Results demonstrate potential of Company’s clustering antibody approach to address key challenges in HHT disease manifestations: restoring ALK1-mediated cellular signaling, preventing and reversing arteriovenous malformations, and preventing HHT-associated anemia

Groundbreaking preclinical profile of Diagonal’s bispecific clustering antibodies supports advancement of lead program, DIAG723, in HHT and PAH

WATERTOWN, Mass., June 12, 2025 (GLOBE NEWSWIRE) -- Diagonal Therapeutics, a biotechnology company focused on correcting dysregulated signaling with clustering antibodies that address the underlying cause of intractable genetic diseases, will present new data supporting the potential of its clustering antibodies as a differentiated, disease-modifying treatment approach for hereditary hemorrhagic telangiectasia (HHT) at the 30^th European Hematology Association (EHA) Congress, taking place June 12-15, 2025 in Milan, Italy.

“HHT is a devastating bleeding disorder with no approved treatments. This disease is accompanied by significant economic burden and impacts to quality of life for patients, due to the extent of treatment needed and consequences of bleeding events,” said Philippe Marambaud, Ph.D., Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research, and Diagonal HHT collaborator. “As someone who has extensively studied several mechanistic approaches for this serious disease, I am highly encouraged by the data supporting Diagonal’s bispecific antibody-mediated receptor clustering approach. With its demonstrated ability to prevent and reverse arteriovenous malformations (AVMs) and normalize cell signaling in multiple translational HHT models, Diagonal’s approach has the potential to significantly impact the lives of individuals living with HHT.”

Data from the presentation demonstrate the ability of clustering antibodies targeting ALK1 and BMPRII receptors to restore cell signaling that is disrupted in HHT. In relevant models of the disease, Diagonal’s bispecific antibodies were shown to preferentially bind to the vascular endothelium, clustering key receptors and activating ALK1-mediated signaling. Administration of Diagonal’s bispecific antibodies was also shown to prevent and reverse AVM pathology in BMP9/10-deficient mice, fully ENG-deficient mice, and mice with a haploinsufficient mutation in ALK1. Results in mouse models of HHT further indicate that administration of the Company’s antibodies prevented the formation of HHT-associated anemia and heart enlargement, and drastically improved survival from 25% to 100% during the study. The effects were also confirmed in HHT patient-derived endothelial cells, demonstrating normalization of homeostatic ALK1 signaling.

“With a thorough understanding of the biology underpinning HHT and our proprietary platform, we have designed highly specific antibodies capable of restoring ALK1-mediated cell signaling lost due to disease-causing mutations to key receptors,” said Patrick Andre, Ph.D., Chief Scientific Officer of Diagonal. “Our data at this year’s EHA Congress provide powerful support for our differentiated approach, reinforcing its disease-modifying potential. We look forward to advancing development of our lead program, DIAG723, toward the clinic in hopes of offering a much-needed treatment option for individuals living with HHT.”

Details for the poster presentation are as follows:

Title: ALK1-BMPRII receptor agonism treats vascular pathology in hereditary hemorrhagic telangiectasia models
Session: Bleeding disorders (congenital and acquired)
Presenter: Andy Sullivan, Director Biology, Diagonal Therapeutics
Presentation Date & Time: Saturday, June 14, 18:30-19:30 CEST
Location: Poster Hall

The presentation will be available on the Diagonal website following the meeting.

About Hereditary Hemorrhagic Telangiectasia (HHT)
‍HHT is a rare disease that affects more than 150,000 people in the U.S. and EU, and for which there are currently no approved therapies. In HHT, loss of function point mutations in members of the TGF-β receptor superfamily complex create abnormal blood vessels that are fragile and susceptible to rupture and bleeding. These bleeding events lead to chronic anemia, necessitating frequent iron infusions or red blood cell transfusions. Internal arteriovenous malformations, if left untreated, are at risk of rupturing, resulting in lung and brain hemorrhage, stroke, heart failure, and death.

About DIAG723
‍DIAG723 is a bispecific antibody designed to address HHT and PAH, in which dysregulated ALK1 signaling at the endothelium drives the formation of fragile arteriovenous malformations or vascular hyperproliferation, respectively. DIAG723 restores signaling lost due to mutations that impair receptor function. In multiple HHT preclinical studies, DIAG723 prevented and reversed arteriovenous malformations – a hallmark of HHT that can cause a host of bleeding-related complications in various organs. In addition, DIAG723 was found to restore signaling in multiple HHT patient donor samples. In preclinical models of PAH, DIAG723 prevented disease development and cardiac remodeling, and improved hemodynamics. DIAG723 also restored normal signaling in pulmonary microvascular endothelial cells derived from multiple PAH donors.

About Diagonal Therapeutics
Diagonal Therapeutics is a biotech company advancing novel disease-modifying clustering antibodies that repair dysregulated signaling implicated in a range of illnesses. The Company's DIAGONAL Product Engine combines proprietary computational and experimental techniques to overcome historical challenges associated with antibody drug discovery and efficiently deliver optimized therapeutic assets. Diagonal's pipeline comprises clustering antibodies designed to selectively address the underlying cause of disease across hematology, hepatology, and nephrology, offering the potential to deliver life-changing therapies for patients. For more information, please visit www.diagonaltx.com.

Media Contact
Marites Coulter
Marites.coulter@deerfieldgroup.com