some therapies, and patient nonadherence contribute to substantial untreated and undertreated populations. Factor XI as a next-generation target: Anthos’ monoclonal antibody targets factor XI and activated factor XIa, aiming to suppress thrombosis more selectively than factor Xa-focused drugs and potentially avoid increasing bleeding. Clinical evidence to date: The drug has shown strong clot reduction in early studies, including a New England Journal of Medicine-published study and a Phase Q proof-of-concept trial, with no major safety signal in the short study window. Phase 3 development in cancer-associated thrombosis: The company’s late-stage program includes two trials totaling more than 2,200 patients, comparing against low-molecular-weight heparin in GI/GU cancers and a DOAC in other cancer types. Company strategy and funding: Anthos, backed by Blackstone and Novartis, says current funding should last through phase 3; it plans to commercialize in the U.S. for cancer thrombosis and partner for larger indications.

Key Arguments: Current anticoagulants are effective at preventing clots but often cause bleeding because they disrupt normal hemostasis, limiting use. Real-world bleeding risk is higher than in controlled trials, which helps explain why many patients remain untreated or undertreated. Targeting factor XI may uncouple clot prevention from bleeding risk, offering a safer anticoagulation strategy. Anthos’ antibody is differentiated by dual inhibition of factor XI and factor XIa, which the company believes may provide more complete suppression of thrombotic activity. Early studies have shown strong efficacy signals, including marked factor XI suppression and no dose-related increase in bleeding. Cancer-associated thrombosis is a strategically attractive initial indication because of clear unmet need and the absence of an FDA-approved drug specifically for that setting.

Data Points: Estimated untreated anticoagulation need: About 30% - Glaspool said about 30% of people remain untreated due to bleeding concerns and treatment burden. Major bleeding in controlled trials: 3–4% - He referenced trial data suggesting only 3 to 4% of patients have a major bleed in controlled studies. Any bleeding in controlled trials: 18% - He cited total bleeding in trials as 18% when all bleeding events are included. Reduction in clots in a published study: Greater than 80% improvement - He said a New England Journal of Medicine study showed more than an 80% reduction in clots versus standard of care. Phase Q study duration: 10 to 12 days - The proof-of-concept TKA/venography study had a short readout window of about 10 to 12 days. Phase 3 patient count: Over 2,200 patients - Combined enrollment for the two phase 3 cancer-associated thrombosis trials. Funding source: Blackstone and Novartis agreement - Anthos was formed through an agreement between Blackstone and Novartis; Blackstone is the financial backer. Current funding runway: Through the end of phase 3 - The company said existing capital should cover the phase 3 clinical program.

Pivotal Quotes: "What we're trying to do is protect you from a thrombus whilst keeping your hemostatic system intact." — John Glaspool: Explaining the therapeutic goal of next-generation anticoagulation. "We believe that factor 11 can pharmacologically uncouple hemostasis and bleeding." — John Glaspool: Describing the scientific rationale for targeting factor XI/XIa. "The only way that we develop new science, and we very much appreciate their support." — John Glaspool: Closing thanks to patients and physicians enrolling in the trials.

Implications: If factor XI inhibition succeeds, it could expand anticoagulation use by reducing bleeding fears and improving adherence. That would be especially important in high-risk groups like cancer patients and could reshape the standard approach to clot prevention.