Project Grant R44CA277853

DEVELOPMENT OF NOVEL THERAPEUTICS FOR CANCER CACHEXIA - PROJECT SUMMARY / ABSTRACT CANCER-INDUCED SKELETAL MUSCLE ATROPHY IS A CENTRAL AND DEFINING FEATURE OF THE CANCER CACHEXIA SYNDROME, A HIGHLY PREVALENT CONDITION THAT AFFECTS OVER 50% OF PATIENTS WITH ADVANCED CANCER AND OVER 500,000 PATIENTS PER YEAR IN THE U.S. IN ADDITION TO BEING HIGHLY PREVALENT, CANCER-INDUCED SKELETAL MUSCLE ATROPHY HAS DEVASTATING CONSEQUENCES FOR PATIENTS; IT REDUCES PHYSICAL FUNCTION AND QUALITY OF LIFE, OFTEN COMPLICATES OR PRECLUDES CANCER TREATMENT, AND STRONGLY PREDICTS EARLY MORTALITY FROM CANCER. UNFORTUNATELY, A PHARMACOLOGIC THERAPY FOR CANCER-INDUCED MUSCLE ATROPHY DOES NOT EXIST. THUS, CANCER-INDUCED SKELETAL MUSCLE ATROPHY REPRESENTS A HIGHLY SIGNIFICANT UNMET MEDICAL NEED WITH BROAD RELEVANCE TO CANCER PATIENTS. A MAJOR GOAL OF EMMYON, INC. IS TO DISCOVER AND DEVELOP A PHARMACOLOGIC THERAPY FOR CANCER-INDUCED SKELETAL MUSCLE ATROPHY. TO THAT END, WE RECENTLY DISCOVERED A NATURAL COMPOUND THAT SIGNIFICANTLY REDUCES CANCER-INDUCED MUSCLE ATROPHY IN FIVE WELL-ESTABLISHED AND DISTINCT IN VIVO MOUSE MODELS OF CANCER. WE THEN USED THAT NATURAL COMPOUND AS A LEAD IN MEDICINAL CHEMISTRY PROGRAM AND DISCOVERED AND PATENTED A CONFIDENTIAL AND PROPRIETARY CHEMICAL DERIVATIVE (EMMY1-06) THAT APPEARS TO BE SIGNIFICANTLY MORE POTENT AND MORE EFFICACIOUS THAN THE LEAD COMPOUND IN AT LEAST TWO DISTINCT MOUSE MODELS OF CANCER-INDUCED MUSCLE ATROPHY. IN THIS PHASE II SBIR PROPOSAL, WE SEEK TO CONTINUE THIS EXCITING WORK BY ADVANCING THE DEVELOPMENT OF EMMY1-06 AND RELATED MOLECULES AS PHARMACEUTICALS FOR CANCER-INDUCED SKELETAL MUSCLE ATROPHY. SPECIFICALLY, WE WILL FURTHER INVESTIGATE EMMY1-06'S SAFETY, EFFICACY, AND MECHANISMS OF ACTION IN SEVERAL DISTINCT AND COMPLEMENTARY MOUSE MODELS OF CANCER-INDUCED MUSCLE ATROPHY THAT INVOLVE MULTIPLE TUMOR TYPES, SEXES, AND AGES; THESE STUDIES WILL SIGNIFICANTLY ADVANCE EMMY1-06 TOWARDS CLINICAL DEVELOPMENT AND COMMERCIALIZATION IN SBIR PHASE III. IN PARALLEL TO OUR DETAILED STUDIES OF EMMY1-06, WE WILL ALSO DESIGN, SYNTHESIZE, AND CHARACTERIZE NOVEL COMPOUNDS THAT ARE STRUCTURALLY RELATED TO EMMY1-06, SEEKING TO DISCOVER ADDITIONAL COMPOUNDS WITH PHARMACOLOGIC PROPERTIES THAT ARE SIMILAR TO OR PERHAPS EVEN BETTER THAN THOSE OF EMMY1-06 IN PRECLINICAL MODELS OF CANCER-INDUCED MUSCLE ATROPHY. TOGETHER, THESE STUDIES WILL RIGOROUSLY ADVANCE THE SCIENTIFIC UNDERSTANDING AND COMMERCIAL DEVELOPMENT OF A HIGHLY PROMISING NEW CLASS OF PHARMACEUTICAL AGENTS. THROUGH THIS WORK, WE HOPE TO ULTIMATELY DISCOVER AND DEVELOP A NEW PHARMACOLOGIC THERAPY THAT COULD BROADLY IMPROVE CLINICAL OUTCOMES FOR MILLIONS OF PATIENTS WHO SUFFER FROM CANCER.