ARCH-backed biotech emerges with $85M and a bold claim: A new human hormone can reverse a key effect of aging
The elderly patient’s muscles didn’t look right beneath the microscope.
He wasn’t just old. He had diabetic myopathy, a complication where muscles degrade faster than normal. The mitochondria die, fibers weaken, and the tissues become so broken up they resemble cracked Dust Bowl earth. “Like cottage cheese,” offers Russ Cox, a Genentech and Jazz Pharma alumn.
But now they looked — healthy. Mitochondria were firing. The fibers perked and stretched.
“These muscles were really looking as if they were muscles of a person 20 years younger,” Sundeep Dugar, the J&J and Bristol-Myers Squibb vet on the other end of the microscope, told Endpoints News.
The patient and others had been injected with a form of flavanol, the metabolites found in grape skins and wine and dark chocolate that lead nutritionists to sometimes recommend those foods for heart health. It’s considered an antioxidant. But the results that Dugar and his collaborator George Schreiner saw, along with earlier animal studies, led them to a bold idea: Flavanoid was actually following biological pathways normally used by a yet undiscovered human hormone, the first of its kind discovered in over 50 years.
“It’s a big deal,” Dugar said. “I think it’s a big deal.”
That was in 2012. Dugar, Schreiner and Cox are now forming a company called Epirium around that finding and the subsequent work they did confirming the new hormone. It’s a rejig of an older, poorly funded group the trio had worked on called Cardero, but now they’ve managed to convince a fleet of topflight investors: Longitude, ARCH, Vertex and Adams Street have joined in an $85 million Series A.
There’s also an investor called Longevity Fund, a group focused on extending human life, and ARCH head Bob Nelsen has made no secret of his desire to live forever. The two hint at an idea the new biotech isn’t particularly shy about: That while they will begin with trials in rare neuromuscular disorders, namely a form of muscular dystrophy called Becker’s, they have ambitions that are much broader.
“They made the investment not just because they think we can do something meaningful in Becker’s muscular dystrophy, but primarily because some of these larger diseases could benefit as well,” Cox, the CEO, told Endpoints. “There’s no question we will evolve.”
Epirium isn’t yet revealing what their claimed new hormone is. They say the long delay has been in trying to secure the intellectual property and that a scientific paper is coming early next year.
It has to do, though, with mitochondria biogenesis, or the creation of new mitochondria. These organelles are often called the ‘engine of the cells’ but they break down with age or with certain diseases and bring the muscles down with them. Exercise is one of the only ways to make more.
“You and I lose 10% of our mitochondria every decade, so by the time you get to my age, you’re underwater as opposed to when you’re 18,” said Cox, a former track and cross country athlete now approaching 60.
Dugar and Schreiner, who worked at Scios before it was bought by J&J for $2.4 billion in 2003, had been enlisted at UC San Diego to investigate why flavanol had biological effects. To emerge from that research claiming to find a new human hormone is bold, particularly without publishing the work. Researchers have long studied flavanol for its cardiovascular impact without arriving at similar conclusions. The hormone would be the first mitochondrial steroid in 50 years, they said.
But the pair conducted 11 proof-of-concept trials on 110 patients and say they saw profound results that appeared to work along each of the three well known mitochondrial pathways. They didn’t follow up on the diabetic myopathy patients long term, but they walked and stood better and that, combined with his muscle slides, was overwhelming.
“This told us that while everyone classifies flavanol as an antioxidant, that couldn’t be true,” said Dugar.
The two set up the parameters for a human equivalent that must operate along the same metabolic path as flavanoid, and soon found it. Cox said that in early meetings, investors were mystified by Epirium’s presentation, but eventually came around.
“Of course, they all went to google it, and couldn’t find a publication on it and said ‘how can that damn be?'” he said.
Epirium will start out with a clinical trial on Becker’s muscular dystrophy patients, one of the groups they studied in the early proof-of-concepts. Becker’s is akin to a less devastating form of Duchenne. When patients’ muscles fire, they release toxins that kill mitochondria and deplete overall muscle tissue. Cox said their hormone should be able to slow or even reverse that muscle loss.
Becker’s may seem an odd starting point given the gene therapies nearing market for muscular dystrophy, but Cox said that their hormone might be used in combination with the flashier approach. For the company as a whole, though, rare diseases are primarily places they already have data and think they might place a foothold for a much larger project, one that includes neurodegeneration and other age-related disorders.
Mitochondria deplete as we age. Epirium says they’ve found a way to make them grow, a chemical exercise.
“I’m not saying I want to call it anti-aging,” said Dugar. “But the question is, if you can really have a separation between your biological age and your chronological age, then, hey – 80 years olds who have healthy mitochondria, will look like they were 60 years old or act like they were 60 years old. Maybe that’s what anti-aging is.”