Thrombasthenia

First participant with Von Willebrand Disease dosed with HMB-002, a novel subcutaneous therapy designed to increase endogenous von Willebrand Factor and Factor VIII levels COPENHAGEN, Denmark and CAMBRIDGE, MA, USA I February 27, 2025 I Hemab Therapeutics, a clinical-stage biotechnology company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, today announced the first participant with Von Willebrand Disease (VWD) has been dosed in Velora Pioneer, a Phase 1/2 clinical trial investigating HMB-002, a potential first-in-class subcutaneous therapy for VWD. “We are excited to advance the clinical development of HMB-002 for Von Willebrand Disease,” said Catherine Rea, MD, PhD, Vice President of Clinical Development at Hemab. “HMB-002 is the first fixed-dose subcutaneously administered antibody-based preventative therapy aiming to transform daily life for patients.” HMB-002 is a monovalent antibody uniquely designed to increase levels of von Willebrand Factor (VWF) and Factor VIII and provide a long-acting, subcutaneous prophylactic treatment for individuals with all types of VWD. Preclinical data for this investigational therapy were first presented at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), showcasing its potential to target the underlying patho-etiology of VWD by stabilizing VWF and promoting sustained hemostatic correction. “Von Willebrand Disease is characterized by a deficiency in VWF activity and sometimes associated with lowered levels of FVIII – both essential to control severe bleeding,” said Dr. Priyanka Raheja, the Royal London Hospital, Barts Health NHS Trust. “HMB-002 functions by increasing VWF and FVIII and could offer a complete disease correction for some and substantial modification for bleeding tendency for others. I am excited to be a contributing investigator on the Phase 1/2 trial.” The Phase 1/2 study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of HMB-002 in individuals with VWD. The initial part of the study will evaluate single ascending doses of HMB-002 in a controlled setting. The first participant was dosed at Richmond Pharmacology in London under the supervision of Principal Investigator, Dr. Ulrike Lorch. The study is actively enrolling participants, with interim data anticipated later this year. “The initiation of the HMB-002 clinical program establishes Hemab as a multi-asset clinical-stage biotech and underscores our unwavering commitment to reimagine blood clotting therapies for people living with a variety of underserved bleeding disorders,” said Benny Sorensen, MD, PhD, CEO of Hemab. “Von Willebrand Disease has been documented for about 100 years. However, the current standard of care is sparse, ancient, and inconvenient. It’s time to leapfrog treatment into the 21 st century, and we believe HMB-002 can become a new back-bone therapy for all types of Von Willebrand Disease.” In addition to Velora Pioneer, Hemab is also conducting Velora Discover , a prospective natural history study collecting data on bleeds, treatments, and quality-of-life elements in people with VWD. Hemab is partnered with Haemnet, a specialist research and communications consultancy in the bleeding disorders community, to conduct VWD 360, the largest-ever natural history study in all types of VWD based on people’s detailed reported lived experience. Recent initial results were shared at EAHAD 2025. About Von Willebrand Disease Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, characterized by quantitative or qualitative defects in Von Willebrand Factor (VWF), often resulting in frequent mucocutaneous bleeding events and heavy menstrual bleeding in women. The severity of bleeding ranges from low-volume events to potentially life-threatening hemorrhages. Chronic blood loss frequently leads to iron deficiency anemia, exacerbating the disease burden and reducing quality of life, particularly for those with clinically understated subtypes. Despite its prevalence, current treatment options for VWD primarily focus on managing symptoms rather than addressing the underlying defect in VWF production or function. About HMB-002 HMB-002 is a monovalent human antibody developed as the first-in-class prophylactic treatment for Von Willebrand Disease targeting the underlying root cause of the disease, a condition driven by a deficiency or defect in Von Willebrand Factor (VWF), a key regulator of hemostasis. By specifically targeting the C-terminal CK domain of VWF, which is distinct from regions critical to its essential interactions, HMB-002 shields the protein from degradation, boosting endogenous levels without compromising its function. Preclinical data suggest strong potential for meaningful therapeutic benefit. For more information, please visit clinicaltrials.gov (NCT06610201). About Hemab Therapeutics Hemab is a multiple clinical-asset biotech company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in Cambridge, MA, and Copenhagen, Denmark, Hemab is progressing a pipeline of innovative therapeutic solutions, leveraging a variety of cutting-edge technologies and approaches to transform the treatment paradigm for patients with high unmet need. The company’s strategic guidance, Hemab 1-2-5 TM , targets building a pipeline of multiple development programs to deliver long-awaited innovation for patients with high unmet need blood-clotting disorders like Glanzmann thrombasthenia, Factor VII Deficiency, Von Willebrand Disease, and others. Learn more at hemab.com . Follow us on LinkedIn , Facebook , Instagram , and X . SOURCE: Hemab Therapeutics

Interim results demonstrate treatment with HMB-001 resulted in >50% reduction in treated bleeds at all tested dose levels In second oral presentation, Hemab presented first preclinical data for HMB-002, a potential novel treatment for Von Willebrand Disease Results from lived experience of Glanzmann thrombasthenia (GT360) and Von Willebrand Disease (VWD 360) natural history studies were included in two additional oral presentations COPENHAGEN, Denmark and CAMBRIDGE, Mass., Feb. 7, 2025 /PRNewswire/ -- Hemab Therapeutics, a clinical-stage biotechnology company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders, today presented interim data from the ongoing evaluation of HMB-001, a novel bispecific antibody in development as first ever prophylactic treatment for the bleeding disorder Glanzmann thrombasthenia (GT). The Phase 2 study consists of a minimum 6-week prospective run-in where participants record bleeds via an electronic bleed diary, followed by 3 months of treatment with HMB-001. Interim efficacy data to date demonstrated >50% reduction in treated bleeds in all 3 tested dose cohorts. Underscoring its potential to address unmet medical needs and to expedite patient access, HMB-001 has been granted Orphan Drug Designation by the U.S. Food and Drug Administration and the UK Medicines and Healthcare products Regulatory Agency has awarded it designation under the Innovative Licensing and Access Pathway. Hemab also unveiled compelling preclinical data for HMB-002, a potential novel treatment for Von Willebrand Disease (VWD). These data were featured as oral presentations at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD) held this week in Milan, Italy. "Glanzmann thrombasthenia is a serious and devastating bleeding disorder where patients often experience in excess of 60-80 treatment-requiring bleeds annually. These interim Phase 2 results signal the potential of a new reality for the Glanzmann thrombasthenia community, bringing us a step closer to a much-needed breakthrough in preventing bleeding," said Kate Madigan, Chief Medical Officer at Hemab. "The preclinical data for HMB-002 highlights its potential to specifically address the underlying patho-etiology and revolutionize care for the Von Willebrand Disease community, offering hope to prevent life-threatening complications and provide patients with a critical new lifeline." Interim pharmacokinetic (PK) data from the Phase 1/2 study of HMB-001 supports the use of weekly or biweekly dosing regimens. Pharmacodynamic (PD) responses are aligned with the mechanism of action, demonstrating a dose-dependent accumulation of activated Factor VII (FVIIa) and enhanced potentiation through TLT-1 binding. Efficacy assessments indicate a reduction of over 50% in treated bleeding episodes at all tested dose levels. In the single ascending dose (SAD) study, doses of 0.2, 0.5, and 1.25 mg/kg were evaluated, while the multiple ascending dose (MAD) study explored biweekly doses of 0.3, 0.6, and 0.9 mg/kg. The findings suggest a safe and effective dosing range of 0.3-0.6 mg/kg, while doses of 0.9 mg/kg and above were associated with elevated D-dimer levels and risk of venous thrombosis. These results provide valuable insights into optimizing dose and regimen for improved outcomes. "Bleeding disorders such as Glanzmann thrombasthenia present significant hardships, including unpredictable and life-altering bleeds, physical pain, social stigma, and emotional isolation. Despite these burdens, preventive treatments have yet to be developed," said Suthesh Sivapalaratnam, MD, PhD, Consultant Hematologist at Barts Health NHS Trust and Associate Professor at Queen Mary University of London. He adds: "With a bleed reduction of greater than 50%, the Phase 2 results highlight the transformative potential of HMB-001, offering people with Glanzmann thrombasthenia and providers a long-awaited breakthrough that could redefine care standards and bring renewed hope to a community in urgent need of innovation." "As a principal investigator in this study, I've seen firsthand how HMB-001 has the potential to significantly improve outcomes for people with Glanzmann thrombasthenia," said Laurent Frenzel, MD, PhD, Head of the Hemophilia Treatment and Research Center at the Necker-Enfants Malades Hospital (Paris Cité). "The Phase 2 data demonstrate promising efficacy and a manageable safety profile, representing a significant advancement in the treatment landscape. I look forward to seeing these results translate into a meaningful impact for those who have long faced limited options and unmet medical needs." Hemab plans to complete Phase 2 study recruitment in the first half of 2025. Hemab presented compelling preclinical data for HMB-002, a monovalent antibody uniquely designed to address VWD by increasing endogenous Von Willebrand Factor (VWF) levels and improving overall hemostasis. Unlike current treatments that often require frequent intravenous infusions or focus on symptom management, HMB-002 has the potential to provide a long-lasting, subcutaneous prophylactic solution that targets the root cause of VWD. Data demonstrate a promising safety and efficacy profile with high-affinity target-selective binding and preservation of key physiological functions of VWF when HMB-002 is bound. Administration of HMB-002 to cynomolgus monkeys resulted in a time-dependent accumulation of VWF, a corresponding rise in VWF activity, and a rise in the amount of another important blood clotting protein called Factor VIII (FVIII). The distribution of different sizes of VWF molecules (multimers) remained largely the same, suggesting that the activity levels of VWF were consistent. These results indicate that HMB-002, by boosting the levels of naturally occurring VWF, has the potential to be an effective, convenient and long-lasting preventive treatment option for people with VWD. The company is actively enrolling participants in VELORA-Discover, a prospective observational study for individuals with Type 1 VWD, to further understand the disease's natural history and support future clinical trials. Hemab's partner Haemnet, a specialist research and communications consultancy in the bleeding disorders community, also presented results from two natural history studies. The Glanzmann's 360 and Von Willebrand Disease 360 studies showcased the unmet needs and burdens the patients face every day. About Glanzmann Thrombasthenia Glanzmann thrombasthenia (GT) is a rare and severe bleeding disorder marked by debilitating, sometimes life-threatening bleeding episodes. Results from an international Glanzmann's 360 (GT360) natural history study revealed the substantial burden of this disease: 88% of the 117 participants reported at least one bleed in the previous week, with 34% of those bleeds requiring medical treatment. These bleeding episodes significantly impact patients' mental health and quality of life, with 67% reporting low mood, 52% reporting emotional problems, and 46% experiencing social isolation. Additionally, 81% of participants reported missing school or work due to bruising or bleeding. To date, there are no effective prophylactic treatment options for GT. About HMB-001 HMB-001 is a subcutaneously administered bispecific antibody that binds and stabilizes endogenous Factor VIIa with one antibody arm and binds to TLT-1 on activated platelets with the other arm. This allows for the accumulation of endogenous Factor VIIa in the body, recruitment of Factor VIIa directly to the surface of the activated platelets, where it is known to facilitate hemostatic plug formation. HMB-001 is designed to be a first-in-class prophylactic treatment for Glanzmann thrombasthenia (GT) with the potential to treat other debilitating rare bleeding disorders. The U.S. Food and Drug Administration granted Fast Track Designation and Orphan Drug Designation to HMB-001 for the treatment of GT while the UK The Medicines and Healthcare products Regulatory Agency has awarded it designation under the Innovative Licensing and Access Pathway (ILAP). For more information, please visit clinicaltrials.gov (NCT06211634). About Von Willebrand Disease Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, characterized by quantitative or qualitative defects in Von Willebrand Factor (VWF), often resulting in frequent mucocutaneous bleeding events and heavy menstrual bleeding in women. Severity of bleeding ranges from low-volume events to potentially life-threatening hemorrhages. Chronic blood loss frequently leads to iron deficiency anemia, exacerbating the disease burden and reducing quality of life, particularly for those with clinically understated subtypes. Despite its prevalence, current treatment options for VWD primarily focus on managing symptoms rather than addressing the underlying defect in VWF production or function. About HMB-002 HMB-002 is a monovalent human antibody developed as the first-in-class prophylactic treatment for Von Willebrand Disease targeting the underlying root cause of the disease, a condition driven by a deficiency or defect in Von Willebrand Factor (VWF), a key regulator of hemostasis. By specifically targeting the C-terminal CK domain of VWF, which is distinct from regions critical to its essential interactions, HMB-002 shields the protein from degradation, boosting endogenous levels without compromising its function. Preclinical data suggest strong potential for meaningful therapeutic benefit. For more information, please visit clinicaltrials.gov (NCT06610201). About Hemab Therapeutics Hemab is a clinical-stage biotech company developing novel prophylactic therapeutics for serious, underserved bleeding and thrombotic disorders. Based in Cambridge, MA, and Copenhagen, Denmark, Hemab is progressing a pipeline of innovative therapeutic solutions, leveraging a variety of cutting-edge technologies and approaches to transform the treatment paradigm for patients with high unmet need. The company's strategic guidance, Hemab 1-2-5TM, targets building a pipeline of multiple development programs to deliver long-awaited innovation for patients with high unmet need blood-clotting disorders like Glanzmann thrombasthenia, Factor VII Deficiency, Von Willebrand Disease, and others. Learn more at hemab.com. Follow us on LinkedIn, Facebook, and X. Media Contact: Peg Rusconi [email protected] 617-910-6217 SOURCE Hemab Therapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

撰文丨王聪 编辑丨王多鱼 排版丨水成文 溶瘤病毒（Oncolytic virus，OV），例如腺病毒、新城疫病毒、细小病毒和呼肠孤病毒等，作为一种很有前景的抗肿瘤方法，正在临床前实验和临床试验中进行研究。 溶瘤病毒在肿瘤细胞中的优先复制和溶瘤作用，以及溶瘤后激活的免疫反应，被认为是溶瘤病毒发挥抗肿瘤作用的主要原因，在治疗恶性肿瘤方面展现出了巨大前景。然而，在临床实践中，溶瘤病毒面临着几大挑战，包括静脉注射安全性问题、免疫原性不足、抗病毒免疫反应等。 2025 年 1 月 17 日，广西医科大学赵永祥教授、石玮教授、张坤教授和钟莉娉教授等人在国际顶尖学术期刊 Cell 上发表了题为：Hyperacute rejection-engineered oncolytic virus for interventional clinical trial in refractory cancer patients（超急性排斥反应工程化的溶瘤病毒用于难治性癌症患者的介入性临床试验）的研究论文。 该研究开发了一种静脉注射的新型溶瘤病毒疗法——携带猪 α1,3GT 基因的重组新城疫病毒（NDV-GT），实现了晚期癌症治疗的重大临床突破。静脉注射后，这种病毒能够将肿瘤伪装的“看起来”像猪器官，引发超急性排斥反应，诱骗免疫系统攻击这些肿瘤，从而阻止肿瘤的生长，甚至完全清除肿瘤。 在临床前研究中，静脉注射的 NDV-GT 在 CRISPR 介导的原发性肝细胞癌猴模型中显示出强大的肿瘤清除能力。在针对 20 名复发/难治性转移性癌症患者的临床试验中，疾病控制率高达 90.00%，且反应持久，未出现严重不良事件和具有临床功能的中和抗体。该研究展示了基因工程改造的溶瘤病毒在癌症治疗中的巨大潜力，并为未来的临床应用奠定了基础。 溶瘤病毒（Oncolytic Viruse，OV）是一类能够选择性感染和杀死肿瘤细胞的病毒，同时激活宿主的抗肿瘤免疫反应。然而，现有的溶瘤病毒在临床应用中存在一些局限性，包括： 免疫原性不足：病毒引发的免疫反应较弱，难以有效抑制肿瘤生长。 静脉注射安全性问题：现有的溶瘤病毒在静脉注射时存在安全性问题，可能对正常组织造成损害。 抗病毒免疫反应：病毒在体内可能引发中和抗体，导致治疗效果减弱。 为了解决这些问题，研究团队开发了一种基于新城疫病毒（Newcastle Disease Virus，NDV）的基因工程溶瘤病毒——NDV-GT，通过将猪源 α1,3 半乳糖基转移酶基因（α1,3GT）整合到 NDV 基因组中，构建了 NDV-GT 病毒，该病毒能够在肿瘤细胞中表达 αGal 抗原，让免疫系统将肿瘤识别为外来的猪器官，从而触发超急性排斥反应，增强抗肿瘤免疫反应。 研究团队在多种肿瘤细胞系（肝癌、卵巢癌、宫颈癌等）和正常细胞系中测试了 NDV-GT 病毒的感染和溶瘤效果，此外，研究团队使用 CRISPR-Cas9 基因编辑技术在食蟹猴中建立了原发性肝癌模型，进一步验证了 NDV-GT 的体内抗肿瘤效果。 这些临床前研究显示： NDV-GT 具有特异性溶瘤效果：NDV-GT 在体外和体内实验中均表现出对肿瘤细胞的特异性杀伤作用，而对正常细胞的影响较小。 NDV-GT 能够触发超急性排斥反应：NDV-GT 感染的肿瘤细胞表达 αGal 抗原，触发超急性排斥反应，导致肿瘤血管栓塞和肿瘤坏死。 NDV-GT 能够增强免疫反应：NDV-GT 不仅直接溶解肿瘤细胞，还通过激活体液和细胞免疫反应，增强了抗肿瘤效果。 在上述临床前研究的基础上，研究团队发起了一项临床试验，招募了23名难治性癌症患者，包括肝癌、卵巢癌、宫颈癌、肺癌、食管癌、直肠癌、乳腺癌和黑色素瘤。这些患者每周接受一次 NDV-GT 静脉注射，持续 8-12 周。通过 PET-CT、CT、MRI 等影像学手段评估肿瘤的缩小情况，并使用免疫学指标评估患者的免疫反应。 临床试验结果显示：NDV-GT 治疗显著增强了患者的免疫反应，包括 T 细胞和树突状细胞的激活，以及多种细胞因子的分泌。在 20 名完成治疗的患者中，疾病控制率（DCR）达到 90%，其中 1 例完全缓解（CR），6 例部分缓解（PR），11 例病情稳定（SD）。在安全性方面，NDV-GT 治疗未引发严重副作用，患者的中和抗体水平虽有轻微上升，但仍在正常范围内，未影响治疗效果。 NDV-GT可有效抑制多种晚期癌症患者的肿瘤进展，且无严重毒性 该研究通过创新性地引入猪源 α1,3GT 基因，成功触发了超急性排斥反应，增强了抗肿瘤免疫反应，克服了现有溶瘤病毒的局限性。在多种复发/难治性转移性癌症中表现出良好的疗效和安全性，具有广泛的临床应用前景。此外，研究团队计划探索 NDV-GT 与其他免疫疗法的联合应用，以进一步提高癌症治疗效果。 总的来说，该研究成功开发了一种基于新城疫病毒的基因工程溶瘤病毒——NDV-GT，通过触发超急性排斥反应，显著增强了抗肿瘤免疫反应。临床前和临床试验结果表明，NDV-GT 在治疗多种难治性癌症中具有显著的疗效和良好的安全性，为溶瘤病毒疗法的发展提供了新的思路和技术支持。 值得一提的是，国际顶尖学术期刊 Nature 发表了题为：How to trick the immune system into attacking tumours 的新闻文章，积极评价了这项研究成果。 广西医科大学赵永祥教授、石玮教授、张坤教授和钟莉娉教授为 Cell 论文的共同通讯作者，广西医科大学钟莉娉教授、甘露博士、中南大学湘雅二医院王冰教授和常德市第一人民医院吴涛主任医师为论文共同第一作者。 论文链接： https://www.cell.com/cell/fulltext/S0092-8674(24)01423-5 设置星标，不错过精彩推文 开放转载 欢迎转发到朋友圈和微信群  微信加群  为促进前沿研究的传播和交流，我们组建了多个专业交流群，长按下方二维码，即可添加小编微信进群，由于申请人数较多，添加微信时请备注：学校/专业/姓名，如果是PI/教授，还请注明。 点在看，传递你的品味