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.”

The 20 un­der 40: In­side the next gen­er­a­tion of bio­phar­ma lead­ers

“Each generation needs a new music,” Francis Crick wrote in 1988, reflecting back on his landmark discovery. Crick was 35, then, in 1953, when he began working with a 23-year-old named James Watson, and 37 when the pair unveiled the double helix. Rosalind Franklin, whose diffraction work undergirded their metal model, was 32.

The model would become the score for a new era in biology, one devoted to cracking the basic structures turning inside life. Subsequent years would bring new conductors and new rhythms: Robert Swanson, 29 when he convinced a 39-year-old Herb Boyer to build a company off his work and call it Genentech; Phillip Sharp, 29 when he discovered RNA splicing and 34 when he co-founded Biogen; Frances Arnold, 36 when she pioneered directed evolution; Feng Zhang, 31 when he published his CRISPR paper.

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Chart-top­ping ven­ture cash? Strong deal flow? In the month Covid-19 ripped around the globe? Yup

It turns out that even sending everyone from the CEO to rank-and-file staffers home to work in the middle of a Category 5 pandemic wasn’t enough to put a crimp in the flow of venture cash into biopharma. And even dealmaking held its own against the howling winds of misfortune — largely because a group of savvy players was quick to adjust to the new reality.

Our deal expert Chris Dokomajilar ran the numbers for us on a month-to-month basis and found that not only was venture money flowing during the panicky month of March, but it was also hitting home in record sums compared to the last 26 months of deal flow.

Say what?

As you can see in the top chart below, Dokomajilar outlined how the industry racked up $2.41 billion in total for March, just barely ahead of one other topper during the heady days of August 2018.

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FDA Commissioner Stephen Hahn and President Donald Trump at a press briefing on March 19, 2020. (AP Images)

Biotech ex­ecs warn that the FDA is fum­bling their re­sponse to the Covid-19 open-door promise, de­lay­ing progress

A few days ago the FDA touted a procedure for Covid-19 meds that committed the agency to immediate action for developers, formalizing a high-speed response that’s been promised for weeks.

Bioregnum Opinion Column by John Carroll

Decisions that once required months would be measured in hours under the Coronavirus Treatment Acceleration Program. “In many cases” trial protocols could be hammered out in less than a single day. If you had a potential solution to the crisis, the appropriate staffer would be in touch “to get studies underway quickly.”

It would be the ultimate high-speed regulatory pathway from Phase I to approval. Red tape was banished.

But it’s clear that for some — and quite likely many — biopharma execs, the actual agency response has not measured up to the promise. Beyond the front ranks of advanced companies in the field, like Gilead, or for drugs endorsed by President Trump, it may not even come close.

“The first response is this form letter everyone gets,” says one biotech CEO who’s reached out to the FDA on Covid-19. And when you try to cut through that, the ball gets dropped as it is passed from top officials to the frontline staff actually charged with getting things done.

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GSK's Hal Bar­ron buys a $250M stake in George Scan­gos' Vir and makes a bee­line to the clin­ic with Covid-19 an­ti­bod­ies

GlaxoSmithKline is diving straight into the swirling waters of Covid-19 R&D work, and investing $250 million to grab a chunk of equity in one of the emerging stars in infectious disease research to make it official.

GSK put out word this morning that it is partnering with Vir Biotechnology $VIR, the infectious disease startup founded in the Bay Area by former Biogen CEO George Scangos. They’re planning a leap into Phase II studies for 2 preclinical antibody candidates — VIR-7831 and VIR-7832 — that have been engineered to target the SARS-CoV-2 spike protein.

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UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

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Ready to de­clare a de­fin­i­tive come­back in two months, Im­munomedics stops PhI­II ear­ly, re­cruits new CEO

More than a year ago, hit by a surprise complete response letter from the FDA, Immunomedics bid its then-CEO, Michael Pehl, adieu and began a 15-month quest to resolve the manufacturing issues cited in the CRL and seek a new leader — all the while moving forward with a Phase III study on its lead drug for metastatic triple-negative breast cancer.

Today the biotech said their stars are finally aligning. Not only is Novartis Oncology vet Harout Semerjian coming on board as CEO to steer what they believe will be a smooth sail to a new PDUFA date in June, Immunomedics has also been informed that their late-stage trial can be stopped early due to “compelling evidence of efficacy.”

An­oth­er day, an­oth­er boat­load for biotech. Deer­field adds $840M to rush of ven­ture dol­lars

The biotech dollars just keep rolling in.

Even as the world economy faces an economic contraction unprecedented in nature, biotech venture capital firms are announcing huge new investment pots. The latest? Deerfield Management Co.

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Small mol­e­cules, bi­o­log­ics and now gene ther­a­pies: Ger­many's Evotec adds an­oth­er feath­er to its R&D cap

German drug discovery company Evotec — which has a thriving rolodex of biopharma partners such as Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk, Pfizer, Sanofi, and Takeda — is now venturing into gene therapies.

The company swallowed Seattle-based Just Biotherapeutics, a company focused on reducing the cost of manufacturing protein therapies last year. It is now setting up a dedicated R&D site for gene therapies in Austria, in an effort to achieve a “modality-agnostic” repertoire — small molecules, biologics and now gene therapies.

A pair of PhI­II fail­ures spells last rites for Men­lo’s once-promis­ing Mer­ck drug

Four months after an intercontinental merger, Menlo Therapeutics is counting yet another pair of trial failures — ones with significant consequences for the companies, their shareholders and the drug.

In two pivotal Phase III trials, Menlo’s lead drug serlopitant failed to treat pruritus associated with prurigo nodularis — basically itchiness from a particular skin disease that causes red lesions on a person’s arms or legs. Serlopitant has long been the company’s only drug and as recently as 2018, it looked promising enough to support a stock price of $37. In April of that year, a Phase II failure demolished the stock price overnight: $35 to $9. Other subsequent stumbles trickled the ticker down to just above $2.