Biotherapeutics, Inc. — Department of Health and Human Services SBIR Phase I: NIAID

Description

Development of Antibiotic Free Clostridium difficile Therapeutics Biotherapeutics IncBTIis an emerging biotech company that synergistically combines the power of advanced computational modeling with translational experimentation to accelerate the development of novel products for precision medicine and healthLead moleculeBTis a novel small molecule therapeutic targeting the Lanthionine Synthetase C LikeLANCLpathway in inflammatory bowel diseaseIBDthat has two open INDs and completed Phase I clinical testing inPreliminary data in mice demonstrates that modulating immune responses by activating the LANCLpathway with BTprovides broader Clostridium difficile strain coverageimproved survivaland relapse protection compared to antibiotic treatmentBackgroundCdifficile is an anaerobic bacterium that has re emerged as a facultative pathogen and can cause diarrheacolitisand deathIn the U SaloneCdifficile infectionCDIwas estimated to affect overpeople withdeaths withindays of the initial diagnosisThe current treatment for Cdifficile is an antibiotic based therapyParadoxicallythe at risk population is adults on regular antibiotics due to the critical role of the gut microbiome in preventing and resolving Cdifficile expansionThis SBIR develops a host based antibiotic free therapeutic that could combat antibiotic resistance and preserve the gut microbiomeOur TechnologyBTI will investigate the therapeutic efficacy and mechanism of action of novel LANCLtargeting drugsBTwith the potential to prevent excessive tissue damaging inflammation and modulate host responses to the gut microbiome during CDIThe Specific Aims are toInvestigate the effect of BTon the post antibiotic gut microbiome in healthy and Cdifficileinfected miceDetermine BTefficacy in the protection from disease recurrence in a mouse model of relapseCharacterize the potential for human translation of BTthrough the ex vivo Cdifficile toxinresponse in human PBMCs and intestinal organoidsExpected outcomesiEstablish the effects of BTon beneficial gut microbiotabutyrogenic bacteriaLactobacillusiiDemonstrate that BTtreatment results in andgtreduction of disease andmortality during the recurrent phaseand iiiGenerate a translational data package that guides the clinical development planThe SBIR Phase II will perform in vivo validation studies with a neonatal pig model of CDI to assess broader Cdifficile strain coverageimproved survivaland relapse protectionFurtherwe will compare therapeutic and prophylactic dosing of BTto current standardantibioticsand developinganti toxin antibodiestherapiesCommercial ApplicationThis application will develop new antibiotic free technologies that prevent recurrencemaintain the indigenous gut microbiomeand offer a prophylactic intervention for CDI that fosters antibiotic stewardship for a $million market while lowering the $billion burden in the U Shealthcare Public Health Relevance This SBIR Phaseapplication will develop new host targetedantibiotic sparing interventions for Clostridium difficile infectionGiven thatof adults who developed healthcare associated diarrhea were positive for Cdifficile and that this bacterium caused almost half a million infections in the U Sthis project is timely as it will guide the development of gut microbiome preserving host targeting alternatives to the widespread use of antimicrobialsThe proposed Cdifficile therapy is a non antibioticanti inflammatory LANCLtargeting small molecule therapeuticBTthat may become an alternative to anti microbial usagecould disrupt a $M market while lowering the $billion burden in U Shealthcare