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.”

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”