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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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Federico Mingozzi (Spark)

Spark touts an­i­mal da­ta for a so­lu­tion to AAV gene ther­a­py's an­ti­body prob­lem

Among all the limitations of using an adeno-associated virus as a vector to deliver a gene — still the most established modality in gene therapy given years of trial and error and finally success — the presence of neutralizing antibodies, whether pre-existing or induced, looms large.

“When I think about the immune responses in AAV, I try to sort of layer them,” Federico Mingozzi, the CSO at Spark Therapeutics, told Endpoints News. “The antibody is the first layer. It’s the first block that you find when you’re trying to do gene transfer.”

Jean-Jacques Bienaimé, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Iterum's fu­ture looks un­cer­tain, af­ter lead an­tibi­ot­ic fails con­sec­u­tive piv­otal stud­ies

While the market for antibiotics remains in tatters — unlike many of its bankrupt (or at the brink of bankruptcy) peers — Iterum is suffering not because its antibiotic isn’t selling, but because the compound has now failed back-to-back late-stage studies.

The experimental drug, sulopenem, was designed to tackle drug-resistant infections with an outpatient focus (in addition to hospitals), to avert those reimbursement challenges that incentivize hospitals to prescribe cheaper, generic broad-spectrum antibiotics.

Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid-August.

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