Anthos Therapeutics Shares New Data from the Landmark AZALEA-TIMI 71 Study Demonstrating the Factor XI Inhibitor Abelacimab Significantly Reduced Bleeding in Patients Regardless of Age or Bleeding Risk

--Data presented at the American College of Cardiology Annual Scientific Session show that the reduction of bleeding with abelacimab compared to rivaroxaban (Xarelto) was even greater in patients ≥75 years old compared to younger patients

--Another analysis from AZALEA-TIMI 71 shows abelacimab, as compared to rivaroxaban (Xarelto), was associated with a greater absolute benefit in patients who are at higher risk for bleeding

/EIN News/ -- CAMBRIDGE, Mass., March 29, 2025 (GLOBE NEWSWIRE) -- Anthos Therapeutics, Inc., a transformative, clinical-stage biopharmaceutical company developing innovative therapies for the treatment of cardiovascular metabolic diseases, is presenting two new analyses from its landmark AZALEA-TIMI 71 study at the American College of Cardiology Annual Scientific Session (ACC.25) demonstrating the novel Factor XI inhibitor abelacimab significantly reduced bleeding in patients regardless of age or bleeding risk. These data will be presented today during the moderated poster sessions from 2:30-4:30pm CT.

In the first analysis, the safety of abelacimab, a novel Factor XI inhibitor, was compared to rivaroxaban, a direct oral anticoagulant (DOAC), by patient age. Inhibition of Factor XI with abelacimab significantly reduced the relative risk of major or clinically relevant non-major (CRNM) bleeding compared with rivaroxaban regardless of age, with potential for greater absolute risk reduction (ARR) with older patients. The ARR in patients 75 years of age and older was 6.2% compared to 4.2% in patients less than 75 years. In addition, abelacimab consistently reduced bleeding risk in patients 75 years of age and older regardless of renal function, body mass index (BMI), and the use of concomitant antiplatelet therapy.

"Patients with atrial fibrillation, particularly older patients, are frequently at a high risk of bleeding. There is a need for safer anticoagulants that can prevent thrombotic events while minimizing excess bleeding,” said Christian T. Ruff, MD, MPH, senior investigator of TIMI Group, director General Cardiology, Brigham and Women's Hospital, and associate professor, Harvard Medical School. “These data show that abelacimab significantly reduced the risk of major or CRNM bleeding, particularly among people over 75 who are vulnerable to such risks, and, if approved, could be a safer alternative for patients needing anticoagulation therapy.”

In the second analysis, the safety of abelacimab was compared to rivaroxaban across a spectrum of bleeding risk, which was determined by using the direct oral anticoagulant (DOAC) score, a clinical tool leveraged to assess the risk of bleeding in patients who are prescribed DOACs. In patients with atrial fibrillation, abelacimab reduced rates of bleeding relative to rivaroxaban regardless of bleeding risk, with greater absolute safety benefit in those at higher bleeding risk. In the rivaroxaban arm, the rates of major or CRNM bleeding per 100 patient years increased stepwise across risk categories from 5.6% in the low risk category to 21.2% in the very high risk category. In contrast, the rates of bleeding in patients in the pooled abelacimab arm were 2.5% in the low-risk category to 7.1% in the very high-risk category. The ARR increased from 3.1% in the low risk category to 14.1% in the very high risk category (p-trend for ARR <0.001). These data suggest that, if approved, abelacimab may be especially attractive in patients with atrial fibrillation who are at high bleeding risk.

"Research shows that 40% of patients with atrial fibrillation are not receiving optimal treatment when it comes to anticoagulation, in large part due to a fear of bleeding. This includes people living with atrial fibrillation who have a higher risk of bleeding, such as the elderly, patients taking anti-platelet agents, and those with other co-morbidities,” said Dan Bloomfield, MD, chief medical officer of Anthos Therapeutics. “These results suggest that abelacimab may be safe across the spectrum of bleeding risk and may make it possible to anticoagulate some of the most vulnerable populations who otherwise would not be treated and therefore left unprotected from the risk of stroke.”

Full results of the AZALEA-TIMI 71 study were published in January of this year in the New England Journal of Medicine (NEJM) and demonstrated a 62% reduction in major or CRNM bleeding with abelacimab 150 mg compared to rivaroxaban 20 mg in patients with atrial fibrillation. Abelacimab is currently in Phase 3 development with the lead indication for the prevention of stroke and systemic embolism in patients with atrial fibrillation (LILAC-TIMI 76), in addition to two studies in patients with cancer-associated thrombosis (ASTER and MAGNOLIA). Data from these trials are expected in the second half of 2026.

AZALEA-TIMI 71 Study of Bleeding Risk by Age

• Relevant Study Details:
  • Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis.
  • Cox proportional hazards were used to examine the primary outcome of major/CRNM bleeding with an interaction term for treatment*age (≥75 vs <75 yrs).
  • Of 1,287 patients, 625 (49%) were ≥75 yrs at baseline. Patients ≥75 had lower BMI (28 vs. 32 kg/m2) and were less likely to be on antiplatelet therapy (17% vs 31%), but more likely to have Creatinine clearance (CrCl) ≤50 mL/min (33% vs. 8%) compared with younger patients (p<0.001 for each).

AZALEA-TIMI 71 Study of Patient-Specific Bleeding Risk

• Relevant Study Details:
  • Both abelacimab doses (90 mg and 150 mg) were pooled for this analysis.
  • Patient-specific bleeding risk was categorized using the previously validated DOAC score.
  • Overall, 8%, 33%, 37%, 16% and 5% of patients were categorized as very low (0-3), low (4-5), moderate (6-7), high (8-9) and very high (10) bleeding risk, respectively.

Media Contact: media@anthostherapeutics.com

About Anthos Therapeutics
Founded by Blackstone Life Sciences (BXLS) in 2019, Anthos Therapeutics is a transformative, clinical-stage biopharmaceutical company with the exclusive global rights from Novartis Pharma AG to develop, manufacture and commercialize abelacimab. For more information, visit the Company’s website and follow on Twitter and LinkedIn.

About the AZALEA-TIMI 71 Study
Launched in February 2021, the AZALEA-TIMI 71 study enrolled 1,287 patients across 95 global study sites, including the U.S. and Canada, Europe and Asia. With a median follow-up of 2.1 years, spanning more than 2,000 patient-years, the AZALEA-TIMI 71 study is the largest and longest head-to-head study of a Factor XI inhibitor compared to a standard-of-care anticoagulant.

About Abelacimab
Abelacimab is a novel, investigational, highly selective, fully human monoclonal antibody that binds tightly to Factor XI to block its activation and prevent the generation of the activated form (Factor XIa). This mimics natural Factor XI deficiency, which is associated with protection from thromboembolic disease.¹

As a monoclonal antibody, abelacimab is not metabolized via the cytochrome P450 system or as a substrate for P-glycoprotein, meaning the risk of drug-drug interactions is very low.² There is no need to adjust the dose based on age or renal/hepatic status.³

Factor XI inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of arterial and venous thromboembolic events.⁴ Abelacimab is the only Factor XI inhibitor being studied for both conditions.

If approved, abelacimab is planned to be dosed subcutaneously (SC) monthly by patients with atrial fibrillation using an autoinjector to maintain near-complete inhibition in a chronic setting. It is also planned to be administered via an initial intravenous (IV) infusion for acute indications requiring immediate onset of action and then followed by subsequent monthly SC administration.

In the AZALEA-TIMI 71 study, abelacimab 150 mg dosed subcutaneously once-monthly, inhibited Factor XI by 99%.⁵ In a PK/PD study, abelacimab administered by IV provided profound suppression of Factor XI within one hour after the start of therapy and maintained near maximal inhibition for up to 30 days.⁶ The results of the AZALEA-TIMI 71 study, published in the January 23, 2025, issue of New England Journal of Medicine (NEJM) showed a 62% reduction in major or clinically relevant non-major bleeding with abelacimab 150 mg compared with rivaroxaban 20 mg in patients with atrial fibrillation who are at moderate-to-high risk of stroke (P<0.001, HR 0.38, 95% Cl 0.24–0.60). Data also showed a 62% reduction in major bleeding alone with abelacimab 150 mg vs. rivaroxaban 20 mg (P=0.001, HR 0.33, 95% CI 0.16-0.66) and an 89% reduction in gastrointestinal (GI) bleeding).⁷

Abelacimab received a Fast Track Designation from the FDA in July 2022 for the treatment of thrombosis associated with cancer. In September 2022, abelacimab was also granted a Fast Track Designation for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

Abelacimab is an investigational agent and is not approved for any indication in any country.

About the DOAC Score
The direct oral anticoagulant (DOAC) score is a clinical tool used to assess the risk of bleeding in patients who are prescribed DOACs, a class of drugs used to prevent and treat thromboembolic disorders such as stroke in atrial fibrillation. The DOAC score helps clinicians evaluate the safety and appropriateness of DOAC therapy for individual patients by considering factors such as age, renal function, history of bleeding, and concurrent use of other medications that may increase bleeding risk.

Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the potential benefit of abelacimab and our goals to further develop and commercialize abelacimab. All statements, other than statements of historical facts, contained in this press release, including statements regarding the company’s strategy, future operations, future financial position, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “become,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. In addition, the forward-looking statements included in this press release represent the company’s views as of the date hereof and should not be relied upon as representing the company’s views as of any date subsequent to the date hereof. The company anticipates that subsequent events and developments will cause the company’s views to change. However, while the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so.

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¹ Goodman et al. Crit Pathways in Cardiol. June 2024
² Hsu et al. J Am Coll Cardiol. Aug. 2021  
³ Hsu et al. J Am Coll Cardiol. Aug. 2021  
⁴ Hsu et al. J Am Coll Cardiol. Aug. 2021  
⁵ TIMI Study Group website, AZALEA 71
⁶ Yi BA et al. J Thromb Haemost. Oct. 2021
⁷ Ruff C et al. N Engl J Med. Jan. 2025