Checkmate for Cachexia?

Eight out of ten patients with advanced cancer suffer from cachexia. The condition is not fully understood and causes fat and muscle loss. It can also compound the side effects of ongoing treatments. Cachexia is also linked to other illnesses, including heart disease HIV, and infectious diseases such as COVID-19.

At Endevica Bio, close to the University of Missouri University Hospital, work is underway to produce a medicine that could slow and even reverse the effects of cachexia. We spoke with Endevica’s founder, Kenneth Gruber, to find out more.

Who’s involved?

First, there was just me! Today, my company is called Endevica Bio, but when I founded it in 2009, it was called Tensive Controls . The origin story actually goes back to the 1980s, when I was studying the cardiovascular effects of melanocortins; that’s when I became interested in developing melanocortin-based drugs. “Tensive” refers to blood pressure; thus, “Tensive Controls” refers to control of blood pressure. 

During a sabbatical from the National Institutes of Health (NIH) spent at Roger Cone’s research laboratory at the Oregon Health Sciences University (OHSU), I explored melanocortins further. Today, I hold six patents (three in the US and three in the EU), which protect the intellectual property I used to develop Endevica’s lead candidate, TCMCB07, and several other peptide therapeutics.

All that said, Endevica is certainly not a one-man show. Our formidable team includes a prominent researcher in the cachexia field, high-quality regulatory and strategic consultants, and professionals experienced in project management and commercialization. We are led by our executive chairman, Russell Potterfield – an entrepreneur with a wide array of product design, business startup, and business exit experiences under his belt. On our board of advisors, we also have a stellar pool of experts: between them there’s decades of experience in pharma and biotech, numerous PhDs, professors, and directors at OHSU.

What research has been done so far? What is the mechanism of action?

TCMCB07 is a first-in-class melanocortin ¾ antagonist peptide. Our first achievement was to successfully engineer structural changes in peptides that improved their ability to cross the blood–brain barrier, extend the drug’s half-life, and mitigate potential side effects. Previous attempts to develop melanocortin-based drugs failed because of cardiovascular side-effects in both experimental and clinical trials.

A US patent for the suppression of cardiovascular side-effects in melanocortin-based therapeutics has now been issued, and related patents are pending. 

Moving ahead, we characterized TCMCB07 and began development. The candidate has demonstrated efficacy and safety in multiple rodent models of different forms of cachexia, as well as in a veterinary hospitals trial in client-owned dogs that were suffering from different forms of cachexia. TCMCB07 has been manufactured successfully at multiple commercial sites, and has a scalable manufacturing process with an acceptable COGS estimate.

Why is this such an important area of research?

We are aiming to reverse cachexia, which the National Cancer Institute defines as “a form of metabolic mutiny in which the body overzealously breaks down skeletal muscle and adipose tissue”. Cachexia is responsible for up to 40 percent of cancer deaths and is prevalent in other diseases like AIDS, COPD, kidney failure, rheumatoid arthritis, and heart failure.

As a researcher recently commented at the 2021 Annual Meeting of the American Association for Cancer Research (AACR), cachexia is “woefully understudied for the outsized impact it has on cancer patients”. We believe that, if we can solve the cachexia problem, it could usher in a new era of cancer treatment in the same way that personalized medicine and checkpoint inhibitors have been used in cancer patients. True treatments for cachexia will not only save lives, but also vastly improve quality of life for cancer patients. This could allow them to resume many aspects of their normal lives, while being treated for their cancer.

When do you think this could reach the clinic?

Our IND-enabling toxicology program has begun for TCMCB07, and we anticipate an IND in the first half of 2022. We are aiming to complete phase I trials by Q3 2022, and begin phase II by Q4 2022. We are still in the early stages of the project, but our present goal for commercialization is in 2025. We have successfully accrued multiple rounds of investment, with the last round providing enough capital to advance the company through phase I and potentially onward into phase II.