TCMCB07 / Endevica, WuXi AppTec - LARVOL DELTA

Endevica Bio Announces First Patient Dosing in Phase 2 Trial in Patients with Stage 4 Metastatic Colorectal Cancer (PRNewswire) - "Endevica Bio, a privately held company developing first-in-class peptide drug candidates, announced today the dose administration for the first patient in a Phase 2 trial for its experimental drug TCMCB07 (B07) to prevent weight loss in cancer patients undergoing chemotherapy. The trial, being conducted in partnership with WuXi Clinical, will include 20 sites and 100 patients who are diagnosed with stage 4 metastatic colorectal cancer. In the trial, patients are dosed with B07 as they begin chemotherapy and during the first several rounds of chemotherapy. The primary endpoint is preventing weight loss, which can lead to a debilitating condition called cachexia, a life-threatening wasting syndrome associated with chronic diseases, including cancer."

Trial status • Cachexia

Optimizing Body Mass Index (BMI) With TCMCB07, The Paradox Trial (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Endevica Bio

New P2 trial • Cachexia • Colorectal Cancer • Oncology • Solid Tumor

Discovery of GSC000580, a novel oral small molecule of MC4R antagonist for treatment of cancer-related body mass loss (AACR 2025) - "TCMCB07, an MC4R antagonist peptide, has shown efficacy in various cancer anorexia rat models but its use is limited due to the requirement for intravenous administration...In vivo, GSC000580 demonstrated dose-dependent significant increase of body weight gain and food intake in cisplatin-induced and aging-related anorexia rat models...Additionally, GSC000580 exhibits the ability of brain penetration, with a brain-to-plasma ratio (b/p) of 0.17. GSC000580 demonstrates promise as a potential clinical treatment for cancer-related body mass loss."

Oncology • LEP • LEPR • MC4R

Endevica Bio to Start Phase 2 Clinical Trial of Drug to Prevent Weight Loss in Cancer Patients (PRNewswire) - "Endevica Bio...today announced the start of a Phase 2 clinical trial of its experimental drug TCMCB07 (B07) to prevent weight loss in certain cancer patients undergoing chemotherapy....The U.S. Food and Drug Administration recently authorized the trial, which will include 100 patients who are diagnosed with stage 4 metastatic colorectal cancer. B07 will be given to patients before they begin chemotherapy and during chemotherapy to measure its effectiveness in preventing weight loss, a common side effect of the cancer treatment."

IND • New P2 trial • Cachexia • Colorectal Cancer • Oncology

A Study to Assess the Safety, Tolerability and Pharmacokinetics of TCMCB07 in Single and Multiple Ascending Doses in Health Subjects (clinicaltrials.gov) - P1 | N=76 | Completed | Sponsor: Endevica Bio | Recruiting ➔ Completed

Trial completion • Cachexia

Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia. (PubMed, J Vet Intern Med) - "TCMCB07 was safe and has potential efficacy in pet dogs with cachexia."

Journal • Anorexia • Cachexia • Cardiovascular • Gastrointestinal Disorder • Head and Neck Cancer • Hypotension • Infectious Disease • Oncology • Oral Cancer • Septic Shock • Solid Tumor

Effect of melanocortin-4 receptor antagonist TCMCB07 on chemotherapy-induced anorexia and weight loss in rats. (ASCO 2023) - "This preclinical trial provides evidence supporting peripheral TCMCB07 antagonism of central melanocortin signaling, increasing food intake and anabolism, ultimately alleviating anorexia, weight loss and muscle wasting over multiple cycles of cisplatin or 5-FU chemotherapy."

Preclinical • Anorexia • Cachexia • Chronic Kidney Disease • Nephrology • Oncology • Renal Disease

Preliminary data from the phase I study of TCMCB07, a study to assess the safety, tolerability and pharmacokinetics of the melanocortin antagonist TCMCB07 in healthy subjects. (ASCO 2023) - P1 | "CB07 was well tolerated by normal healthy volunteers. Though the Phase 1 study was not designed to study efficacy, a modest difference was observed between placebo and active for body weight change and hunger. Results warrant further examination in a randomized Phase 2 study in cancer patients experiencing cachexia."

Clinical • P1 data • PK/PD data • Anorexia • Cachexia • Chronic Kidney Disease • Nephrology • Oncology • Renal Disease

A Study to Assess the Safety, Tolerability and Pharmacokinetics of TCMCB07 in Single and Multiple Ascending Doses in Health Subjects (clinicaltrials.gov) - P1 | N=97 | Recruiting | Sponsor: Endevica Bio

New P1 trial • Cachexia

Development of a Therapeutic Peptide for Cachexia Suggests a Platform Approach for Drug-like Peptides. (PubMed, ACS Pharmacol Transl Sci) - "Based on this, we designed an MC4R antagonist peptide, TCMCB07, that successfully treated many forms of cachexia...A change in its C-terminal amino acid sequence slows hepatic clearance. This modification is transferable to other peptides in this class, suggesting a platform approach for producing drug-like peptides."

Journal • Cachexia

Endevica Bio Reports TCMCB07 Preserves Lean Body Mass in Preclinical Cancer Cachexia Study (Businesswire) - "Endevica Bio...presented new data from a recent preclinical study with its lead compound TCMCB07 at the 6th Cancer Cachexia Conference in August 27-29, 2021...The researchers evaluated efficacy of TCMCB07 with subcutaneous administration in two recently developed mouse cachexia models of orthotopic pancreatic cancer and head and neck cancer. The data demonstrate that TCMCB07 can preserve lean mass as well as attenuate muscle wasting and body weight loss during cancer cachexia....'We are looking forward to studying TCMCB07 further and commencing clinical trials in the beginning of 2022.'"

New trial • Preclinical • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Pancreatic Cancer

Pharmacokinetics and safety of TCMCB07, a melanocortin-4 antagonist peptide in dogs. (PubMed, Pharmacol Res Perspect) - "Therapy was tolerated well as determined by physical examination, clinical pathology, and cardiovascular parameters; darkening of the coat was noted with treatment and resolved with discontinuation. Pharmacokinetics are described and further study in the naturally occurring canine model is warranted."

Clinical • Journal • PK/PD data • Cachexia • Cardiovascular

Endevica Bio Begins IND-Enabling Toxicology Studies (Businesswire) - "Endevica Bio...has signed an agreement with Wuxi AppTec to begin toxicology studies for TCMCB07, its investigational therapeutic for cancer cachexia. These studies will support an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA), which will allow it to commence clinical trials....Results from these toxicology studies are expected to be announced by December 2021. Endevica expects to file its IND by the first quarter of 2022."

IND • Preclinical • Oncology