The lat­est up­date on NK­TR-214/Op­di­vo from Nek­tar and Bris­tol-My­ers will keep the con­tro­ver­sy burn­ing over the ORR rate

Nek­tar Ther­a­peu­tics $NK­TR man­aged to slide 1 out of its 38 evalu­able stage 4 melanoma pa­tients in­to the win col­umn with its close­ly-watched 3-month up­date on Op­di­vo/NK­TR-214’s ob­jec­tive re­sponse rate. That man­aged to nudge up the ORR from 50% — a fig­ure that rout­ed Nek­tar’s stock at AS­CO — to 53%, which isn’t like­ly to con­vince any of the crit­ics that the biotech and its part­ners at Bris­tol-My­ers Squibb have come up with the kind of com­bo that can change the stan­dard of care in the field.

But if you ex­pect any­one di­rect­ly in­volved in this study to step back from the en­thu­si­as­tic pro­jec­tions that were made on the first op­ti­mistic da­ta points, you’d be flat wrong.

Adi Diab

While the cru­cial ORR bare­ly budged, Adi Diab from MD An­der­son point­ed straight to a high­er com­plete re­sponse rate, at 24% — “which is not seen with an­oth­er com­bi­na­tion.” He’s al­so of­fer­ing a thumbs up to a 76% dis­ease con­trol rate — up from 71% at AS­CO — as ev­i­dence that they’re on to some­thing spe­cial.

Sev­er­al an­a­lysts — in­clud­ing some in the Ever­cor­eISI team — had been look­ing for some­thing in the 60%-plus range for the ORR to win back the en­thu­si­asm that has drained away for NK­TR-214, a drug that a needy Bris­tol-My­ers Squibb paid $1.85 bil­lion up­front to part­ner on ear­li­er in the year. The drug is de­signed to bind to the CD122 re­cep­tor on the sur­face of CD-8 and CD-4 pos­i­tive im­mune cells to whip up an at­tack on var­i­ous can­cers.

And Diab says they can see ex­act­ly that re­sponse in pa­tients with pos­i­tive bio­mark­er re­sults for the tu­mor mi­croen­vi­ron­ment.

As it stands, the re­searchers have a drug that ap­pears to have clear­ly waned in the more ma­ture 7.2-month me­di­an fol­lowup time for PIV­OT-02, drop­ping from 64% at the first cut of the da­ta at SITC last year. And just days ago Bris­tol-My­ers out­lined im­pres­sive 4-year over­all sur­vival re­sults from Check­Mate-067: 53% for Op­di­vo plus Yer­voy com­bo, 46% for Op­di­vo alone, and 30% for Yer­voy alone.

Diab, though, be­lieves that with bet­ter ex­pe­ri­ence us­ing the drug, and bet­ter ed­u­ca­tion for physi­cians and pa­tients, the re­sponse rate can climb back up to 60%-plus. As for Yer­voy, he adds, the CT­LA-4 has a well known tox pro­file that leads to a high rate of ad­verse events that of­ten pre­vent pa­tients from com­plet­ing treat­ment.

“We should not do com­par­isons with oth­er tri­als, it’s not kosher,” Diab tells me at one point in our con­ver­sa­tion. “But of course we’re go­ing to do it.”

There’s been some in­tense con­tro­ver­sy over their chances with this IL-2 drug, which us­es pe­gy­la­tion tech to elim­i­nate the draw­backs of the orig­i­nal ther­a­py – Pro­leukin — that made it too tox­ic to use at full mea­sure, in turn lim­it­ing its ef­fi­ca­cy.

One like­ly take­down of the Nek­tar de­fense should come soon from Aaron Wed­lund, the ex-Ker­ris­dale an­a­lyst who wrote a lengthy di­a­tribe on NK­TR-214, which he con­sid­ers will make IL-2 the next IDO, an­oth­er drug class once wide­ly hailed as the next big thing in can­cer drug com­bos now bad­ly tar­nished fol­low­ing a cat­a­stroph­ic Phase III com­bo fail­ure with Keytru­da.

Bris­tol-My­ers en­thu­si­as­ti­cal­ly bought in­to the next-gen IL-2 drug ap­proach as it’s been un­suc­cess­ful­ly de­fend­ing its PD-1/L1 crown against a hard-charg­ing Mer­ck, which has pushed Keytru­da and chemo com­bos in­to the fore­front of the lung can­cer mar­ket. IL-2, they said, would be the next log­i­cal step to PD-1 and CT­LA-4, with Yer­voy.

Any­thing that puts this drug back in the Pro­leukin cat­e­go­ry, with more IL-2 suc­ces­sors in the pipeline, won’t be wel­come by the de­vel­op­ers.

It’s im­por­tant to keep in mind that a bunch of short in­vestors had fun — and made mon­ey — pulling Nek­tar’s stock down from some stun­ning highs that it had en­joyed. Rais­ing doubts is good for spurring cor­rec­tions, and Nek­tar’s stock has tum­bled bad­ly. The ju­ry will re­main out, though, un­til the Phase III pro­gres­sion-free sur­vival da­ta comes due around the spring of 2020.

Un­til then, and maybe even af­ter, this de­bate will con­tin­ue to rage.

The DCT-OS: A Tech­nol­o­gy-first Op­er­at­ing Sys­tem - En­abling Clin­i­cal Tri­als

As technology-enabled clinical research becomes the new normal, an integrated decentralized clinical trial operating system can ensure quality, deliver consistency and improve the patient experience.

The increasing availability of COVID-19 vaccines has many of us looking forward to a time when everyday things return to a state of normal. Schools and teachers are returning to classrooms, offices and small businesses are reopening, and there’s a palpable sense of optimism that the often-awkward adjustments we’ve all made personally and professionally in the last year are behind us, never to return. In the world of clinical research, however, some pandemic-necessitated adjustments are proving to be more than emergency stopgap measures to ensure trial continuity — and numerous decentralized clinical trial (DCT) tools and methodologies employed within the last year are likely here to stay as part of biopharma’s new normal.

Onno van de Stolpe, Galapagos CEO (Thierry Roge/Belga Mag/AFP via Getty Images)

Gala­pa­gos chops in­to their pipeline, drop­ping core fields and re­or­ga­niz­ing R&D as the BD team hunts for some­thing 'trans­for­ma­tive'

Just 5 months after Gilead gutted its rich partnership with Galapagos following a bitter setback at the FDA, the Belgian biotech is hunkering down and chopping the pipeline in an effort to conserve cash while their BD team pursues a mission to find a “transformative” deal for the company.

The filgotinib disaster didn’t warrant a mention as Galapagos laid out its Darwinian restructuring plans. Forced to make choices, the company is ditching its IPF molecule ’1205, while moving ahead with a Phase II IPF study for its chitinase inhibitor ’4617.

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An­oth­er failed tri­al for Or­p­hazyme's 'pipeline-in-a-pro­duc­t' leaves shad­ow on drug's fu­ture

The tumultuous ride for Orphazyme continued on Friday as the company announced that a pivotal trial for its lead drug arimoclomol failed yet again, this time in the treatment of ALS, seeding doubt in a drug that had recently been cleared by the FDA for priority review. The latest failure casts a darker shadow on the upcoming decision despite Orphazyme’s upbeat outlook.

In a statement, the Danish biotech announced that the drug did not meet its primary or secondary endpoints evaluating function and survival. But the company has not announced any data surrounding the failure, instead saying that it will publish the complete results later this year.

Angela Merkel (AP Photo/Michael Sohn)

Covid-19 roundup: Pfiz­er sub­mits vac­cine for full ap­proval; Merkel op­pos­es Biden pro­pos­al to sus­pend IP for vac­cines

Pfizer and BioNTech said Friday that they’ve submitted a biologics license application to the FDA for full approval of their mRNA vaccine for those over the age of 16.

How long it will take the FDA to decide on the BLA will be set once it’s been formally accepted by the agency.

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, previously told Endpoints News that the review of the BLA should take between three and four months, but it may be even faster than that.

As­traZeneca caps PD-L1/CT­LA-4/chemo com­bo come­back with OS win. Is treme­li­mum­ab fi­nal­ly ready for ap­proval?

AstraZeneca’s closely-watched POSEIDON study continues to be the rare bright spot in its push for an in-house PD-L1/CTLA-4 combo.

Combining Imfinzi and tremelimumab with physicians’ choice of chemotherapy helped patients with stage IV non-small cell lung cancer live longer, the company reported — marking the first time the still-experimental tremelimumab has demonstrated an OS benefit.

For AstraZeneca and CEO Pascal Soriot, the positive readout — which is devoid of numbers — offers much-needed validation for the big bet they made on Imfinzi plus tremelimumab, after the PD-L1/CTLA-4 regimen failed multiple trials in head and neck cancer as well as lung cancer.

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In­cyte ponies up $12M to set­tle char­i­ty foun­da­tion kick­back claims; US ex­er­cis­es op­tion for more dos­es of mon­key­pox vac­cine

One in a string of lawsuits targeting copay charity foundations, the DOJ has been hunting drugmaker Incyte for what prosecutors alleged was a kickback scheme to court patients. Now, Incyte is clearing its name.

Incyte will shell out $12.6 million to settle claims it funneled funds through a charity foundation to cover federal copays for patients taking its JAK inhibitor Jakafi, the DOJ said this week.

Stéphane Bancel, Getty

Mod­er­na CEO brush­es off US sup­port for IP waiv­er, eyes more than $19B in Covid-19 vac­cine sales in 2021

Moderna is definitively more concerned with keeping pace with Pfizer in the race to vaccinate the world against Covid-19 than it is with Wednesday’s decision from the Biden administration to back an intellectual property waiver that aims to increase vaccine supplies worldwide.

In its first quarter earnings call on Thursday, Moderna CEO Stéphane Bancel shrugged off any suggestion that the newly US-backed intellectual property waiver would impact his company’s vaccine or bottom line. Still, the company’s stock price fell by about 9% in early morning trading.

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CEO Khurem Farooq (Gyroscope)

Hours be­fore ex­pect­ed de­but, Gy­ro­scope post­pones its IPO as 2 oth­er biotechs hold the line on their march to Nas­daq

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

In a surprising turn of events, UK-based Gyroscope Therapeutics has postponed its IPO mere hours before it was set to debut on Nasdaq.

Working on a gene therapy for wet AMD, Gyroscope was all set and ready to go public earlier this week, setting terms for a $142 million raise with a price range of $20 to $22. But in the wee hours of Friday morning, the company put out a press release saying they would delay their debut “in light of market conditions,” CEO Khurem Farooq said in a statement.

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Karyopharm taps long­time Pfiz­er, Am­gen vet to steer the ship; With Mer­ck in the rearview mir­ror, Roger Perl­mut­ter stakes his claim to a CEO job — and it's a sur­pris­ing choice

Like many who work in biopharma, Richard Paulson got started in the field because of a love of science.

Paulson had just finished business school and was looking to start a career that married his two passions. While looking for jobs, he thought of his grandmother who had struggled with Alzheimer’s disease, recalling how he saw first-hand what innovative medicines can do for patients. Ultimately, he started his first job in the space as a sales rep at Glaxo Wellcome, one of GlaxoSmithKline’s predecessors before its merger with SmithKline Beecham in 2000.