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It’s time to sit up and take notice of mitochondria

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CohBar CEO on the development of a “true portfolio” of mitochondria based therapeutics.

US biotech company CohBar is developing mitochondria-based therapeutics for the treatment of chronic and age-related diseases. The company is focused on creating therapeutics that offer the potential to address a broad range of diseases because of the underlying impact of mitochondrial dysfunction.

CohBar’s lead compound is currently in the Phase 1b stage of a clinical trial for non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease that is closely related to obesity, pre-diabetes and diabetes.

Longevity.Technology: Founded by (and indeed named after) two of the world’s leading age-related disease researchers, Drs Pinchas Cohen and Nir Barzilai, CohBar’s approach to target mitochondria in order to treat disease is a fascinating one. We caught up with the company’s CEO Steven Engle to learn more about where CohBar stands today.

Back in 2001, CohBar’s founders discovered a novel group of naturally occurring peptide sequences within the mitochondrial genome.

“That was a stunner – after 100 years of studying mitochondria, all of a sudden we discover that they’ve got these peptides,” says Engle. “But the second part is that these peptides influence organs and systems all over the body – metabolics, cardiovascular, oncology and things like that. And so what we’re doing is we’re taking advantage of that science, in what we call mitochondria based therapeutics.”

CEO Steven Engle
CohBar’s CEO Steven Engle.

To date, the company has discovered more than 100 mitochondrial derived peptides and generated over 1,000 analogue compounds of those peptides.

 


 

“We have 100 keys up on the wall, and we’re pulling them down one at a time to see what biological locks they unlock.”

 


 

“That’s a fairly unusual situation – rarely does a company start out with that many opportunities,” says Engle, likening the situation to the time when companies were finding multiple possibilities inside the cellular genome.

“But we’re not trying to fix mitochondria – what we expect with these 100 peptides is that there will be functionality there that affects all sorts of things,” he adds. “We have 100 keys up on the wall, and we’re pulling them down one at a time to see what biological locks they unlock. We’re taking the original peptide and then building analogues around it to find an even better molecule, that is more potent, has better function, or even has better longevity.”

CohBar is essentially creating a standard pharmaceutical or biotech compound, but the company is doing that starting with these special peptides.

“We think this gives us the benefit of over a billion years of evolution inside the mitochondria, because these have been conserved inside the DNA for that period of time, so our expectation is that there’s a primary purpose in each of these,” adds Engle. “What’s also fascinating in these molecules, is that some are very strong binders, and some are not so strong. Some end up binding at a nanomolar level, which means just tiny amounts of it have an effect. We think that’s because the mitochondria are basically controlling a number of systems and organs in the body, which is something that nobody understood before.”

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“We’re building a real portfolio, where each one of these programs has a family of molecules that are completely different than the next one.”

 


 

For its lead compound targeting NASH, CohBar expects to have results on its Phase 1b trial by the second quarter of this year. In addition, the company has four preclinical programs focused on fibrotic diseases, COVID-19 associated Acute Respiratory Distress Syndrome (ARDS), CXCR4-related cancer and orphan diseases and cancer immunotherapy. CohBar hopes to move the fibrotic disease and COVID-19 programmes into clinical trials by 2022.

“We’re building a real portfolio, where each one of these programs has a family of molecules that are completely different than the next one,” says Engle. “Sometimes you hear a company has a portfolio, but it’s just one drug in five different indications. What we’re talking about is a true portfolio, and we think that gives us multiple shots on goal.”

CohBar CEO on the development of a “true portfolio” of mitochondria based therapeutics for the treatment of chronic and age-related diseases.
CohBar scientists at work in the lab.

With more and more companies emerging with a focus on mitochondria, does Engle feel any pressure from having more players in the market?

“The first one or two that work will change everything, so that’s the key, we just need to get there,” he says. “So it’s exciting to see more people working on mitochondria and I’m always looking for ways to help any of the other company CEOs. Because if one of us succeeds, it will bolster the whole group up.”

“Do we think some of these peptides are going to work directly on some aging mechanism that we may not even know yet?” asks Engle. “Yeah, that’s a possibility in our minds, because we really haven’t explored all the possibilities yet.”

 


“People are listening – at an investor level, once you bring up mitochondria, they sit up straight and start taking notes.”

 


 

And Engle believes that the mitochondria story is now starting to resonate beyond the scientific community.

“People are listening – at an investor level, once you bring up mitochondria, they sit up straight and start taking notes,” he says. “I’ve said to several bank analysts, who often have panels at their conferences on diabetes or other major diseases, that in another year or two they are going to have a specific panel that’s just on mitochondria.”

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“And one of the things that fascinates me about the whole thing is how the awareness in the general population is changing. The high performance people have become very focused on mitochondria, whether it’s the Paleo f(x) folks or Bulletproof, there’s an enormous amount of energy going into digging into this stuff.”

Images courtesy of CohBar

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Danny Sullivan
Contributing Editor Danny has worked in technology communications for more than 15 years, spanning Europe and North America. From bionics and lasers to software and pharmaceuticals – and everything in between – he’s covered it all. Danny has wide experience of technology publishing and technical writing and has specific interest in the transfer from idea to market.
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