A novel small molecule Bax activator as an oral therapeutic for the treatment of lung cancer.

PROJECT SUMMARY Problem to be SolvedLung cancerLCis the leading cause of cancer related deaths in the United StatesU Sand worldwideIna total ofmillion new cases were estimated globallyaccounting forof all new cancer diagnosesAlthough significant improvements in disease management and treatment have emergedthe prognosis for the majority of LC patients remains poor due to innate and acquired resistance to therapyLC is a significant burden to the U Shealthcare system because of costs associated with patient care$billionand lost productivity due to premature death$billionThere remains an unmet need for new therapies to compliment or replace existing treatments and improve outcomes for patientsProduct and Long term GoalCYDis a small molecule Bclassociated X proteinBaxactivator being developed as an oral therapeutic that disrupts cancer progression by inhibiting phosphorylation of amino acid residue serineSand activating Bax pro apoptotic functionThis Phase I SBIR project aims to demonstrate the feasibility of oral doses of CYDas a well tolerated and efficacious therapeutic in a mouse xenograft model of LCand investigate dose response relationshipsTechnological InnovationCYDtargets a binding pocket adjacent to Sto inhibit phosphorylation and directly activate Bax induced apoptosisPotent inhibitory activity was demonstrated in vitro against LC cell lines and in several mouse models of human LC when administered intraperitoneallyNo signs of toxicity were observed in all studieswhich is correlated with lower levels of Bax expression in healthy cells and tissuesPhase I ObjectivesThis Phase I SBIR project aims to demonstrate the feasibility of oral doses of CYDas a safe and effective therapeutic in ALC xenografts and to also define a dose response relationshipPhase II studies will further invetigate ADME and toxicokinetic studies in preparation for an investigational new drug application with the FDACommercial OpportunityThe American Cancer Society projects that overnew instances of LC will be diagnosed in the USA duringand greater thanare estimated to express wild type BaxWhile the patient population most susceptible to treatment is yet to be definedit is expected that CYDwill find use as a single agent or in combination therapy against a large portion of these cancersPreliminary models forecast that the peak potential revenue for CYDcan approach $billion annually PROJECT NARRATIVE Lung cancerLCis the leading cause of cancer related deaths in the United StatesU Sand worldwideThis Phase I SBIR proposal will demonstrate the feasibility of a novel small molecule Bax activator as an oral therapeutic for lung cancer