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.

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Af­ter 4 years of furor, the FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. And this time they plan to squash it

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition.

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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UP­DAT­ED: Ac­celeron of­fers thumbs up on a PhII suc­cess for would-be block­buster drug — and shares rock­et up

There’s no public data yet, but Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

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Civi­ca and Blue Cross Blue Shield launch new ven­ture to low­er gener­ic prices

Five years after Martin Shkreli put a smug face to the volatile prices companies can charge even for generic drugs, payers and governments are coming up with outside-the-box solutions.

The latest fix is a new venture from the Blue Cross Blue Shield Association, 18 of its members and Civica, the generics company founded in 2018 by hospitals fed up with high prices for drugs that had long-since lost patent protection. While Civica focused on drugs that hospitals purchased, the new company will aim to lower prices on drugs that, like Shkreli’s Daraprim, are purchased by individuals.

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Merck Invests in State-Of-The-Art Biotech Development Facility in Switzerland

Mer­ck KGaA match­es lofty R&D goals with €250M in­vest­ment in­to a new clin­i­cal man­u­fac­tur­ing site in Switzer­land

As Merck KGaA strives to prove itself as a capable biopharma R&D player, it has begun construction on a €250 million facility dedicated to developing and manufacturing drugs for use in clinical trials.

The German drugmaker chose a location at Corsier-sur-Vevey, Switzerland, where it already has a commercial manufacturing site, in order to “bridge together research and manufacturing.”

“This investment in the Merck Biotech Development Center reflects our commitment to speed up the availability of new medicines for patients in need, and confirms the importance of Switzerland as our prime hub for the manufacturing of biotech medicines,” CEO Stefan Oschmann said at the groundbreaking ceremony, according to a statement.

Breast can­cer ap­proval in tow, As­traZeneca, Dai­ichi armed an­ti­body scores in key gas­tric can­cer study

AstraZeneca kicked off Monday with a flurry of good news. Apart from unveiling positive results on its stroke trial testing its clot-fighter Brilinta, and welcoming its experimental IL-23 inhibitor brazikumab back from Allergan — the British drugmaker also disclosed some upbeat gastric cancer data on its HER2-positive oncology therapy it is collaborating on with Daiichi Sankyo.

Buoyed by the performance of its oncology drugs, last March AstraZeneca chief Pascal Soriot bet big to partner with Daiichi on the cancer drug, with $1.35 billion upfront in a deal worth up to roughly $7 billion. Roughly 8 months later, as 2019 drew to a close, the FDA swiftly approved the drug — trastuzumab deruxtecan — for use in breast cancer, months ahead of the expected decision date.

Sor­ren­to shrugs off an anony­mous pri­vate eq­ui­ty group’s $1B of­fer to buy the com­pa­ny

San Diego-based Sorrento Therapeutics isn’t going the M&A route — at least not today.

The biotech caused quite a stir when it put out word a few weeks ago that an unidentified private equity group was bidding a billion dollars-plus for the company. The news drove a quick spike in the company’s share price as investors hooked up for the ride — that didn’t happen.

The update sparked a 5% drop in the share price $SRNE ahead of the bell. It’s now trading just above $4, without any evidence that the $7 price looked like it was firm.