Blue­bird has a promis­ing new up­date on its BC­MA CAR-T for mul­ti­ple myelo­ma, but is it still the leader?

Nick Leschly / Boston Globe, End­points News

Blue­bird bio $BLUE un­veiled its lat­est up­date on its close­ly-watched BC­MA-tar­get­ing CAR-T for mul­ti­ple myelo­ma to­day of­fer­ing a slate of sol­id ev­i­dence that demon­strates the promise that at­tract­ed Cel­gene $CELG to their am­bi­tious col­lab­o­ra­tion on this drug. But with a ri­val Chi­nese group mak­ing a splash at AS­CO this year, the biotech may be see­ing its sta­tus as the fron­trun­ner in the field start to fade a bit.

In the first new da­ta to come out since late last year, blue­bird of­fered an up­date on 18 pa­tients in four dif­fer­ent dos­ing co­horts in search of in­sights on dura­bil­i­ty, dos­ing and safe­ty for bb2121.

With 18 pa­tients evalu­able for ef­fi­ca­cy, there were 15 in what blue­bird termed ac­tive dos­ing reg­i­mens above the min­i­mum for bb2121, and all of them achieved an ob­jec­tive re­sponse. Twelve achieved a very good par­tial re­sponse to com­plete re­sponse, as­so­ci­at­ed with longer sur­vival times. And of the 4 pa­tients evalu­able for min­i­mal resid­ual dis­ease sta­tus, all were MRD neg­a­tive with on­ly a few or no myelo­ma cells in cir­cu­la­tion.

That is all ex­cel­lent.

Up un­til now, blue­bird and Cel­gene were wide­ly viewed as the lead­ers in the BC­MA field. But Nan­jing Leg­end’s da­ta out this morn­ing may well put that sta­tus in ques­tion.

I asked blue­bird CEO Nick Leschly about that over the week­end.

His re­sponse, with a smile: “We are com­plete­ly, con­struc­tive­ly para­noid no mat­ter what.”

Short trans­la­tion: Blue­bird is hap­py where they are and con­fi­dent about mov­ing to next steps as their part­ner Cel­gene lays the foun­da­tion for a ground­break­ing reg­is­tra­tional study that may well get start­ed lat­er this year. But they all know it won’t be easy or free of chal­lenges — now or in the fu­ture as ri­val ther­a­pies line up to chal­lenge them.

Da­ta from tri­als that don’t in­volve head-to-head de­signs with­in the con­struct of the same study are no­to­ri­ous­ly dif­fi­cult to com­pare. In Leg­end’s case, says Leschly, it seems ev­i­dent that the pa­tients weren’t as sick and hadn’t failed the same mul­ti­ple of drugs that blue­bird re­cruit­ed for.

That makes it “ap­ples and or­anges,” he says, adding “that doesn’t mean it isn’t great da­ta.”

All of it, notes Leschly, helps val­i­date the tar­get, while blue­bird is sat­is­fied that it has the right drug to take for­ward. Its next-gen drug, bb21217, will come up be­hind it as Cel­gene preps for the piv­otal BC­MA study to some. “It’s all go, go, go” on bb2121, says Leschly, whose of­fi­cial ti­tle is chief blue­bird.

“All these pa­tients are do­ing in­cred­i­bly well,” says the CEO about his lead ther­a­py, point­ing to par­tial re­spons­es in their study that re­flect­ed a near era­sure of can­cer. These drugs face a high bar on demon­strat­ing ef­fi­ca­cy, he adds, and bb2121 comes through with fly­ing col­ors.

Blue­bird came to AS­CO with a few things to prove. It need­ed to prove that its drug works in a broad­er num­ber of pa­tients. And it need­ed to prove that the safe­ty is­sues around cy­tokine re­lease syn­drome were man­age­able.

Blue­bird’s CEO is com­ing out of AS­CO be­liev­ing that he’s an­swered those chal­lenges.

I asked Leschly about the de­bate over the 4-1BB cos­tim­u­la­to­ry do­main its drug us­es, and the the­o­ry that it could be safer than the CD28 al­ter­na­tives on the mar­ket.

Leschly’s re­mark: he’s learned to “be care­ful of open­ing your mouth be­fore you know what you’re talk­ing about.”

The 4-1BB do­main does seem to help dura­bil­i­ty, he adds, but he’s hes­i­tant to say that it ex­tends to safe­ty at this point. It’s just too ear­ly.

Blue­bird’s ex­ecs say they still have to de­cide ex­act­ly which dose to take in­to the next phase of their study (and I pressed them on it), as they add new pa­tients and pre­pare for the piv­otal study to come.

Cel­gene is clear that they want to start en­rolling for the piv­otal study this year, says Leschly. And with 50% of the US com­mer­cial rights re­sid­ing at blue­bird, he’s ready for the next step.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

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Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

Editor’s note: This is a live story and will be updated.

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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See­los Ther­a­peu­tics 'tem­porar­i­ly' stops study in rare neu­ro dis­or­der for busi­ness rea­sons

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

Alec­tor cuts 11% of work­force as it dou­bles down on late-stage neu­ro pro­grams part­nered with GSK, Ab­b­Vie

A month after revealing plans to concentrate on its late-stage immuno-neurology pipeline, Alector is trimming its headcount by 11%.

The layoffs will impact around 30 employees across the organization, the company disclosed in an SEC filing, adding that the plan will “better align the company’s resources” with the new strategy. With $712.9 million in cash, cash equivalents and investments as of the end of 2022, Alector believes the reserves will now get it through 2025.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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Hugo Peris, Spiral Therapeutics CEO

Hear­ing-fo­cused biotech grabs trio of pro­grams from Oton­o­my's fire sale

Otonomy may be shutting down, but the lessons learned there will live on at another biotech working on new treatments for hearing loss.

San Francisco-based Spiral Therapeutics has bought certain assets related to three of Otonomy’s programs, ranging from data, patent rights, and know-how to inventory. That includes data around Otonomy’s twice-failed lead program, OTO-104 (Otividex), a sustained-exposure formulation of dexamethasone.

No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

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