Blue­bird, Cel­gene add a promis­ing chap­ter to their suc­cess sto­ry with BC­MA-tar­get­ing CAR-T — and turn it around with in­vestors

CHICA­GO — Right now at Cel­gene $CELG and blue­bird $BLUE, it’s all about the Kar­M­Ma — and they’re look­ing to bur­nish theirs at AS­CO.

Nick Leschly

In a peek at the first batch of high­ly promis­ing da­ta to hit at AS­CO, in­ves­ti­ga­tors are am­pli­fy­ing ev­i­dence of pos­i­tive ob­jec­tive re­sponse rates for the drug, with an en­cour­ag­ing pro­gres­sion-free sur­vival rate of close to a year to il­lus­trate its po­ten­tial dura­bil­i­ty for pa­tients with far ad­vanced cas­es of mul­ti­ple myelo­ma — par­tic­u­lar­ly in the high-dose group. And it all looks tai­lor made for pri­or­i­ty han­dling at the FDA.

Ex­pec­ta­tions for this drug, though, have been pumped sky high — which might ex­plain why blue­bird’s stock slid deep­er in pre-mar­ket trad­ing Mon­day, down about 7%. Stalling myelo­ma by about a year may well be em­braced by the FDA, but with­out cur­ing cas­es a sig­nif­i­cant group of ob­servers came away ear­ly on dis­ap­point­ed by the drug’s prospects. Sev­er­al an­a­lysts, in­clud­ing Bri­an Sko­r­ney, came back with a sol­id score on the da­ta, and by Mon­day af­ter­noon the stock price had bounced back in­to the green.

The up­date keeps Cel­gene’s on­go­ing piv­otal study of the BC­MA-tar­get­ing bb2121 — Kar­M­Ma — square­ly in the CAR-T spot­light as one of the next big pro­grams to watch. Equipped with both break­through and PRIME des­ig­na­tions in the US and Eu­rope, reg­u­la­tors will like­ly be ready to whisk it through to the mar­ket with pos­i­tive da­ta. And re­searchers are mak­ing the case that their lead­ing BC­MA ef­fort has the legs to be a first-in-class con­tender for the ini­tial wave of BC­MA CAR-Ts.

Do­ing that re­quires ev­i­dence of dura­bil­i­ty, a re­li­able dose re­sponse and a clear safe­ty pro­file that won’t stall or kill their ther­a­py dur­ing the last stretch of this race.

“The dan­ger with some ear­ly pre­sen­ta­tions of the da­ta is, are they go­ing to be re­flec­tive when you get more pa­tients and more time,” says CEO Nick Leschly.  And you can add more drug.

For 11 pa­tients with high BC­MA ex­pres­sion get­ting the 450 mil­lion cell dose, the strin­gent com­plete re­sponse/com­plete re­sponse rate was 54.5%, with very good par­tial re­spons­es of 27.3% and 9% in the par­tial re­sponse group — a 91% ORR. Among low ex­pressers, that fell to 37.5% for CRs while the VG­PRs swelled to 50% and par­tial re­spons­es hit 12.5% — for a 100% ORR. Among 22 pa­tients get­ting a 150 mil­lion-plus dose, the CR rate was 50% with 36.4% VG­PRs and 9.1% PRs — a 95.5% ORR.

The over­all ob­jec­tive re­sponse rate in the study at this point was 80.6%.

High­light­ing dura­bil­i­ty, the re­searchers are post­ing a me­di­an progress-free sur­vival rate of 11.8 months among 18 pa­tients who re­ceived an ac­tive dose of 150 mil­lion CAR-T cells-plus. That com­pares well with the 2.7 months reg­is­tered for pa­tients on the in­ef­fec­tive dose used in the study, set­ting a base­line to un­der­score the ef­fi­ca­cy. In 16 pa­tients who were MRD (min­i­mal resid­ual dis­ease) — neg­a­tive, or a deep­er lev­el of com­plete re­mis­sion, the mPFS was 17.7 months.

Ge­of­frey Porges hailed the re­sults, but not­ed that in­vestors could be left want­i­ng more on the up­side. He not­ed:

We pre­vi­ous­ly sug­gest­ed that me­di­an PFS would be reached at 12 months in this up­dat­ed dataset and there­fore see the re­sult as most­ly con­fir­ma­to­ry, al­though some in­vestors may be dis­ap­point­ed that PFS was not clos­er to ~15 months.

Late last year at ASH blue­bird post­ed a 94% over­all re­sponse rate for bb2121, with a jaw-drop­ping 56% com­plete re­sponse rate among a small group of 18 pa­tients in heav­i­ly pre­treat­ed ac­tive dose co­horts. Three of those 10 CRs, though, were un­con­firmed at the time of the pre­sen­ta­tion in At­lanta.

“What we’re see­ing here that there is a clear dose re­sponse,” says blue­bird R&D chief David David­son. “To see a me­di­an PFS of 11.8 months in this heav­i­ly pre­treat­ed pa­tient pop­u­la­tion is very en­cour­ag­ing.”

And now they plan to bake every­thing they’ve learned in­to Kar­M­Ma.

To be sure, there con­tin­ued to be plen­ty of ev­i­dence of tox­i­c­i­ty, with a high rate of cy­tokine re­lease syn­drome — more than 80% in the high­er dose ranges — to raise con­cerns. One in three pa­tients ex­pe­ri­enced trou­bling cas­es of neu­ro­tox­i­c­i­ty. But the key point for the in­ves­ti­ga­tors here is that there have been no treat­ment-re­lat­ed deaths; CRS cas­es are be­ing han­dled with­out the grade 5 events that can halt or even kill a CAR-T pro­gram like this, as Juno found out to their own re­gret.

As far as Leschly is con­cerned, there’s al­so every rea­son to be­lieve that the bb2121 team can now stay well ahead of its ri­vals at J&J and Leg­end. J&J has just nailed an FDA OK for its own Phase I/II study for BC­MA CAR-T LCAR-B38M (JNJ-68284528), and they will look to jump on the fast track to an ac­cel­er­at­ed OK.

That drug is “not in­flu­enc­ing us in any shape or form,” says Leschly, adding that “we’ve treat­ed very dif­fer­ent pa­tient pop­u­la­tions.” Blue­bird’s pa­tients have been through as many as 7 or 8 lines of ther­a­py, and they’re too far ahead now for any new ar­rivals to catch up.

 Says Leschly: “We’re off to the races.” And they don’t ex­pect to get passed by any new­com­ers.

“As you said, the re­sults are en­cour­ag­ing based on what’s cur­rent­ly avail­able to pa­tients in 4th line and be­yond,” says Leschly. “As long as we can con­tin­ue to de­liv­er these re­sults in Kar­M­Ma, we have a path to get to these pa­tients in 4th line.”

Im­age: Nick Leschly (YouTube)

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

UP­DAT­ED: Gink­go Bioworks re­sizes the de­f­i­n­i­tion of go­ing big in biotech, rais­ing $2.5B in a record SPAC deal that weighs in with a whop­ping $15B-plus val­u­a­tion

Ginkgo Bioworks execs always thought big. But today should redefine just how big an upstart biotech player can dream.

In the largest SPAC deal to clear the hurdles to Nasdaq, the biotech that envisioned everything from remaking synthetic meat to a whole new approach to developing drugs has joined forces with one of the biggest disruptors in biotech to slam the Richter scale on dealmaking.

Soon after becoming the darling of the VC crew and clearing the bar on a $4 billion valuation, Ginkgo — a synthetic biotech player out to reprogram cells with industrial efficiency — has now struck a deal to go public in the latest leviathan SPAC that sets its pre-money valuation at $15 billion. In one swift vault, Ginkgo will combine with Harry Sloan’s Soaring Eagle Acquisition Corp. and leap into the public markets.

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FDA un­veils six ICH guide­lines ahead of meet­ing with Health Cana­da

A sign that the FDA’s non-Covid-related processes are beginning to normalize: The release of six guidelines from the International Council of Harmonisation.

Years in development, the ICH documents offer an international perspective on drug development, with these latest guidelines covering everything from recommendations to support the classification of drug substances, featured in the M9 guidance, to standards for nonclinical safety studies for pediatric medicines in the S11 guideline.

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Sanofi, Glax­o­SmithK­line, Boehringer ac­cused of play­ing games, de­stroy­ing emails re­lat­ed to law­suit over con­t­a­m­i­nat­ed Zan­tac

A recent court filing raises new questions about how major pharma companies like Sanofi, GlaxoSmithKline, and Boehringer Ingelheim have dealt with a lawsuit related to recalls of certain over-the-counter heartburn drugs due to the presence of a potentially cancer-causing substance found in them.

More than 70,000 people who took Sanofi’s Zantac and other heartburn drugs containing ranitidine, which have been recalled over the past two years, have sued the manufacturers, including generic drugmakers, and other retailers and distributors as part of a consolidated suit before US District Court Judge Robin Rosenberg in Florida.

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Al Sandrock, Biogen R&D chief (Biogen via YouTube)

UP­DAT­ED: Bio­gen push­es in a fresh stack of chips and starts prep­ping a glob­al R&D game plan af­ter watch­ing the cards turn on ear­ly throm­bolyt­ic da­ta

After patiently steering through a decade-long journey for its early-stage clinical work, a small Tokyo biotech has clinched a deal to out-license its lead thrombolytic agent to US heavyweight Biogen — which sees a potentially game-changing impact on the clot-busting field after taking a careful look at some upbeat Phase IIa data.

Three years after Biogen anted up $4 million to gain an option on the drug from TMS, the big US biotech is making a small bet to beef up its stroke portfolio. The BD team inked a deal to go ahead and grab rights to the drug for $18 million, with another $335 million in milestone cash on the table for a successful outcome.

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Chris Garabedian (Xontogeny)

Per­cep­tive Ad­vi­sors, Xon­toge­ny bring the band back and then some with a $515M sec­ond fund sniff­ing out lead com­pounds

When Perceptive Advisors and startup accelerator Xontogeny initially teamed up on an early-stage VC round in 2019, the partners hoped to prove their investments could be a force multiplier for early-stage companies. Now, with that proof of concept behind them, the pair have closed a second VC round worth more than double the money.

Dubbed PXV Fund II and headed by Xontogeny CEO and former Sarepta head Chris Garabedian, the $515 million fund will target 10 to 12 early-stage preclinical companies with Series A rounds in the $20 million to $40 million range with opportunities for Series B follow-ups. The oversubscribed fund is bringing the band back with initial investors from PXVI as well as new investors that include “top-tier” asset managers, endowments, foundations, family offices, and individual investors.

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A clos­er look at the FDA’s more than 700 pan­dem­ic-re­lat­ed record re­quests to re­place on­site in­spec­tions

As the pandemic constrained the FDA’s ability to travel for onsite manufacturing inspections, the agency increasingly turned to requesting records to fill the gap, even for hundreds of US-based facilities.

FDA explains in its guidance on manufacturing inspections during the pandemic that the agency can request records (not to be confused with the FDA’s remote interactive evaluations) directly from facilities “in advance of or in lieu of” certain onsite inspections. Companies are legally required to fulfill those requests because a denial may be considered limiting an inspection, which could lead to the FDA deeming a drug made at that site to be adulterated.

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Stephen Squinto, Gennao Bio CEO (Gennao)

Alex­ion co-founder Stephen Squin­to is back in the game as CEO, this time for a small gene ther­a­py play­er

With his name already behind a rare disease success story in Alexion, Stephen Squinto was looking for a great story to drive him to jump back into the biotech game. He found that in a fledging non-viral gene therapy company, and now he’s got a few backers on board as well.

On Tuesday, Gennao Bio launched with a $40 million Series A co-led by OrbiMed and Logos Capital with participation by Surveyor Capital. The biotech, which is looking to use its cell-penetrating antibody platform to deliver nucleic acid “payloads” during into the nucleus, had to rush for its initial series — and had a name change along the way.

Alvotech takes Ab­b­Vie to court over al­leged patent 'mine­field' sur­round­ing megablock­buster Hu­mi­ra

AbbVie has so far been successful in shooing away competition to its megablockbuster Humira, deploying a number of patents and settlements to keep biosimilars off the US market until 2023. But one Icelandic drugmaker doesn’t want to wait — and on Tuesday, it filed a lawsuit challenging what it called a patent “minefield.”

Alvotech has accused AbbVie of trying to “overwhelm” and “intimidate” it with “an outrageous number of patents of dubious validity,” according to court documents. The company is currently seeking approval for its Humira copycat AVT02, which AbbVie says would infringe upon 62 patents.