NGM Bio un­veils pos­i­tive PhII NASH re­sults to some unim­pressed in­vestors

NGM Bio got up ear­ly this morn­ing in South San Fran­cis­co ready to pro­claim an in­ter­im win of its lead NASH drug, aldafer­min, in the fourth and fi­nal leg of a lengthy Phase II pro­gram. The re­sults of com­par­ing drug to place­bo were pos­i­tive, the com­pa­ny said, set­ting up some ex­pec­ta­tions for a fi­nal read­out in ear­ly 2020.

But in­vestors weren’t quite buy­ing it. The stock $NGM has slid around 18%.

So what’s wrong?

It may be help­ful to re­mem­ber, first of all, that NASH is a block­buster sized mar­ket that’s en­ticed mul­ti­ple biotech play­ers from In­ter­cept and Madri­gal to Gen­fit and Viking, and any signs of ear­ly hope or doom — es­pe­cial­ly as com­pared to oth­er ri­vals, de­spite the dan­gers of cross-tri­al com­par­isons — could cast dif­fer­ent lights on the da­ta.

David Wood­house

With that, here’s what NGM has re­port­ed about the 38-pa­tient tri­al: A 24-week treat­ment with once-dai­ly 1 mg aldafer­min, or NGM282, met the pri­ma­ry end­point re­gard­ing changes in ab­solute liv­er fat con­tent achiev­ing a drop of 7.9% ver­sus 2.0% on place­bo as mea­sured by MRI-es­ti­mat­ed pro­ton den­si­ty fat frac­tion (p<0.05).The change in rel­a­tive LFC came in at a dra­mat­ic -39.6% over -5.9% in the place­bo arm.

The com­pa­ny al­so not­ed that 72% of the aldafer­min group achieved 5% or more ab­solute re­duc­tion in LFC, com­pared to 17% of those tak­ing place­bo.

That’s in­deed pos­i­tive, and rough­ly in line with the Phase II da­ta Madri­gal pre­vi­ous­ly re­port­ed for their MGL-3196 (-36.3% rel­a­tive re­duc­tion on drug vs 9.6% on place­bo). But it fell short of the 57-60% me­di­an rel­a­tive change and 77-91% re­spon­der rate that Viking post­ed last year, spark­ing a surge in share price.

Hsiao Lieu

Some­thing else might al­so be dri­ving the con­cern: a spike in cho­les­terol lev­els (LDL-C to be spe­cif­ic) at week 2 of treat­ment. While NGM con­tends it’s noth­ing they didn’t know from pre­vi­ous Phase II co­horts, that it’s a di­rect ef­fect of FGF19’s in­hi­bi­tion of the clas­si­cal bile acid syn­the­sis path­way and that it was quick­ly re­solved by statin treat­ment, a mean in­crease of 47.6 mg/dL in LDL-C rel­a­tive to a 103.5 mg/dL base­line could be alarm­ing to a pa­tient pop­u­la­tion that al­ready has height­ened car­dio­vas­cu­lar risks.

CEO David Wood­house main­tained they are pleased with the in­ter­im find­ings, part of an ex­pan­sive clin­i­cal cam­paign fund­ed by a $200 mil­lion-plus part­ner­ship with Mer­ck and a $107 mil­lion IPO a few months ago.

“Aldafer­min con­tin­ues to be dif­fer­en­ti­at­ed with what we be­lieve is an in­dus­try-lead­ing pro­file as a monother­a­py for the po­ten­tial treat­ment of NASH, as few drugs in de­vel­op­ment for this dis­ease have shown mean­ing­ful meta­bol­ic, an­ti-in­flam­ma­to­ry and an­ti-fi­brot­ic ac­tiv­i­ty,” CMO Hsiao Lieu added in a state­ment. “Through­out our Phase 2 pro­gram, we’ve seen a re­la­tion­ship be­tween aldafer­min’s im­pact on bio­mark­ers of dis­ease and sub­se­quent his­tol­ogy re­sults. To that end, we look for­ward to the biop­sy da­ta read­out for Co­hort 4, which will fur­ther in­form plan­ning ac­tiv­i­ties for our Phase 3 study.”

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.

“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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US biosim­i­lar launch­es about to turn a cor­ner

The US biosimilar industry has lingered in the shadow of the European market since the US pathway for approvals was initiated in 2009.

Ten years later (or less than five years since the first FDA approval of a biosimilar), and just 42% (11 out of 26) of FDA-approved biosimilars have launched. But in the next three months (see chart below), a clutch of new biosimilars will hit the market, including new ones in oncology, hinting at a wave of uptake.

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. File photo

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.

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