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.”

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; 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.

I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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BAR­DA slows its $9B en­gine for new Covid-19 ther­a­peu­tics

The Biomedical Advanced Research and Development Authority is cooling its jets in looking for new, potential Covid-19 treatments, at least in the near term.

An HHS spokesperson told Endpoints News via email, “to date, BARDA has obligated more than $9 billion for the development and/or purchase of 13 therapeutics, beginning in February 2020 with support to develop Regeneron’s monoclonal antibody therapeutic. Therapeutics are an important element of the COVID-19 response, and we are focused on the programs currently underway and/or in negotiation using the funds available to us.”

Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.

Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Marshall Fordyce, Vera CEO

Gene ther­a­py play­er turned kid­ney spe­cial­ist Ve­ra drops a dud in lead­up to Nas­daq, pric­ing well be­low range

Vera Therapeutics took a big risk at the start of the year, pivoting away from its gene editing mission statement to chase a lead kidney drug instead — and they doubled down with an IPO just months later. But investors don’t seem impressed with Vera’s promise, and now the biotech is looking at a far more scaled-back offering.

On Friday, Vera priced its 4.35-million-share IPO at $11 per share, well below its targeted range of $14 to $16 and good for $47.58 million in proceeds. The biotech will start trading Monday under the ticker $VERA.

Darren Ji, Elpiscience CEO (Lilly Asia Ventures)

Kept an ocean away from its sci­en­tif­ic ad­vi­sors, Shang­hai's Elpi­science keeps up the clin­i­cal progress, re­fu­els for its I/O pipeline

When Elpiscience pooled $100 million for its Series B in late 2019, CEO Darren Ji promised to move what he described as one of the broadest immuno-oncology pipelines swiftly through the clinic in both the US and China.

Then a pandemic got in the way — but not by much. The Shanghai-based biotech managed to keep testing its 4-1BB/PD-L1 drug, get an OX40 agonist cleared for clinical trials (nabbing a collaboration with Junshi in the process), while in-licensing a Phase I bispecific from California’s TRIGR Therapeutics.

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