Project Grant R41HD112274

NOVEL SMALL MOLECULE DRUG CANDIDATE FOR THE PREVENTION OF BRONCHOPULMONARY DYSPLASIA - PROJECT SUMMARY/ABSTRACT CMTX BIOTECH IS A DRUG DEVELOPMENT COMPANY WORKING TO COMMERCIALIZE A PROPRIETARY, CLINICAL-STAGE, SMALL- MOLECULE DRUG CANDIDATE FOR THE PREVENTION OF RESPIRATORY DISTRESS SYNDROME (RDS) AND ITS LONG-TERM SEQUELAE, BRONCHOPULMONARY DYSPLASIA (BPD), IN PRETERM INFANTS. BPD IS A CHRONIC RESPIRATORY DISEASE THAT OCCURS IN PRETERM INFANTS WHO DEVELOP RDS FROM A COMBINATION OF LUNG IMMATURITY, INFLAMMATION, AND MECHANICAL INJURY FROM VENTILATION. BPD IS THE MOST COMMON ADVERSE OUTCOME OF PRETERM DELIVERY, AFFECTING UP TO 75% OF INFANTS BORN BEFORE 28 WEEKS OF GESTATION WORLDWIDE. EVERY YEAR IN THE U.S., APPROXIMATELY 380,000 OF THESE INFANTS ARE BORN, OF WHICH 50,000 ARE EXTREMELY LOW GESTATIONAL AGE NEWBORNS (ELGANS), 35% (18,000) OF WHICH DEVELOP BPD. THE MEDIAN COST OF HOSPITALIZATION ASSOCIATED WITH BPD DURING THE FIRST YEAR IN VERY LOW BIRTH WEIGHT INFANTS IS $377,871 PER INFANT, COMPARED TO $175,836 PER INFANT WITHOUT BPD. THERE ARE CURRENTLY NO FDA-APPROVED DRUGS SPECIFICALLY FOR THE PREVENTION AND TREATMENT OF BPD. THE CURRENT STANDARD OF CARE IS FOCUSED ON MINIMIZING LUNG DAMAGE AND PROVIDING RESPIRATORY SUPPORT WITH THE USE OF BRONCHODILATORS, DIURETICS, ANTIBIOTICS, SURFACTANT, AND STEROIDS, INCLUDING ANTENATAL STEROID TREATMENT OF THE MOTHER BEFORE PRETERM BIRTH. MOST AGENTS THAT ARE PRESCRIBED TO PREVENT BPD ARE ALSO USED FOR THE MANAGEMENT OF ESTABLISHED BPD, AND THESE THERAPIES LACK SOLID EVIDENCE OF EFFICACY. A RECENT CLINICAL STUDY CONCLUDED THAT HYDROCORTISONE IS NOT EFFECTIVE AT PREVENTING BPD IN PREMATURE INFANTS OR IMPROVING THEIR SURVIVAL. THERE REMAINS A CRITICAL UNMET NEED FOR SAFE AND EFFECTIVE THERAPEUTICS FOR THE PREVENTION OF BPD. OUR LEAD DRUG CANDIDATE IS A PLEIOTROPIC MATRIX METALLOPROTEINASE (MMP) MODULATOR WHICH INHIBITS PATHOLOGICALLY- EXCESSIVE COLLAGENOLYSIS AND RESOLVES SYSTEMIC INFLAMMATION. SAFETY OF THE COMPOUND HAS ALREADY BEEN DEMONSTRATED IN INVESTIGATIONAL NEW DRUG (IND)-ENABLING STUDIES. THE DRUG HAS BEEN EVALUATED IN A NUMBER OF CLINICAL TRIALS FOR THE TREATMENT OF DISEASES AS DISPARATE AS AIDS-RELATED KAPOSI'S SARCOMA, RECURRENT HIGH- GRADE GLIOMAS, REFRACTORY METASTATIC CANCER, ACNE, ROSACEA AND PERIODONTITIS. THE SPECIFIC AIMS OF THIS STTR ARE TO DETERMINE THE ABILITY OF OUR LEAD DRUG CANDIDATE TO PREVENT THE ONSET OF BPD IN A PRETERM PIGLET MODEL, AND TO EVALUATE ITS EFFECT ON THE PATHOGENESIS OF BPD AND INFLAMMATORY PATHWAYS. OUR LONG-TERM GOAL IS TO OBTAIN APPROVAL FROM THE FDA AND COMPARABLE INTERNATIONAL REGULATORY AUTHORITIES TO MARKET OUR DRUG CANDIDATE AS A SAFE AND EFFECTIVE INTERVENTION. WE ANTICIPATE THAT OUR DRUG CANDIDATE WILL INHIBIT BPD PROGRESSION, MITIGATE ACUTE LUNG INJURY AND RESPIRATORY DISTRESS, REDUCE THE NEED FOR INTENSIVE CARE AND INTUBATION, AND IMPROVE CLINICAL OUTCOMES FOR PRE-TERM INFANTS, INCLUDING OVERALL SURVIVAL. SUCCESSFUL COMPLETION OF THESE STUDIES WILL ALLOW CMTX BIOTECH TO ADVANCE OUR LEAD DRUG CANDIDATE TOWARDS CLINICAL TRIALS FOR THE PREVENTION OF BPD.