CRISPR/Cas9 pi­o­neer Chad Cow­an en­lists in Mus­tang Bio’s CAR-T quest

Chad Cow­an

The tech race spawned by a block­buster scram­ble to the top of the emerg­ing CAR-T sec­tor has in­spired a tie-up be­tween one of the pi­o­neer­ing sci­en­tists in­volved with CRISPR/Cas9 gene edit­ing and an up-and-com­er can­cer drug de­vel­op­er that is work­ing on a game plan to over­take the lead­ers — which are way out front right now.

The sci­en­tist is Chad Cow­an, a re­searcher at the Har­vard Stem Cell In­sti­tute who al­lied ear­ly on with the CRISPR/Cas9 team that launched CRISPR Ther­a­peu­tics un­der gene edit­ing star Em­manuelle Char­p­en­tier.

In a new deal an­nounced this morn­ing, Cow­an has signed on to han­dle the pre­clin­i­cal work for new drugs slat­ed to join the pipeline at a well-fi­nanced Mus­tang Bio $MBIO. And Mus­tang al­so in-li­censed CRISPR/Cas9 tech from Har­vard to use on off-the-shelf CAR-T drugs as No­var­tis and Gilead/Kite roll out the first per­son­al­ized drugs in the field. Cow­an will do the re­search at Beth Is­rael Dea­coness Med­ical Cen­ter.

Man­ny Litch­man

Mus­tang CEO Man­ny Litch­man told me re­cent­ly that the next gen­er­a­tion of CAR-T drugs to hit the mar­ket can be both more ef­fec­tive and cheap­er when it comes to treat­ing blood can­cers and sol­id tu­mors, a key part of the off-the-shelf ef­fort that looks to sup­plant the ex­pen­sive land­mark ther­a­pies made from each pa­tient’s cells.

“Look in the black box of man­u­fac­tur­ing,” Litch­man told me, and you can see “dozens of pa­ra­me­ters that can vary.”

En­list­ing Cow­an, a sci­en­tif­ic founder at CRISPR Ther­a­peu­tics, is a big plus at this ear­ly stage of the game for Mus­tang.

Litch­man is the for­mer head of on­col­o­gy BD at No­var­tis, where he was present at the cre­ation of the Penn/No­var­tis deal that set the phar­ma gi­ant down the path to­ward an his­toric CAR-T ap­proval. He was pro­gram head of CTL019 for awhile. And he’s fol­low­ing in much the same path that the pi­o­neers — along with Kite and Juno — did, let­ting the sci­en­tif­ic founders do the ear­ly-stage re­search work that will be used to set up the fast-paced piv­otal de­vel­op­ment pro­grams to come.

In Mus­tang’s case, that al­so in­volves Stephen For­man’s lab­o­ra­to­ry at City of Hope Na­tion­al Med­ical Cen­ter and top re­searchers at the Fred Hutchin­son Can­cer Re­search Cen­ter, where Oliv­er Press and Bri­an Till have been build­ing a T cell ther­a­py which ex­press­es a CD20-spe­cif­ic chimeric anti­gen re­cep­tor. That work has ex­pand­ed Mus­tang’s pipeline to 6 clin­i­cal and pre­clin­i­cal ef­forts.

Says Litch­man:

CRISPR/Cas9’s demon­strat­ed pre­ci­sion may en­able us to more ef­fec­tive­ly and ac­cu­rate­ly de­liv­er our CAR T ther­a­pies and to en­hance the tu­mor killing abil­i­ty and per­sis­tence of the CAR T cells in the pa­tient’s body, which could lead to safer and more po­tent treat­ments. We look for­ward to work­ing with Dr. Cow­an and his team on this ex­cit­ing col­lab­o­ra­tion to ac­cel­er­ate the de­vel­op­ment of the next gen­er­a­tion of CAR T ther­a­pies.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,200+ biopharma pros reading Endpoints daily — and it's free.

Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,200+ biopharma pros reading Endpoints daily — and it's free.

Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.

The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.

FDA lifts hold on Abeon­a's but­ter­fly dis­ease ther­a­py, paving way for piv­otal study

It’s been a difficult few years for gene and cell therapy startup Abeona Therapeutics. Its newly crowned chief Carsten Thiel was forced out last year following accusations of unspecified “personal misconduct,” and this September, the FDA imposed a clinical hold on its therapy for a form of “butterfly” disease. But things are beginning to perk up. On Monday, the company said the regulator had lifted its hold and the experimental therapy is now set to be evaluated in a late-stage study.

Roche faces an­oth­er de­lay in strug­gle to nav­i­gate Spark deal past reg­u­la­tors — but this one is very short

Roche today issued the latest in a long string of delays of its $4.3 billion buyout of Philadelphia-based Spark Therapeutics. The delay comes as little surprise — it is their 10th in as many months — as their most recent delay was scheduled to expire before a key regulatory deadline.

But it is notable for its length: 6 days.

Previous extensions had moved the goalposts by about 3 weeks to a month, with the latest on November 22 expiring tomorrow. The new delay sets a deadline for next Monday, December 16, the same day by which the UK Competition and Markets Authority has to give its initial ruling on the deal. And they already reportedly have lined up an OK from the FTC staff – although that’s only one level of a multi-step process.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 67,200+ biopharma pros reading Endpoints daily — and it's free.

KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

Merck’s 2017 bet on KalVista Pharmaceuticals may have soured, after the UK/US-based biotech’s lead drug failed a mid-stage study in patients with diabetic macular edema (DME).

Two doses of the intravitreal injection, KVD001, were tested against a placebo in a 129-patient trial. Patients who continued to experience significant inflammation and diminished visual acuity, despite anti-VEGF therapy, were recruited to the trial. Typically patients with DME — the most frequent cause of vision loss related to diabetes — are treated with anti-VEGF therapies such as Regeneron’s flagship Eylea or Roche’s Avastin and Lucentis.

UP­DAT­ED: Ob­sE­va makes case for best-in-class hor­mone sup­pres­sive ther­a­py in pos­i­tive uter­ine fi­broid study

About a month after the Swiss biotech disclosed a failed late-stage study in its IVF program, ObsEva on Monday unveiled positive pivotal data on its experimental treatment for heavy menstrual bleeding triggered by uterine fibroids.

ObsEva in-licensed the drug, linzagolix, from Japan’s Kissei Pharmaceutical in 2015. Two doses of the drug (100 mg and 200 mg) were tested against a placebo in the 535-patient Phase III study, dubbed PRIMROSE 2, in patients who were both on and off hormonal add-back therapy (ABT).

Samit Hirawat. Bristol-Myers Squibb

Bris­tol-My­ers is mak­ing a bee-line to the FDA with pos­i­tive liso-cel da­ta — but is it too late in the CAR-T game?

Bristol-Myers Squibb came to ASH this past weekend with a variety of messages on the new cancer drugs they had acquired in the big Celgene buyout, including liso-cel, the lead CAR-T program picked up in the $9 billion Juno acquisition. And one of the most important was that they had the pivotal efficacy and safety data needed to snag an approval from the FDA next year, with the BLA on track for a filing this month.