Stéphane Bancel, Moderna CEO (Jeff Rumans)

'Learned a lot last year': Af­ter Covid-19 suc­cess, Mod­er­na's Stéphane Ban­cel plans to give rest of pipeline a big push

A year ago, Stéphane Ban­cel would have de­scribed Mod­er­na as cau­tious — walk­ing step-by-step to in­ves­ti­gate whether mR­NA vac­cines could pre­vent a host of virus­es. Then the pan­dem­ic hit, and the Cam­bridge, MA-based biotech got a multi­bil­lion-dol­lar wind­fall to pro­duce the world’s sec­ond-ever au­tho­rized mR­NA vac­cine in a mat­ter of months.

What’s next? Ban­cel is plan­ning a big ac­cel­er­a­tion and ex­pan­sion of the rest of the pipeline, in­clud­ing the com­pa­ny’s Phase III-ready can­di­date for cy­tomegalovirus (CMV), which was the lead pro­gram be­fore Covid-19 came around.

“We have a fi­nan­cial means that we nev­er had be­fore,” Ban­cel said. The com­pa­ny’s stock $MR­NA, which sold for un­der $20 for most of 2019, is now fly­ing at close to $150 apiece.

“The ap­petite to in­vest in in­no­v­a­tive vac­cines is, I would say, al­most lim­it­less,” he added.

As part of its sec­ond an­nu­al Vac­cines Day Wednes­day, Mod­er­na of­fered up­dates on its key pro­grams, in­clud­ing vac­cines for res­pi­ra­to­ry syn­cy­tial virus (RSV), CMV, HIV and the flu. It al­so read out 6-month da­ta for its Covid-19 vac­cine, and pre­clin­i­cal re­sults that sug­gest its boost­er can­di­dates pro­duce a suf­fi­cient im­mune re­sponse against new vari­ants.

“For 10 years, we be­lieved mR­NA vac­cines could be high-ef­fi­ca­cy, fast and with great man­u­fac­tur­ing scale-up. Now we know that,” Ban­cel said.

First up is Mod­er­na’s CMV vac­cine, which is sched­uled to en­ter Phase III lat­er this year. The can­di­date com­bines six mR­NAs in a sin­gle vial; the mR­NAs en­code for two anti­gens lo­cat­ed on the sur­face of CMV. Why so many mR­NAs? To pro­vide a broad spec­trum of neu­tral­iz­ing an­ti­bod­ies, thus max­i­miz­ing the chance of ef­fi­ca­cy, Ban­cel ex­plained.

“Some bi­ol­o­gy is straight­for­ward like Covid. The spike pro­tein, as we’ve shown, is enough,” he said. “But for very com­plex virus­es, what we need to do to help ed­u­cate the im­mune sys­tem is to make a lot of dif­fer­ent an­ti­bod­ies.”

Sev­en-month da­ta from a Phase II study show the can­di­date, mR­NA-1647, was gen­er­al­ly well-tol­er­at­ed, ac­cord­ing to Mod­er­na. In CMV-seroneg­a­tive par­tic­i­pants who re­ceived three dos­es, neu­tral­iz­ing an­ti­body geo­met­ric mean titers (GMTs) against ep­ithe­lial cell in­fec­tion were at least 20-fold high­er than the base­line GMT of the CMV-seropos­i­tive group, the biotech said. And in CMV-pos­i­tive pa­tients who re­ceived three dos­es, neu­tral­iz­ing an­ti­body GMTs in­creased to at least 6.8-fold over base­line.

CMV is a com­mon virus that in­fects more than half of adults by the time they’re 40, ac­cord­ing to the CDC. Most peo­ple show no symp­toms — but about 1 in 5 ba­bies born with the in­fec­tion suf­fer long-term health prob­lems.

Once you’re in­fect­ed with CMV, you have it for life, Ban­cel said. And it’s be­lieved that while your im­mune sys­tem spends a lot of en­er­gy fight­ing CMV, it’s spend­ing less en­er­gy on oth­er things, like fight­ing can­cer, he added.

“I al­ready be­lieve that CMV could have a very pro­found both midterm im­pact on birth de­fects, and po­ten­tial­ly long-term im­pact on can­cer in­ci­dence and over­all health of peo­ple,” Ban­cel said.

Mod­er­na al­so read out in­ter­im Phase I da­ta for its RSV vac­cine, mR­NA-1345. There’s cur­rent­ly no vac­cine ap­proved for RSV, the lead­ing cause of res­pi­ra­to­ry ill­ness in young chil­dren, al­though sev­er­al drug­mak­ers, in­clud­ing Glax­o­SmithK­line, are rac­ing to de­vel­op one. The Phase I study is as­sess­ing mR­NA-1345 in younger adults (18 to 49 years old), old­er adults (65 to 79 years old) and chil­dren (be­tween 1 and just un­der 5 years old).

The in­ter­im analy­sis came from the younger adult co­horts, which are ful­ly en­rolled. At one-month post-vac­ci­na­tion, a sin­gle shot of ei­ther 50 μg or 100 μg was well-tol­er­at­ed, and the can­di­date boost­ed neu­tral­iz­ing an­ti­body titers against both serotypes of RSV with “no ap­par­ent dose re­sponse,” Mod­er­na said.

The geo­met­ric mean fold rise in neu­tral­iz­ing an­ti­body rel­a­tive to base­line was at least 20.5 for RSV-A and at least 11.7 for RSV-B, the com­pa­ny added. It plans on ex­plor­ing po­ten­tial com­bi­na­tions of the can­di­date with its oth­er vac­cines against oth­er res­pi­ra­to­ry pathogens in chil­dren and old­er adults.

As for HIV, Mod­er­na plans to launch three Phase I tri­als this year, in­clud­ing one in col­lab­o­ra­tion with the In­ter­na­tion­al AIDS Vac­cine Ini­tia­tive (IAVI) and the Bill and Melin­da Gates Foun­da­tion. That can­di­date, mR­NA-1644, will aim to use a “nov­el ap­proach” to elic­it HIV neu­tral­iz­ing an­ti­bod­ies, Mod­er­na said, with the study aim­ing to iden­ti­fy and use mul­ti­ple anti­gens for germline tar­get­ing and im­muno-fo­cus­ing. A sec­ond vac­cine hope­ful, mR­NA-1574, a col­lab­o­ra­tion with the NIH, will use a sim­i­lar ap­proach with mul­ti­ple na­tive-like trimer­ic anti­gens.

Ban­cel said mR­NA has the po­ten­tial to over­come the unique chal­lenges of de­vel­op­ing a vac­cine for HIV — in­clud­ing its abil­i­ty to rapid­ly mu­tate — by com­bin­ing high ef­fi­ca­cy with speed and flex­i­bil­i­ty of man­u­fac­tur­ing.

“If you think about old tech­nol­o­gy like pro­tein tech­nol­o­gy, it takes so long to make a prod­uct. It is so ex­pen­sive to de­vel­op a sin­gle drug that it lim­its what you can do,” he said. But mR­NA is like a piece of soft­ware — it’s al­ways the same man­u­fac­tur­ing process.

“We can move in 30 days from a se­quence to a prod­uct ready to go in­to clin­i­cal tri­al, we can move very quick­ly for vari­ants of virus evo­lu­tion, and that in­creas­es again the ef­fi­ca­cy of a prod­uct and al­lows you to adapt to bi­ol­o­gy,” Ban­cel said.

Ban­cel al­so has a high-ef­fi­ca­cy flu vac­cine in the works, which is ex­pect­ed to en­ter Phase I this year. Even­tu­al­ly, he hopes to ex­plore com­bi­na­tion can­di­dates that pro­tect against the flu, SARS-CoV-2, RSV and hu­man metap­neu­movirus (hM­PV).

“This is re­al­ly the big is­sue. If you could have a prod­uct that had high-ef­fi­ca­cy in Covid, high-ef­fi­ca­cy in flu and high-ef­fi­ca­cy in RSV, you will have a mas­sive im­pact on pub­lic health, and hos­pi­tal­iza­tion and mor­tal­i­ty of el­der­ly,” he said.

Yes­ter­day, Mod­er­na an­nounced that its Covid jab — the com­pa­ny’s crown jew­el — proved more than 90% ef­fec­tive against all cas­es af­ter an up­dat­ed re­view of 900-plus cas­es from the Phase III COVE study. It was 95% ef­fec­tive against se­vere cas­es, and a study with 33 Phase I par­tic­i­pants showed that an­ti­bod­ies per­sist­ed 6 months af­ter the sec­ond dose.

The com­pa­ny is now push­ing for­ward with boost­er can­di­dates to ad­dress con­cern­ing vari­ants, which were shown to elic­it neu­tral­iz­ing titers in mice that were sim­i­lar to those pro­duced against the orig­i­nal virus.

“There’s a lot of things that I think we are do­ing dif­fer­ent­ly as we look for­ward, which is why I think we can re­al­ly com­press the time­lines of vac­cine de­vel­op­ment,” Ban­cel said. “I think the agency and the in­dus­try learned a lot last year.”

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

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Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

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New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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