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.
Public Health Relevance Statement: PROJECT NARRATIVE In patients who suffer from cancer, muscle wasting is very common and has devastating consequences, including reduced quality of life and overall health, interference with cancer treatment, increased complications from cancer treatment, and reduced survival. Unfortunately, right now, we do not have any medicines to help prevent or treat muscle wasting in patients suffering from cancer. To help address this issue, we propose a Phase II SBIR study to investigate and develop new and promising potential medicines for cancer-induced muscle wasting.
Project Terms: Acids; Affect; ages; Age; Animals; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cultured Cells; Chemistry; Pharmaceutical Chemistry; Medicinal Chemistry; Pharmaceutic Chemistry; Clinical Research; Clinical Study; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Fruit; dietary fruit; Goals; Health; Herb; Human; Modern Man; Lead; Pb element; heavy metal Pb; heavy metal lead; Medicine; mortality; Muscular Atrophy; Muscle Atrophy; muscle breakdown; muscle degradation; muscle deterioration; muscle loss; muscle wasting; Legal patent; Patents; Patients; Quality of life; QOL; Safety; Structure-Activity Relationship; chemical structure function; structure function relationship; Syndrome; Testing; Tissues; Body Tissues; Work; ursolic acid; Muscular Weakness; Muscle Weakness; improved; Clinical; Phase; Physiologic; Physiological; Medical; Series; Chemicals; Muscle function; muscle bulk; muscle mass; muscle form; Malignant Tumor of the Lung; Pulmonary Cancer; Pulmonary malignant Neoplasm; lung cancer; Malignant neoplasm of lung; Voluntary Muscle; Skeletal Muscle; Atrophic; Atrophy; programs; Oral; Physical Function; cancer complication; carcinogenesis; Cancer Induction; success; tumor growth; novel; Property; response; Advanced Malignant Neoplasm; Advanced Cancer; Adverse effects; cancer therapy; Cancer Treatment; Malignant Neoplasm Therapy; Malignant Neoplasm Treatment; anti-cancer therapy; anticancer therapy; cancer-directed therapy; Malus domestica; Apple; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; pharmaceutical; Pharmacologic Substance; preventing; prevent; Address; Dose; Pre-Clinical Model; Preclinical Models; in vivo; mRNA Expression; Cancer Model; CancerModel; Cancer Patient; Scientific Advances and Accomplishments; scientific accomplishments; scientific advances; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; sex; Development; developmental; Advanced Development; designing; design; Outcome; innovate; innovative; innovation; Cellular model; Cell model; new drug treatments; new drugs; new pharmacological therapeutic; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel pharmaco-therapeutic; novel pharmacological therapeutic; novel therapy; novel therapeutics; murine model; mouse model; commercialization; tumor; FDA approved; skeletal muscle atrophy; skeletal muscle breakdown; skeletal muscle loss; skeletal muscle protein loss; skeletal muscle wasting; cancer associated cachexia; cancer induced cachexia; cancer-associated muscle wasting; cancer-induced muscle atrophy; cancer-induced muscle loss; cancer-induced muscle wasting; cancer-related cachexia; tumor-induced cachexia; tumor-induced muscle wasting; cancer cachexia; clinical development; pancreatic tumor model; pancreatic cancer model; KPC genetically-engineered mouse; KPC mouse; KPC murine; LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx-1-Cre; LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre; KPC model; C-26 colon; C26 colon; C26 colon adenocarcinoma; colon 26; colon-26; C26 tumor; pharmacologic; Natural Compound; naturally occurring compound
