Blue­bird, Cel­gene jump off to a promis­ing start in the marathon race to de­vel­op a CAR-T for mul­ti­ple myelo­ma

The clin­i­cal race to de­vel­op a rel­a­tive­ly safe BC­MA-tar­get­ing CAR-T for mul­ti­ple myelo­ma is un­der­way, and it’s start­ing with a pre­lim­i­nary Po­laroid af­ter the first few promis­ing paces out of the gate for a hand­ful of pa­tients treat­ed with bb2121 by blue­bird bio $BLUE.

The biotech, part­nered with myelo­ma pow­er­house Cel­gene $CELG, of­fered up a clear­ly pos­i­tive ear­ly snap­shot show­ing that 7 of 9 evalu­able pa­tients re­spond­ed to the ther­a­py, with two com­plete re­spons­es, one near­ly com­plete re­sponse and four par­tial re­spons­es in­di­cat­ing that more than half of their tar­get­ed pre­can­cer­ous cells had been elim­i­nat­ed. And in a field that has man­aged to raise re­peat­ed red flags on safe­ty, blue­bird was clear­ly chuffed that in­ves­ti­ga­tors so far had seen none of the dam­ag­ing side ef­fects that has plagued the CAR-T field from its ear­li­est days.

Blue­bird’s shares soared 27% on the news as in­vestors bought in to a strong ear­ly start.

Gena Wang, Jef­fries

Gena Wang at Jef­feries summed it up like this:

Ef­fi­ca­cy da­ta for bb2121 an­ti-BC­MA CART cells was re­port­ed for the first 9 re­lapsed re­frac­to­ry mul­ti­ple myelo­ma (R/R MM) pts in 3 dose co­horts. All 6 pts in co­hort 2 (15E+7 cells) and co­hort 3 (45E+7 cells) achieved re­spons­es (2 sCR and 1 VG­PR in co­hort 2 and 3 PRs in co­hort 3). The 2 sCR sus­tained with 4-6 mon fol­low-up. The ORR in the first 9 pts was 78% (7/9). All pts re­ceived a me­di­an of 6 pri­or ther­a­pies in­clud­ing au­tol­o­gous stem cell trans­plant. Longer fol­low-up would be im­por­tant to eval­u­ate du­ra­tion of re­sponse as well as pos­si­bil­i­ty of PR con­vert­ing in­to CR. We see the ini­tial da­ta as one of the best vs. oth­er BC­MA-tar­get­ing pro­grams.

With­out dose-lim­it­ing ev­i­dence of tox­i­c­i­ty, in­ves­ti­ga­tors will be able to amp up the treat­ment, look­ing for a more durable re­sponse. And that could make a big dif­fer­ence as it weighs in against the oth­er de­vel­op­ers in this race, in­clud­ing a Penn team which is al­so rolling out ad­di­tion­al da­ta soon with pre­clin­i­cal ef­forts un­der­way at Cel­lec­tis/Pfiz­er and Au­to­lus. Juno jumped in­to the race in Au­gust.

Blue­bird is us­ing the same ba­sic cell en­gi­neer­ing ap­proach as the clin­i­cal lead­ers in the field, like Kite, ex­tract­ing T cells from pa­tients and en­gi­neer­ing them to go af­ter a can­cer tar­get — in this case B-cell mat­u­ra­tion anti­gen, a pro­tein which is found on the sur­face of the tar­get­ed cells. It’s wide­ly con­sid­ered an ex­cel­lent tar­get for com­bat­ting a lethal dis­ease.

But get­ting these cells to pop­u­late and mul­ti­ply with a ther­a­peu­tic ef­fect in pa­tients has been a vex­ing, and some­times fa­tal, chal­lenge. Ear­ly on in­stances of cy­tokine re­lease syn­drome held back ear­ly ef­forts, with some — very sick — pa­tients dy­ing in the process. Ear­li­er this year Juno stunned in­vestors with the news that cere­bral ede­mas had killed four pa­tients in two stud­ies, forc­ing a very brief clin­i­cal hold that the FDA was will­ing to lift just a few days lat­er af­ter the biotech said that re­mov­ing flu­dara­bine from the pre­con­di­tion­ing reg­i­men would solve the neu­ro­tox­i­c­i­ty is­sue.

Then, af­ter treat­ing on­ly 12 more pa­tients, two more died of cere­bral ede­mas. The FDA has not tak­en ac­tion, but Juno put the lead tri­al back on vol­un­tary hold, leav­ing them in lim­bo while Kite races ahead to an ac­cel­er­at­ed fil­ing now planned for Q1 2017.

Sig­nif­i­cant­ly, blue­bird’s team is us­ing a cy/flu con­di­tion­ing reg­i­men in its mul­ti­ple myelo­ma pro­gram, once again rais­ing ques­tions about Juno’s judg­ment in restart­ing its con­tro­ver­sial study. And Baird’s

Bri­an Sko­r­ney, Baird

Bri­an Sko­r­ney added a healthy note of skep­ti­cism on Thurs­day, ob­serv­ing that the CAR-T field has been roiled aplen­ty by un­ex­pect­ed set­backs along the way. He wrote:

Af­ter a se­ries of pa­tient deaths as­so­ci­at­ed with oth­er CAR T pro­grams at Juno, which Cel­gene has an al­most 10% stake in, blue­bird’s Phase 1 re­sults are even more im­pres­sive. How­ev­er, we re­main health­ily skep­ti­cal on the CAR T space, as it re­mains to be seen whether these re­sults will hold up long term and if safe­ty is­sues arise.

The num­bers for blue­bird are small and pre­lim­i­nary, but in this field small and pre­lim­i­nary are still im­por­tant mile­stones when you’re hop­ing to ad­vance an im­por­tant new way to treat mul­ti­ple myelo­ma. Many, many more snap­shots of clin­i­cal progress lie ahead. And an­a­lysts will in­spect each one for every sign of suc­cess and fail­ure.

That on­ly hap­pens when the stakes are high.

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Daniel O'Day

No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,100+ biopharma pros reading Endpoints daily — and it's free.

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.”

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,100+ biopharma pros reading Endpoints daily — and it's free.

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.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,100+ biopharma pros reading Endpoints daily — and it's free.

H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,100+ biopharma pros reading Endpoints daily — and it's free.