Stéphane Bancel, Moderna CEO (Endpoints JPM20/Jeff Rumans)

Mod­er­na's flu da­ta of­fer a clear les­son: mR­NA is­n't mag­ic

Last fall, as their Covid-19 vac­cine crossed the fin­ish line, Mod­er­na un­veiled plans to take its new­ly proven mR­NA plat­form and use it to ef­fec­tive­ly change how the world blocks hu­man­i­ty’s most per­sis­tent vi­ral foes.

In ad­di­tion to their pre-ex­ist­ing vac­cine pro­grams, ex­ec­u­tives an­nounced new ones for flu, where vac­cines have chron­i­cal­ly un­der­per­formed, and HIV, which has elud­ed every in­oc­u­la­tion ef­fort over near­ly 40 years. In flu, the oth­er mR­NA vac­cine com­pa­nies — BioN­Tech (with Pfiz­er), Trans­late Bio (un­der Sanofi), and Cure­Vac (with GSK) — all had sim­i­lar am­bi­tions, hop­ing to make shots that were as high as 80% ef­fec­tive.

Fri­day morn­ing, though, cast doubt on those lofty hopes. Mod­er­na be­came the first com­pa­ny to re­lease da­ta on an mR­NA flu can­di­date, and they looked, well, fine.

The com­pa­ny showed the shot could suc­cess­ful­ly in­duce an­ti­bod­ies against the four fam­i­lies of flu virus­es that cur­rent killed virus and pro­tein-based vac­cines do. But noth­ing in the ear­ly da­ta sug­gest­ed it was any bet­ter at in­duc­ing those an­ti­bod­ies, ex­perts said.

Ef­fec­tive­ly, the com­pa­ny re­pro­duced the same old shot in fan­cy new clothes.

“It’s just as good as what we have right now,” said Pe­ter Palese, who stud­ies flu and flu vac­cines at the Ic­ahn School of Med­i­cine. “But I don’t think what we have seen so far is break­ing new ter­ri­to­ry or re­al­ly open­ing up a com­plete­ly new tech­nol­o­gy.”

Or, as his col­league Flo­ri­an Kram­mer put it on twit­ter: “mR­NA is not a sil­ver bul­let.”

An mR­NA ver­sion of the ex­ist­ing flu shots could still be use­ful and of­fer a cou­ple ad­van­tages, but they al­so come with their own of­ten over-looked short­com­ings. Chief among them is the shot’s re­ac­to­genic­i­ty — i.e., its ten­den­cy to cause sig­nif­i­cant headaches, fever and oth­er un­pleas­ant side ef­fects in the days af­ter in­oc­u­la­tion.

Mod­er­na’s da­ta showed that, like its Covid-19 vac­cine, its flu shot caused more ad­verse re­ac­tions than pro­tein-based or live virus vac­cine. On a con­fer­ence call, an­a­lysts ar­gued that could stand in the way of Mod­er­na’s greater am­bi­tion of build­ing a sin­gle sea­son­al shot that com­bines flu, RSV and Covid-19 vac­cine — a vi­sion that’s on­ly fea­si­ble with mR­NA.

If just the flu and coro­n­avirus shot each trig­gered such side ef­fects on their own, SVB Leerink’s Mani Foroohar not­ed, how re­ac­to­genic would they be com­bined?

Pe­ter Palese

But just an mR­NA flu shot alone could pose safe­ty ques­tions, Palese said. The lipid nanopar­ti­cles that car­ry the mR­NA to cells al­so act as an ad­ju­vant, stim­u­lat­ing the in­nate im­mune sys­tem. That boosts the pro­tec­tion peo­ple re­ceive, but it could have long-term ef­fects if giv­en an­nu­al­ly.

The flu vac­cines most peo­ple cur­rent­ly re­ceive are not ad­ju­vant­ed. Gen­er­al­ly, on­ly those over 65 re­ceive an ad­ju­vant­ed flu vac­cine such as Flu­zone.

“I think there has been pro­vi­sion­al­ly a re­luc­tance to use ad­ju­vants for vac­cines against in­fluen­za, be­cause one doesn’t want to give an ad­ju­vant every year, con­tin­u­ous­ly for 60 or 70 years of some­one’s life,” he said.

Mod­er­na ex­ec­u­tives cau­tioned against mak­ing too sweep­ing of a com­par­i­son be­tween vac­cines be­fore re­sults came in from a head-to-head tri­al. And they point­ed to oth­er ar­eas ex­perts agree mR­NA could have an ad­van­tage.

For ex­am­ple, mR­NA can be made faster than tra­di­tion­al egg or cell-grown flu shots. In the­o­ry, that could give Mod­er­na and oth­er mR­NA com­pa­nies more time to make sure the flu strains in the vac­cine match the flu strains cir­cu­lat­ing in the fall, chip­ping away at a prob­lem that in some years can make the sea­son­al shot as lit­tle as 19% ef­fec­tive.

Stephen Hoge

How much they chip away will de­pend on how fast Mod­er­na can make the shot. Palese doubt­ed the ad­van­tage will be sig­nif­i­cant, but Mod­er­na pres­i­dent Stephen Hoge not­ed the com­pa­ny al­ready plans to man­u­fac­ture an Omi­cron-spe­cif­ic vari­ant in 100 days. To­day, by con­trast, of­fi­cials have to se­lect strains in Feb­ru­ary.

Ul­ti­mate­ly, though, the im­pact of Mod­er­na’s tech­nol­o­gy — or Trans­late’s or BioN­Tech’s — may come down to whether they can do more than just make mR­NA ver­sions of oth­er shots.

Those ef­forts present far greater tech­ni­cal chances but al­so far greater op­por­tu­ni­ty. The biotech said Fri­day it would now ad­vance a can­di­date that it de­signed sim­i­lar­ly to pro­posed “uni­ver­sal” flu vac­cines that can pro­tect against all strains, a long-sought holy grail that has had mixed re­sults in the clin­ic.

The com­pa­ny is al­so work­ing to ad­vance its pro­gram for an HIV vac­cine, the great­est prize in vac­ci­nol­o­gy for more than three decades. Louis Pick­er, an im­mu­nol­o­gist at Ore­gon Health and Sci­ence Uni­ver­si­ty fo­cused on HIV, cau­tioned any­one against get­ting their hopes up on it.

“At this point mR­NA vac­cine tech­nol­o­gy, by it­self, does very lit­tle to counter the ma­jor ob­sta­cles to HIV vac­cine ef­fi­ca­cy,” he said in an email.

But mR­NA can be very help­ful, he said. For the last 12 years, the HIV vac­cine field has been try­ing to build shots that can elic­it ul­tra-rare an­ti­bod­ies that can neu­tral­ize all of the many di­verse strains of HIV.

Hilde­gund Ertl

mR­NA, Pick­er said, is unique in al­low­ing re­searchers to quick­ly and it­er­a­tive­ly de­sign new con­structs and test them in hopes of even­tu­al­ly hit­ting on the right de­sign. Mod­er­na is now putting the first such blue­print in Phase I, though Pick­er is pret­ty con­fi­dent the first shot on goal is go­ing to miss.

“Re­al suc­cess is not a fore­gone con­clu­sion,” he said, “And if it hap­pens is quite a way off in the fu­ture.”

Oth­er re­searchers agree. Hilde­gund Ertl, who has worked on HIV vac­cines at the Wis­tar In­sti­tute, point­ed in an email to an NIH pa­per from this week study­ing Mod­er­na’s HIV shot in mon­keys. The mon­keys were giv­en the vac­cine and then ex­posed to HIV. Most weren’t in­fect­ed but those who were didn’t seem to sup­press the virus at all, sug­gest­ing a very poor re­sponse.

“I’m not hold­ing my breath,” Ertl said.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; 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.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

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