Diagonal Therapeutics Initiates Phase 1/2 Clinical Trial for DIAG723, a Clustering Antibody for the Treatment of HHT
Innovation in Clustering Antibody Platform
Diagonal Therapeutics is developing a novel clustering antibody therapeutic using its proprietary DIAGONAL platform technology. Unlike conventional antibodies that simply block receptors, this platform features an innovative mechanism that physically clusters target receptors, strongly amplifying intracellular signaling. The lead pipeline candidate, 'DIAG723,' induces the formation of a complex between the activating receptors ALK1 (Activin receptor-like kinase 1) and BMPRII (Bone morphogenetic protein receptor type II), fundamentally blocking abnormal angiogenesis. This approach, which goes beyond merely alleviating symptoms, has the potential to become the first disease-modifying therapy to address the underlying genetic cause, garnering significant attention in the industry.
Unmet Needs in the HHT Treatment Market and Clinical Entry
Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular disease affecting approximately 1.4 million people worldwide, but there are currently no approved treatments. Current treatments involve bevacizumab to temporarily inhibit angiogenesis or physical hemostatic methods and nasal surgery for nosebleeds. Diagonal has obtained FDA Orphan Drug Designation (ODD) and a positive opinion from the European Medicines Agency (EMA) based on the promising preclinical results of DIAG723. In the first half of 2026, the company will begin a global Phase 1/2 clinical trial (NCT07623525) to evaluate the safety and efficacy in multiple cohorts, bringing it closer to a fundamental therapeutic breakthrough.
New Paradigm in Vascular Disease Treatment and Expansion to PAH
Diagonal is not limited to HHT and is preparing to expand the indications to pulmonary arterial hypertension (PAH), a major cause of death from cardiovascular disease. PAH is a life-threatening condition in which pulmonary blood vessels narrow, leading to heart failure. Recently, Merck's Winrevair (ingredient: sotatercept) was approved, creating a multi-billion dollar market. DIAG723 exhibits a unique mechanism that normalizes the ALK1/BMPRII signaling system, inhibits vascular remodeling, and induces physiological restoration of blood vessels. Therefore, in subsequent Phase 1/2 trials, the company plans to expand the evaluation to PAH patients, aiming to change the paradigm of vascular diseases.
Large-Scale Funding and Distinct Advantages Over Competitors
Despite the challenging biotech investment market, Diagonal successfully raised $125 million (approximately 170 billion KRW) in a Series B funding round in January 2026, led by Sanofi Ventures and Janus Henderson Investors. This follows the $128 million Series A funding in April 2024, securing a total of $253 million in funding for clinical development. A competitor, Vaderis Therapeutics, is preparing to enter Phase 3 clinical trials in the spring of 2026 with its oral AKT inhibitor, 'VAD044' (ingredient: engasertib), suggesting a fierce race. However, Diagonal expects to enhance its long-term value through the technological gap of its antibody drug platform, which boasts high cell target selectivity and safety.
The initiation of the Phase 1/2 clinical trial for DIAG723 represents a key milestone in securing a leading position in the global HHT treatment market, which has significant unmet needs and is projected to grow to $2.43 billion by 2035. In the short term, the clinical data will serve as a testbed to demonstrate the safety and pharmacokinetic efficacy of the unique 'DIAGONAL' receptor clustering technology in humans. In the medium to long term, the expansion of indications to the PAH market, which has been pioneered by Merck's Winrevair, will maximize the target market value. This will be an opportunity to demonstrate the value of the technological platform in competition with Vaderis' oral AKT inhibitor, VAD044, which is scheduled to enter Phase 3 clinical trials. With cumulative funding of $253 million, including Series B, there is also the potential for developing additional pipeline products based on the platform and establishing large-scale licensing (L/O) partnerships with global pharmaceutical companies.