APH-0907

By Aphios Corp.

For oral delivery of insulin APH-0907 is a nanoencapsulation of insulin in biodegradable polymer nanospheres [US Patent]. Nanoencapsulation is being used to protect the protein macromolecules/nanoparticles during the stomach passage; the residence time in the stomach will be short compared to the protein release rate from the polymer nanospheres. Animal data demonstrates that nanoencapsulated insulin was protected in the stomach and then transported to the blood. When protein nanoparticles reach the gut, they are transported across the lining, which may be mediated by M cells in the lymphatic tissue of the gut. Alternatively, the protein can be mobilized from nanospheres and rapidly transported to the systemic circulation by the epithelial cells. Both the polymer "shell" and the protein macromolecules/nanoparticles are intended to enable and regulate this stage of drug transport. With the optimal combination of the biodegradable polymer nanospheres, shell properties, and protein characteristics, we anticipate a significant improvement in the oral bioavailability of protein therapeutics. We believe that our oral delivery nanotechnology will be applicable to large as well small protein molecules since we have demonstrated that our protein nanoparticles technology is independent of size and molecular weight (MW). Proprietary Nanoencapsulation Process APH-0907 is manufactured by Aphios' proprietary and patented PNS process. In PNS, a biodegradable biopolymer is dissolved in SuperFluids™, mixed with the target in solution or as a slurry of nanoparticles at operating pressures, and the mixture is decompressed into an aqueous solution, liquid nitrogen or an empty vessel (spray dryer); as a result of decompression, polymer nanospheres are formed, encapsulating the therapeutic target. In Vitro Characteristics of PNS In vitro release characteristics of insulin from polymer nanospheres were evaluated by re-suspending lyophilized nanospheres in phosphate-buffered saline at a pH of 7.4. Absorption of the solution was then measured at 280 nm at different time intervals. Release characteristics of insulin from these polymer nanospheres are shown over a 5-½ hour period. In Vivo Characteristics of PNS - Three groups of four chronic diabetic BB/Wor male rats were used to evaluate the efficacy of polymer nanoencapsulated insulin. One group was given 2 mL of the test formulation using standard gavage method. A second group received oral non-encapsulated insulin, administered by gavage at the concentration based on the animals' day of diabetes onset. A third group received injected insulin (PZI, Eli Lilly) therapy at the dose consistent with their day of onset of diabetes. The animals were bled prior to treatment and at 0.5, 1, 2, 4, 8, and 16 hours after treatment. - This in vivo oral gavage study of nanoencapsulated insulin conducted in diabetic mice showed a significant decrease in glucose levels after oral administration, causing statistically significant decreases in glucose levels at 1 and 2 hours post-administration. Injected insulin also resulted in statistically significant decreased glucose levels; while injectable insulin, given orally, did not cause statistical decreases in glucose levels. Partnering Opportunities We are seeking a strategic corporate partner to continue the development of APH-0907 as an oral insulin product for diabetics.