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.”

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Deborah Dunsire

The fourth CGRP mi­graine drug is here. Time for Lund­beck to prove it's worth $2B

They may be late, but Lundbeck is now officially in the game for preventing migraine with CGRP drugs.

The FDA has OK’d eptinezumab, the prize in Lundbeck’s $2 billion acquisition of Alder. Like rival offerings from Amgen/Novartis, Eli Lilly and Teva, the antibody blocks the calcitonin gene-related peptide, which is believed to dilate blood vessels in the brain and cause pain.

It will now be sold as Vyepti. The company has yet to announce a price. Amgen and Novartis had set the wholesale acquisition cost of their pioneering Aimovig at $6,900 for a year’s supply before raising it slightly this year; Lilly and Teva had followed suit with Emgality and Ajovy.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Special report

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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