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.”

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Vas Narasimhan (Photographer: Jason Alden/Bloomberg via Getty Images)

No­var­tis de­tails plans to axe 8,000 staffers as Narasimhan be­gins sec­ond phase of a glob­al re­org

We now know the number of jobs coming under the axe at Novartis, and it isn’t small.

The pharma giant is confirming a report from Swiss newspaper Tages-Anzeiger that it is chopping 8,000 jobs out of its 108,000 global staffers. A large segment will hit right at company headquarters in Basel, as CEO Vas Narasimhan axes some 1,400 of a little more than 11,000  jobs in Switzerland.

The first phase of the work is almost done, the company says in a statement to Endpoints News. Now it’s on to phase two. In the statement, Novartis says:

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Lina Gugucheva, NewAmsterdam Pharma CBO

Phar­ma group bets up to $1B-plus on the PhI­II res­ur­rec­tion of a once dead-and-buried LDL drug

Close to 5 years after then-Amgen R&D chief Sean Harper tamped the last spade of dirt on the last broadly focused CETP cholesterol drug — burying their $300 million upfront and the few remaining hopes for the class with it — the therapy has been fully resurrected. And today, the NewAmsterdam Pharma crew that did the Lazarus treatment on obicetrapib is taking another big step on the comeback trail with a €1 billion-plus regional licensing deal, complete with close to $150 million in upfront cash.

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How pre­pared is bio­phar­ma for the cy­ber dooms­day?

One of the largest cyberattacks in history happened on a Friday, Eric Perakslis distinctly remembers.

Perakslis, who was head of Takeda’s R&D Data Sciences Institute and visiting faculty at Harvard Medical School at the time, had spent that morning completing a review on cybersecurity for the British Medical Journal. Moments after he turned it in, he heard back from the editor: “Have you heard what’s going on right now?”

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Scoop: Roche scraps one of two schiz­o­phre­nia PhII tri­als af­ter fail­ing the pri­ma­ry end­point

Roche has terminated one of two Phase II trials testing its drug ralmitaront in patients with schizophrenia, the Big Pharma confirmed to Endpoints News.

The study was terminated last month, according to a June 22 update to the registry on clinicaltrials.gov. Begun in September 2020, the trial was looking at ralmitaront in patients with acute schizophrenia. The trial enrolled 286 patients out of an originally planned 308.

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(AP Photo/Gemunu Amarasinghe)

Some phar­ma com­pa­nies promise to cov­er abor­tion-re­lat­ed trav­el costs — while oth­ers won't go that far yet

As the US Department of Health and Human Services promises to support the millions of women who would now need to cross state lines to receive a legal abortion, a handful of pharma companies have said they will pick up employees’ travel expenses.

GSK, Sanofi, Johnson & Johnson, BeiGene, Alnylam and Gilead have all committed to covering abortion-related travel expenses just four days after the Supreme Court overturned Roe v. Wade and revoked women’s constitutional right to an abortion.

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Aurobindo Pharma co-founders P. V. Ram Prasad Reddy (L) and K. Nityananda Reddy

Au­robindo Phar­ma re­ceives warn­ing let­ter from In­di­a's SEC fol­low­ing more FDA ques­tion marks

Indian-based generics manufacturer Aurobindo Pharma has been in the crosshairs of the FDA for several years now, but the company is also attracting attention from regulators within the subcontinent.

According to the Indian business news site Business Standard, a warning letter was sent to the company from the Securities Exchange Board of India, or SEBI.

The letter is related to disclosures made by the company on an ongoing FDA audit of the company’s Unit-1 API facility in Hyderabad, India as well as observations made by the US regulator between 2019 and 2022.

David Veitch, Basilea CEO

Basilea toss­es an on­col­o­gy drug back to Mer­ck, dou­bling down on an­tibi­otics in re­vamp

Swiss biotech Basilea Pharmaceutica has shed one of its last pipeline ties with oncology as it makes a move to concentrate on antibiotics in a race to profitability next year. And they’ve followed up on that with news of a Phase III success they believe can help expand prospects for a key franchise player.

The company put out word on Monday that the execs are handing rights to the FGFR inhibitor derazantinib back to Merck by the end of this year as it shuts down clinical work on the tumor checkpoint controller lisavanbulin. They’re still working on partnering that out along with their TTK/PLK1-inhibitor BAL0891 and preclinical oncology assets.

New Charles River Laboratories High Quality (HQ) Plasmid DNA Centre of Excellence at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. (Charles River)

Charles Riv­er Lab­o­ra­to­ries to start cell and gene ther­a­py man­u­fac­tur­ing at UK site in Sep­tem­ber

While Massachusetts-based Charles River Laboratories has been on an acquisition spree, they are not against planting their flag. The latest move by the company sees them crossing the pond to establish a manufacturing site in the UK.

The company on Tuesday opened its cell and gene therapy manufacturing center at Bruntwood SciTech’s Alderley Park in Cheshire, United Kingdom. The expansion follows Charles River’s acquisition of Cognate BioServices and Cobra Biologics in 2021 for $875 million. Cognate is a plasmid DNA, viral vector and cell therapy CDMO.