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.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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Blueprint CEO Jeff Albers (file photo)

Blue­print plots re­turn to FDA with new Ay­vak­it da­ta in rare con­di­tion — and the an­a­lysts cheer

Over a decade after launch, Blueprint Medicines nabbed the first approval for their first drug earlier this year. Now, as they move forward with a Roche-partnered global launch, they’re touting data that could push them into more patients.

The Jeff Albers-led Cambridge biotech released their full pivotal data for Ayvakit in patients with advanced systemic mastocytosis. In one 53-person study, they showed that 76% of patients responded to the drug, 36% had complete responses and that on average their responses lasted for just over 3 years. A smaller, 32-patient study had a 75% response rate and most were still responding after 10.4 months, the last follow-up.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Anthony Coyle (Repertoire)

Flag­ship's merged biotech Reper­toire nets ex-Pfiz­er CSO An­tho­ny Coyle as R&D chief

Flagship is building a big-name C-suite at its new, $220 million merged biotech.

Repertoire Immune Medicines, which already boasts former Bioverativ chief John Cox as its CEO, announced yesterday that Anthony Coyle, the former Pfizer CSO and the founding CEO of Pandion, will join as their head of R&D.

“As we progress clinical trials for our multi-clonal T cell candidates in immuno-oncology, Tony’s deep expertise in cellular immunology and novel therapeutic development will help us achieve our vision of creating a new class of transformative medicines for patients,” Cox said in a statement.

Scripps reach­es $10M set­tle­ment with gov­ern­ment over al­le­ga­tions NIH grants weren't prop­er­ly ac­count­ed for

Scripps Research Institute has settled a case with the Justice Department alleging claims of misappropriated funds, the US attorney for the district of Maryland announced late last week.

Prosecutors said the institute improperly used NIH-funded research grants for non-grant related activities, including working on new grant applications, teaching activities and other administrative tasks. As part of the settlement, Scripps has agreed to pay $10 million.

President Donald Trump (via AP Images)

Signs of an 'Oc­to­ber Vac­cine Sur­prise' alarm ca­reer sci­en­tists. HHS con­tin­ues to claim Azar “will de­fer com­plete­ly to the FDA"

President Donald Trump, who seems intent on announcing a Covid-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the FDA and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Trump — who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA — will take matters into his own hands, running roughshod over the usual regulatory process.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.