Endevica Bio has announced the dosing of its first patient in a Phase 2 clinical trial evaluating TCMCB07 (B07), a novel peptide drug candidate designed to prevent weight loss in cancer patients undergoing chemotherapy. The trial focuses specifically on patients diagnosed with stage 4 metastatic colorectal cancer, a population particularly vulnerable to developing cachexia.
The study, conducted in partnership with WuXi Clinical, will include 100 patients across 20 clinical sites. Participants will receive TCMCB07 at the initiation of chemotherapy and during the first several treatment cycles, with the primary endpoint being the prevention of weight loss that can lead to cachexia.
"This marks an important milestone in our commitment in developing a potentially life changing treatment for cachexia," said Russell Potterfield, Chief Executive Officer and Executive Chair of Endevica. "Each trial brings us closer to offering a viable solution for this debilitating disease, and we remain dedicated to making a lasting impact on the lives of those affected."
Understanding Cachexia and the Unmet Medical Need
Cachexia is a life-threatening wasting syndrome characterized by unintentional weight loss exceeding 10%, including both muscle and fat tissue. The condition is associated with chronic diseases, particularly cancer, and typically involves symptoms such as diarrhea, weakness, and fever lasting at least 30 days. Notably, cachexia signals malnutrition and is driven by altered nutrient utilization and increased inflammation.
Dr. Daniel Marks, Chief Medical and Scientific Officer of Endevica Bio, emphasized the significance of this trial: "We are incredibly excited to have our first patient dosed with B07 in individuals diagnosed with metastatic colorectal cancer who are undergoing chemotherapy. Since there is no FDA approved therapeutic for cancer cachexia, this trial is a crucial step to provide a therapy for an area of huge unmet clinical need, and we look forward to the results."
Mechanism of Action and Preclinical Evidence
TCMCB07 is a melanocortin-3/4 antagonist peptide specifically designed to cross the blood-brain barrier and modulate previously inaccessible target receptors that influence the body's behavioral and metabolic responses to chronic illness.
The drug candidate has shown promising results in preclinical studies. Research published in the Journal of Clinical Investigation in November 2024 demonstrated that TCMCB07 improved appetite and preserved both lean mass and fat mass in rodent models of cancer receiving chemotherapy. The study also revealed that peripheral administration of the drug stabilized weight, preserved heart mass, and offered some protection of lean mass following repeated chemotherapy cycles.
Importantly, when combined with a growth differentiation factor 15 antibody, the treatment effectiveness was enhanced, with no notable side effects or additional chemotherapy-related toxicities observed.
Clinical Development Progress
Endevica Bio completed its Phase 1 clinical trial of TCMCB07 earlier in 2024, with preliminary findings supporting a favorable safety profile and signs of efficacy. The current Phase 2 trial represents a critical next step in the development pathway.
The study's focus on metastatic colorectal cancer patients is particularly relevant, as this population frequently experiences significant weight loss during treatment. Colorectal cancer begins in the colon or rectum, with metastasis occurring when cancer cells spread to other parts of the body.
Potential Impact on Cancer Care
If successful, TCMCB07 could address a significant gap in supportive care for cancer patients. Cachexia not only diminishes quality of life but can also limit patients' ability to tolerate full doses of chemotherapy, potentially compromising treatment outcomes.
"The potential to alleviate chemotherapy-induced anorexia and weight loss could benefit millions of patients worldwide," noted Dr. Marks. "By preserving muscle mass and improving nutritional status, we hope to enhance both quality of life and treatment efficacy for patients battling advanced cancer."
The results of this Phase 2 trial are eagerly anticipated by clinicians and patients alike, as they could pave the way for the first FDA-approved therapy specifically targeting cancer cachexia, a condition that has long been recognized as a serious complication of cancer and its treatment.
