Targeting the Neuroscience of Human Misery

Endevica Bio Founder and Chief Scientific and Medical Officer Daniel Marks dreams a lot. When he considers what he would tell someone who asks him what Endevica Bio does, he says, “We endeavor to solve problems of human misery.” That’s it.

The company takes its name from its mission to endeavor to solve human misery by developing therapies that overcome the limitations of modern medical modalities. 

Endevica says its synthetic peptide mimetics, which it calls peptidomimetics, possess the positive features of peptides but potentially eliminate most of the liabilities such as a tendency to fall apart when in solution, resulting in a very short half-life, and tendency to bind to the wrong place. 

“A peptide is complex enough that it has a very sophisticated and exclusive set of receptors that it binds to and a peptidomimetic takes care of that and adds other features of safety and more drug-like qualities,” says Marks.

Endevica Bio currently has two investigational therapies advancing through its pipeline: lead candidate mifomelatide, in phase 2 clinical testing as a therapeutic to combat cancer cachexia, or involuntary weight loss; and a phase 1-ready candidate that addresses obesity. 

Preserving body mass in cancer: Tackling cachexia

“Appetite is such a fundamental part of being a human being, that it is a powerful determinant of quality of life,” says Marks. “So, losing your appetite is not trivial. It's a very big deal. Our drug clearly reverses this in a number of chronic inflammatory states in chronic diseases, especially in cancer. Unlike losing weight by dieting, with cancer the weight you lose is just as much from muscle as it is from body fat.”

Roughly a third of cancer patients die not from the cancer but from involuntary wasting away. Mifomelatide acts directly on the brain signals triggered by illness that contribute to this process.    

“If you feel sick, what do you mean by that?” Marks says. “Well, that sensation is created by a limited set of receptors in the brain. Our drug is able to go in and interact with those receptors in a favorable way and allow people to return from this state of weight loss, muscle wasting, not feeling good, and not having an appetite.”

Mifomelatide, given by injection, blocks the activation of the melanocortin system in the brain that occurs when people are sick. In a phase 1 clinical study, treatment with mifomelatide induced a robust increase in appetite and body mass with no safety signals other than a couple of modest skin reactions, which smoothed the way to launching a phase 2 trial in April 2025. 

“Those patients (in the study), over just five days of therapy, gained on average about 1.4 to 1.5 kilograms of extra body mass,” Marks noted. “Their appetite went up by about a third, a huge increase. And they had improvements in quality of life measures that surrounded food questions like: How much did you enjoy your meal today and how easy was it for you to finish your food today?”

For the phase 2 randomized controlled trial, Endevica is enrolling 120 newly diagnosed patients with metastatic colorectal cancer who are undergoing chemotherapy and testing three different doses of mifomelatide compared to placebo. 

“The goal is for them to gain or maintain their weight, and this will potentially allow them to receive more of their planned chemotherapy, improve quality of life, and we think eventually improve survival as well,” says Meghan Joly, Endevica’s lead clinical scientist. 

The company has 15 sites activated in the United States and some additional sites in the wings ready to go. It projects completing the trial in the third quarter of 2026, with data analysis to follow. 

While conducting the randomized controlled trial of mifomelatide, Endevica has taken steps to allow expanded access to the drug for cancer patients who do not qualify for the trial, on a case-by-case basis.

The company’s first expanded access protocol is to offer mifomelatide treatment to about 100 patients with advanced unresectable pancreatic ductal adenocarcinoma, which it plans to start in January 2026. 

“We're really excited that we can collect data about the efficacy of the drug in this new population as well,” Joly says. “We can look at trajectories of weight change, we can look at quality of life measures, we can look at survival.”

Mirror biology: Targeting weight loss

In October 2025, Endevica unveiled 710GO, an oral synthetic peptide mimetic that targets the melanocortin system in the brain, but this time for potential weight loss that the company says could redefine the therapeutic landscape for general obesity treatment. The company’s research in obese non-human primates shows that co-agonism of the melanocortin 3 and 4 receptors (MC3R/MC4R) drives robust weight loss, unlocking the melanocortin system as a differentiated mechanism of action to complement and rival current GLP-1 receptor agonist obesity treatments, which all fall into the general class of incretins. Different from melanocortin agonists, incretins are designed to provide negative feedback from the gut telling you you have eaten too much, and common side effects include nausea and diarrhea.

“The system that we are manipulating is designed to be a more normal physiologic weight regulator over a long period of time,” Marks says. “It is what sets the weight set point for the body. And it uses this weight set point, uses a lot of tools including GLP-1 and other things to regulate body weight, but it is the core place where body weight is determined and regulated.” 

Marks notes that this is not the first time companies have targeted obesity in this way. However, Endevica has discovered how to safely deliver this drug orally in obese non-human primate models and induce remarkable weight loss without any of the vomiting, diarrhea, and gastrointestinal distress that is typical of available weight loss drugs. It also complements GLP-1 receptor agonists, and the hope is that after a phase 1 study as a monotherapy, which is slated to potentially start in the first quarter of 2026 in Australia, the company can conduct studies in combination with several of the GLP-1s currently on the market.

Small company, big waves: Endevica’s ambitious future

These are ambitious plans for a small biotech that so far has been funded by a single family office. Endevica is planning to engage investors to fund the clinical studies. CEO Russell Potterfield says it’s a great time to seek outside investors: “We're at a great entry point for an investor today because we have a significant number of inflection points coming through the course of 2026. And then we'll have another course of inflection points through the course of 2027. There's been a tremendous amount of de-risking that's occurred.”

Endevica Bio wants to raise capital now, and perhaps a crossover in the second half of 2026 based on phase 2 data in obesity and cachexia. “You could exit programs at that time, and we would begin having conversations about the best way to maximize the value of the programs and to maximize the value of the investment,” says Potterfield. “That is likely at the end of phase 2 for the obesity programs, when you have 13 week data, which is the gold standard today for incretins, but you would also have some pretty advanced data in a second cancer type in a second clinical trial in the cachexia drug.”