Es­ca­lat­ing R&D woes spur fresh M&A chat­ter for cash-rich Gilead

Gilead CSO Nor­bert Bischof­berg­er

Four years af­ter Gilead ac­quired mo­melo­tinib in its $510 mil­lion buy­out of YM Bio­Sciences, the big — and what ap­pears to be in­creas­ing­ly un­lucky — biotech was forced to re­port that the drug per­formed poor­ly in its two Phase III myelofi­bro­sis tri­als. And the fourth straight pipeline flop quick­ly spurred fresh spec­u­la­tion that Gilead will soon have to tap in­to its big cash re­serves for a ma­jor ac­qui­si­tion.

The JAK in­hibitor scored on a non-in­fe­ri­or­i­ty show­down with Jakafi (In­cyte’s rux­oli­tinib) in spleen re­duc­tion, but blew the key sec­ondary end­point of non-in­fe­ri­or­i­ty for the to­tal symp­tom score that was used to mea­sure the drugs. And it failed a sep­a­rate Phase III su­pe­ri­or­i­ty com­par­i­son against best avail­able treat­ment at week 24.

It all adds up to a fresh pipeline mess at Gilead, which saw its shares $GILD de­cline 1.25% Thurs­day morn­ing, shav­ing off more than a bil­lion dol­lars of its $100 bil­lion mar­ket cap. In­cyte {IN­CY}, mean­while, saw its shares shoot up 7% on the news, as spec­u­la­tion mount­ed that Gilead may now be pressed hard to make a bid for the com­pa­ny.

By the num­bers: mo­melo­tinib: 6.7%; BAT: 5.8%; 95 per­cent CI: -8.9% to +10.2%; p=0.90. And be­cause it didn’t suc­ceed on su­pe­ri­or­i­ty on the pri­ma­ry score, in­ves­ti­ga­tors didn’t run the num­bers on sec­ondary end­points.

That’s not what the com­pa­ny want­ed or need­ed to see. But af­ter high­light­ing some pos­i­tive trends from the two late-stage stud­ies, Gilead plans to see if reg­u­la­tors are feel­ing gen­er­ous about its prospects.

“The re­sults from both the SIM­PLI­FY-1 and SIM­PLI­FY-2 stud­ies in­di­cate that mo­melo­tinib pro­vides some treat­ment ben­e­fit, in­clud­ing ben­e­fit on ane­mia-re­lat­ed end­points,” said Nor­bert Bischof­berg­er, PhD, Ex­ec­u­tive Vice Pres­i­dent of Re­search and De­vel­op­ment and Chief Sci­en­tif­ic Of­fi­cer. “We plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps.”

The set­back on mo­melo­tinib comes near the end of what has turned in­to a grim year for Gilead. A re­cent run­down of its work on the NASH drug GS-4997 sparked con­sid­er­able skep­ti­cism from an­a­lysts, who want to see much more com­pelling num­bers be­fore they buy in.

Gilead re­cent­ly wrote off sim­tuzum­ab, along with the late-stage drug GS-5745 for ul­cer­a­tive col­i­tis and Crohn’s. And it’s top car­dio prospect — ele­clazine (GS-6615) — failed a late-stage study as well, sig­nif­i­cant­ly re­duc­ing its chances of be­com­ing the big new drug that Gilead needs as hep C wanes.

As the R&D hole keeps get­ting deep­er, some won­der if Gilead will be forced back to the deal ta­ble to buy some­thing big. Its hep C fran­chise may be wan­ing, but it cre­at­ed a huge wind­fall in cash re­serves. And Leerink’s Ge­of­frey Porges be­lieves that this lat­est black cloud comes with a sil­ver lin­ing, adding In­cyte to the list of big takeover tar­gets. On Thurs­day morn­ing he not­ed:

GILD in­di­cat­ed that they plan to dis­cuss these re­sults with reg­u­la­to­ry au­thor­i­ties to de­ter­mine the next steps, but it seems like­ly that mo­melo­tinib, which has been in de­vel­op­ment since 2009, will be writ­ten off, end­ing the po­ten­tial of yet an­oth­er small “bolt on” ac­qui­si­tion. One con­se­quence of this dis­ap­point­ment, how­ev­er, is that it does re­store IN­CY to the list of fea­si­ble can­di­dates for ac­qui­si­tion by Gilead, since they would no longer face the oblig­a­tion to di­vest one of the over­lap­ping JAK pro­grams.

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
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.

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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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Jake Van Naarden, Josh Bilenker, Nisha Nanda (Credit: Loxo, Aisling Capital)

Josh Bilenker and his Loxo crew are tak­ing the reins on on­col­o­gy R&D at Eli Lil­ly, culling the weak and map­ping a new path

Josh Bilenker, Jake Van Naarden and Nisha Nanda came out of Eli Lilly’s $8 billion Loxo Oncology buyout with a bundle of cash and plenty of choices on what they could do next. Start a new company, go public. Live on the beach in 5-star luxury. Contemplate the stars — in their own observatory.

So what are they doing?

They formed a new executive team that is taking over the management of Eli Lilly’s hundreds-strong oncology R&D group — essentially using Loxo as a base for a bold new experiment in Big Pharma R&D in an attempt to create a true biotech environment with the deep pockets of a top-15 industry player. They’ve recruited David Hyman from Memorial Sloan Kettering to join the team as chief medical officer. And the mandate includes culling out the oncology pipeline, highlighting their star prospects and going after new programs wherever they can find the best prospects.

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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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