As­traZeneca and Mod­er­na take a big, ear­ly step for­ward in their quest to prove mR­NA works in hu­mans

Mene Pan­ga­los, As­traZeneca

Biotech uni­corn Mod­er­na has re­vamped its de­vel­op­ment struc­ture, pulled back the veil on more of its R&D work and spot­light­ed a sig­nif­i­cant clin­i­cal step for­ward for one of its most ad­vanced — though still very ear­ly-stage — mes­sen­ger RNA ther­a­pies in the pipeline.

Tack­ling the very am­bi­tious work of re­gen­er­at­ing car­dio tis­sue — long one of the Holy Grails in stem cell ther­a­py — Mod­er­na’s close part­ners at As­traZeneca say they got the safe­ty and ef­fi­ca­cy da­ta they were look­ing for on AZD-8601 in Phase I. Work­ing with a bio­mark­er at this stage, in­ves­ti­ga­tors tracked ex­pres­sion of VEGF-A pro­tein in the skin — giv­ing them some ear­ly con­fi­dence that a tech­nol­o­gy ini­tial­ly de­vel­oped at Har­vard had some re­al proof-of-mech­a­nism ev­i­dence to back it up with. That in turn has in­spired As­traZeneca to take the next step on the mes­sen­ger RNA front as it jour­neys in­to Phase II, where they will look for more sol­id ev­i­dence of its re­gen­er­a­tive pow­ers among pa­tients un­der­go­ing coro­nary artery by­pass graft­ing.

The first clin­i­cal snap­shot, says Mod­er­na CFO Lorence Kim, “looks like a lo­cal, tran­sient surge of growth fac­tor,” which is what the biotech and its Big Phar­ma part­ner was look­ing for in try­ing to achieve in a tar­get­ed way what sys­temic stem cell treat­ments failed so spec­tac­u­lar­ly at.

Re­gen­er­at­ing tis­sue presents some huge chal­lenges to re­searchers, along with the po­ten­tial for some huge re­wards. That’s what in­spired As­traZeneca CEO Pas­cal So­ri­ot to buy in­to Mod­er­na for hun­dreds of mil­lions of dol­lars.

“I think we’ve made great progress,” Mene Pan­ga­los, an ex­ec­u­tive vice pres­i­dent at As­traZeneca, tells me. Build­ing on “re­al­ly cool pre­clin­i­cal da­ta on wound heal­ing,” in­ves­ti­ga­tors will now see if they can use this tech­nol­o­gy to “re­store func­tion to the heart.”

The fo­cus on clin­i­cal de­vel­op­ment at Mod­er­na now — af­ter spend­ing sev­er­al years stealth­ily work­ing on its pre­clin­i­cal pro­grams — in­cludes mR­NA-2416, a new OX40L im­munother­a­py that will set out to try a brand new ap­proach in I/O. And it’s look­ing to spur liv­er ex­pres­sion of ther­a­peu­tic pro­teins with mR­NA-3704, for methyl­malonic acidemia (MMA), a lethal rare liv­er dis­ease.

Stéphane Ban­cel

Ear­ly on, Mod­er­na set up 5 sub­sidiary as­set ve­hi­cles for its pro­grams. But now CEO Stephane Ban­cel and the board are opt­ing to strip the com­part­ments down, pool­ing their 16 an­nounced pro­grams in­to a sin­gle pipeline that will of­fer a quick snap­shot of how its build­ing new ther­a­peu­tics on the mR­NA plat­form that they’ve built.

Re­search/pre­clin­i­cal de­vel­op­ment will re­port to Mod­er­na Pres­i­dent Stephen Hoge, while clin­i­cal de­vel­op­ment will op­er­ate un­der Tal Zaks, Mod­er­na’s Chief Med­ical Of­fi­cer. R&D teams will be “aligned around three core ma­trixed ther­a­peu­tic ar­eas — in­fec­tious dis­eases, im­muno-on­col­o­gy and rare liv­er dis­eases.”

This way, Ban­cel ex­plains, ex­ecs can en­cour­age bet­ter line of sight across all the work be­ing done at a com­pa­ny that has swelled to 550 staffers, while adding some am­bi­tious build­ing plans to prep for the man­u­fac­tur­ing work that needs to be done.

STAT has been ham­mer­ing Mod­er­na re­peat­ed­ly for a slate of sup­posed short­com­ings at the Cam­bridge, MA-based trend­set­ter. At­tract­ed by the biotech’s rep for a multi­bil­lion-dol­lar val­u­a­tion very ear­ly on, along with a stealthy ap­proach to R&D, the on­line health­care news pub has sought to poke holes in the sto­ry wher­ev­er it can.

Step by step, though, Mod­er­na has been open­ing up both ex­ter­nal­ly and in­ter­nal­ly, re­veal­ing some wild­ly am­bi­tious sci­ence, the first steps in hu­man stud­ies and a maze of daunt­ing tech chal­lenges they’ll need to over­come in the long quest to achieve new drug ap­provals.

The biotech has a long way to go, but now it wants you to know more about where it plans to get to.

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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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.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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