Milk Exosomes Enable Oral administration and Long-Term Room-Temperature Shelf Stability of Monoclonal Antibody-Derived Medical Countermeasures

The Tiny Cargo Company has innovated a novel drug delivery platform comprised of milk exosomes, complete with a platform-based loading technique for a wide range of therapeutics including peptides, small molecules, large biologics, and monoclonal antibodies, as well as novel methods of lyophilizing, breaking cold-chain reliance of MCMs developed using our technology. Our technology platform is underpinned by worldwide patent applications including claims on: 1) Methods of industrially isolating milk exosomes; 2) Platform-based loading of exogenous drugs into milk exosomes; 3) Composition of matter of milk exosomes loaded with exogenous peptides, small molecules, complex biologics and monoclonal antibodies; 4) Oral administration of novel exosomal compositions of matter, and; 5) Composition of lyophilized milk exosomes with loaded cargoes. One of Tiny Cargo’s leading pipeline drugs is a novel composition of matter known as XoLacta, which is comprised of milk exosomes loaded with a potent radiotherapeutic peptide at >95% efficiency, then lyophilized and stored at room temperature, breaking cold-chain reliance. Stability at room temperature (25?) has been confirmed at over 12 months. XoLacta is a radiomitigator for use as a Medical Countermeasure to combat Gastrointestinal Acute Radiation Syndrome, with FDA approval to begin Animal Rule studies in murine and porcine models of lethal radiation exposure. We have accumulated the appropriate funds and resources to partner with Lovelace biomedical and The Armed Forces Radiobiology Research Institute to accomplish trials associated with XoLacta development. While this work is conducted with partnering CROs, we have begun deploying our platform-based loading approach to accomplish high-efficiency loading of other exogenous cargoes. Indeed, we have confirmed loading of numerous small molecules (>95% efficiency), peptides (>95% efficiency), large biologics (>97% efficiency), and monoclonal antibodies (>60% efficiency). Using this platform based approach, many of these drug cargoes have been validated in cell and animal assays, confirming our ability to: 1) load a variety of drug cargoes with our platform-based approach; 2) lyophilize, or freeze dry, the composition to enable long-term shelf stability, and; 3) Administer capsule or rehydrated liquid orally to deliver drugs to internal cellular targets.Our goal in this SBIR proposal is to receive monoclonal antibodies of particular interest as MCMs from the United States Government, then load them within GMP-grade milk exosomes produced at our facility in Roanoke, Virginia, and lyophilize for shelf-stability testing. Aim 1 will be to optimize our loading approach to ensure >80% loading of mAb into milk exosomes, while Aim 2 will be to validate >12 month shelf-stability at room temperature (25? +/- 2?), while also evaluating at accelerated degradation temperatures (40? +/- 2?), with time points for both temperatures spread across 6 months.