ALK1

Diagonal is advancing its lead program to treat the underlying cause of hereditary hemorrhagic telangiectasia (HHT)WATERTOWN, Mass., Oct. 08, 2024 (GLOBE NEWSWIRE) -- Diagonal Therapeutics, a biotechnology company pioneering a new approach to discovering and developing agonist antibodies, today announced they will participate in multiple presentations at Cure HHT’s upcoming 15th HHT International Scientific Conference, taking place in Mandelieu-la-Napoule, France, October 15-19th, 2024. HHT is a severely debilitating bleeding disorder caused by mutations in ALK1 or Endoglin genes. These mutations lead to severe nosebleeds and gastrointestinal bleeds that lead to transfusion-dependent anemia. People with HHT are also at risk for life-threatening arteriovenous malformation (AVM) ruptures in critical organs such as the liver, lungs, and brain. The disease affects roughly 150,000 people in the United States and European Union. “We’re grateful to Cure HHT for inviting us to speak at their 15th annual meeting, which focuses on advancements in HHT research and emerging therapeutic options for patients. The need for better treatment options is evident, and we are pleased to be able to provide an update on our lead program," said Alex Lugovskoy, Ph.D., Chief Executive Officer of Diagonal. “While still early, our ALK1 agonist antibody, designed specifically for people with HHT, has demonstrated the ability to prevent and reverse the formation of AVMs in two HHT-relevant in vivo models and restored normal signaling in patient-derived cells. We hope these data can translate to significant patient benefit in the clinic." Details on the presentations are as follows: Poster: Bispecific antibodies targeting the ENG-ALK1-BMPRII axis as a novel approach for the treatment of HHT Presenter: JC Hus, Ph.D., Senior Director, Informatics, Diagonal Therapeutics Invited Talk: Therapeutic Potential of ALK1 Activating Drugs in HHT Models Presenter: Philippe Marambaud, Ph.D., Professor, Institute of Molecular Medicine, Feinstein Institutes for Medical Research and Diagonal Therapeutics scientific collaborator Invited Talk: Advancing a New Approach to Tackle the Root Cause of HHT Presenter: Eric Duhaime, SVP, Finance and Corporate Development, Diagonal Therapeutics About Hereditary Hemorrhagic Telangiectasia (HHT) HHT is a rare disease that affects more than 150,000 people in the US and EU, and for which there are currently no approved therapies. In HHT, mutations in the TGF-β receptor superfamily complex create two types of abnormal blood vessels – telangiectasias and arteriovenous malformations (AVMs) – 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. AVMs, if left untreated, may result in lung and brain hemorrhage, stroke, heart failure, and death. Diagonal’s agonist antibody candidates reactivate dormant signaling, addressing the root cause of the disease. About Diagonal TherapeuticsDiagonal Therapeutics is a biotech company pioneering a new approach to discovering and developing agonist antibodies. The Company's DIAGONAL platform combines proprietary computational and experimental techniques to overcome historical challenges associated with agonist antibody drug discovery. Diagonal's emerging pipeline – discovered using the DIAGONAL platform – has the potential to deliver life-changing therapies to patients by tackling the underlying cause of disease. For more information, please visit www.diagonaltx.com.Media Contact:Cory Trombleemedia@diagonaltx.com

MONDAY, Sept. 23, 2024 -- For patients with hereditary hemorrhagic telangiectasia (HHT), pomalidomide yields a significant reduction in epistaxis severity, according to a study published in the Sept. 19 issue of the New England Journal of Medicine . Hanny Al-Samkari, M.D., from Massachusetts General Hospital in Boston, and colleagues conducted a randomized, placebo-controlled trial to assess the safety and efficacy of pomalidomide for HHT. Patients were randomly assigned to receive 24 weeks of pomalidomide at a dose of 4 mg daily or matching placebo (95 and 49 patients, respectively). After a planned interim analysis met a prespecified threshold for efficacy, the trial was closed to enrollment in June 2023. The researchers found that the baseline mean Epistaxis Severity Score was 5.0 ± 1.5, consistent with moderate-to-severe epistaxis. The mean difference between the pomalidomide and placebo groups in the change from baseline in the Epistaxis Severity Score was −0.94 points at 24 weeks. The mean between-group difference in the change in the HHT-specific quality-of-life score was −1.4 points. The pomalidomide group more often had adverse events, including neutropenia, constipation, and rash. "The benefits of pomalidomide were most apparent over the course of the second 12 weeks of the trial, persisted during the four weeks after the end of the treatment period, and were not dependent on HHT genotype or baseline epistaxis severity," the authors write. Bristol Meyers Squibb donated the pomalidomide and matching placebo.

Diagonal’s lead programme is being developed for the treatment of hereditary haemorrhagic telangiectasia. Credit: dimid_86 / Shutterstock.com. Biotechnology company Diagonal Therapeutics has announced its launch, raising $128m through a Series A financing round for its new approach to discovering and developing agonist antibodies. BVF Partners and Atlas Venture jointly led the financing round with participation from Checkpoint Capital, Frazier Life Sciences, Lightspeed Venture Partners, RA Capital Management, Velosity Capital and Viking Global Investors. The company plans a new approach to develop antibodies to address the underlying causes of severely debilitating disease. The funds will be utilised to advance its Diagonal platform and the development of a pipeline of new therapeutics. The platform merges computational and experimental approaches to detect rare agonist antibodies that can re-activate deficient signalling pathways. See Also: Obsidian raises $160.5m to advance TIL cell therapy programme Harnessing pharmacovigilance to turn reactive investigation into active discovery Diagonal will also use the funds to progress its lead programme for hereditary haemorrhagic telangiectasia (HHT) through clinical proof-of-concept. The asset activates a receptor complex in the TGF-β superfamily that is genetically impaired in HHT. In preclinical models, agonist antibodies of Diagonal demonstrated the ability to hinder and reverse the formation of pathological vascular malformations associated with HHT. The company also discovered antibody candidates against four complex targets, which could pave the way for new treatments for severe diseases such as pulmonary arterial hypertension. Diagonal Therapeutics co-founder Alex Lugovskoy stated: “We are fundamentally changing how agonist antibody therapies are developed. “The Diagonal platform allows us to overcome technical limitations that hindered agonist antibody discovery in the past, and we have demonstrated that we can efficiently advance novel drug candidates for diseases where patients have limited or no treatment options. “Our approach enables us to treat a wide range of disorders where signalling pathways have been disrupted with agonist antibodies that have superior potency and selectivity, tunable and sustained pharmacology, excellent developability and low immunogenicity.”