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.

Turned back at the FDA, Im­muno­Gen is ax­ing 220 staffers, sell­ing pro­grams and hun­ker­ing down for a new PhI­II gam­ble

After being stymied by FDA regulators who were unconvinced by ImmunoGen’s $IMGN desperation shot at an accelerated OK based on a secondary endpoint, the struggling biotech is slashing its workforce, shuttering R&D projects and looking for buyers to pick up some of its experimental cancer assets as it goes back into a new Phase III with the lead drug.

We found out last month that the FDA had batted back their case for an accelerated approval of their antibody-drug conjugate mirvetuximab soravtansine, which had earlier failed a Phase III study for ovarian cancer. Now the other shoe is dropping.

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Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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As­traZeneca chal­lenges Roche on front­line SCLC af­ter seiz­ing an in­ter­im win — and Mer­ck may not be far be­hind

The crowded playing field in the PD-1/L1 marketing game is about to get a little more complex.

This morning AstraZeneca reported that its CASPIAN study delivered a hit in an interim readout for their PD-L1 Imfinzi combined with etoposide and platinum-based chemotherapy options for frontline cases of small cell lung cancer, a tough target which has already knocked back Bristol-Myers’ shot in second-line cases. The positive data  — which we won’t see before they roll it out at an upcoming scientific conference — give AstraZeneca excellent odds of a quick vault to challenging Roche’s Tecentriq-chemo combo, approved 3 months ago for frontline SCLC in a landmark advance.

“This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options,” noted AstraZeneca cancer R&D chief José Baselga in a statement.

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Bridge­Bio takes crown for biggest biotech IPO of 2019, as fel­low uni­corn Adap­tive rais­es of­fer­ing size and price

Bridge­Bio Phar­ma and Adap­tive Biotech­nolo­gies have not just up­sized IPO of­fer­ings — the pair of uni­corns have al­so raised their of­fer­ing prices above the range, haul­ing in a com­bined $648.5 mil­lion.

Neil Ku­mar’s Bridge­Bio Phar­ma, found­ed in 2015, has a sta­ble of com­pa­nies fo­cused on dis­eases that are dri­ven by de­fects in a sin­gle gene — en­com­pass­ing der­ma­tol­ogy, car­di­ol­o­gy, neu­rol­o­gy, en­docrinol­o­gy, re­nal dis­ease, and oph­thal­mol­o­gy — and can­cers with clear ge­net­ic dri­vers. The start­up mill birthed a pletho­ra of firms such as Ei­dos, Navire, QED Ther­a­peu­tics and Pelle­Pharm, which func­tion as its sub­sidiaries.

Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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FDA re­jects Ac­er's rare dis­ease drug, asks for new tri­al — shares crater

Ac­er Ther­a­peu­tics’ bid to re­pur­pose celipro­lol — a be­ta-block­er on the mar­ket for hy­per­ten­sion — as a treat­ment for a rare, in­her­it­ed con­nec­tive tis­sue dis­or­der has hit a se­vere set­back. The New­ton, Mass­a­chu­setts-based com­pa­ny on Tues­day said the FDA re­ject­ed the drug and has asked for an­oth­er clin­i­cal tri­al.

The com­pa­ny’s shares $AC­ER cratered near­ly 77% to $4.47 in Tues­day morn­ing trad­ing.