MyoKar­dia steps clos­er to the launch of a ground­break­ing heart tri­al af­ter find­ing its low-dose start­ing point

MyoKar­dia $MYOK is one step clos­er to launch­ing a piv­otal tri­al for its ge­net­i­cal­ly tar­get­ed lead heart drug.

In the sec­ond part of their two-step Phase II tri­al, the South San Fran­cis­co-based biotech says it land­ed pos­i­tive da­ta for a slate of end­points with their low-dose ap­proach to ob­struc­tive hy­per­trophic car­diomy­opa­thy. That’s en­cour­ag­ing them to drop off the top and bot­tom dos­es from the full scale up and fo­cus on the 5 mg, 10 mg and 15 mg steps in the range.

But there’s a catch. The low-dose 2 mg-step-up-to-5 mg arm did hit goals for most end­points, but at that lev­el their drug mava­camten al­so failed to achieve a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in peak VO2 (ex­er­cise ca­pac­i­ty as mea­sured by an in­crease in oxy­gen con­sump­tion), which the com­pa­ny out­lined ear­li­er as the in­tend­ed pri­ma­ry end­point for their piv­otal study, dubbed EX­PLOR­ER-HCM.

In fact, that was the on­ly end­point that didn’t achieve sta­tis­ti­cal sig­nif­i­cance with a p val­ue of 0.121.

“That is the one mea­sure that did not hit sta­tis­ti­cal sig­nif­i­cance, but that is not sur­pris­ing,” MyoKar­dia CEO Tas­sos Gi­anakakos tells me. The re­searchers want­ed to find the bot­tom of an ef­fec­tive range, and they have plen­ty of proof-of-con­cept da­ta from about 20 pa­tients in both co­horts to con­vince them they have good rea­son to be­lieve it will work when they move to a place­bo-con­trolled reg­is­tra­tion study with a dose that starts out at 5 mg and can rise to 15 mg. They add that you al­so shouldn’t just dis­miss the pos­i­tive trend that they saw at the low dose.

MyoKar­dia is break­ing new ground in this study in many ways, and not just with the first new drug to be stud­ied for this con­di­tion. It’s a small com­pa­ny tak­ing on heart dis­ease, a field dom­i­nat­ed by gi­ants like No­var­tis, which have the means to mount huge, long-run­ning stud­ies that cost a for­tune. But the biotech isn’t tak­ing on mass car­dio con­di­tions — it’s look­ing to break up its re­search pro­gram in­to tight­ly con­tained buck­ets of ge­net­i­cal­ly de­fined pa­tient groups. Its lead drug tar­gets a mu­ta­tion in heart pro­teins which forces the heart to squeeze more, thick­en­ing heart mus­cles and cre­at­ing a cas­cade of ef­fects and symp­toms that can lead to afib­ril­la­tion and death.

So they’ve been look­ing for the Goldilocks for­mu­la­tion that can achieve the right serum con­cen­tra­tions of the drug — per­mit­ting physi­cians to step up from a low dose that may well prove ef­fec­tive for a large chunk of pa­tients be­fore go­ing on to find the right lev­el for the rest, while not over­step­ping their in­tend­ed im­pact on the heart.

MyoKar­dia — which has seen its hot stock more than triple in val­ue since its first read­out from their mid-stage study — had out­lined a time­line for launch­ing the reg­is­tra­tion study be­fore the end of 2017. Now dos­ing is ex­pect­ed to get start­ed in the sec­ond quar­ter.

That’s lat­er than what they had en­vi­sioned last sum­mer, con­cedes the CEO. But the ex­ec­u­tive team wants to take time for two sit-downs with the FDA, fol­low­ing up to make sure reg­u­la­tors are com­fort­able with the da­ta they have, the de­sign of the piv­otal tri­al and the piv­otal goals they’ll be us­ing, stick­ing with peak VO2 for the pri­ma­ry.

MyoKar­dia is hold­ing back from pro­vid­ing a time­line on the read­out from the EX­PLOR­ER study. They want to get the FDA’s sign off and start dos­ing pa­tients, judg­ing how fast they can re­cruit the pa­tients they need. Then they’ll tell the world what to ex­pect.

If they’re right, MyoKar­dia could well be on the way to pi­o­neer­ing some­thing rad­i­cal­ly new — and that’s no easy task.

Im­age: MyoKar­dia CEO Tas­sos Gi­anakakos. MYOKAR­DIA

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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