Development of Novel Small Molecule Therapies for Skeletal Muscle Atrophy

DESCRIPTION (provided by applicant): Skeletal muscle atrophy is a widespread and serious medical problem. Frequent causes of skeletal muscle atrophy include orthopedic injuries, bed rest, advanced age, cancer, heart failure, COPD, diabetes, stroke, renal failure, critical illness and spinal cord injury. Effects of skeletal muscle atrophy include weakness, reduced activity, falls, fractures, debilitation, prolonged hospitalization and rehabilitation, nursing home placement, and increased mortality. Although skeletal muscle atrophy has broad clinical impact, a pharmacologic therapy for muscle atrophy does not exist, and current therapeutic approaches (nutrition and physical rehabilitation) are often ineffective and/or unfeasible. Thus, skeletal muscle atrophy represents an enormous unmet medical need and market worldwide. The overall goal of Emmyon, Inc. is to develop a pharmacologic therapy for skeletal muscle atrophy. In preliminary studies, Emmyon's founders at the University of Iowa discovered a confidential and proprietary small molecule compound (compound A) that: 1) inhibits skeletal muscle atrophy, stimulates muscle hypertrophy, and increases strength and exercise capacity in mice; and 2) stimulates protein accretion and cellular hypertrophy in cultured skeletal myotubes from humans and mice. Based on this work, the University of Iowa applied for patents containing use claims for compound A in the prevention and treatment of skeletal muscle atrophy. Emmyon is in the final stages of negotiating an exclusive license to this intellectual property. From a commercialization standpoint, compound A is an attractive lead compound for pharmaceuticals that could prevent and treat muscle atrophy in humans and companion animals. However, composition-of-matter claims, which are critical for pharmaceutical development, are not possible. Thus, to develop a pharmaceutical for skeletal muscle atrophy, one of Emmyon's central R&D goals is to discover and develop potent and effective novel chemical entities (NCEs) whose structures are based on compound A. These NCEs will enable composition-of-matter claims, and may possess significantly improved pharmacologic characteristics relative to compound A. In this phase I STTR study, Emmyon will identify potent and effective compound A-based novel chemical entities (NCEs) with high commercial potential as pharmaceuticals. A series of patentable compound A-based NCEs will be synthesized and compared to compound A in human skeletal myotubes. NCEs with increased potency and/or efficacy relative to compound A will then be tested for their capacity to reduce skeletal muscle atrophy in mice. In Phase II studies, Emmyon will carry the most promising NCE forward into pharmacokinetic and toxicology studies in rats and dogs, and then an IND application. The initial clinical study would be geared towards FDA approval for the prevention and treatment of muscle atrophy in orthopedic patients. Subsequent studies would be geared towards FDA approval for other causes of skeletal muscle atrophy, which are also predicted to be amenable to these NCEs.