Weighed down by safe­ty con­cerns of JAK port­fo­lio, Pfiz­er hatch­es a deal to go a dif­fer­ent di­rec­tion in rheuma­toid arthri­tis

Days af­ter con­ced­ing that its block­buster JAK in­hibitor flunked a post-mar­ket­ing safe­ty study, Pfiz­er has signed off on a brand new ap­proach to rheuma­toid arthri­tis.

The de­ci­sion trig­gers a new li­cens­ing deal with Bel­gian biotech Im­cyse, a part­ner since 2017. The mile­stones are mod­est at up to $180 mil­lion, but what mat­ters more for the small­er play­er might be Pfiz­er’s promise to in­vest in its next fi­nanc­ing round on top of the cash pay­ment.

Front and cen­ter in the deal are Imo­topes, a class of syn­thet­ic pep­tides de­signed to block the im­mune re­spons­es to blame for au­toim­mune dis­eases. Each Imo­tope con­sists of a com­bi­na­tion of T cell epi­topes.

It works, ac­cord­ing to Im­cyse, by gen­er­at­ing Imo­tope-spe­cif­ic cy­tolyt­ic CD4 T cells that can take out anti­gen-pre­sent­ing cells and lym­pho­cytes spe­cif­ic to the au­toanti­gen:

Im­cyse’s ap­proach to im­mune tol­er­ance could al­so be con­sid­ered as “im­mune-dele­tion” of the spe­cif­ic im­mune cells in­volved in the im­mune re­ac­tion rather than “im­mune-sup­pres­sion”; this is quite unique and dis­tinc­tive­ly dif­fer­ent from what most oth­ers in the field are try­ing to ac­com­plish, e.g. in­duc­tion of T(regs).

Hav­ing stud­ied how the mech­a­nism works up close for the past three years, Mike Vin­cent — CSO of the in­flam­ma­tion and im­munol­o­gy re­search unit — will now join Im­cyse’s sci­en­tif­ic ad­vi­so­ry board.

His team has been weath­er­ing some storms as safe­ty con­cerns cloud the JAK port­fo­lio they’ve in­vest­ed heav­i­ly on, whether in rheuma­toid arthri­tis, atopic der­mati­tis or oth­er dis­eases.

But don’t ex­pect Imo­topes to come to the res­cue soon. Pfiz­er and Im­cyse are work­ing to op­ti­mize mol­e­cules and push the lead can­di­dates in­to the clin­ic, at which point the phar­ma gi­ant will take over.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,500+ biopharma pros reading Endpoints daily — and it's free.

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?”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Richard Pazdur (via AACR)

Time lim­its on ac­cel­er­at­ed ap­provals? FDA's on­col­o­gy chief Rick Paz­dur eyes po­ten­tial re­forms via in­ter­na­tion­al ap­proach­es

The spotlight on the accelerated approval pathway continues to shine bright, with the FDA’s top oncology official writing in an opinion that the pathway may be strengthened with bits and pieces of what other regulators in Europe and elsewhere have done with their expedited approval pathways, such as adding expiration dates for these faster approvals to ensure they confirm clinical benefit in a timely manner.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,500+ biopharma pros reading Endpoints daily — and it's free.

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%.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 129,500+ biopharma pros reading Endpoints daily — and it's free.