Vaderis Therapeutics Announces The New England Journal of Medicine Publishes Engasertib Proof-of-Concept and Long-Term Extension Results, Highlighting the Therapy's Potential for Patients with Hereditary Hemorrhagic Telangiectasia

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Vaderis Therapeutics AG

02 Dec, 2025, 14:00 GMT

  • In the 12-week Proof-of-Concept study, engasertib demonstrated dose-dependent improvements across multiple measures of epistaxis and related patient-reported impact
  • The long-term Open-Label Extension showed deepening and sustained epistaxis control through 12 months
  • Engasertib exhibited a favorable tolerability and safety profile across the full study duration

BASEL, Switzerland and LINCOLNSHIRE, Il., Dec. 2, 2025 /PRNewswire/ -- Vaderis Therapeutics today announced that data from its randomized, double-blind, placebo-controlled, multi-center proof-of-concept study and long-term extension of engasertib (VAD044) in Hereditary Hemorrhagic Telangiectasia (HHT) have been published in The New England Journal of Medicine (NEJM).

This peer-reviewed publication marks an important milestone following initial release of study information in August 2024 (see "Vaderis Announces Positive Clinical Proof-of-Concept Trial in HHT"). The NEJM publication further reinforces the scientific rigor and potential clinical relevance of the data.

"These early data suggest that engasertib's targeted AKT inhibition has the potential to deliver clinically meaningful improvements in bleeding for patients with HHT.  These findings provide encouraging signs that we may be on a promising path toward a much-needed treatment option for this community, which remains without approved therapies," said Hanny Al-Samkari, MD, The Peggy S. Blitz Endowed Chair in Hematology/Oncology at the Mass General Brigham Cancer Institute, Associate Professor of Medicine at Harvard Medical School and the co-lead principal investigator in the study.

Study Design and Objectives

The Proof-of-Concept study enrolled 75 adults with moderate-to-severe HHT across the United States and European sites. Participants were randomized to receive oral engasertib (30 mg, 40 mg) or placebo for 12 weeks, followed by a long-term open-label extension. (ClinicalTrials.gov Identifier: NCT05406362)

  • Primary Endpoint: Safety and tolerability
  • Secondary Endpoints: Epistaxis frequency & duration, Epistaxis Severity Score (ESS), Patient Global Impression of Change (PGI-C)

Highlights from Published Results

  • Bleeding Reduction: In the 40 mg arm, there was a 41% reduction in mean epistaxis duration and 28% reduction in frequency, versus 24% and 18% reductions, respectively, in the placebo arm.
  • Patient-Reported Outcomes: 61% of patients in the 40 mg group rated their clinical condition as "Much Better" on the PGI-C, compared to 27% for placebo.
  • Safety: Engasertib was generally well tolerated. The most common adverse events, as are typically seen with this mechanism of action, were mild-to-moderate rash and hyperglycemia, reversible or manageable with supportive care.
  • Long-Term Open-Label Extension: Sustained and amplified benefits were observed over the course of 12 months of additional treatment in participating patients, including a 66% reduction in mean bleeding duration, a 55% reduction in mean bleeding frequency

"The publication of our results in The New England Journal of Medicine strengthens our conviction in the potential of engasertib to address the significant unmet need in HHT," said Azmi Nabulsi, MD, MPH, President & CEO, Vaderis Therapeutics.  "With this important milestone as our foundation, we are moving forward with confidence as we prepare to initiate the Phase 3 HEROIC study in the first half of 2026."

About HHT

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic vascular disorder (prevalence ~1 in 3,800) characterized by recurrent severe epistaxis, anemia, and visceral arteriovenous malformations (AVMs). Despite the significant disease burden, there are currently no approved therapies for HHT globally.

About Vaderis Therapeutics

Vaderis Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and advancing transformative treatments for rare vascular diseases. By targeting the underlying pathophysiology, the company aims to bring first-in-class targeted therapies to patients in need. For more information, visit www.vaderis.com.

Forward-Looking Statement

This press release contains forward-looking statements regarding the development and potential approval of engasertib and related programs. Actual results may differ materially from those described due to risks, uncertainties, and the complexities of clinical development and regulatory review.

Medical Information

Engasertib has not been approved for use in any country for any indication.  Information in this press release is for medical and scientific reference only and is not intended to promote, recommend, or suggest use of this product. The safety and efficacy of engasertib have not been established by any regulatory authority.

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