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.”

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.

Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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Mene Pangalos, AstraZeneca R&D chief (AstraZeneca via YouTube)

A day af­ter Mod­er­na vac­cine re­sults, ru­mors swirl of pend­ing As­traZeneca da­ta

A day after Moderna and the NIH published much-anticipated data from their Phase I Covid-19 vaccine trial, attention is turning to AstraZeneca which, according to a UK report, is expected to publish its own early data tomorrow.

ITV’s Robert Peston reported that AstraZeneca will publish the Phase I data in The Lancet. 

AstraZeneca and Moderna represent the two most ambitious Covid-19 vaccine efforts, having set the quickest timelines for approval (though they were recently joined in that regard by the Pfizer-BioNTech partnership) and some of the loftiest goals in total doses. Yet there is even less known about AstraZeneca’s vaccine’s effect on humans than there was about Moderna’s before yesterday. Although, in a controversial move, Moderna released some statistics from its Phase I in May, AstraZeneca has yet to say anything about what it saw in its Phase I trial — a move consistent with the scientific convention to withhold data until it can be published in a peer-reviewed journal.

Ludwig Hantson, Alexion CEO

Why pay $4B for a steady di­et of dis­ap­point­ment? Porges turns thumbs down on Alex­ion’s M&A strat­e­gy, of­fers some point­ers

When Alexion announced recently that it was paying $1.4 billion to bag Portola and its underperforming Factor Xa inhibitor reversal agent, you could hear the head-scratching going on around virtual Wall Street.

Why was Alexion going down the discount lane for new products? And why something like this? Analysts have been urging Alexion to get serious about M&A for years if it was serious about diversifying the company beyond Soliris and its successor drug. But this wasn’t the kind of heavy-impact deal they were looking for.

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Mil­li­pore­Sig­ma to build new $20 mil­lion, 12,000-square-foot lab in Switzer­land

On the heels of opening a new laboratory in Shanghai last week, MilliporeSigma is continuing its construction push.

The Merck KGgA life science subsidiary announced Wednesday its intentions to build a new $20 million lab in Buchs, Switzerland to support its reference materials business. It’s estimated that the new facility will be completed in December 2021 and open in early 2022 and is expected to be 12,000 square feet.

Stéphane Bancel, Moderna CEO (Steven Ferdman/Getty Images)

‘Plan­ning to vac­ci­nate every­one in the US,’ Mod­er­na out­lines ef­forts to sup­ply their Covid-19 vac­cine as man­u­fac­tur­ing ramps up ahead of PhI­II

Twelve days from the planned start of their Phase III pivotal trial, the executive crew at Moderna has set up the manufacturing base needed to begin production of the first 500,000 doses of their Covid-19 vaccine with plans to feed it into a global supply chain. But the initial batches will likely be ready in the US first, where company CEO Stéphane Bancel plans to be able to vaccinate everyone.

“We have started making commercial product at-risk, and will continue to do so every day and every week of the month,” Bancel told analysts during their morning call on the Phase I data just published in the New England Journal of Medicine.

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Covid-19 roundup: Vac­cine by end of 2020? Ken Fra­zier warns hype do­ing 'grave dis­ser­vice'

When it comes to setting expectations about a Covid-19 vaccine, Ken Frazier does not mince words.

Over a month after first casting doubts on the aggressive 12- to 18-month timeframe championed by the US government and his biopharma peers, the Merck CEO again cautioned against any hype around a quick vaccine approval.

In a wide-ranging interview with Harvard Business School professor Tsedal Neeley that touched other big topics such as race, Frazier emphasized that vaccines take a long time to develop. He would know: Out of the seven new vaccines introduced around the world in the past 25 years, four came from Merck.

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