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.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

'This is not go­ing to be good': Mod­er­na CEO Ban­cel warns of a 'ma­te­r­i­al drop' in vac­cine ef­fi­ca­cy as Omi­cron spreads

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer, new GSK global head of vaccines R&D

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

With on­ly burns to show in gene ther­a­py, Astel­las inks deal with AAV spe­cial­ist Dyno in push for a bet­ter cap­sid

On the hunt for a better AAV capsid for gene therapy, Eric Kelsic’s Dyno Therapeutics has set itself apart with its focus on machine learning to help speed discovery. Now, Japanese drugmaker Astellas — fresh off a slate of gene therapy burns — is taking a bet on Dyno as it looks to the future.

Astellas and Dyno will work together as part of an R&D pact to develop next-gen AAV vectors for gene therapy using Dyno’s CapsidMap platform directed at skeletal and cardiac muscle, the companies said Wednesday. Under the terms of the deal, Dyno will design AAV capsids for gene therapy, while Astellas will be responsible for conducting preclinical, clinical and commercialization activities for gene therapy product candidates using the capsids.

As first Omi­cron case in US crops up, re­searchers won­der: which an­ti­bod­ies, vac­cines will hold up?

As Covid-19 drug and vaccine developers race to figure out which of their products might be hampered by the new variant, the CDC on Wednesday afternoon announced the first confirmed case of the Omicron variant (B.1.1.529) in the US, found in San Francisco.

The unidentified individual was a traveler who returned from South Africa on Nov. 22, 2021, was fully vaccinated, and had mild symptoms that the CDC described as improving. All close contacts have been contacted and have tested negative, the centers said.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.