Sem­ma steps to­ward the clin­ic af­ter demon­strat­ing ef­fect of po­ten­tial di­a­betes cure in land­mark an­i­mal stud­ies

The re­search team at the well-fund­ed Sem­ma Ther­a­peu­tics has cleared one of the last re­main­ing hur­dles to get­ting a po­ten­tial cure for di­a­betes in­to hu­man stud­ies. And if they’re right, it marks a ma­jor pre­clin­i­cal mile­stone for a resur­gent re­gen­er­a­tive med­i­cine field fo­cused on a new gen­er­a­tion of stem cell ther­a­pies.

Fe­li­cia Pagli­u­ca

Fe­li­cia Pagli­u­ca, VP of cell bi­ol­o­gy re­search and de­vel­op­ment at the Cam­bridge, MA-based biotech, told the 2019 In­ter­na­tion­al So­ci­ety for Stem Cell Re­search meet­ing in LA Sat­ur­day that their stem cell-de­rived islets per­formed as hoped for — pro­duc­ing in­sulin — in a study in­volv­ing non-hu­man pri­mates whose im­mune sys­tems had been flat­tened to pre­vent a re­jec­tion. In a sep­a­rate study in­volv­ing two pigs, a pack­age of these en­gi­neered islets con­tained in a spe­cial­ly de­signed pack­age were used suc­cess­ful­ly to gen­er­ate in­sulin with­out need­ing an im­muno­sup­pres­sant to pro­tect against a re­ac­tion.

“For the first time ever the de­vice pro­tects the cell,” Pagli­u­ca told me in a pre­view of to­day’s ses­sion, of­fer­ing ev­i­dence from a large an­i­mal mod­el that the tech­nol­o­gy func­tions with blood glu­cose lev­els, spurring in­sulin se­cre­tion as need­ed. “They re­al­ly show quite con­sis­tent re­spon­sive­ness.”

And that’s with­out fi­bro­sis, with­out cell suf­fo­ca­tion, while watch­ing the in­te­gra­tion of cell ther­a­py in­to host tis­sue.

Bas­tiano San­na

It’s ex­cit­ing, says Sem­ma CEO Bas­tiano San­na, to see the “cu­ra­tive po­ten­tial” of this cell ther­a­py.

Re­al­ly? A cure? For a mass mar­ket dis­ease like di­a­betes?

If that all seems a bit too won­der­ful to be be­lieved, think about where Pagli­u­ca is com­ing from. Stem cell ther­a­pies had their hey­day well over a decade ago as the next big thing in med­i­cine — an overnight sen­sa­tion which sput­tered out in fail­ure as the sur­vivors went back in­to the lab to do the hard work nec­es­sary to make it a re­al­i­ty. That long pe­ri­od of qui­et bred con­sid­er­able skep­ti­cism, es­pe­cial­ly af­ter the first wave of promised cures failed to ma­te­ri­al­ize. And she’s watched it play out as re­gen­er­a­tive med­i­cine made its come­back.

One of those pi­o­neer­ing sci­en­tists who stayed in the lab was Sem­ma sci­en­tif­ic founder and Har­vard pro­fes­sor Doug Melton, who pub­lished a land­mark study 5 years ago out­lin­ing how he had suc­cess­ful­ly used stem cells to cre­ate in­sulin-pro­duc­ing pan­cre­at­ic be­ta cells that were in­sert­ed in bulk in­to mice and suc­cess­ful­ly pro­tect­ed from an im­mune re­sponse — a break­through in re­gen­er­a­tive med­i­cine. And he’d been work­ing on the cure for more than 20 years, which he start­ed fol­low­ing his son’s di­ag­no­sis of Type 1 di­a­betes. 

They’ve raised $158 mil­lion over 4 years at Sem­ma to get to this stage, stand­ing on the thresh­old of a pair of small hu­man stud­ies set to launch next year. They’ll now see if they can re­pro­duce in hu­mans what they did in the non-hu­man pri­mates and pigs: first by run­ning a small study with an im­muno­sup­pres­sant, fol­lowed by the use of their de­vice in an­oth­er study lat­er next year that will avoid im­muno­sup­pres­sants.

CAR-T and gene ther­a­pies have come along to demon­strate cu­ra­tive po­ten­tial, but the CEO says it’s been frus­trat­ing to see the first wave of these ther­a­pies tar­get­ed at tiny pa­tient pop­u­la­tions. “We’re very ex­cit­ed about bring­ing the cu­ra­tive po­ten­tial of cell ther­a­pies in­to a large in­di­ca­tion.”

They’re tak­ing it step by step.

No­body is rolling out a mass tri­al for Type 2 di­a­betes. The first goal is to go af­ter some of the Type 1 di­a­betes pa­tients who are the hard­est to treat, with nowhere left to turn to rein in the au­toim­mune dis­ease. Af­ter that, they can turn to the broad­er Type 1 pop­u­la­tion be­fore mov­ing on, per­haps in­to par­tic­u­lar sub­groups of Type 2.

Ini­tial­ly, the goal will be to get the islets to do the work need­ed to safe­ly pro­duce in­sulin for these pa­tients at a re­li­able lev­el. These stem cell-de­rived islets will have to be able to be man­u­fac­tured at scale. And there’s work un­der­way to see if there’s a uni­ver­sal cell de­sign that can be used to avoid the need for the de­vice they use — some­thing Melton com­pares to a tea bag.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.