Telangiectasis

▎药明康德内容团队编辑Diagonal Therapeutics公司今日宣布完成1.28亿美元的A轮融资。获得资金将用于支持该公司专有的DIAGONAL技术平台和创新药物管线的进一步发展，发现和开发激动性抗体（agonist antibody），包括其用于治疗遗传性出血性毛细血管扩张症（HHT）的主打在研项目。在HHT的临床前模型中，Diagonal的激动性抗体防止并逆转了病理性畸形血管的形成。本轮融资由BVF Partners和Atlas Venture共同领投，Lightspeed Venture Partners、RA Capital Management、Frazier Life Sciences、Viking Global Investors、Velosity Capital和Checkpoint Capital参与投资。大多数获得批准上市的抗体通过抑制细胞功能发挥作用，而Diagonal公司开发的激动性抗体通过结合两个受体并将它们聚集在一起来激活信号通路。鉴于每个受体和抗体之间存在许多潜在的结合位点，其中只有一小部分会导致所需的激动活性。这使得识别或理性设计激动性抗体变得困难。新闻稿指出，DIAGONAL平台解决了这一挑战，结合专有的计算和实验技术，使Diagonal的科学家能够以前所未有的速度和高度保真度筛选数十亿种组合。使用该平台，Diagonal公司已经发现了针对四个复杂靶标的候选抗体，为治疗多种严重疾病提供了新的途径，其中包括：遗传性出血性毛细血管扩张症：HHT是一种单基因突变导致的罕见疾病。HHT患者中，TGF-β受体超家族复合体的突变产生了两种异常血管类型，它们易于破裂和出血。这些出血事件导致慢性贫血，如果不接受治疗，可能导致肺部和大脑出血、中风、心力衰竭和死亡。Diagonal的激动性抗体可重新激活休眠的信号通路，解决疾病的根本原因。肺动脉高压（PAH）：在PAH患者中，由于抗增殖和促增殖信号的失衡引起患者血管狭窄。Diagonal的激动性抗体可以纠正信号通路平衡并恢复血管壁的稳态。Alex Lugovskoy博士是Diagonal Therapeutics公司的首席执行官兼联合创始人。在他20多年的生物技术职业生涯里，他曾经担任Dragonfly Therapeutics的首席运营官，Morphic Therapeutic的首席开发官，Merrimack Pharmaceuticals的副总裁，和渤健的药物发现副主任。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] Diagonal Therapeutics Launches with $128 Million in Financing to Pioneer a New Approach to Discovering and Developing Agonist Antibodies to Tackle the Underlying Causes of Severely Debilitating Diseases. Retrieved April 3, 2024, from https://www.diagonaltx.com/news/diagonal-therapeutics-launches-with-128-million-in-financing-to-pioneer-a-new-approach-to-discovering-and-developing-agonist-antibodies-to-tackle-the-underlying-causes-of-severely-debilitating-diseases免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

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.”

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.