Project Grant R44AI170237

NOVEL ANTIRETROVIRAL THERAPY DELIVERY PLATFORM FOR INFANTS AND YOUNG CHILDREN: ORAL DISPENSABLE STRIPS (ODS) - PROJECT SUMMARY APPROXIMATELY 3.4 MILLION CHILDREN UNDER 15 YEARS LIVE WITH HIV AND REQUIRE REGULAR TREATMENT. WORLDWIDE ESTIMATES FOR HIV-RELATED DEATHS AMONG CHILDREN ARE AS HIGH AS 110,000 ANNUALLY AND ARE OFTEN CAUSED BY POOR PATIENT AND CAREGIVER ADHERENCE. CAUSES FOR POOR ADHERENCE ARE MAINLY ROOTED IN THE LOW PALATABILITY OF EXISTING FORMULATIONS (LIQUIDS, FAST-DISSOLVING TABLETS), THE COMPLEXITY OF PREPARATION AND ADMINISTRATION, AND ISSUES RELATED TO PATIENT PRIVACY AND SOCIAL HIV STIGMA. OAK THERAPEUTICS, INC. IS AN EARLY-STAGE PHARMACEUTICAL RESEARCH COMPANY THAT SPECIALIZES IN THE FORMULATION AND MANUFACTURING OF PROPRIETARY SUPPORT MATRIX STRIPS COMPOSED OF ORAL-DISINTEGRATING POLYMERS TO FORM ORAL DISSOLVABLE STRIPS (ODS). OAK THERAPEUTICS IS DEVELOPING AN ODS PLATFORM THAT SUPPORTS A MULTI-DRUG PEDIATRIC FORMULATION FOR THE CURRENT STANDARD OF CARE FOR HIV (FIXED-DOSE COMBINATION ANTIRETROVIRAL THERAPY CONSISTING OF ABACAVIR/ LAMIVUDINE/ DOLUTEGRAVIR, ALD-ODS) AND HAS DEMONSTRATED PROOF OF CONCEPT THROUGH BIOEQUIVALENCE STUDIES IN THE SBIR FUNDED PHASE I PROJECT. IN THIS SBIR PHASE II PROPOSAL, WE AIM TO COMPLETE THE ALD-ODS DEVELOPMENT AND DEVELOP GMP-COMPLIANT MANUFACTURING TECHNIQUES. TOWARDS THAT, IN AIM 1, ADDITIONAL PROPERTIES SUCH AS FLEXIBILITY, DOSING ACCURACY, AND STORAGE STABILITY WILL BE TESTED TO OPTIMIZE THE ODS. IN AIM 2, THE OPTIMAL ALD-ODS CANDIDATE WILL BE COMPARED TO TRIUMEQ-PD THE REFERENCE DRUG LEVEL (RDL) TO STUDY THE IN VIVO TOXICOLOGY PROFILE IN RODENTS, PHARMACOKINETIC PROFILE IN DOGS, AND STABILITY STUDIES IN VITRO. IN AIM 3, WE WILL INITIATE THE TECHNOLOGY TRANSFER TO DEVELOP A HIGHLY EFFICIENT, INTEGRATED MANUFACTURING PROCESS FOR LARGE-SCALE PRODUCTION OF ALD-ODS AND TEST ITS SUITABILITY FOR GMP STANDARD COMPLIANCE TOWARDS COMMERCIALIZING THE PRODUCT. THE FINAL ALD-ODS PRODUCT WILL BE THE FIRST PEDIATRIC FORMULATION TO CONTAIN ALL THE RECOMMENDED FIRST-LINE DRUGS FOR HIV IN A SINGLE, MONO-LAYER MUCOADHESIVE FORMULATION WITH EASILY ADJUSTABLE DOSING TO SIMPLIFY ADMINISTRATION FOR CAREGIVERS. POST PHASE II, THE RESULTS FROM THE IN-VIVO BIOAVAILABILITY, SAFETY, AND STABILITY STUDIES, WILL BE PACKAGED FOR AN ABBREVIATED NEW DRUG APPLICATION (ANDA) TOWARDS SUBMISSION TO THE FDA. SUCCESSFUL COMPLETION OF THIS PROJECT WILL HELP TO SECURE THE INTEREST OF PHARMACEUTICAL COMPANIES WITH WHOM OAK THERAPEUTICS WILL ENGAGE TO COMPLETE CLINICAL TRIALS AND LAUNCH ALD- ODS INTO THE MARKET.