Cure­Vac’s lead mR­NA pro­gram flunks a crit­i­cal PhI­Ib study, rais­ing ques­tions for high-pro­file biotech uni­corns

In­g­mar Ho­err

Cure­Vac’s lead­ing mR­NA pro­gram CV9104, a prostate can­cer vac­cine, has failed a crit­i­cal Phase IIb study. And that sting­ing set­back for the most ad­vanced clin­i­cal study in the field will raise fresh ques­tions about a com­plex new tech­nol­o­gy that has at­tract­ed bil­lions of dol­lars in in­vest­ment cash.

The Ger­man biotech re­port­ed that not on­ly did CV9104 fail the pri­ma­ry end­point on im­prov­ing over­all sur­vival, there was al­so no im­prove­ment on pro­gres­sion-free sur­vival over a place­bo.

Cure­Vac’s can­cer vac­cine is a 6-mR­NA con­coc­tion aimed at whip­ping up an im­mune sys­tem at­tack by en­cod­ing for 6 anti­gens over ex­pressed in prostate can­cer.

The Ger­man biotech – run by CEO In­g­mar Ho­err – has raised $360 mil­lion for its work, pri­mar­i­ly backed by Ger­man bil­lion­aire Di­et­mar Hopp along with ad­di­tion­al fund­ing from Bill Gates’ foun­da­tion, both in­trigued by the rev­o­lu­tion­ary po­ten­tial of in­struct­ing cells to pro­duce ther­a­peu­tics.

The most promi­nent com­pa­ny in the mes­sen­ger RNA space is Mod­er­na, a Boston-based biotech which has raised $1.9 bil­lion and just this week de­tailed a full pipeline of 5 clin­i­cal-stage ther­a­pies and an­oth­er 7 pre­clin­i­cal projects. Mod­er­na CEO Stephane Ban­cel is al­so work­ing on a can­cer vac­cine with Mer­ck, but he’s al­ready sought to dis­tin­guish their ap­proach to an in­di­vid­u­al­ly tai­lored ther­a­py with the shared-anti­gen ap­proach that Cure­Vac has.

I asked Ban­cel about the Cure­Vac set­back, and he re­spond­ed:

“Can­cer vac­cines con­tin­ues to be a high risk en­deav­or, which is why we part­nered with Mer­ck, a leader in im­muno-on­col­o­gy.”

Whether that kind of dis­tinc­tion will help Mod­er­na avoid get­ting dinged by Cure­Vac’s fail­ure, though, has yet to be seen. Mod­er­na has come un­der re­peat­ed at­tack by STAT’s Dami­an Garde, who has fo­cused on ques­tions re­gard­ing the tech­nol­o­gy and Mod­er­na’s cau­tious ap­proach in tack­ling vac­cines first, with a lead­ing ef­fort on pan­dem­ic flu. But that’s the long game that Ban­cel is de­ter­mined to play as he lines up his own first round of da­ta on those pro­grams deemed most like­ly to suc­ceed.

The lat­est fail­ure at Cure­Vac al­so fol­lows a wave of clin­i­cal flops for can­cer vac­cines in gen­er­al, which proved far too weak to di­rect a sig­nif­i­cant im­mune sys­tem at­tack on can­cer. That first-wave fail­ure was fol­lowed by check­point in­hibitors, which ef­fec­tive­ly take the brake off the im­mune sys­tem, as well as per­son­al­ized vac­cines that seek out the in­di­vid­ual anti­gens that will make the most com­pelling dif­fer­ence for pa­tients. But that is al­so still very ear­ly in the de­vel­op­ment process.

Cure­Vac’s next step will like­ly fo­cus on a com­bo ap­proach, match­ing their mR­NA tech with check­points, chemo and so on, which is al­ready part of the plan.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.