A can­cer vac­cine that might work? Mod­er­na posts 'promis­ing' ear­ly snap­shot for Mer­ck-part­nered pro­gram and raids Bris­tol My­ers for a new can­cer R&D chief

Re­mem­ber that per­son­al­ized can­cer vac­cine Mod­er­na was de­vel­op­ing?

As the world awaits da­ta from its late-stage Covid-19 can­di­date, the mR­NA play­er is in­ter­rupt­ing its most in­ten­sive­ly watched pro­gram with an up­beat ear­ly snap­shot of da­ta from its mes­sen­ger RNA can­cer vac­cine mR­NA-4157. And the Mod­er­na team is us­ing the oc­ca­sion to in­tro­duce a new chief for their on­col­o­gy unit, raid­ed from Bris­tol My­ers Squibb’s can­cer group.

When com­bined with Mer­ck’s Keytru­da in the Phase I KEYNOTE-603 tri­al, re­searchers re­port, the vac­cine ap­pears some­what ef­fec­tive in shrink­ing tu­mors. Among 10 pa­tients with HPV-neg­a­tive head and neck squa­mous cell car­ci­no­ma, the over­all re­sponse rate is 50%: 2 com­plete re­spons­es and 3 par­tial re­spons­es. And it is trans­lat­ing to con­sid­er­able ben­e­fit over the PD-1 in­hibitor alone:

Me­di­an pro­gres­sion free sur­vival (mPFS) is 9.8 months, which com­pares fa­vor­ably to the pub­lished ORR and mPFS of 14.6% and 2.0 months re­spec­tive­ly, for Keytru­da monother­a­py. In­clud­ing four pa­tients with sta­ble dis­ease, the Dis­ease Con­trol Rate (DCR) is 90% (9/10). Me­di­an du­ra­tion of re­sponse has not been reached.

“The da­ta are pre­lim­i­nary and the sam­ple size is small, but it is promis­ing,” Uni­ver­si­ty of Ari­zona pro­fes­sor Julie Bau­man, who’s pre­sent­ing the in­ter­im da­ta at The So­ci­ety for Im­munother­a­py of Can­cer’s An­nu­al Meet­ing, said in a state­ment. “A phase I tri­al is about safe­ty first and fore­most, and we now know this treat­ment is safe and tol­er­a­ble. But, we al­so have a strong sig­nal to point us to fur­ther study this in head and neck can­cer.”

Jef­feries an­a­lyst Michael Yee ob­served that the re­sults com­pare fa­vor­ably even with the Keytru­da/chemo com­bo, the stan­dard of care in first-line treat­ment, which yields an ORR of 36% and mPFS of 4.9 months.

“While 4/5 re­spon­ders achieved PR af­ter 2 dos­es of Keytru­da pri­or to mR­NA-4157, all 4 re­spons­es deep­ened af­ter mR­NA-4157 ad­min­is­tra­tion w/ 2 PRs con­vert­ing to CRs,” he wrote “Add’l, one pt pro­gressed on Keytru­da, but start­ed to re­spond af­ter mR­NA-4157.”

In the mi­crosatel­lite sta­ble col­orec­tal car­ci­no­ma group, though, no re­spons­es were ob­served out of 17 pa­tients.

With a clean tol­er­a­bil­i­ty so far, Mod­er­na now plans to ex­pand the HN­SCC co­hort to 40 pa­tients. For each one, the com­pa­ny tai­lor makes a vac­cine with mes­sen­ger RNA that en­codes up to 20 neoepi­topes that its al­go­rithms pre­dict would stir up the strongest im­mune re­sponse.

It will be do­ing so un­der the lead­er­ship of Praveen Aa­nur, who’s jump­ing from Bris­tol My­ers Squibb to be­come Mod­er­na’s ther­a­peu­tic area head for on­col­o­gy de­vel­op­ment. Aa­nur spent the last 7 years work­ing on Bris­tol My­ers’ im­muno-on­col­o­gy pipeline. He re­ceived an MBBS from Ban­ga­lore Uni­ver­si­ty, an MPH from the Uni­ver­si­ty of Al­aba­ma and an MBA from Co­lum­bia Uni­ver­si­ty School of Busi­ness.

Can­cer vac­cines are gain­ing trac­tion among hefty bio­phar­ma play­ers again as new biotechs spring up fol­low­ing a se­ries of clin­i­cal dis­as­ters among the gen-1 play­ers. Re­gen­eron is al­lied with BioN­Tech — now a house­hold name thanks to its Pfiz­er-part­nered Covid-19 ef­fort — on a Phase II test­ing a 4-anti­gen can­di­date, while Roche re­cent­ly shelled out $200 mil­lion for a neoanti­gen pro­gram.

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.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; 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.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

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.