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)

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.

Den­mark's Gen­mab hits the jack­pot with $500M+ US IPO as small­er biotechs rake in a com­bined $147M

Danish drugmaker Genmab A/S is off to the races with perhaps one of the biggest biotech public listings in decades, having reaped over $500 million on the Nasdaq, as it positions itself as a bonafide player in antibody-based cancer therapies.

The company, which has long served as J&J’s $JNJ key partner on the blockbuster multiple myeloma therapy Darzalex, has asserted it has been looking to launch its own proprietary product — one it owns at least half of — by 2025.

FDA over­rides ad­comm opin­ions a fifth of the time, study finds — but why?

For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.

A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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