MAA Laboratories Inc. — Department of Health and Human Services SBIR Phase I: 102

Description

PROJECT SUMMARY It is estimated thatof anti cancer small molecules and up toof late stage investigational compounds are poorly soluble in waterand such compounds are often associated with significant clinical problemssuch as inconsistent dosing and variable pharmacokineticsPKDasatinib is an orally bioavailable tyrosine kinase inhibitorTKIindicated for the treatment of chronic myelogenous leukemiaCMLand acute lymphoblastic leukemiaALLMarketed formulations of dasatinib exhibit a number of solubility issuesincluding pH dependent solubilitysignificant drug interactions with antacidsand inter dose and inter patient variabilityInconsistent dosing and variable bioavailability can lead to significant therapeutic problemssuch as adverse eventspoor patient adherenceand decreased clinical efficacyIn this Phase I SBIR projectMAA Laboratories will use their proprietary drug delivery technologythe NanoContTMto create a stable nanoformulation of dasatinibwhich is expected to have improved solubility and oral bioavailability relative to the marketed dasatinib formulationThe NanoContTM drug delivery technology is built on a continuous manufacturing platform and uses a combination of proprietary formulations and process conditions and a patented polymer coating process to create drug nanoformulationsi ecomposed of pharmaceutical crystalsnm in diameterwith unchanged crystalslong term product stabilityandgtyearsand enhanced clinical benefitsThe specific objective of this proposal is to advance one of MAAandapos s initial nanoformulated drug productsdasatinibMAACthrough formulation development and preclinical studiesincluding side byside performance comparisons with the currently marketed dasatinib formulationThe central hypothesis of this SBIR Phase I project is that the NanoContTM drug delivery technology can be used to create a stable nanoformulation of dasatinib that exhibits improved oral bioavailability and therapeutic efficiency relative to the currently marketed dasatinib formulationIn Aiman optimized nanoformulation of MAACwill be generated and aqueous solubility and in vitro dissolution will be measured relative to the marketed formulation of dasatinibIn Aimthe oral bioavailability of MAACwill be investigated relative to the marketed formulation in nude miceIn Aimwe will perform preclinical anti leukemia therapeutic efficiency studies in mice using multiple ascending doses of MAACand the dasatinib marketed formulationThe proposed studies will establish proof of concept for a novel nanoformulation of dasatinib using direct comparisons to the marketed formulationA successful result will generate an optimized MAACproduct with an improved PK profileand will prepare this product for IND enabling safety toxicology studies and IND submission as part of an SBIR Phase II project PROJECT NARRATIVE Many active pharmaceutical ingredients are insoluble in water and are therefore not readily absorbed by the body after oral administrationMAA Laboratories has developed an innovative drug delivery technology that is designed to formulate difficult to dissolve drugs into drug products with significantly improved solubility and oral bioavailabilityThe proposed studies will accelerate MAAandapos s efforts to develop a novel formulation of an antileukemia drug product that currently has significant deficiencies related to dosing and bioavailabilitywhich will provide an improved therapeutic option for patients with leukemia