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.”

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News writer Nicole DeFeudis has posted a snapshot of all the companies, universities and hospital-based groups now racing through the clinic, ranking them according to their place in the pipeline as well as the latest remarks available on timelines. And we’ll keep this lineup updated right through the end of the year, as the checkered flags start to fall, possibly as early as October.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.

Bayer's Marianne De Backer with Endpoints founder John Carroll, Endpoints@JPM20 (Jeff Rumans for Endpoints News)

UP­DAT­ED: Hunt­ing a block­buster, Bay­er forges an $875M-plus M&A deal to ac­quire women’s health biotech

Bayer has dropped $425 million in cash on its latest women’s health bet, bringing a UK biotech and its non-hormonal menopause treatment into the fold.

KaNDy Therapeutics had its roots in GlaxoSmithKline, which spun out several neuroscience drugs into NeRRe Therapeutics back in 2012. Five years later the team created a new biotech to focus solely on NT-814 — which they considered “one of the few true innovations in women’s health in more than two decades.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.

Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Eisai moves to 200 Metro Blvd. by late 2021 (ON3)

Ei­sai is cre­at­ing a new US cor­po­rate, R&D HQ in Roche’s old Nut­ley, NJ cam­pus

Eight years after Roche pulled up stakes from Nutley, NJ in a major R&D reorganization, Japan’s Eisai is moving its US corporate and research hub into their old campus.

Now the ON3 property, Eisai — a longtime Biogen partner focused on neurodegenerative disorders like Alzheimer’s — will bring together a staff of up to 1,200 employees. And execs are pitching the move to the New Jersey campus as a cultural game-changer.

DFC CEO Adam Boehler and Kodak CEO Jim Continenza (Kodak)

Covid-19 roundup: Cure­Vac beefs up its uni­corn IPO dreams as bil­lion­aire own­er takes this Covid-19 mR­NA play­er on a forced march to Nas­daq; Ko­dak's $765M deal is put on hold

When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.

Ugur Sahin, BioNTech CEO

Covid-19 roundup: Pfiz­er-backed BioN­Tech plans to seek FDA OK for a new vac­cine 'as ear­ly as' Oc­to­ber — ahead of the elec­tion

BioNTech execs say they’re on track to get their late-stage data on a Covid-19 vaccine — partnered with Pfizer — into the hands of regulators as early as October.

In their Q2 release Tuesday morning, the biotech reported that investigators could have late-stage data as early as October, and they won’t be wasting any time in hustling that over to the FDA.

“I am incredibly proud of our team, who has worked tirelessly to initiate our BNT162 Phase 2b/3 trial in record time and put us in a position to seek regulatory review as early as October of this year, if our trials are successful,” said Ugur Sahin, BioNTech’s CEO and co-founder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.

Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.

Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,200+ biopharma pros reading Endpoints daily — and it's free.