Bris­tol-My­ers las­sos the next big thing in I/O, grabs '214 rights in a record $3.6B deal with Nek­tar

Af­ter fig­ur­ing for days in a swirling mix of ru­mors about a pos­si­ble buy­out, Nek­tar Ther­a­peu­tics $NK­TR is putting an end to the buzz with a record, multi­bil­lion-dol­lar part­ner­ship deal with Bris­tol-My­ers Squibb for a mi­nor­i­ty share of its ear­ly-stage im­muno-on­col­o­gy drug NK­TR-214.

Look­ing for a ma­jor new com­mer­cial op­por­tu­ni­ty to fol­low up on its two big I/O lead­ers — Op­di­vo and Yer­voy — Bris­tol-My­ers has forged a broad deal that will give the big biotech an ex­clu­sive de­vel­op­ment pe­ri­od to pur­sue a broad new com­bo de­vel­op­ment pro­gram cov­er­ing 20 in­di­ca­tions in­volv­ing 9 tu­mors, match­ing ‘214 with Op­di­vo and Yer­voy.

Stephen Dober­stein

Bris­tol-My­ers $BMY is pay­ing Nek­tar $1.85 bil­lion in cash — in­clud­ing $850 mil­lion for an eq­ui­ty stake — in ex­change for a 35% rev­enue split on ‘214. There’s an­oth­er $1.78 bil­lion in mile­stones, of which $1.43 bil­lion is for near-term de­vel­op­ment and reg­u­la­to­ry mile­stones. That brings the to­tal at stake to $3.63 bil­lion.

That’s a new record for the deal­mak­ing charts, with num­bers that clear­ly in­di­cate that Bris­tol-My­ers — al­ready part­nered with Nek­tar on one small Op­di­vo pact — was not the on­ly in­ter­est­ed part­ner to hunt rights for this drug.

The deal gives Bris­tol-My­ers a pe­ri­od of ex­clu­siv­i­ty on these in­di­ca­tions and tu­mors that ex­tends to a com­mer­cial launch or sev­er­al years af­ter the ef­fec­tive date of the deal. And while the com­pa­ny has 14 months to get them un­der­way, the first tri­als are al­ready be­ing ramped up with a shot at reg­is­tra­tional da­ta that could start rolling in in about 18 to 24 months, ac­cord­ing to the Nek­tar team.

They’re plan­ning an R&D jug­ger­naut, one that will re­quire 15,000 pa­tients and a deep-pock­et play­er like Bris­tol-My­ers, which is all in on I/O as Mer­ck and ri­vals look to over­come their fron­trun­ner sta­tus.

“For years we’ve known how im­por­tant that path­way was but no one was able to safe­ly ac­cess that,” says Stephen Dober­stein, head of R&D for Nek­tar. “This was a sin­gu­lar achieve­ment, a re­al tour de force of pro­tein en­gi­neer­ing.”

And per­haps most im­por­tant­ly for Bris­tol-My­ers and Nek­tar, it’s an achieve­ment Dober­stein and oth­ers be­lieve will not be eas­i­ly mim­ic­ked by any­one else look­ing to achieve the same re­sult.

“There’s a re­al­ly spe­cial syn­er­gy be­tween NK­TR-214 and the way it ba­si­cal­ly changes the im­mune sys­tem and how that syn­er­gizes with the mech­a­nism of ac­tion of Op­di­vo,” adds Jonathan Za­levsky, Nek­tar’s chief sci­en­tif­ic of­fi­cer.

Saurabh Sa­ha

“We now have three ther­a­pies in im­muno-on­col­o­gy with val­i­dat­ed mech­a­nisms in IO which have shown clin­i­cal ben­e­fit,” says Saurabh Sa­ha, se­nior vice pres­i­dent and glob­al head of trans­la­tion­al med­i­cine at Bris­tol-My­ers: PD-1 (Op­di­vo), CT­LA-4 (Yer­voy) and now ‘214. “The T cell is the war­head against can­cer cells,” he adds. And sci­en­tists in both groups are ea­ger to con­tin­ue a broad pro­gram that doesn’t just spur a CD4/CD8 T cell at­tack on the can­cer cells, but al­so rais­es the lev­el of PD-L1 ex­pres­sion on T cells, get­ting them to reach more pa­tients more ef­fec­tive­ly.

Bris­tol-My­ers isn’t just hand­ing over a block­buster up­front. The I/O leader is al­so pay­ing 67.5% to 78% of the clin­i­cal tri­al costs in­volved in the com­bo stud­ies. And the pact leaves Nek­tar with sole pric­ing pow­er, part of a pack­age that leans heav­i­ly in its fa­vor.

The ther­a­py — an in-house project at Nek­tar which has a unique tar­get in the IL-2 path­way — is de­signed to bind to the CD122 re­cep­tor on the sur­face of CD-8 and CD-4 pos­i­tive im­mune cells to whip up an at­tack on var­i­ous can­cers.

That pro­file fit Bris­tol-My­ers per­fect­ly when Nek­tar ear­li­er struck a not un­com­mon 50/50 deal to use their drug in com­bi­na­tion with Op­di­vo (nivolum­ab), match­ing a ther­a­py aimed at dri­ving an im­mune re­sponse with a pop­u­lar check­point block­buster that helps take the brakes off the as­sault.

Jonathan Za­levsky

But Nek­tar at­tract­ed the in­dus­try spot­light at SITC last No­vem­ber with a med­ley of ear­ly-stage da­ta points that un­der­scored ‘214’s wide-rang­ing po­ten­tial. And then Bloomberg stirred the pot a few days ago with a re­port quot­ing sources claim­ing that Nek­tar — a hot­ly buzzed about M&A tar­get — was scout­ing deals, in­clud­ing a po­ten­tial sale.

With that kind of steamy spec­u­la­tion in a hot­house en­vi­ron­ment for biotech ac­qui­si­tions, Nek­tar’s shares have more than tripled in the last 4 months. Those M&A ru­mors were ini­tial­ly damp­ened by to­day’s news of a mega-part­ner­ship in­stead of a buy­out. And dis­ap­point­ed in­vestors quick­ly drove down Nek­tar’s shares more than 3% ear­ly Wednes­day morn­ing, with the stock jump­ing in­to the green by mid-morn­ing as some up­beat as­sess­ments of the deal be­gan to cir­cu­late.

At SITC, Nek­tar’s in­ves­ti­ga­tors not­ed some high­lights on ‘214, in­clud­ing:

•In treat­ment-naïve first-line pa­tients with stage IV melanoma, re­searchers tracked re­spons­es in 7 of 11 pa­tients (63%), with 2 com­plete re­spons­es — no vis­i­ble signs of the dis­ease — and 5 par­tial re­spons­es. Not all of these num­bers are pre­cise. It’s im­por­tant to note though that one of the CRs and one of the PRs were un­con­firmed — em­pha­siz­ing just how ear­ly these re­sults were.

•Among 13 kid­ney can­cer pa­tients with one or more base­line scans, re­spons­es were ob­served in 6 (46%), with 1 com­plete re­sponse and 5 par­tials.

•For a small group of 4 pa­tients with ad­vanced PD-L1/neg­a­tive non-small cell lung can­cer, the in­ves­ti­ga­tors tracked a re­sponse in 3 (75%), with 1 com­plete and 2 par­tials.

“Sin­gle-agent nivolum­ab is known for all these in­di­ca­tions, with a 34% re­sponse for melanoma,” Mary Tagli­a­fer­ri, a top re­searcher at Nek­tar, told me last No­vem­ber. A com­bi­na­tion could prove to be sig­nif­i­cant­ly bet­ter.

That is par­tic­u­lar­ly im­por­tant for Bris­tol-My­ers, which earned $5 bil­lion from Op­di­vo sales last year. While on track to be­come a megablock­buster, new PD-1/L1 check­points are com­ing along that threat­en to over­whelm and com­modi­tize the first bunch of pi­o­neers, of­ten with lit­tle clear da­ta to dis­tin­guish one from an­oth­er. That leaves the fron­trun­ners look­ing for new and bet­ter ways to dis­tin­guish their drugs with com­bi­na­tions in­volv­ing ear­ly-stage ef­forts like this.

For Bris­tol-My­ers, the Nek­tar pro­gram of­fers a clear path to main­tain­ing a lead­er­ship role in I/O.

Ham­mer­ing away at these mech­a­nisms, the bio­mark­ers in­volved and the way these com­bi­na­tions work, says Sa­ha, is cru­cial to the longterm suc­cess of these drugs for pa­tients.

Adds Sa­ha: “This is the on­ly way we’re go­ing to be able to con­quer can­cer.”

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 $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday 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 on his plans to surgically dissect and reassemble the portfoloio, 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.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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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.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?

Sanofi’s big week in­cludes a promis­ing PhI­II for an or­phan dis­ease drug, with plans for a pitch to the FDA

The biopharma R&D food chain is paying off with a plan at Sanofi to pitch regulators on a new drug for an orphan disease called cold agglutinin disease.

The pharma giant ushered out a statement Tuesday morning — after it spelled out plans to radically restructure the company, abandoning cardio and diabetes research altogether — saying that their C1s inhibitor sutimlimab had cleared the pivotal study.