Novel Drug Delivery Platform as Medical Countermeasure for treatment of Gastrointestinal Radiation Damage

Project Summary/Abstract The Tiny Cargo Company offers a unique, orally administered medical countermeasure for treatment and prevention of the gastrointestinal (GI) side effects of cancer radiation therapy (RT). Our therapeutic is comprised of milk-derived extracellular vesicles (mEVs) loaded with a safe and highly effective radioprotective drug – a formulation that we call Milactatm. RT complications include nausea, vomiting, pain and dyspepsia, mucosal barrier breakdown, and nutrient malabsorption - with long-term effects that can also include cumulative and irreversible scarring of the gut. Presently, there are no treatments to prevent or mitigate these side-effects of RT. Our world-wide exclusive license from Virginia Tech includes pending patents for the composition and method of drug loading into mEVs of our radioprotective drug, as well as methods for industrially scalable production and isolation of pharmaceutical-grade mEVs from bovine milk. mEVs are subject to minimal regulation by the FDA and our radioprotective drug is a novel, short 9 amino acid peptide (RPRPDDLEI) mimicking the C-Terminus of the human gap junction protein Connexin 43. Our technical premise is that encapsulation of RPRPRDDLEI in mEVs will enable oral delivery and protection of our fragile peptide therapeutic in digestive juices prior to uptake in GI-tract cells. Our preliminary data indicates an optimized mEV-drug loading approach, demonstration of uptake of mEVs by gut cells/tissues following oral administration and in vitro data that our RPRPDDLEI-mEV formulation provides potent levels of radioprotection to cultures of the rat GI-tract derived primary cell line IEC-6, comparable to Phase III Clinical Trial therapeutic αCT1. In two aims we will: 1) Undertake testing in vivo of the prophylactic efficacy of our mEV-RPRPDDLEI formulation (i.e., Milacta) in a mouse model of whole-body irradiation, and; 2) Determine the optimal dosing regimens (i.e. prophylactic, post- irradiation, dual-treatment) for maximized radioprotection. Tiny Cargo’s technology meets an urgent clinical need that could increase patient uptake and compliance with highly effective radiation-based cancer mitigation strategies, as well as providing a medical technology that is likely to be of high strategic interest to the US and our military. Moreover, our mEV-based and drug loading method represents a platform technology that in the future could be adapted for other “difficult-to-drug” biologics, including microRNAs and other therapeutic peptides, thereby providing new licensing and commercial collaborative opportunities for Tiny Cargo as it develops its business plan and pipeline beyond mitigation of the effects of radiation therapy in cancer patients.