Preclinical development of the first orally-active substance for the treatment of preeclampsia

第一种治疗先兆子痫的口服活性物质的临床前开发

• 批准号: 10066967
• 金额: $ 56.62万
• 依托单位: MIRZYME THERAPEUTICS LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10066967
• 关键词: Preclinical; development; first; orally; active

Preeclampsia is a hypertensive disease of pregnancy that kills over 500,000 infants each year and for which there are currently no approved prophylactic or therapeutic treatments. Current management options are inadequate as it involves delivering the baby by Caesarean section, regardless of gestational maturity. Our studies show that preeclampsia is a 'double hit' vascular disease due to a defect in protective pathways of heme oxygenase-1 (Hmox1) and Vascular Endothelial Growth Factor (VEGF) signalling. This enabled the development of a novel therapy to target these proteins to ameliorate the disease in different disease models and identify a subset of patients who may potentially benefit from such a treatment. The orally active, small molecule, MZe786 is a unique form of aspirin chemically modified to release vasoprotective hydrogen sulphide and acts like a supercharged Aspirin(r) that has been shown to prevent preeclampsia in several experimental models. Recent studies showed that MZe786 is effective in improving the maternal and fetal outcomes in experimental models of preeclampsia. The protective role of Mze786 in preeclampsia was further confirmed by its ability to reduce soluble Flt-1, a natural antagonist of VEGF, and a valuable predictive biomarker, to determine disease outcome. The results strongly support the development of this novel molecule in the prevention and treatment of preeclampsia. MZe786 has been granted an Innovation Passport by The Medicines and Healthcare products Regulatory Agency (MHRA) that fast-track development of the molecule, which for the first time offers an opportunity to solve this significant global issue.This award will allow MirZyme to progress to clinical development of MZe786\. Once these studies are successfully completed and we gain MHRA approval for human trials, this product will be positioned to be the drug to deliver real patient benefits in this indication. Ongoing discussions have suggested that investor interest is predicated on entry into clinical studies, and the management expect this grant will unlock significant investment into the UK.

先兆子痫是一种妊娠高血压疾病，每年导致超过50万婴儿死亡，目前还没有批准的预防或治疗方法。目前的管理选择是不够的，因为它涉及到剖腹产分娩的婴儿，无论妊娠成熟。我们的研究表明，先兆子痫是一种“双重打击”血管疾病，由于血红素氧合酶-1（Hmox 1）和血管内皮生长因子（VEGF）信号传导的保护途径缺陷。这使得能够开发一种新的治疗方法来靶向这些蛋白质，以改善不同疾病模型中的疾病，并确定可能从这种治疗中受益的患者子集。口服活性小分子MZe 786是一种独特的阿司匹林化学修饰形式，可释放血管保护性硫化氢，其作用类似于增压阿司匹林（r），已在几种实验模型中显示可预防先兆子痫。最近的研究表明，MZe 786在先兆子痫的实验模型中可有效改善母体和胎儿的结局。Mze 786在先兆子痫中的保护作用通过其减少可溶性Flt-1（VEGF的天然拮抗剂和有价值的预测生物标志物）以确定疾病结果的能力进一步证实。这些结果强烈支持这种新型分子在预防和治疗先兆子痫中的发展。MZe 786已被美国药品和保健品管理局（MHRA）授予创新护照，该护照将快速跟踪分子的开发，这是第一次为解决这一重大全球问题提供机会。该奖项将使MirZyme能够推进MZe 786的临床开发。一旦这些研究成功完成，我们获得MHRA批准进行人体试验，该产品将被定位为在该适应症中为患者提供真实的益处的药物。正在进行的讨论表明，投资者的兴趣取决于进入临床研究，管理层预计这笔赠款将释放对英国的重大投资。