10066967Preclinical development of the first orally-active substance for the treatment of preeclampsiaClosedCollaborative R&DInnovate UKPreeclampsia is a life-threatening hypertensive disease of pregnancy that affects millions of women worldwide and results in the deaths of over 500,000 infants each year. Current management options are inadequate, typically involving early delivery of the baby by Caesarean section, regardless of gestational maturity. This project seeks to address the urgent need for a therapeutic solution with the development of MZe786, an orally active, small molecule designed to target key pathways implicated in preeclampsia. MZe786 is a chemically modified form of aspirin that releases vasoprotective hydrogen sulphide, offering a novel mechanism to prevent preeclampsia. Preclinical studies have shown that MZe786 effectively improves both maternal and fetal outcomes in experimental models of preeclampsia. The molecule has demonstrated its ability to reduce levels of soluble Flt-1, a natural antagonist of Vascular Endothelial Growth Factor (VEGF) and a critical biomarker for predicting disease outcomes. Our vision for this project is to progress MZe786 through preclinical formulation development ready for clinical formulation manufacturing, ultimately positioning it as a first-in-class treatment for preeclampsia. The key objectives include refining the formulation of MZe786 to enhance its solubility and stability, ensuring it meets regulatory standards, and preparing for the clinical manufacturing phase. Solid dispersion formulation strategy will be used as it offers higher solubility and stability compared to blend-in capsule method. This that the drug can be administered as a reconstituted oral solution, suitable for both animal studies and human trials. The innovative approach of using a solid dispersion technique significantly enhances the drug's bioavailability, positioning it more effectively for successful clinical trials and eventual market entry. In parallel, we are also advancing M-PREG, a digital diagnostic tool designed to identify high-risk pregnancies and guide the use of MZe786 both in clinical trials and in clinical practice. This tool will play a crucial role in patient risk stratification, ensuring that the drug is used effectively and safely in the targeted population. Our ongoing work includes planning the regulatory pathway for M-PREG to achieve UKCA certification, which is essential for its integration into clinical practice. This project is innovative not only in its development of a new therapeutic for preeclampsia but also in its holistic approach, combining treatment with advanced diagnostics. The anticipated outcomes will position MZe786 as a groundbreaking solution to a significant global health challenge, potentially unlocking further investment and accelerating its path to market.