WATERTOWN, Mass., July 16, 2026
Diagonal Therapeutics has reached a significant milestone in rare disease drug development by announcing that the first patient has been dosed in the Phase 1/2 DIAMOND clinical trial evaluating DIAG723, a first-in-class clustering agonist antibody for the treatment of Hereditary Hemorrhagic Telangiectasia (HHT). The randomized, double-blind, placebo-controlled multicenter study marks the company’s transition into clinical evaluation of a novel therapy designed to restore ALK1 signaling, the genetically disrupted pathway responsible for the abnormal blood vessel formation, recurrent bleeding, anemia, and arteriovenous malformations (AVMs) associated with HHT. As there are currently no approved therapies specifically for HHT, the initiation of the DIAMOND trial represents an important advancement in the search for disease-modifying treatments for this rare vascular disorder. The milestone also strengthens Diagonal Therapeutics’ position in precision biologics by advancing its proprietary clustering antibody platform into human clinical development.
Phase 1/2 DIAMOND Trial Targets the Root Cause of HHT
The DIAMOND (NCT07623525) study is enrolling up to 93 adults with HHT in a Phase 1/2, multicenter, randomized, placebo-controlled trial designed to evaluate the safety, tolerability, pharmacokinetics, target-engagement biomarkers, and preliminary efficacy of subcutaneously administered DIAG723. The trial includes three parts, beginning with single ascending-dose evaluation, followed by multiple ascending-dose cohorts to assess reductions in nosebleed frequency, improvements in hematologic parameters, and overall clinical benefit. A third cohort will investigate patients living with both HHT and pulmonary arterial hypertension (PAH). Unlike current management strategies that primarily address symptoms, DIAG723 is engineered to restore normal ALK1 signaling, directly targeting the molecular defect responsible for fragile blood vessels and AVM formation. This innovative mechanism has the potential to transform treatment from supportive care to true disease modification, offering new hope for patients living with this lifelong genetic condition.
Preclinical Evidence Supports Disease-Modifying Potential
Prior preclinical studies demonstrated that DIAG723 prevented and reversed key manifestations of HHT, including the development of arteriovenous malformations, while improving disease-associated anemia and vascular abnormalities. The antibody utilizes Diagonal Therapeutics’ proprietary clustering agonist technology, which brings receptors together at the cell surface to reactivate impaired biological signaling pathways. By correcting the underlying molecular dysfunction rather than treating only recurrent bleeding episodes, the investigational therapy could significantly improve long-term patient outcomes. DIAG723 has already received Orphan Drug Designation from both the U.S. FDA and the European Medicines Agency (EMA), underscoring its potential importance in addressing a rare disease with substantial unmet medical need. These regulatory recognitions, combined with encouraging preclinical findings, position the candidate as one of the most promising emerging therapies for HHT currently entering clinical evaluation.
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Rare Disease Innovation Advances Precision Biopharma
The dosing of the first patient in the DIAMOND clinical trial represents an important milestone not only for Diagonal Therapeutics but also for the broader rare disease and vascular medicine communities. HHT affects thousands of individuals worldwide and is associated with chronic bleeding, iron deficiency, repeated transfusions, and potentially life-threatening complications caused by AVMs in the lungs, brain, and liver. By advancing a first-in-class disease-modifying biologic into clinical testing, the company is pursuing a therapeutic strategy capable of correcting the genetic signaling defect driving disease progression. If clinical results confirm the encouraging preclinical data, DIAG723 could establish a new treatment paradigm for HHT while validating Diagonal Therapeutics’ clustering antibody platform for additional genetically driven disorders. The initiation of patient dosing therefore marks a significant step forward in the evolution of precision medicine, rare disease therapeutics, and next-generation antibody innovation.
Source: Diagonal Therapeutics press release
