WATERTOWN, Mass., June 18, 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, today announced that both the U.S. Food and Drug Administration (FDA) granted orphan drug designation (ODD) to DIAG723, a novel, bispecific antibody, for the treatment of hereditary hemorrhagic telangiectasia (HHT). Additionally, the European Medicines Agency (EMA) provided a positive opinion for ODD, confirming that DIAG723 meets the criteria for designation as an orphan drug in the European Union.

HHT is a rare genetic disorder caused by loss-of-function mutations in genes encoding ALK1 (ACVRL1) and endoglin (ENG) receptors, which impair signaling pathways that regulate vascular development and result in the formation of telangiectasias and arteriovenous malformations (AVMs). These malformations are prone to rupture, causing bleeding events, chronic anemia, and life-threatening complications. Treatment strategies for HHT are limited to symptom management as there are currently no approved therapeutics for the disease.

“DIAG723 represents a powerful new approach to treating HHT, supported by a robust preclinical data package that has demonstrated its ability to address the key disease manifestations. Our receptor clustering approach unlocks the disease-modifying potential by directly targeting the dysregulated biology causing HHT,” said Alex Lugovskoy, Ph.D., Chief Executive Officer of Diagonal Therapeutics. “Receiving orphan drug designation from the FDA and a positive opinion from the EMA emphasizes the critical need for effective treatments for HHT and reinforces the potential of DIAG723 to significantly improve the lives of people and families affected by the disease.”

DIAG723 is a bispecific antibody designed to cluster key extracellular receptors to restore ALK1 signaling, promoting vascular quiescence. Preclinical studies demonstrate the disease-modifying potential of DIAG723’s receptor-clustering mechanism of action, confirming its ability to restore ALK1-mediated cellular signaling, prevent and reverse AVM formation, prevent HHT-associated anemia, and improve survival in preclinical models.

The FDA’s ODD program is designed to support the development and evaluation of new treatments for serious and life-threatening rare diseases affecting fewer than 200,000 people. The FDA orphan drug designation qualifies Diagonal for various incentives, including the potential for market exclusivity upon approval. The EMA Orphan Medicinal Products Regulation (Regulation (EC) No 141/2000) defines an orphan medicinal product as one intended for diseases affecting fewer than 5 in 10,000 people across the EU.

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 in endothelial cells 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, cardiac remodeling, and improved hemodynamics. DIAG723 also restored normal signaling in pulmonary microvascular endothelial cells derived from multiple PAH donors. DIAG723 has received orphan drug designation from the US FDA and the EMA for the treatment of HHT.

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.

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Marites Coulter
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