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

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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.