Af­ter a crush­ing PhI­II fail­ure, Cy­to­ki­net­ics says its next-gen mus­cle drug is lin­ing up well in PhII — but big chal­lenges loom

For the past 6 months, Cy­to­ki­net­ics $CYTK CEO Robert Blum has been hold­ing things to­geth­er in the wake of a dev­as­tat­ing late-stage dis­as­ter that swept away its lead mus­cle drug. He takes pride in the fact that he was able to sol­dier on with­out gut­ting the staff. And now the biotech and its part­ners at Astel­las are step­ping for­ward with their fol­low-up drug — look­ing to per­suade in­vestors that they can learn from the griev­ous set­back and make a come­back in the field of strength­en­ing pa­tients af­flict­ed by a range of ail­ments.

It’s not go­ing to be easy or quick. In­vestors took a close look at the da­ta to­day and the fall­out end­ed dri­ving the biotech’s stock down 17%.

Robert Blum

Ini­tial­ly cod­ed CK-2127107 and now called relde­sem­tiv — which re­places the de­funct tirasem­tiv — Blum touts the new con­tender as be­ing a safer, bet­ter ap­proach to amp­ing up mus­cles. Tirasem­tiv, he says, was done in by the fact that the drug pen­e­trat­ed the blood brain bar­ri­er,  caus­ing dizzi­ness and lim­it­ing dos­ing. This time around, he says, their next-gen ap­proach won’t have that lim­i­ta­tion.

Now in a line­up of mid-stage stud­ies, in­ves­ti­ga­tors for the com­pa­ny rolled out the first snap­shot of Phase II da­ta for spinal mus­cu­lar at­ro­phy. And the da­ta raise some ques­tions, even as Blum high­lights the dose ef­fect among the 70 pa­tients. 

Not sur­pris­ing­ly, the low 150 mg dose used in the study failed to gen­er­ate a sta­tis­ti­cal­ly sig­nif­i­cant re­sult for a 6-minute walk test — one of the stan­dard end­points avail­able to de­vel­op­ers in the are­na. That’s not un­usu­al in a study like this, which goes in search of ham­mer­ing out the right dose to go in­to a reg­is­tra­tion study. The 450 mg did get to sta­tis­ti­cal sig­nif­i­cance at 4 weeks, and then slipped be­low a sig­nif­i­cant re­sponse at 8 weeks.

Ac­cord­ing to re­searchers, the 450 mg dose of the drug in­creased walk­ing dis­tance by 35.63 me­ters (p= 0.0037) at week four and 24.89 me­ters (with a p val­ue of 0.0584) at week eight rel­a­tive to place­bo. There was al­so a sig­nif­i­cant in­crease in Max­i­mal Ex­pi­ra­to­ry Pres­sure —which mea­sures res­pi­ra­to­ry mus­cles — at the low and high dose at 8 weeks, but nei­ther dose scored un­der the 0.05 mark at 4 weeks, which sug­gests a pos­si­ble im­prove­ment over time.

I asked Blum about the 6-minute test re­sults. Slid­ing ef­fi­ca­cy over a short pe­ri­od like that — a shift al­so seen in the low­er dose arm of the study — could sig­ni­fy that the drug has on­ly a tran­sient ef­fect, which could prove a se­ri­ous threat.

Blum, though, bat­ted it back, in­sist­ing that the down­ward shift was due sole­ly to the small pa­tient pop­u­la­tion in­volved. Re­searchers have the chance to dou­ble up on that dose in a piv­otal study, he adds. And fu­ture work would al­so ex­tend out end­points on ef­fi­ca­cy to 12 weeks.

“That’s with­in the noise of sta­tis­tics this size,” the CEO says. “We don’t see that as a ta­per­ing.”

“This is the first of four such stud­ies,” adds the CEO. “These da­ta lend sup­port for the mech­a­nism and the mol­e­cule. We know relde­sem­tiv is more po­tent, more pen­e­tra­ble in­to mus­cle.”

Re­searchers at Cy­to­ki­net­ics and Astel­las are now fo­cused on ALS, COPD and frailty in the el­der­ly, though they may even­tu­al­ly go down the path of sar­cope­nia as the FDA works on new reg­u­la­to­ry path­ways for ag­ing. This par­tic­u­lar pro­gram, says Blum, isn’t di­rect­ly com­pet­i­tive with the oth­er SMA drugs in the clin­ic, such as the one PTC and Roche are re­port­ing on to­day, or Bio­gen’s pi­o­neer­ing Spin­raza. A drug like theirs can be nice­ly com­ple­men­tary to any oth­er drugs tar­get­ed di­rect­ly at the dis­ease.

Where do they go from here? Blum isn’t talk­ing time­lines yet, as he cau­tious­ly moves for­ward to­ward fi­nal­iz­ing an­oth­er piv­otal tri­al. Fail­ure isn’t go­ing to be an op­tion.

Hal Barron and Rick Klausner (GSK, Lyell)

Ex­clu­sive: GSK’s Hal Bar­ron al­lies with Rick Klaus­ner’s $600M cell ther­a­py start­up, look­ing to break new ground blitz­ing sol­id tu­mors

LONDON — Chances are, you’ve heard little or nothing about Rick Klausner’s startup Lyell. But that ends now.

Klausner, the former head of the National Cancer Institute, former executive director for global health at the Gates Foundation, co-founder at Juno and one of the leaders in the booming cell therapy field, has brought together one of the most prominent teams of scientists tackling cell therapy 2.0 — highlighted by a quest to bridge a daunting tech gap that separates some profound advances in blood cancers with solid tumors. And today he’s officially adding Hal Barron and GlaxoSmithKline as a major league collaborator which is pitching in a large portion of the $600 million he’s raised in the past year to make that vision a reality.

“We’ve being staying stealth,” Klausner tells me, then adding with a chuckle: “and going back to stealth after this.”

“Cell therapy has a lot of challenges,” notes Barron, the R&D chief at GSK, ticking off the resistance put up by solid tumors to cell therapies, the vein-to-vein time involved in taking immune cells out of patients, engineering them to attack cancer cells, and getting them back in, and more. “Over the years Rick and I talked about how it would be wonderful to take that on as a mission.”

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Pfizer, South San Francisco — Jeff Rumans for Endpoints News

Pfiz­er takes aim at a flag­ship fran­chise at Sanofi and Re­gen­eron — and scores a few di­rect hits

Count Pfizer in as a top player in the blockbuster game of JAK1 inhibitors.
Over the weekend the pharma giant posted some stellar Phase III efficacy data for their heavyweight contender abrocitinib in atopic dermatitis (eczema) that lines up ahead of a booming Dupixent (dupilumab), a blockbuster in the portfolios of Regeneron and Sanofi. And they put some real distance ahead of Eli Lilly’s trailing Olumiant, which made a delayed initial arrival on the market for rheumatoid arthritis after the FDA hobbled it with some additional hurdles on safety concerns.
JADE-MONO-1 scores well for Pfizer, teeing up what will be an intensely followed breakdown of the JADE MONO-2 data, which the pharma giant recently top-lined as “similar” to the first Phase III when tested against a placebo — a control group that has been easily outclassed by all the drugs in this market niche.
As of now, Pfizer looks to be equipped to run into the review stage — advantaged by a breakthrough therapy designation that is intended to speed up the regulatory process.
Here’s what physicians and patients are likely to be confronted with in the not too distant future, as Pfizer goes about the tricky business of getting a JAK inhibitor past regulators at the FDA and EMA.
Lined up side by side we see:
IGA response rate (clear or nearly clear skin)

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First place fin­ish: Eli Lil­ly just moved to fran­chise leader with their sec­ond mi­graine drug OK in 1 year

In a rare twist for Eli Lilly’s historically slow-moving R&D group, the pharma giant has seized bragging rights to a first-in-class new drug approval. And all signs point to an aggressive marketing followup as they look to outclass some major franchise rivals hobbled by internal dissension.

The FDA came through with an OK for lasmiditan on Friday evening, branding it as Reyvow and lining it up — once a substance classification comes through from the DEA — for a major market release. The oral drug binds to 5-HT1F receptors and is designed to stop an acute migraine after it starts. That makes it a complementary therapy to their CGRP drug Emgality, which has a statistically significant impact on preventing attacks.

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Allogene HQ Open House on September 17, 2019 in South San Francisco. (Jeff Rumans, Endpoints News)

The next 10 years: Where is biotech head­ed?

The last 10 years have seen a revolution in drug development. Timelines have shortened, particularly in oncology. Regulators have opened up. Investment has skyrocketed. China became a player. Biotechs have multiplied as gene and cell therapy has exploded — offering major new advances in the way diseases are treated, and sometimes cured.

So where are we headed from here? I journeyed out to San Francisco in September to discuss the answer to that question at Allogene’s open house. If the last 10 years have been an eye-opener, what does the next decade hold in store?

Patrick Mahaffy, Getty Images

Court green-lights Clo­vis case af­ter de­tail­ing ev­i­dence the board ‘ig­nored red flags’ on false safe­ty and ef­fi­ca­cy da­ta

Clovis investors have cleared a major hurdle in their long-running case against the board of directors, with a Delaware court making a rare finding that they had a strong enough case against the board to proceed with the action.

In a detailed ruling at the beginning of the month that’s been getting careful scrutiny at firms specializing in biotech and corporate governance, the Delaware Court of Chancery found that the attorneys for the investors had made a careful case that the board — a collection of experts that includes high-profile biotech entrepreneurs, a Harvard professor and well-known investigator as well as Clovis CEO Patrick Mahaffy — repeatedly ignored obvious warnings that Mahaffy’s executive crew was touting inflated, unconfirmed data for their big drug Roci. Serious safety issues were also reportedly overlooked while the company continued a fundraising campaign that brought in more than a half-billion dollars. And that leaves the board open to claims related to their role in the fiasco.

The bottom line:

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Bill Gates backs Gink­go Biowork­s' $350M raise to fu­el the buzzy syn­thet­ic bi­ol­o­gy 'rev­o­lu­tion'

If you want to understand Ginkgo Bioworks, the name should suffice: Bioworks, a spin off “ironworks,” that old industrial linchpin devoted to leveraging scale as a wellspring for vast new industries capable of remaking society. Ginkgo wants to be the ironworks for the revolution it’s heralded with as much fanfare as they can, playing off of one of the buzziest technologies in biotech.

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UCB bags a ri­val to Soliris in $2.1B buy­out deal — but will an in­creas­ing­ly vig­i­lant FTC sign off?

UCB is buying out Ra Pharma $RARX, announcing an acquisition deal that rings up at $48 a share, or $2.1 billion net of cash, and puts them toe-to-toe with Alexion on a clinical showdown.

Ra shares closed at $22.70 on Wednesday.

There’s a small pipeline in play at Ra, but UCB is going for the lead drug — a C5 inhibitor called zilucoplan in Phase III for myasthenia gravis (MG) looking to play rival to Alexion’s Soliris. Soliris has the market advantage, though, with a much earlier approval in MG in late 2017 that UCB feels confident in challenging.

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A new play­er is tak­ing the field in a push for a he­mo­phil­ia A gene ther­a­py, and it’s a big one

BioMarin, the execs at Spark (and buyer-to-be Roche) as well as the Sangamo/Pfizer team have a new rival striding onto the hemophilia block. And it’s a big one.

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Stuck with a PhI­II gene ther­a­py fail­ure at 96 weeks, Gen­Sight prefers the up­beat as­sess­ment

Two years after treatment, the best thing that GenSight Biologics $SIGHT can say about their gene therapy for vision-destroying cases of Leber Hereditary Optic Neuropathy is that it’s just a bit better than a placebo — just maybe because one treatment can cover both eyes.

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