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)

Alice Shaw, Lung Cancer Foundation of America

Top ALK ex­pert and can­cer drug re­searcher Al­ice Shaw bids adieu to acad­e­mia, hel­lo to No­var­tis

Jay Bradner has recruited a marquee oncology drug researcher into the ranks of the Novartis Institutes for BioMedical Research. Alice Shaw is jumping from prestigious posts intertwined through Mass General, Harvard and Dana-Farber to take the lead of NIBR’s translational clinical oncology group.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Flu Virus (Source: CDC)

FDA ex­pands Xofluza ap­proval as Roche strug­gles to catch loom­ing flu mar­ket

As a potentially powerful flu season looms, so does a big test for Roche and its new flu drug, Xofluza. The Swiss giant just got a small boost in advance of that test as the FDA expanded Xofluza’s indication to include patients at high risk of developing flu-related complications.

Xofluza (baloxavir marboxil) was approved last October in the US, the first landmark flu drug approval in 20 years and a much-needed green light for a company that had watched its leading flu drug Tamiflu get eaten alive by generics. Like its predecessor, the pill offered a reduction in flu symptoms but not a cure.

EMA backs sev­en ther­a­pies, in­clud­ing Mer­ck­'s Ebo­la vac­cine

The first-ever Ebola vaccine is on the precipice of approval after the European Medicine’s Agency (EMA) backed the Merck product in this week’s roster of recommendations.

The drugmaker $MRK began developing the vaccine, christened Ervebo, during the West African outbreak that occurred between 2014 and 2016, killing more than 11,000.

The current outbreak in the Democratic Republic of Congo (DRC) has shown case fatality rates of approximately 67%, the agency estimated. Earlier this year, the WHO declared the outbreak — which so far has infected more than 3,000 people — a public health emergency of international concern.

Ronald Herb­st fol­lows Med­Im­mune ex­o­dus to Pyx­is CSO post; Jeff God­dard to suc­ceed CEO of AIT Bio­science

→ The outflow of top execs from MedImmune continues to fill the leadership ranks of smaller biotechs. The latest to take off is Ronald Herbst, the head of oncology research, who’s assuming the CSO post at Pyxis Oncology.  

Herbst was part of the old MedImmune organization AstraZeneca CEO Pascal Soriot restructured earlier this year, reorganizing the company and eliminating the storied subsidiary as a separate organization.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.

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