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.”

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Albert Bourla, Pfizer CEO (Efren Landaos/Sipa USA/Sipa via AP Images)

Pfiz­er makes an­oth­er bil­lion-dol­lar in­vest­ment in Eu­rope and ex­pands again in Michi­gan

Pfizer is continuing its run of manufacturing site expansions with two new large investments in the US and Europe.

The New York-based pharma giant’s site in Kalamazoo, MI, has seen a lot of attention over the past year. As a major piece of the manufacturing network for Covid-19 vaccines and antivirals, Pfizer is gearing up to place more money into the site. Pfizer announced it will place $750 million into the facility, mainly to establish “modular aseptic processing” (MAP) production and create around 300 jobs at the site.

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Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

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In­no­force opens new man­u­fac­tur­ing site in Chi­na

Innoforce is off to the races at its new site in the city of Hangzhou, China.

The Chinese CDMO announced last week that it has started manufacturing at the new facility, which was built to offer process development and manufacturing operations for RNA, plasmid DNA, viral vectors and other cell therapeutics. It will also serve as Innoforce’s corporate HQ.

The company said it’s investing more than $200 million in the 550,000-square-foot manufacturing base for advanced therapies. The GMP manufacturing facility features space for producing plasmids with three 30-liter bioreactors. For viral vector manufacturing, Innoforce also has 200- and 500-liter bioreactors at its disposal, along with eight suites to make cell therapies. The site also includes several labs and warehouse spaces.

Vas Narasimhan, Novartis CEO (Thibault Camus/AP Images, Pool)

No­var­tis bol­sters Plu­vic­to's case in prostate can­cer with PhI­II re­sults

The prognosis is poor for metastatic castration-resistant prostate cancer (mCRPC) patients. Novartis wants to change that by making its recently approved Pluvicto available to patients earlier in their course of treatment.

The Swiss pharma giant unveiled Phase III results Monday suggesting that Pluvicto was able to halt disease progression in certain prostate cancer patients when administered after androgen-receptor pathway inhibitor (ARPI) therapy, but without prior taxane-based chemotherapy. The drug is currently approved for patients after they’ve received both ARPI and chemo.

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Nkarta CEO Paul Hastings at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Nkar­ta un­der­scores safe­ty of CAR-NK, boasts ear­ly re­spons­es

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In a new update from its Phase I dose escalation study, the South San Francisco-based biotech reported that seven out of 10 patients treated with the highest doses of its NK cell therapy, NKX019, achieved a complete response, translating to a complete response rate of 70%.

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According to an SEC filing, the company has raised $31,761,186 in its latest funding round, which includes 17 investors. The filing lists six names attached to the company, including Meredith Fisher, a partner at Mass General Brigham Ventures and Mediar’s acting CEO.

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We now know why Verve’s lead candidate was placed on hold last month by US regulators.

In an SEC filing, Verve laid out the FDA’s conditions for lifting the hold on its lead therapy, VERVE-101. That includes submitting preclinical data about potency differences in human versus non-human cells, risks of gene editing germline cells, and off-target analyses in non-hepatocyte cell types.

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Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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