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.

Deborah Dunsire. Lundbeck

UP­DAT­ED: Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

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Scott Gottlieb, AP Images

Scott Got­tlieb has a new board po­si­tion to add to the re­sume — and this one is fo­cused on a fa­vorite sub­ject

Scott Gottlieb has another position to add to his lengthy roster of boards and advisory roles in the wake of his departure from the helm of the FDA.

He’ll be joining the advisory board of FasterCures, a think tank which former junk bond king Michael Milken set up to help drive more drugs to the market, looking to accelerate drug R&D. That’s a subject close to the heart of Gottlieb, who blazed a trail at the FDA focused on hustling up the process. That helped endear him to the industry, making him one of the most popular commissioners in FDA history.

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Karyopharm lines up $150 mil­lion cash in­jec­tion to back con­tro­ver­sial drug launch

Karyopharm has entered into a royalty agreement worth up to $150 million to back the launch of their multiple myeloma drug — recently approved by the FDA over the objections of a majority of the agency’s outside experts.

The deal with HealthCare Royalty Partners, worth $75 million now and $75 million once certain regulatory and commercial milestones have been reached, will fund the commercialization of Karyopharm’s oral SINE compound Xpovio (selinexor) for patients with multiple myeloma who have already had at least four prior therapies. The money will help Karyopharm as it markets its newly approved drug and pushes through clinical trials testing the drug on refractory multiple myeloma patients with one to three therapies and patients with treatment-resistant diffuse large B-cell lymphoma. It will give Karyopharm a cushion through mid-2021.

Af­ter a run of CT­LA-4 com­bo fail­ures, sci­en­tists spot­light a way to make it work — in se­lect pa­tients

CTLA-4/PD-(L)1 combinations have been one of the El Dorados of oncology, its promise forever behind that next hill but apparently unattainable after a series of pivotal clinical failures. But researchers at New York’s Memorial Sloan Kettering Cancer Center and the Technical University of Munich think they may know how to fix what’s wrong and boost the drive to next-gen cancer combos.

In a preclinical animal research program, researchers found that within a cell, checkpoints rely on a specific molecule — RNA-sensing molecule RIG-I — to work. If that sounds familiar, it’s because it has already been identified as a target for boosting immune responses and was subject to at least one Phase I/II trial. Pfizer in December allied itself with Kineta with $15 million upfront and $505 million in potential milestones to develop RIG-I immunotherapies, and three years ago Merck purchased German upstart Rigontec for $137 million upfront and over $400 million in potential milestones for the same purpose.

Pur­due Phar­ma files for bank­rupt­cy as first step in $10B opi­oid set­tle­ment

It’s settled. Purdue Pharma has filed for bankruptcy as part of a deal that would see the OxyContin maker hand over $10 billion in cash and other contributions to mitigate the opioid crisis — without acknowledging any wrongdoing in the protracted epidemic that’s resulted in hundreds of thousands of deaths.

The announcement came two weeks after news of a proposed settlement surfaced and largely confirm what’s already been reported.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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