Development of targeted, safe and effective drugs against pancreatic ductal adenocarcinoma (PDAC) by leveraging a novel, comprehensive, computational drug discovery approach

Pancreatic ductal adenocarcinomaPDACis the fourth leading cause of cancer death in the United States with a median survival of andltmonths and ayr survival rate ofThe aggressive biology and resistance to currently used therapeutic agents underscore the clear unmet need for the development of effective therapies against PDACDevelopment of therapeutically important small molecules has benefited from computational drug discovery methods over three decadesHoweverthese approaches suffer from significant limitationstwoXAR has developed a computational drug discovery approach that overcomes these limitationsBuilding on our prior success in identifying candidate drugs for hepatocellular carcinomaHCCwe propose to use an artificial intelligenceAIdriven platform developed by twoXAR to identify new drug candidates as potential effective therapies for PDACIn preliminary studieswe showed that TXRa lead candidate selected based on our platform for efficacy against HCC significantly inhibited growth ofaHCC cell linesbut not healthy hepatocytes andborthotopic mouse HCC patient derived xenograftsPDXMoreovercwe also used our AI based approach to predict validated candidates for rheumatoid arthritisRAmultiple sclerosisMSand typediabetesT DThe efficiency in drug discovery resulting from computational models provides an opportunity to build a portfolio of drug programs that traditional discovery methods donandapos t allow for without hundreds of millions of dollars and many yearstwoXAR s approach to developing drug pipeline through partnerships and spin outs enables us to apply our technology broadly across therapeutic areasput drug development in the hands of expert drug developersand create a portfolio of drug programs that significantly increases the probability of a twoXAR discovered treatment benefiting patientsIn the current Phase I SBIR proposalwe will identify candidate drugs to treat PDACusing our platformThe specific aims areAimLeverage twoXAR s AI platform to identify lead candidates to treat PDACMilestoneScreen at leasthits that emerge based on aggregate scoring and identify at leastleads for further analysis and in vitro in vivo validationAimUse industry standard preclinical assays to validate lead drug candidatesMilestoneIdentification of a primary lead candidate for the treatment of PDACAfter successful completion of the proposed studieswe will develop the identified lead candidate for the treatment of PDAC through a Phase II SBIR mechanism to conduct mechanism of actionMoAsafetyand efficacy studies followed by early feasibility human studieswith the overarching goal of regulatory submission to the FDA and market commercialization Pancreatic ductal adenocarcinomaPDACis the fourth leading cause of cancer death in the United States with a median survival of andltmonthsand resistance to currently used therapeutic agentstwoXAR has developed an artificial intelligenceAIdriven platform to identify new drug candidates as potential effective therapiesIn the current Phase I SBIR proposalwe will identify candidate drugs to treat PDAC using our platform