A Two-Part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Subcutaneous Doses of TCMCB07 on Healthy Male and Female Subjects

This study will test an experimental drug named TCMCB07 for the treatment of cancer cachexia. Cachexia is a syndrome characterized by weight loss, anorexia, weakness or lack of energy, and anemia. Cachexia occurs in many cancers, usually at the advanced stages of disease.

Start Date12 Jul 2022

Sponsor / Collaborator

Endevica Bio

100 Clinical Results associated with Mifomelatide

100 Translational Medicine associated with Mifomelatide

100 Patents (Medical) associated with Mifomelatide

Literatures (Medical) associated with Mifomelatide

02 Jan 2025·Journal of Clinical Investigation

Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats

Article

Author: Newton, Samuel D ; Norgard, Mason A. ; Marks, Daniel L. ; Grossberg, Aaron J. ; Chen, Xu ; Zhu, Xinxia ; Norgard, Mason A ; Levasseur, Peter R ; Zhang, Emma ; Marks, Daniel L ; Grossberg, Aaron J ; Newton, Samuel D. ; Gu, Qingyang ; Potterfield, Russell ; Gruber, Kenneth A ; Gruber, Kenneth A. ; Bai, Peng

Cancer patients undergoing chemotherapy often experience anorexia and weight loss that substantially deteriorates overall health, reduces treatment tolerance and quality of life, and worsens oncologic outcomes. There are currently few effective therapeutic options to mitigate these side effects. The central melanocortin system, which plays a pivotal role in regulating appetite and energy homeostasis, presents a logical target for treating anorexia and weight loss. In this preclinical study, we evaluated the efficacy of TCMCB07, a synthetic antagonist of the melanocortin-4 receptor, in mitigating anorexia and weight loss in several rat models of chemotherapy: cisplatin, 5-fluorouracil, cyclophosphamide, vincristine, doxorubicin, and a combination of irinotecan and 5-fluorouracil. Our results indicate that peripheral administration of TCMCB07 improved appetite, stabilized body weight, preserved fat and heart mass, and slightly protected lean mass after multiple cycles of chemotherapy. Furthermore, combining TCMCB07 with a growth differentiation factor 15 antibody enhanced treatment effectiveness. Similar effects from TCMCB07 treatment were observed in a rat tumor model following combination chemotherapy. No notable adverse effects nor increased chemotherapy-related toxicities were observed with TCMCB07 treatment. These findings suggest that peripheral administration of TCMCB07 holds promise as a therapeutic approach for alleviating chemotherapy-induced anorexia and weight loss, potentially benefiting numerous patients undergoing chemotherapy.

01 Nov 2023·Journal of Veterinary Internal Medicine

Safety of TCMCB07, a melanocortin‐4 antagonist peptide, in dogs with naturally occurring cachexia

Article

Author: Axiak-Bechtel, Sandra M ; Wright, Zachary M ; Selting, Kimberly A ; Mills, Tracy ; Milner, Rowan J ; Fox-Alvarez, Stacey A ; Flesner, Brian K ; Fagman, Lana I ; Bergman, Philip J ; Gruber, Kenneth A ; Qi, LeAnn ; Callahan, Michael F ; Yoshimoto, Sean K ; Aherne, Michael ; Leach, Stacey B ; Newton-Northup, Jessica R ; Chretin, John D ; White, Carrie R ; Tate, Deborah J ; Young, Kaylee A ; Allen, Justin W

AbstractBackgroundThe melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs.Hypothesis/ObjectivesThe objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4‐week time period.AnimalsFourteen dogs with cachexia of any underlying cause, except cancer of the oral cavity or gastrointestinal tract, were eligible for enrollment with informed client consent.MethodsThis study was a prospective, 1‐armed open‐label trial. Physical examination, complete blood count, chemistry panel, and owner‐assessed quality of life surveys were checked at weeks 1, 2, and 4. Due to potential for bradycardia and hypotension, Holter monitoring and blood pressure evaluations were scheduled at pre‐enrollment and week 4.ResultsFourteen dogs completed the trial. Significant changes detected included increased mean body weight (18.6‐19.5 kg, P < .02), increased body condition score (median Tufts 5‐point thin dog scale score P < .004 and WSAVA muscle condition score P < .02) and increased mean blood urea nitrogen (21.79‐30.43 mg dL−1, P < .004). On quality of life surveys, pet owners perceived their dog appeared to be panting less (P < .002) and that the general health improved (P < .03). Four dogs had a change in coat pigmentation. The peak plasma concentration of TCMCB07 in cachectic dogs was similar to that in healthy beagle dogs.Conclusions and Clinical ImportanceTCMCB07 was safe and has potential efficacy in pet dogs with cachexia.

13 May 2022·ACS Pharmacology & Translational Science

Development of a Therapeutic Peptide for Cachexia Suggests a Platform Approach for Drug-like Peptides

Article

Author: Gruber, Kenneth A. ; Van Doren, Steven R. ; Tao, Ya-Xiong ; Newton Northup, Jessica ; Gallazzi, Fabio ; Jiang, Shaokai ; Ji, Ren-Lai

During the development of a melanocortin (MC) peptide drug to treat the condition of cachexia (a hypermetabolic state producing lean body mass wasting), we were confronted with the need for peptide transport across the blood-brain barrier (BBB): the MC-4 receptors (MC4Rs) for metabolic rate control are located in the hypothalamus, i.e., behind the BBB. Using the term "peptides with BBB transport", we screened the medical literature like a peptide library. This revealed numerous "hits"-peptides with BBB transport and/or oral activity. We noted several features common to most peptides in this class, including a dipeptide sequence of nonpolar residues, primary structure cyclization (whole or partial), and a Pro-aromatic motif usually within the cyclized region. Based on this, we designed an MC4R antagonist peptide, TCMCB07, that successfully treated many forms of cachexia. As part of our pharmacokinetic characterization of TCMCB07, we discovered that hepatobiliary extraction from blood accounted for a majority of the circulating peptide's excretion. Further screening of the literature revealed that TCMCB07 is a member of a long-forgotten peptide class, showing active transport by a multi-specific bile salt carrier. Bile salt transport peptides have predictable pharmacokinetics, including BBB transport, but rapid hepatic clearance inhibited their development as drugs. TCMCB07 shares the general characteristics of the bile salt peptide class but with a much longer half-life of hours, not minutes. 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.

News (Medical) associated with Mifomelatide

20 Dec 2024

·www.prnewswire.com

Endevica Bio to Start Phase 2 Clinical Trial of Drug to Prevent Weight Loss in Cancer Patients

A peptide called TCMCB07 will be administered to patients who are diagnosed with stage 4 metastatic colorectal cancer and will undergo chemotherapy. NORTHBROOK, Ill., Dec. 20, 2024 /PRNewswire/ -- Endevica Bio, a privately held company developing first-in-class peptide drug candidates, 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. Weight loss can lead to cachexia, a life-threatening wasting syndrome associated with chronic diseases including cancer. Cachexia is estimated to affect millions of people worldwide. "This is a pivotal step in finding a solution for those who suffer from weight loss when they undergo treatment for cancer," said Russell Potterfield, Chief Executive Officer and Executive Chair of Endevica. "We are excited to offer hope to patients and their families to address a condition for which there are no effective treatments available. We believe that B07 could be the breakthrough solution and are excited to begin enrolling patients in our trial." Endevica Bio this year completed a Phase 1 clinical trial of B07, a peptide, for cancer-related cachexia, with preliminary findings supporting its strong safety and efficacy. A separate study, published in November in the Journal of Clinical Investigation, showed that B07 improved the appetite and preserved lean mass and fat mass in rodent models of cancer chemotherapy. The study showed the strong potential of B07 to alleviate chemotherapy-induced anorexia and weight loss for millions of patients worldwide. Chemotherapy is the standard of care when treating most advanced malignancies. The side effects have a significant detrimental impact on a patient's quality of life and decrease the ability of patients to complete their full chemotherapy routine. Proactively treating chemotherapy-induced anorexia and weight loss can provide an overall better outcome for patients by improving their ability to tolerate treatments and allowing them greater self-sufficiency. "Patients who develop cachexia face limited treatment options due to fat and muscle wasting," said Dr. Daniel Marks, Chief Medical and Scientific Officer at Endevica Bio. "In our Phase 2 clinical trial, we hope to demonstrate that by taking a proactive approach before chemotherapy begins, we will prevent weight loss that can lead to cachexia and ultimately improve patients' outcomes during treatment." About TCMCB07 TCMCB07 is a melanocortin‐3/4 antagonist peptide candidate in clinical development for the treatment of cachexia. It is designed to be a first-in-class peptide drug with the ability to cross the blood-brain barrier and act on previously inaccessible target receptors to modulate the body's behavioral and metabolic response to chronic illness. Pre-clinical animal trial results show significant lean muscle mass retention (e.g., a reversal of the cachectic condition) during administration of the drug. The results are consistent in cachexia arising from many different types of chronic disease. About Endevica Bio Endevica Bio creates first-in-class peptide drug candidates. Endevica Bio's technology platform, protected by a family of patents and pending applications, allows for the modification of peptides to modulate activity of important drug targets behind the blood-brain barrier. More information can be found at . Media Contact: Dan Childs Next Solutions Group (NSG) [email protected] SOURCE Endevica Bio WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 1

19 Jan 2023

·www.businesswire.com

Endevica Bio Raises $10 Million in Series B Financing to Advance Development of TCMCB07 for Treatment of Cachexia

NORTHBROOK, Ill.--( BUSINESS WIRE )-- Endevica Bio , a company developing first-in-class peptide drug candidates with better safety and efficacy properties, has closed a $10 million Series B funding. The existing investors had full participation rights in the round and purchased all of the shares that were being made available. Endevica expects to use the proceeds from the financing for continuing the research and development of TCMBO7, its melanocortin‐3/4 antagonist peptide candidate, for the treatment of cachexia, as well as for working capital or other general corporate purposes. “We have never been more encouraged about the future of our company and the research it is doing to treat those suffering from cachexia,” said Russell Potterfield, CEO and Executive Chairman of Endevica. “Having recently completed the Single Ascending Dose (SAD) arm of the Phase 1 study of TCMB07 which demonstrated it was well-tolerated at a dose above the anticipated therapeutic dose with no significant adverse events observed, we look forward to the release of results from the Multiple Ascending Dose (MAD) arm of the Phase 1 study that was completed the end of December.” Mr. Potterfield continued, “This funding will enable us to advance our research and development of TCMB07, which we believe has the potential to address a macro-scale patient population with cachexia, a condition that worsens health outcomes of patients with many chronic illnesses, not only cancer. As we add to our scientific team over the next few months, we look forward to advancing the clinical development of TCMB07, achieving additional milestones, and helping the millions of people suffering with cachexia.” Cachexia is a life-threatening aspect to many diseases. The 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, fatigue, a reduced quality of life and reduced survival. In advanced cases, cachexia can lead to multi-organ failure due to high metabolic rate-induced apoptosis. According to the American Society of Clinical Oncology, cachexia is highly prevalent across malignancies, impacting approximately half of patients with advanced cancer. About TCMCB07 TCMCB07 is a melanocortin‐3/4 antagonist peptide candidate in clinical development for the treatment of cachexia. It is designed to be a first-in-class peptide drug with the ability to cross the blood-brain barrier and act on previously inaccessible target receptors to modulate the body’s behavioral and metabolic response to chronic illness. Pre-clinical animal trial results show significant lean muscle mass gain (e.g., a reversal of the cachectic condition) during the administration of the drug. The results are consistent in cachexia arising from many different types of chronic disease. About Endevica Bio Endevica Bio creates first-in-class peptide drug candidates. Endevica’s technology platform, protected by a family of patents and pending applications, allows for the modification of peptides to modulate activity of G-protein coupled receptors behind the blood-brain barrier. Endevica’s initial drug candidate, TCMCB07, is designed to treat cachexia, which is caused by many diseases like cancer, renal failure and congestive heart failure. More information can be found at www.endevicabio.com .

Phase 1ASCO

15 Nov 2022

·pipelinereview.com

Endevica Reports Positive TCMCB07 Data from Single Ascending Dose Portion of Phase 1 Clinical Trial in Cachexia

NORTHBROOK, IL, USA I November 15, 2022 I Endevica Bio , a company developing first-in-class peptide drug candidates with better safety and efficacy properties, reports initial positive results from the single ascending dose (SAD) arm of the Phase 1 study of its melanocortin‐3/4 antagonist peptide candidate, TCMCB07, for the treatment of cachexia. The study was designed to assess the safety, tolerability, and pharmacokinetics of TCMCB07 in healthy volunteers. Data from the SAD arm showed that TCMCB07 was well-tolerated at a dose above the anticipated therapeutic dose. There were no significant adverse events observed. A multiple ascending dose (MAD) arm is ongoing and is expected to be completed by the end of December 2022. “This is an exciting milestone for what we believe could be a first-in-class cachexia therapeutic,” said Russ Potterfield, CEO and Executive Chairman of Endevica. “Our mission is to create the next generation of peptide drugs with better safety and efficacy properties. The data that we have seen so far suggest that TCMCB07 will continue to advance in clinical development, furthering this mission.” Cachexia is a life-threatening aspect to many diseases. The 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, fatigue, a reduced quality of life and reduced survival. In advanced cases, cachexia can lead to multi-organ failure due to high metabolic rate-induced apoptosis. According to the American Society of Clinical Oncology, cachexia is highly prevalent across malignancies, impacting approximately half of patients with advanced cancer. Daniel Marks, M.D., Ph.D., Chief Medical Officer of Endevica said, “It is gratifying to see more than a decade of scientific work move through a successful Phase 1 clinical trial. Cachexia is a common condition that leads to a great deal of human misery. It is exciting to think that we are a step closer to offering patients relief from this devastating condition.” About TCMCB07 TCMCB07 is a melanocortin‐3/4 antagonist peptide candidate in clinical development for the treatment of cachexia. It is designed to be a first-in-class peptide drug with the ability to cross the blood-brain barrier and act on previously inaccessible target receptors to modulate the body’s behavioral and metabolic response to chronic illness. Pre-clinical animal trial results show significant lean muscle mass gain (e.g., a reversal of the cachectic condition) during the administration of the drug. The results are consistent in cachexia arising from many different types of chronic disease. About Endevica Bio Endevica Bio creates first-in-class peptide drug candidates. Endevica’s technology platform, protected by a family of patents and pending applications, allows for the modification of peptides to modulate activity of G-protein coupled receptors behind the blood-brain barrier. Endevica’s initial drug candidate, TCMCB07, is designed to treat cachexia, which is caused by many diseases like cancer, renal failure and congestive heart failure. More information can be found at www.endevicabio.com . SOURCE: Endivica Bio

Phase 1Clinical ResultASCO

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Indication	Highest Phase	Country/Location	Organization	Date
Cachexia	Phase 2	US	Endevica Bio	20 Dec 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05529849 (ASCO2023)	Phase 1	-	-	TCMCB07	(fsqnsdzqvq) = The most common study-related adverse event was injection site reaction, graded 1 mild, or 2 moderate out of 5 (NCI CTCAE) nghebxmefz (ymhfdwumvb )	-	31 May 2023
NCT05529849 (ASCO2023)	Phase 1	-	-	Placebo		-	31 May 2023
NCT05529849 (BusinessWire) Manual	Phase 1	Cachexia	-	TCMCB07	(uzryxgwemr) = There were no significant adverse events observed. idfchdvgzp (nnbfbwszho )	Positive	15 Nov 2022

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