Diagonal Therapeutics Secures $125M Series B to Advance First-in-Class Clustering Antibody DIAG723 for Rare Genetic Diseases
核心洞察
Diagonal Therapeutics (搜索) closed an oversubscribed $125 million Series B financing co-led by Sanofi Ventures (搜索) and Janus Henderson Investors (搜索) to advance its clustering antibody platform.
The company's lead candidate DIAG723 (搜索) is a first-in-class, disease-modifying therapy designed to correct the root cause of hereditary hemorrhagic telangiectasia (搜索) and pulmonary arterial hypertension (搜索).
DIAG723 (搜索) demonstrated robust disease-modifying activity in preclinical models, preventing and reversing arteriovenous malformations and restoring normal signaling in patient-derived cells.
Diagonal Therapeutics (搜索) has secured $125 million in an oversubscribed Series B financing round to advance its innovative clustering antibody platform, with lead candidate DIAG723 (搜索) poised to enter clinical trials in 2026. The financing was co-led by Sanofi Ventures (搜索) and Janus Henderson Investors (搜索), with participation from new investors Deep Track Capital (搜索), EcoR1 Capital (搜索), Logos Capital, Balyasny Asset Management L.P., and Woodline Partners LP, alongside all existing investors.
The proceeds will primarily support the clinical development of DIAG723 (搜索), a first-in-class, disease-modifying clustering antibody designed to address the underlying causes of hereditary hemorrhagic telangiectasia (搜索) (HHT) and pulmonary arterial hypertension (搜索) (PAH). Diagonal expects to initiate its first-in-human trial for DIAG723 in HHT patients during the first half of 2026.
Novel Clustering Antibody Approach
Unlike traditional antibody drugs that block signaling pathways, Diagonal's clustering antibodies bind to cellular receptors and force them together in specific configurations. These structural changes result in different signals that can reactivate disrupted pathways. DIAG723 (搜索) specifically targets the ALK1 signaling complex, which is impaired in both HHT and PAH.
"DIAG723 (搜索) has exhibited robust disease-modifying activity in several preclinical models of HHT and PAH, demonstrating its ability to prevent and reverse disease pathology and restore normal signaling in cells derived from patients," said Alex Lugovskoy, Ph.D., Founder and CEO of Diagonal Therapeutics (搜索).
Addressing Significant Unmet Medical Needs
HHT affects more than 330,000 people in the U.S. and EU, with no currently approved therapies. The rare genetic disease results from loss-of-function mutations in TGF-β receptor (搜索) superfamily complex members, creating abnormal blood vessels that are fragile and prone to rupture. These bleeding events drastically reduce quality of life, result in emergency room visits and hospitalizations, and lead to chronic anemia (搜索) requiring frequent iron infusions or blood transfusions.
PAH impacts an estimated 200,000 patients globally as a rare, progressive, life-threatening disorder. Current treatments can manage symptoms and slow progression, but loss-of-function mutations in BMPR2 (搜索) or BMPRII (搜索) downregulation leads to impaired ALK1 signaling, causing vascular hyperproliferation and ultimately death due to right ventricular failure.
Preclinical Efficacy Data
In multiple HHT preclinical studies, DIAG723 (搜索) prevented and reversed arteriovenous malformations and anemia, a hallmark complication of the disease. The drug also restored signaling in multiple HHT patient donor samples. In preclinical PAH models, DIAG723 prevented disease development and cardiac remodeling while improving hemodynamics and restoring normal signaling in pulmonary microvascular endothelial cells from multiple PAH donors.
DIAG723 (搜索) has received orphan drug designation from both the US FDA and EMA for HHT treatment.
Strategic Investment and Pipeline Expansion
"Diagonal's unique clustering antibody approach has the potential to address the root cause of genetic diseases that originate from impaired receptor signaling," said Paulina Hill, Ph.D., Partner at Sanofi Ventures (搜索), who will join Diagonal's Board of Directors. The financing will also enable advancement of additional clustering antibody therapeutics in the company's pipeline, including unnamed prospective treatments for iron overload (搜索) and chronic kidney disease (搜索).
The company had originally planned separate drugs for HHT and PAH but discovered that a single clustering antibody could impact both conditions by reactivating the ALK1 signaling complex. "Given that we are addressing the foundational defect in these diseases, that gives us a lot of confidence that it would be a mechanism that could be beneficial in patients," Lugovskoy noted.