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.

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.

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.

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.

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Left to right, top to bottom: Carl Gordon, Adam Stone, Peter Moglia, David Schenkein, Robert Nelsen, Carol Gallagher; Srinivas Akkaraju, Ray Debbane, Jim Flynn, Peter Kolchinsky, Thilo Schroeder, Brad Bolzon

UP­DAT­ED: The top 100 bio­phar­ma ven­ture in­vestors at the mega­bil­lions deal ta­ble

The VC crowd took a step back last year, but nevertheless maintained a furious pace of new investments in therapeutic tech platforms and biotech startups. And the top 100 players completely dominated the megabillions game.

Just looking at the number of deals done by each of the top 100, OrbiMed came in at the top, with 20, followed by Alexandria (18), Perceptive (16) and the ubiquitous RA Capital at 16. It’s impossible to say exactly how much they invested in total — those numbers are only rarely provided — but it is clear from the numbers assembled by Chris Dokomajilar at DealForma who’s most likely to be found sitting at the table during the go-go days of biotech investing.

Dokomajilar tracked $14.06 billion in biotech venture investing last year, a dip from the frenzied pace of $16.02 billion in 2018 and more than $10 billion higher than he recorded for 2010, as the economy was recovering from a profound economic crisis.

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Rahul Ballal, Imara

As sick­le cell pa­tients find new op­tions, NEA-found­ed Imara pitch­es mid-stage al­ter­na­tive for $86M IPO

November 2019 proved to be a fruitful month for patients with blood disorders known as hemoglobinopathies. Within days, the FDA ushered two drugs for sickle cell disease and another for beta thalassemia to the market — livening up a barren field.

Imara, a relatively young plower, is riding on that enthusiasm as it shoots for an $86.25 million IPO.

Imara emerged from New Enterprise Associates’ orphan drug accelerator Cydan in 2016 as a single-product company. $77.3 million in private financing later IMR-687 remains the sole asset in its pipeline; the difference is the drug is now in Phase II for sickle cell disease, with topline data slated for later this year and two other mid-stage beta thalassemia studies lined up.

UP­DAT­ED: RA joins glob­al syn­di­cate to back a $98M round for CAN­bridge

A Beijing-based rare disease and oncology player has raised $98 million to help fund the expansion of its pipeline as well as a commercial portfolio.

CANbridge put out word Tuesday that the global private equity player General Atlantic joined forces with Chinese CRO Wuxi AppTec to lead the Series D, with both ready to chip in an extra $10 million each under the right conditions. The syndicate includes RA Capital Management, Hudson Bay Capital Management, YuanMing Prudence Fund and Tigermed.

Carol Robinson, Professor Dame Carol Robinson Research Group

UP­DAT­ED: Drug dis­cov­ery in HD: Ox­ford spin­of­f's mass spec­trom­e­try ap­proach scores fresh fund­ing

The technology used to detect explosives at airports — mass spectrometry — is being piloted as an engine for drug discovery.

Mass spectrometry is a tool designed to measure with profound accuracy the mass of a single molecule. Typically, mass spectrometers can be used to identify unknown compounds, to quantify known compounds, and to determine the structure and chemical properties of molecules.

Lars Fruergaard Jørgensen, chief executive officer of Novo Nordisk A/S, (via Getty Images)

The list of the 11 block­busters-to-be in line for a 2020 launch high­light agony and ec­sta­sy of drug R&D

For all the talk about unmet medical need and patients first and so on, the key criteria investors watch for any new drug in the pipelines is peak sales projection. Are you going to hit the blockbuster mark, at $1 billion-plus, or are you going to be an also-ran in the sales department?

Of course, analysts’ peak sales projections by themselves are of limited value in many cases. When the PCSK9 drugs started arriving 5 years ago, Repatha was billed as a $2.5 billion peak earner. They’re nowhere near that, with new competition threatening current levels. And if Biogen’s controversial Alzheimer’s drug aducanumab (submission planned but not on the list) is approved, per chance, will payers cover it?

Maybe not. And then those $10 billion in peak sales assumptions would go straight down the drain.

But, analysts are analysts, and peak sales projections have to be factored in when assessing the top experimental drugs up for a launch in the year ahead.

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UP­DAT­ED: Chi­na ap­proves flu drug be­ing tout­ed as a po­ten­tial coro­n­avirus treat­ment amid a rush of clin­i­cal stud­ies

One of the three drugs that China’s Ministry of Science and Technology has tapped as potential COVID-19 treatments to watch has notched its first Chinese OK — for the flu.

While there’s no proof yet that fapilavir, or favipiravir, is the cure that patients and physicians are yearning for, it stands out for a unique constellation of qualities. It’s been commercially available in Japan for several years (unlike Gilead’s experimental remdesivir) yet it’s new to China (unlike the malaria drug chloroquine phosphate). Perhaps more importantly, a domestic biotech — Zhejiang Hisun Pharma — owns the rights to manufacture and market the drug, preempting any concerns about patents.

FDA goes on high alert as coro­n­avirus rais­es threat to drug man­u­fac­tur­ing and clin­i­cal tri­als grind to a halt

The FDA isn’t quite sure just what the coronavirus outbreak in China will mean for the US pharma industry, but it has the potential to trigger a host of troublesome issues around the supply chain the country is directly plugged into.

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