Af­ter Ro­va-T bust, Ab­b­Vie plans new sol­id tu­mor as­sault, li­cens­ing next-gen CAR-T tech from Cal­i­br

Af­ter its dis­ap­point­ing Ro­va-T flop last month, Ab­b­Vie is shoring up its sol­id tu­mor bets with a fresh­ly inked re­search deal that should elic­it new strate­gies for tu­mor at­tack. This time, Ab­b­Vie is hop­ing to use po­ten­tial­ly safer, next-gen CAR-Ts that have been cook­ing in the labs of a San Diego re­search in­sti­tute for the past few years.

The phar­ma gi­ant is buy­ing an ex­clu­sive four-year li­cense to tech de­vel­oped at the Cal­i­for­nia In­sti­tute for Bio­med­ical Re­search — bet­ter known as Cal­i­br — to in­ter­ro­gate some of its own can­cer tar­gets, in­clud­ing sol­id tu­mors. Cal­i­br is bring­ing to the ta­ble a plat­form based on a “switch­able” CAR-T cell. I talked with Travis Young, Cal­i­br’s di­rec­tor of pro­tein sci­ences, last Fri­day to find out what that ac­tu­al­ly means. Young tells me it’s about re­duc­ing tox­i­c­i­ty and get­ting a more durable re­sponse from CAR-Ts, which are known to cause safe­ty is­sues.

Travis Young

“CAR-Ts are po­tent, and they can cause tox­i­c­i­ty in the clin­ic,” Young said. “This is about tun­abil­i­ty. We’re call­ing this a switch, but it’s re­al­ly more like a light dim­mer. We want to tune ac­tiv­i­ty and elim­i­nate can­cer cells with­out caus­ing that tox­i­c­i­ty.”

They do that by us­ing an­ti­body-based switch mol­e­cules to con­trol the ac­ti­va­tion and anti­gen speci­fici­ty of CAR-T cells. Young said it’s im­por­tant to note this ap­proach dif­fers from the in­creas­ing­ly pop­u­lar “kill switch” tac­tic, which has been tout­ed as a way to make CAR-Ts safer.

“Rather than killing off the cells in the case of an ad­verse event, this is more proac­tive,” Young said.

The part­ner­ship has both Cal­i­br and Ab­b­Vie do­ing pre­clin­i­cal work, while Ab­b­Vie alone will be re­spon­si­ble for clin­i­cal de­vel­op­ment and com­mer­cial­iza­tion. Cal­i­br, of course, will get mile­stones and roy­al­ties if cer­tain tar­gets are met, but the duo was tight-lipped on fi­nan­cial de­tails of the deal.

The main fo­cus of the col­lab­o­ra­tion will be Ab­b­Vie’s can­cer tar­gets, but Cal­i­br is al­so work­ing on a liq­uid tu­mor pro­gram of its own that might come in­to play down the road. Young said the yet-named pro­gram is a CD19 tar­get­ed switch­able CAR-T ther­a­py, which the in­sti­tute plans to take in­to Phase I for lym­phoma in 2019. As part of the deal, Ab­b­Vie has the op­tion to li­cense that pro­gram (and oth­ers at Cal­i­br). That op­tion ex­pires in four years, how­ev­er.

You didn’t used to see re­search in­sti­tutes mov­ing pro­grams in­to the clin­ic, but its be­com­ing an in­creas­ing­ly pop­u­lar strat­e­gy for non-prof­it re­search cen­ters and uni­ver­si­ties. The idea is that it helps them cre­ate a source of rev­enue in­de­pen­dent from the fed­er­al gov­ern­ment and phil­an­thropy.

Matt Trem­blay

“We’re at the head of this new theme to take your as­sets — your IP orig­i­nat­ed at the in­sti­tute — and take them for­ward in­to clin­i­cal de­vel­op­ment,” Cal­i­br and Scripps Re­search COO Matt Trem­blay told me. 

This is some­thing I dis­cussed with Dave Gib­bons, who han­dles com­mer­cial li­cens­ing at the biotech-heavy cam­pus at UC San Diego, last year. By de-risk­ing pro­grams and de­vel­op­ing up to IND, “you’d have a tremen­dous­ly more valu­able as­set for li­cens­ing,” Gib­bons said.

Ab­b­Vie’s on­col­o­gy and clin­i­cal de­vel­op­ment ex­per­tise will be a boon to the re­source-slim Cal­i­br, but the phar­ma gi­ant was al­so in need of this deal. The com­pa­ny dis­ap­point­ed in­vestors in March when news that its Ro­va-T pro­gram post­ed poor mid-stage re­sults for third-line non-small cell lung can­cer. That was a re­al blow, con­sid­er­ing it was hoped to be a $5 bil­lion earn­er for the com­pa­ny.

Ge­of­frey Porges at Leerink post­ed a scathing as­sess­ment of Ab­b­Vie’s sit­u­a­tion short­ly af­ter the news.

“On­col­o­gy is the key growth busi­ness seg­ment for Ab­b­Vie af­ter the loss of ex­clu­siv­i­ty for Hu­mi­ra in 2023, and to­day’s re­sults and reg­u­la­to­ry de­ci­sion call in­to ques­tion the vi­a­bil­i­ty of the com­pa­ny’s cur­rent sol­id tu­mor strat­e­gy,” he wrote.

Per­haps Cal­i­br’s tech will give their sol­id tu­mor strat­e­gy more hope.

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.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus -- chop­ping di­a­betes, car­dio and slash­ing costs in com­pa­ny-wide re­org

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy reveal tomorrow with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

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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.”

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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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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.

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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.

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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.