Cachexia is a life-threatening aspect to many diseases including cancer. The obvious symptoms of this disease include lack of appetite, and a loss of muscle disproportionate to the reduction in caloric intake. People suffering from cachexia often have a more difficult time doing day-to-day tasks and a reduced quality of life. In advanced cases, cachexia can lead to multi-organ failure due to high metabolic rate-induced apoptosis.
The National Cancer Institute estimates that up to 40% of cancer deaths are directly due to cachexia, and it is likely a significant factor in other cancer fatalities. In addition to cancer, many other diseases produce cachexia: renal failure, infections, rheumatoid arthritis, or any other disease that elevates proinflammatory cytokines. Hyperactivity of the central melanocortin (MC) system appears to be a common factor in cachexia. In small animal models of cachexia (e.g. cancer, renal failure, endotoxemia) interventricular administration of MC4 receptor (MC4R) antagonist peptides consistently reverses these cachexic states. Further, MC4R knockout mice are resistant to the development of cachexia. We developed a MC4R antagonist peptide (TCMCB07) that produces body weight and muscle gain, and a reversal of cachexia in both rodents and dogs. As part of our drug development efforts, we developed a veterinary hospital canine cachexia trials network across the U.S. Using this network, we demonstrated the ability of TCMCB07 to reverse cachexia in client-owned dogs, with concomitant evidence of safety.
Our cachexia therapeutic, TCMCB07, has its IND enabling toxicology program underway with an IND and the beginning of Phase 1 human trials anticipated in 1st quarter 2022.