Diagonal Therapeutics Initiates Natural History Study of Adults Living with Hereditary Hemorrhagic Telangiectasia (HHT), a Rare Bleeding Disorder with No Approved Treatments
Diagonal Therapeutics Initiates Natural History Study of Adults Living with Hereditary Hemorrhagic Telangiectasia (HHT), a Rare Bleeding Disorder with No Approved Treatments
Study conducted in partnership with Cure HHT will inform future clinical trials and treatment options for people living with HHT
Company recently progressed DIAG723 into IND-enabling studies for HHT and pulmonary arterial hypertension (PAH)
Watertown, Mass., Mar. 4, 2025 – Diagonal Therapeutics, a biotechnology company focused on correcting dysregulated signaling with multispecific antibodies that address the underlying cause of intractable genetic diseases, today announced the initiation of a natural history study for hereditary hemorrhagic telangiectasia (HHT) in partnership with patient advocacy group Cure HHT. This first-of-its-kind non-interventional, observational, longitudinal evaluation aims to characterize the variability of patient-reported outcomes, including epistaxis (nosebleeds), hematologic support, and quality of life (QoL).
“Our ongoing collaboration with Cure HHT has been instrumental in building strong connections with the HHT community, and we express our heartfelt gratitude to the many individuals living with HHT who volunteered to participate in this critical study,” said Alex Lugovskoy, Ph.D., Chief Executive Officer of Diagonal. “This study is designed to capture daily changes and adjustments in behavior related to the extensive symptom burden associated with the disease, while informing efficient trial design to accelerate the development of novel treatments.”
HHT is an autosomal dominant genetic disorder in which abnormal blood vessel formation leads to bleeding that can be serious or life-threatening. The prevalence of HHT has been estimated at 1.5 to 2 per 10,000 people or approximately 1.4 million people worldwide1. There are currently no approved drugs that target the disease. Current treatments used to address the disease manifestations include off-label drugs previously approved for cancer indications.
“Given the lack of approved therapies, we are excited to expand our partnership with Diagonal on their natural history study and believe it will play a pivotal role in advancing a validated body of knowledge surrounding HHT’s natural history, progression and variability across affected adults,” said Marianne Clancy, MPA, Executive Director of Cure HHT. “By prioritizing studies that illuminate the full scope and impact of HHT, we ignite a new era of discovery to accelerate the development of breakthrough treatments that directly target disease-driving biology, bringing renewed hope for individuals and families seeking life-changing solutions.”
Diagonal recently presented a health economic and outcomes research (HEOR) analysis focused on the cost and clinical burden in people living with HHT at the 2024 American Society of Hematology (ASH) annual meeting, with results demonstrating that the healthcare costs associated with HHT have been significantly underestimated.
The prospective natural history study is ongoing and aims to enroll more than 100 adults in the U.S. with a confirmed diagnosis of HHT. Throughout the 13-month evaluation period, subjects will record healthcare utilization, hematologic support, daily epistaxis scores, and other periodic (electronic) patient-reported outcomes (ePROS) on a study-specific mobile application developed by Diagonal. Subjects will participate in regular check-ins with study staff via telehealth.
In addition to providing important insights into the disease, the analysis of primary and secondary study outcomes will help to inform the design of future randomized clinical trials and FDA interactions. Diagonal recently progressed DIAG723, a bispecific agonist antibody designed to restore normal biological signaling in people living with HHT, into IND-enabling studies. DIAG723 is also being developed for people living with PAH.
References
1. Grosse, S., Boulet, S., Grant, A. et al. The use of US health insurance data for surveillance of rare disorders: hereditary hemorrhagic telangiectasia. Genet Med 16, 33–39 (2014). https://doi.org/10.1038/gim.2013.66
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 at the endothelium 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 and cardiac remodeling, and improved hemodynamics. DIAG723 also restored normal signaling in pulmonary microvascular endothelial cells derived from multiple PAH donors.
About Diagonal Therapeutics
Diagonal Therapeutics is a biotech company advancing novel disease-modifying antibodies that repair aberrant 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 emerging pipeline comprises multispecific biologics designed to selectively address the underlying cause of disease, offering the potential to deliver life-changing therapies for patients. For more information, please visit www.diagonaltx.com.
An amazing possible breakthrough that would, if successful, be of such benefit to HHT patients. Having HHT is like living on a knife edge waiting for the next disastrous bleed or worse.
It may not come to fruition in my lifetime, as I’m 74, but would give hope to many people.
Great news for so many people like me struggling with this disorder! Unfortunately this is going to be little to late for me because I’m in end stages of this disorder and I have little time left because my bleeding has become very severe and it’s getting harder and harder to stop the nose bleeds! But I pray that a cure or at least treatments are found soon! Thanks 🙏
This is such encouraging news about HHT. I am 72 and have lived with the effects of this disorder for decades. I had my first stroke when I was 46 years old, and2 subsequent strokes. I have had procedures to address AVM ‘S 3 times. I have had multiple iron infusions. I may not live long enough to see a treatment for HHT but I have hope for those younger than myself. I have a daughter 45 with this also. I hope research can continue for all those who have been affected by HHT. My mother never knew a name for this. But she had nosebleeds and anemia as did her mother and grandmother. I also had an uncle that had nosebleeds and strokes. It is a life changing disorder for many of us. I was taken out of the workforce at an early age and had many medical bills due to the effects of HHT. My daughter has had a problem with blood clots and recently had to have surgery to remove clots because a Stent put in years ago failed. I pray that funding will come so you can continue this important work. Thank you for all you are doing to help HHT patients. God bless you.
This is so encouraging to have potential treatment available for those of us that suffer from HHT
Thank you to all for continuing to look for solutions to help find a cure.