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Preliminary results indicate HHT patients are significantly impacted by bleeding events, with consistency in severity reporting at months one and three of the study Final study analysis will inform design of interventional clinical trial, initiating in 2026, assessing DIAG723, a first-in-class, disease modifying treatment designed specifically to address the underlying cause of HHT WATERTOWN, Mass., Dec. 04, 2025 (GLOBE NEWSWIRE) -- Diagonal Therapeutics, a biotechnology company developing disease-modifying clustering antibodies that correct dysregulated signaling in severe genetic diseases, will present interim data from its natural history study, HHT IMPACT, for hereditary hemorrhagic telangiectasia (HHT) at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 6-9, 2025 in Orlando, Florida. HHT is a rare disease in which abnormal blood vessel formation causes bleeding events that can be serious or life-threatening, and for which there are currently no approved therapies. Initiated in partnership with the leading patient advocacy organization, Cure HHT, HHT IMPACT is designed to characterize patient-reported outcomes in HHT, including epistaxis (nosebleed) frequency, severity, and duration, hematologic support, and quality of life (QoL), using a novel patient-reporting instrument, the “During My Day Diary,” as well as established assessment tools, such as Epistaxis Severity Score (ESS). “The interim results from HHT IMPACT describe a patient population whose quality of life is deeply affected by HHT, with nearly two-thirds of participants reporting daily nosebleeds and nearly forty percent reporting multiple nosebleeds per day,” said John Lee, M.D., Ph.D., Chief Medical Officer of Diagonal Therapeutics. “Insights from this natural history study will inform the design of our first-in-human clinical trial of DIAG723, which will start enrolling mid-2026. With its unique receptor clustering mechanism, DIAG723 has the potential to prevent and reverse all manifestations and complications associated with HHT by directly addressing the root cause of the disease. We are grateful to all the individuals participating in this study and look forward to applying the valuable learnings toward advancing a much needed, disease-modifying treatment for this serious disease.” HHT IMPACT enrolled 109 adult HHT patients with moderate-to-severe bleeding. The study implemented and validated the "During My Day Diary," which captured the frequency, duration, and intensity of each epistaxis event. Results from the interim analysis confirm the significant burden of HHT: Majority of patients reported daily epistaxis, including a large proportion reporting several epistaxis events per day.Nearly half of the participants reported being anemic in the three months prior to enrollment.Participants averaged more than 20 nosebleeds per month and a mean duration of nearly 20 minutes per bleeding event. The final analysis will be presented at a future scientific congress and will report on additional characterization of bleeding events and QoL assessments, with further evaluation of the impact HHT has on activities of daily living. Details for the poster presentation are as follows: Title: An interim assessment of bleeding events in a prospective natural history study of hereditary hemorrhagic telangiectasia patients using a validated bleeding scale and a novel daily reporting instrumentPresenter: John Lee, M.D., Ph.D., Chief Medical Officer, Diagonal TherapeuticsPoster ID: 2702Poster Session: Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Poster ILocation: OCCC – West Halls B3-B4Poster Date & Time: Saturday, December 6, 5:30-7:30 pm EST The poster will be available on the Diagonal website following the meeting. About Hereditary Hemorrhagic Telangiectasia (HHT) HHT is a rare disease that affects more than 330,000 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-ß receptor superfamily complex create abnormal blood vessels that are fragile and susceptible to rupture and bleeding. These bleeding events drastically reduce quality of life, result in emergency visits and hospitalizations, and lead to chronic anemia, necessitating frequent iron infusions or red blood cell transfusions in many patients. Solid organ arteriovenous malformations, if left untreated, are at risk of rupturing, resulting in lung and brain hemorrhage, stroke, heart failure, and death. About HHT IMPACT Natural History StudyHHT IMPACT is a first-of-its-kind non-interventional, observational, longitudinal evaluation characterizing the variability of HHT patient-reported outcomes, including nosebleeds, hematologic support, and quality of life. The study is fully enrolled, and complete data are anticipated in 2026. To learn more about the HHT Impact study in partnership with Cure HHT, please visit: https://curehht.org/hhtimpact/. About DIAG723‍DIAG723 is a bispecific antibody designed to address HHT and PAH, in which dysregulated ALK1 signaling in endothelial cells 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 and anemia – a hallmark of HHT that can cause a host of bleeding-related complications in various organs. DIAG723 was also 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. DIAG723 has received orphan drug designation from the US FDA and the EMA for the treatment of HHT. About Diagonal TherapeuticsDiagonal Therapeutics is a biotech company advancing novel disease-modifying clustering antibodies that repair dysregulated 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 pipeline comprises clustering antibodies designed to selectively address the underlying cause of disease across hematology, hepatology, and nephrology, offering the potential to deliver life-changing therapies for patients. For more information, please visit www.diagonaltx.com. Media Contactmedia@diagonaltx.com

Diagonal Therapeutics is building a pipeline of antibody agonists rather than receptor blockers. Diagonal Therapeutics is taking shape, launching with $128 million and backed by the likes of BVF Partners, Atlas Venture and RA Capital to develop a pipeline of antibody agonists.  The company will use this significant financial firepower to accelerate development of its pipeline of four assets. Two of these candidates are more advanced, including a lead asset targeting the inherited bleeding disorder hereditary hemorrhagic telangiectasia (HHT) and a runner-up designed to treat pulmonary arterial hypertension (PAH).  Unlike conventional antibody development, Diagonal is working on candidates that activate broken signaling pathways rather than inhibit them. The HHT asset, for example, reignites a receptor in the TGF-β superfamily, with preclinical models showing that the agonist antibodies “prevent and reverse the formation of pathological vascular malformations,” the company said in a release. The $128 million will pay for at least a proof-of-concept study for the HHT program, the company noted in its announcement, though a full cash runway was not specified.  Diagonal is led by CEO Alex Lugovskoy, Ph.D., an entrepreneur-in-residence at Atlas who’s had previous C-suite stints at Dragonfly Therapeutics and Morphic Therapeutic. Diagonal's platform is the byproduct of computational and scientific advancements made in the last five to 10 years, Lugovskoy told Fierce Biotech. “I think more and more people will start using those types of approaches to all kinds of antibody engineering techniques, which is a blend of experimental and computational,” the CEO said in an interview. Diagonal’s stated PAH ambitions come days after Merck & Co.’s much-hyped Winrevair (sotatercept) received FDA approval for the condition, resetting the competitive landscape. Lugovskoy conceded that unlike HHT, which lacks treatment options, Winrevair is a “significant advance” for PAH patients. But he said that because the drug acts as an activin receptor ligand trap rather than a fix for genetic mutations, the worst case scenario for Diagonal is that its own candidate—if approved—is synergistic on the marketplace.  “I do not see us directly competing with sotatercept because what we are doing is promoting missing signaling, whereas [Merck is] inhibiting excessive activin signaling,” Lugovskoy said. Diagonal has a good sense of Winrevair's capabilities, with Acceleron's former vice president of biology, Patrick Andre, Ph.D., now Diagonal's chief scientific officer. Merck got hold of Winrevair when it acquired Acceleron for $11.5 billion in 2021.  Equipped with new cash, Lugovskoy expects Diagonal will grow its head count in the single digits, with most of the new jobs centered on building clinical capabilities.