The focus of our research activities is development of novel small molecules and recombinant fusion proteins targeting the Angiopoietin-Tie2 signaling pathway. This receptor tyrosine kinase signaling pathway is known for its gatekeeper functions in the vasculature, including promoting vascular stability and counteracting inflammation and apoptosis in the endothelium. Due to its critical cellular function, the Angiopoietin-Tie2 signaling pathway is a therapeutic target for a wide range of different diseases involving vascular dysfunction.
At the moment we are focusing on acute respiratory distress syndrome (ARDS), as a host-directed therapeutic for COVID-19, primary open-angle glaucoma, and acute and chronic kidney disease. Two major approaches to activate the Angiopoietin-Tie2 pathway are by using analogs or mimetics of the endogenous agonist ligand Angiopoietin-1, or by inhibiting phosphatases that act as inhibitors of phosphorylated Tie2 receptor tyrosine kinase.
For the identification of novel small molecule chemical starting points (hits), we are following an artificial intelligence (AI)-based approach in collaboration with our partner Cyclica.
Currently there are no approved biomarkers for detection of glaucoma progression or severity, with intraocular pressure only being a risk factor for glaucoma. GDF15 is an attractive biomarker for determining the severity and progression of glaucoma. Mannin is developing a prototype for a point of care in vitro diagnostic (IVD) device to detect GDF15 in aqueous humor samples. The IVD has several advantages over conventional clinical tests, with potential to be a first-in-class diagnostic test allowing ophthalmologists to monitor glaucoma progression in patients at their office.