SBIR-STTR Award

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.

Public Health Relevance Statement:


Public Health Relevance:
Skeletal muscle atrophy is a widespread and serious medical problem, but lacks a medical therapy. In this phase I STTR study, Emmyon, Inc. will generate new chemical compounds and test them in muscle cells and mice to determine if these compounds promote muscle cell growth and reduce muscle atrophy. Effective compounds will represent promising potential medicines for skeletal muscle atrophy, and will be carried towards human patients in phase II studies.

Project Terms:
Affect; Anabolism; Anterior Cruciate Ligament; base; Bed rest; Canis familiaris; celecoxib; cell growth; Characteristics; Chemicals; Chemistry; Chronic Obstructive Airway Disease; Clinical; Clinical Research; commercialization; companion animal; Critical Illness; design; Development; Diabetes Mellitus; Disease; Dose; drug discovery; Drug Kinetics; Elderly; Evaluation; Exercise; falls; FDA approved; fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; Fracture; Goals; Government; Health; Heart failure; Hospitalization; Human; human data; human subject; Hypertrophy; improved; In Vitro; in vitro Model; inhibitor/antagonist; Injury; Intellectual Property; Iowa; Kidney Failure; Lead; Legal patent; Licensing; ligament injury; Malignant Neoplasms; Marketing; Mediation; Medical; Medicine; Methods; Mortality Vital Statistics; mouse model; mRNA Expression; Mus; Muscle Cells; Muscle Fibers; Muscle function; muscle hypertrophy; muscle strength; Muscular Atrophy; novel; Nursing Homes; nutrition; Nutritional; Orthopedics; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Phase; phase 2 study; Physical Rehabilitation; Plants; prevent; Prevention; programs; Proteins; public health relevance; Quadriceps Muscle of the Thigh; Quality of life; Rattus; Rehabilitation therapy; Relative (related person); Research; research and development; Safety; Secondary to; Series; skeletal; Skeletal muscle structure; Small Business Technology Transfer Research; small molecule; Spinal cord injury; Staging; stroke; Structure; Testing; Therapeutic; Tomatoes; Toxicology; Universities; Work

Skeletal muscle atrophy diminishes the health and quality of life of tens of millions of people in the US alone. Frequent causes of muscle atrophy (which often co-exist in the same patient) include aging, malnutrition, muscle disuse, critical illness, certain medications, and a broad range of chronic illnesses including cancer, heart failure, COPD, diabetes, renal failure, cirrhosis, rheumatoid arthritis, and HIV/AIDS. Frequent effects of muscle atrophy include weakness, impaired activity, falls, prolonged hospitalization, delayed rehabilitation, loss of independent living, and increased mortality. However, despite its broad clinical impact, skeletal muscle atrophy lacks a medical therapy and thus represents an enormous unmet medical need. A major goal of Emmyon, Inc. is to discover and develop a pharmaceutical for skeletal muscle atrophy. In our Phase I STTR project, we designed and synthesized a series of novel chemical entities (NCEs), which were then subjected to primary screening in cultured skeletal myotubes, followed by secondary investigations in a mouse model of immobilization-induced muscle atrophy. Through these studies, we discovered (and subsequently patented) a confidential and proprietary small molecule compound (EMMY1-19) that potently and effectively reduces skeletal muscle atrophy in vivo. In this Phase II SBIR proposal, Emmyon seeks to advance the development of EMMY1-19 and related molecules as pharmaceuticals for skeletal muscle atrophy. Specifically, we will further investigate EMMY1-19's safety, efficacy, and mechanisms of action in two distinct and complimentary mouse models of muscle atrophy (immobilization-induced and age-related muscle atrophy); together, these studies will significantly advance our understanding of EMMY1-19 and, if successful, significantly advance EMMY1-19 towards final development and commercialization in SBIR Phase III. In parallel to those studies, we will design and synthesize a new and expanded series of 200 additional NCEs, which will be screened and compared to EMMY1-19 in cultured human skeletal myotubes and mouse models of skeletal muscle atrophy; through these studies, we hope to identify additional NCEs with pharmacologic properties that are similar to or perhaps even better than those of EMMY1-19. Altogether, through these studies, we hope to rigorously advance the scientific understanding and commercial development of a highly promising new class of pharmaceutical agents for skeletal muscle atrophy.

Public Health Relevance Statement:
PROJECT NARRATIVE Skeletal muscle atrophy, also known as muscle wasting, is a widespread and serious condition that affects tens of millions of people in the US alone. Unfortunately, right now, we do not have any medicines to help prevent or treat skeletal muscle atrophy in patients. To help address this issue, we propose a Phase II SBIR study to investigate and develop new and promising potential medicines for skeletal muscle atrophy.

Project Terms:
Address; Advanced Development; Affect; age related; Aging; AIDS/HIV problem; analog; Atrophic; base; Chemicals; Chemistry; Chronic Disease; Chronic Obstructive Airway Disease; Cirrhosis; Clinical; commercialization; Critical Illness; design; Development; Diabetes Mellitus; drug discovery; endurance exercise; Evaluation; exercise capacity; falls; Fasting; FDA approved; Food; Fracture; Gene Expression; Goals; Government; Health; Heart failure; Hospitalization; Human; Hypertrophy; Immobilization; Impairment; in vivo; Independent Living; Investigation; Iowa; Kidney Failure; Lead; Legal patent; Limb structure; Malignant Neoplasms; Malnutrition; Mediator of activation protein; Medical; Medicine; mortality; mouse model; mRNA Expression; Mus; Muscle; Muscle Cells; Muscle Fibers; muscle form; Muscular Atrophy; novel; Patients; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; phase 1 study; prevent; programs; Property; Proteins; Quality of life; Rehabilitation therapy; Rheumatoid Arthritis; Safety; Sales; Scientific Advances and Accomplishments; screening; Series; skeletal; Skeletal Muscle; skeletal muscle wasting; Small Business Innovation Research Grant; Small Business Technology Transfer Research; small molecule; Structure-Activity Relationship; Testing; Transcription Regulatory Protein; Universities; Work