The Tiny Cargo Company offers a unique, orally administered medical countermeasure for treatment andprevention of the gastrointestinal (GI) side effects of cancer radiation therapy (RT). Our therapeutic iscomprised of milk-derived extracellular vesicles (mEVs) loaded with a safe and highly effectiveradioprotective 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 thatcan also include cumulative and irreversible scarring of the gut. Presently, there are no treatments toprevent or mitigate these side-effects of RT. Our world-wide exclusive license from Virginia Tech includespending 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 frombovine 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 proteinConnexin 43. Our technical premise is that encapsulation of RPRPRDDLEI in mEVs will enable oraldelivery and protection of our fragile peptide therapeutic in digestive juices prior to uptake in GI-tractcells. Our preliminary data indicates an optimized mEV-drug loading approach, demonstration of uptakeof mEVs by gut cells/tissues following oral administration and in vitro data that our RPRPDDLEI-mEVformulation provides potent levels of radioprotection to cultures of the rat GI-tract derived primary cellline IEC-6, comparable to Phase III Clinical Trial therapeutic αCT1. In two aims we will: 1) Undertaketesting in vivo of the prophylactic efficacy of our mEV-RPRPDDLEI formulation (i.e., Milacta) in a mousemodel 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 urgentclinical need that could increase patient uptake and compliance with highly effective radiation-basedcancer mitigation strategies, as well as providing a medical technology that is likely to be of high strategicinterest to the US and our military. Moreover, our mEV-based and drug loading method represents aplatform technology that in the future could be adapted for other "difficult-to-drug" biologics, includingmicroRNAs and other therapeutic peptides, thereby providing new licensing and commercialcollaborative opportunities for Tiny Cargo as it develops its business plan and pipeline beyond mitigationof the effects of radiation therapy in cancer patients.
Public Health Relevance Statement: PROJECT NARRATIVE
Tiny Cargo has developed a novel drug delivery system combining non-immunogenic bovine
milk derived EVs (mEVs) with highly potent peptide therapeutics for treatment of
gastrointestinal radiation damage following Radiation Therapy. The successful
commercialization of this technology will allow for more intensive radiation therapy regimens
and a reduction in cancer recurrence, thus increasing quality of life and lifetime expectancy for
those afflicted with cancer; additionally, this research will provide an effective medical
countermeasure to the US military to protect against radiation exposure in the field, a key focus
of BARDA. Most importantly, this research will establish mEVs loaded with peptide therapeutics
as a novel drug delivery platform capable of treating a wide range of diseases via a patient
compliance oral uptake route, advancing clinical treatment of diseases from glioblastoma
multiforme to ischemic cardiac disease, representing a new modality in treatment.
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