Cooperative Agreement 2228069

SBIR PHASE II: AN OMICS-BASED COMPUTATIONAL DRUG DESIGN AND DISCOVERY PLATFORM FOR NEXT GENERATION MICROBIOME THERAPEUTICS -THE BROADER/COMMERCIAL IMPACT OF THIS SMALL BUSINESS INNOVATION RESEARCH (SBIR) PHASE II PROJECT FOCUSES ON THE HUMAN GUT MICROBIOME, THE COMPLEX AND DYNAMIC COMMUNITY OF MICROORGANISMS RESIDING IN THE GASTROINTESTINAL TRACT. THE GUT MICROBIOME INFLUENCES A VARIETY OF HUMAN DISEASES, SUCH AS TYPE 2 DIABETES AND INFLAMMATORY BOWEL DISEASE. COLLECTIVELY, THESE DISEASES AFFLICT MORE THAN 120 MILLION PEOPLE AND COST MORE THAN $580 BILLION IN PATIENT TREATMENTS IN THE US ANNUALLY. THE CURRENT STANDARD CARE OF TREATMENTS FOR MANY OF THESE DISEASES HAVE VARIABLE EFFICACY AND SERIOUS SIDE EFFECTS. THERE IS INCREASING INTEREST IN MODULATING THE GUT MICROBIOME USING MICROBIOME THERAPEUTICS, I.E., THERAPEUTICS COMPRISING LIVING BACTERIA, AS A NEW GENERATION OF DRUGS FOR DIFFICULT-TO-TREAT DISEASES. HOWEVER, THE INDUSTRY CURRENTLY LACKS A RELIABLE APPROACH TO SYSTEMATICALLY AND COST-EFFECTIVELY DEVELOPING EFFECTIVE MICROBIOME THERAPEUTICS. SPECIFICALLY, THE LARGEST BARRIER TO MICROBIOME THERAPEUTIC DEVELOPMENT IS THE LACK OF PREDICTIVE PRECLINICAL MODELS TO TRANSLATE EARLY-STAGE RESEARCH INTO DRUG DISCOVERY AND DEVELOPMENT. THE PROPOSED PROJECT SEEKS TO ADDRESS THE BARRIER TO THE USE OF MICROBIOME THERAPEUTICS BY DEVELOPING A FIRST-OF-ITS-KIND COMPUTATIONAL PLATFORM, AS THE FIRST COMPREHENSIVE, COMPUTATIONAL, DRUG DESIGN AND DISCOVERY PLATFORM. CURRENTLY, THE DEVELOPMENT OF MICROBIOME THERAPEUTICS IS BASED ON A SERIES OF EXPERIMENTAL AND STATISTICAL STEPS THAT IDENTIFY THE POTENTIAL MICROBIAL STRAINS FOR TARGET THERAPEUTIC CANDIDATES IN AN EMPIRICAL AND ITERATIVE PROCESS. AS A RESULT, THIS APPROACH REQUIRES EXTENSIVE ITERATIVE IN VITRO AND IN VIVO EXPERIMENTS, WHICH SUBSTANTIALLY INCREASE THE LENGTH AND COST OF THE DEVELOPMENT PROGRAMS. THESE CHALLENGES HAVE RESULTED IN AN INEFFICIENT AND UNPREDICTABLE MICROBIOME THERAPEUTIC DEVELOPMENT PROCESS, LIMITING THE NUMBER OF EFFICACIOUS MICROBIOME THERAPEUTICS THAT COULD SAVE MILLIONS OF LIVES WORLDWIDE. THIS PROJECT ADDRESSES THESE CHALLENGES BY RELIABLY AND COST-EFFECTIVELY IDENTIFYING THERAPEUTIC CANDIDATES FOR A WIDE RANGE OF INDICATIONS. THIS PLATFORM COULD REPLACE THE CURRENT ITERATIVE AND UNPREDICTABLE DEVELOPMENT PROCESS IN THE DRUG DISCOVERY STAGE. THE UTILITY OF THE PLATFORM WILL BE DEMONSTRATED BY DEVELOPING NEW THERAPEUTIC CANDIDATES FOR TYPE 2 DIABETES AND VALIDATING THE EFFICACY OF THESE CANDIDATES IN PRECLINICAL STUDIES. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.