#AACR20 roundup: Tecen­triq/Xtan­di com­bo fails to show OS ben­e­fit, halt­ing Roche's PD-L1 push in­to prostate can­cer

For the first time in its 100-year-plus his­to­ry, the Amer­i­can As­so­ci­a­tion for Can­cer Re­search is host­ing its an­nu­al meet­ing com­plete­ly on­line. Here’s a glance at some of the ab­stracts — which dropped ear­ly Mon­day — mak­ing the rounds:

Roche con­ced­ed that Tecen­triq failed to help prostate can­cer pa­tients live longer when added to Xtan­di, Pfiz­er and Astel­las’ main­stay an­dro­gen re­cep­tor an­tag­o­nist. The Phase III study dubbed IM­bas­sador en­rolled 759 pa­tients with metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer who had been treat­ed with one pri­or line of chemother­a­py and had pro­gressed af­ter tak­ing an­dro­gen syn­the­sis in­hibitors.

On the pri­ma­ry end­point of over­all sur­vival, no dif­fer­ence was ob­served be­tween the Tecen­triq/Xtan­di and Xtan­di groups. In fact, the me­di­an OS for the com­bo group was slight­ly short­er at 15.2 months com­pared to 16.6 months on the monother­a­py arm.

“Sub­group analy­ses were con­sis­tent with the pri­ma­ry end­point,” the in­ves­ti­ga­tors added in an ab­stract.

Re­searchers had hy­poth­e­sized that Xtan­di may en­hance IFNɣ sig­nalling and sen­si­tive tu­mor cells to an im­mune at­tack. Mid-stage da­ta from Mer­ck have fu­eled that hope, but with the ex­cep­tion of a bio­mark­er-based OK for Keytru­da that po­ten­tial­ly in­clud­ed prostate can­cer, no PD-(L)1 drugs have been ap­proved for the in­di­ca­tion.

Roche is spon­sor­ing a small, open-la­bel study to eval­u­ate us­ing Tecen­triq in the neoad­ju­vant set­ting. Mer­ck, the leader in the check­point field, has a trio of Phase III tri­als un­der­way, pair­ing Keytru­da with Xtan­di, Lyn­parza as well as chemo.

A Chi­nese biotech rais­es ear­ly hope for next-gen CAR-T 

Will the next break­through in CAR-T be made in Chi­na? Gra­cell Bio is build­ing its case for it.

The Shang­hai-based biotech is re­port­ing re­sults from the first five adult pa­tients treat­ed with its al­lo­gene­ic CAR-T for re­lapsed/re­frac­to­ry T-cell acute lym­phoblas­tic leukemia. In a nut­shell:

4 pts achieved MRD neg­a­tive com­plete re­spons­es (MRD- CR) at D28 eval­u­a­tion: 3 of them re­mained MRD- at fol­low-up re-eval­u­a­tions (D118, 61, 161, re­spec­tive­ly, and none was bridged to HSCT); 1 just achieved MRD- CR at D28 and fol­low-up re­sults will be up­dat­ed at the meet­ing. 1 pt achieved MRD+ CR at D14 but had re­lapsed dis­ease at D29.

For the pa­tients with a re­sponse, in­ves­ti­ga­tors doc­u­ment­ed peak ex­pan­sions of the ge­net­i­cal­ly en­gi­neered T cells be­tween the first and sec­ond weeks af­ter in­fu­sion of GC027.

Gra­cell at­tract­ed a well-heeled syn­di­cate — fea­tur­ing 6 Di­men­sions, Temasek and Lil­ly Asia Ven­tures — on the promise to over­come mul­ti­ple con­straints of tra­di­tion­al CAR-T: shrink­ing the man­u­fac­tur­ing process from two weeks to one day, low­er­ing the cost, as well as tweak­ing genes to avoid strong im­mune re­ac­tions.

But they weren’t ex­act­ly able to avoid the safe­ty pit­falls that plagued the ear­li­er prod­ucts. Four pa­tients ex­pe­ri­enced grade 3 cy­tokine re­lease syn­drome and the oth­er one had grade 4 CRS along with el­e­vat­ed lev­els of IL6, IFNγ and TN­Fα — though all were re­solved af­ter treat­ment and sup­port­ive care.

Mer­ck

Af­ter be­ing knocked by a re­jec­tion from the FDA ear­li­er this year, Mer­ck has re­cent­ly re­filed a 6-week dos­ing sched­ule for Keytru­da. At AACR, the phar­ma gi­ant un­veiled the clin­i­cal re­sults be­hind the ap­pli­ca­tion.

The ma­jor take­away from co­hort B of KEYNOTE-555, the com­pa­ny said, is that ad­min­is­ter­ing 400 mg of Keytru­da every six weeks yields com­pa­ra­ble ef­fi­ca­cy and safe­ty as 200 mg every three weeks. At the in­ter­im analy­sis, over­all re­sponse rate was 38.6% — a da­ta point that adds to pre­vi­ous phar­ma­co­ki­net­ic num­bers.

Mer­ck has al­ready se­cured ap­proval in Eu­rope for the less fre­quent reg­i­men, Q6W, which it said would of­fer greater flex­i­bil­i­ty for pa­tients. It didn’t dis­close de­tails from the FDA’s com­plete re­sponse let­ter.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Thank you, next: Take­da hands Ovid $196M cash to rein back in Phase III-ready seizure drug, re­viv­ing bat­tered stock

Soticlestat made it.

Takeda is bringing the drug back into its fold more than four years after first entrusting the team at Ovid with the mid-stage clinical work. For all that — generating what they saw as positive Phase II data in Dravet syndrome and Lennox-Gastaut syndrome — the biotech has been rewarded with $196 million in upfront cash, with another $660 million reserved for regulatory and commercial milestones.

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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepreneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film “Fantastic Voyage,” the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his and his co-founders’ own accounts, along with some seed cash from friends and family.

Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

It occasionally occurs to Paul Sekhri that if they pull this off, his company will be on the front page of the New York Times and a lead story in just about every major news outlet on the planet. He tries not to dwell on it, though.

“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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