Diagonal Therapeutics to Present New Preclinical Data Demonstrating Disease-Modifying Potential of DIAG723 in Pulmonary Arterial Hypertension at 2025 ERS Congress

Results demonstrate that DIAG723, the Company's lead clustering antibody, can prevent PAH, offering the potential as a first-in-class PAH treatment

WATERTOWN, Mass., Sept. 29, 2025 /PRNewswire/ -- 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 preclinical data supporting the potential of its lead clustering antibody, DIAG723, as a disease-modifying treatment for pulmonary arterial hypertension (PAH) at the European Respiratory Society (ERS) Congress 2025, taking place September 27 – October 1, 2025 in Amsterdam, Netherlands.

PAH is a progressive and life-threatening disorder in which imbalanced pro- and anti-proliferative signaling leads to hyperproliferation of cells, causing narrowing of the pulmonary arteries, increasing pulmonary arterial pressure, right ventricle hypertrophy, heart failure and eventually death. Defective ALK1 signaling has been implicated in the onset and progression of PAH. DIAG723 is a first-in-class bispecific antibody designed to cluster ALK1 and BMPRII receptors to stimulate antiproliferative signaling, preventing the formation of PAH while improving symptoms.

"Though there are several approved treatments for PAH, patients remain at risk for early mortality due to this devastating disease. While newer PAH treatments have demonstrated potential to improve patient outcomes, they may upset the delicate balance of intracellular signaling towards the unintended appearance of a hereditary hemorrhagic telangiectasia (HHT)-like phenotype," said Patrick Andre, Ph.D., Chief Scientific Officer of Diagonal Therapeutics. "Our encouraging preclinical results demonstrate the potential of our receptor clustering approach to induce beneficial effects on key hemodynamic and cardiac remodeling parameters by stimulating ALK1 signaling, a strategy also being used for the treatment of HHT. We look forward to advancing DIAG723 into the clinic in hopes of delivering a disease-modifying treatment option for individuals living with PAH."

The data demonstrates that DIAG723 restores ALK1:BMPRII signaling in vitro, as confirmed by assessment of SMAD1 activation and ID1 gene expression. In the Sugen-Hypoxia model, the gold-standard experimental method that induces pulmonary arterial hypertension preclinically, treatment with DIAG723 provided benefits across hemodynamic and cardiac remodeling parameters. Following four weeks of treatment, DIAG723 effectively prevented increases in mean pulmonary arterial pressure (mPAP) and reversed right ventricular (RV) hypertrophy and remodeling. Notably, DIAG723 outperformed standard-of-care comparator, sildenafil, in reversing changes to RV systolic pressure (RVSP) and pulmonary artery acceleration time (PAAT) with biweekly treatment.

Details for the poster presentation are as follows:

Title: ALK1:BMPRII receptor clustering by an agonist bispecific antibody (DIAG723) prevents PAH development in the rat Sugen-Hypoxia model
Abstract Number: PA4087
Poster Session: Pulmonary arterial hypertension: new molecular pathways and new therapeutic insights
Presenter: Andy Sullivan, Director Biology, Diagonal Therapeutics
Presentation Date & Time: Monday, September 29, 12:30-14:00 CEST

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

About Pulmonary Arterial Hypertension (PAH)
PAH is a rare, progressive, life-threatening disorder that impacts an estimated 192,000 patients globally. Current PAH treatments can manage symptoms and slow disease progression but there have been reports of the formation of telangiectasia, epistaxis and pulmonary shunting with recent modulators of the pro-proliferative pathway. In PAH, loss of function mutations in BMPR2 or BMPRII downregulation leads to impaired ALK1 signaling that causes vascular hyperproliferation, narrowing the pulmonary arterial walls and resulting in elevated pulmonary arterial pressure and ultimately death due to right ventricular failure.

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 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. 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. 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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SOURCE Diagonal Therapeutics