Nek­tar wants every­one to stay calm as they car­ry on with NK­TR-214, but #AS­CO18 spurs a stam­pede

CHICA­GO — Bris­tol-My­ers Squibb $BMY has gone all in on Nek­tar’s $NK­TR ap­proach to amp­ing up their check­point strat­e­gy, part­ner­ing on NK­TR-214. But in­stead of tak­ing a bow at #AS­CO18 on pos­i­tive da­ta, re­searchers spent the week­end ex­plain­ing why their lat­est da­ta read­out from a small study shouldn’t be cause for pan­ic.

It’s not what they were look­ing for, to put it mild­ly.

Mary Tagli­a­fer­ri

Un­like most of the more close­ly-watched pro­grams here at AS­CO, the re­searchers in­volved nev­er of­fered a pre­view of the da­ta that came out Sat­ur­day evening. And that was a se­ri­ous mis­step, par­tic­u­lar­ly as the re­porters cov­er­ing this ses­sion strug­gled to fig­ure out what was be­ing re­port­ed — and what it meant.

As it hap­pens, in­ves­ti­ga­tors ex­e­cut­ed a two-stage tri­al process, sign­ing up a small group of pa­tients to test the drug in dif­fer­ent can­cer types, then mov­ing on to the next stage with a new group of re­cruits. Do­ing that, says Mary Tagli­a­fer­ri, the chief med­ical of­fi­cer at Nek­tar, meshed well with their strat­e­gy for jump­ing in­to late-stage stud­ies as they com­mu­ni­cat­ed with reg­u­la­tors.

“The goal,” she tells me, “was al­ways to as­sess mov­ing very quick­ly in­to Phase III.”

In­vestors, though, weren’t hap­py with the way this all came down, and they bolt­ed when the mar­ket opened, with Nek­tar’s stock plung­ing a sting­ing 32% — ex­act­ly the kind of rout that Bris­tol-My­ers (down 1.6%) doesn’t need right now as it tries to re­store con­fi­dence in its pipeline. And it kept get­ting worse lat­er in the day, with shares down 42%.

Here’s what Nek­tar has found so far.

In their melanoma project, re­searchers saw that 11 of 13 pa­tients treat­ed with a com­bi­na­tion of Op­di­vo and NK­TR-214 re­spond­ed in round 1 — which is out­stand­ing. But, when they added 15 more pa­tients, they on­ly boost­ed their re­sponse rate by 3 pa­tients. And 3 out of 15 is not out­stand­ing.

In kid­ney can­cer, the step one re­sponse rate of 64% was fol­lowed up with an over­all step 2 rate of 46%.

In­vestors hate to see a falling re­sponse rate, for any rea­son, as it in­di­cates a prob­lem that can se­ri­ous­ly af­fect a can­cer drug’s longterm fi­nan­cial suc­cess.

Twit­ter’s day-trad­ing crew picked it up from there, with all sorts of #AS­CO18 chat­ter about a tri­al dis­as­ter in the mak­ing. And as of­ten hap­pens, Twit­ter is not a great source of re­al-time in­for­ma­tion, par­tic­u­lar­ly when the com­pa­nies failed to ex­plain what the num­bers meant with an­a­lysts.

In the fol­lowup dis­cus­sion, though, Tagli­a­fer­ri of­fered the ra­tio­nale that it’s ear­ly days for the sec­ond batch­es of pa­tients and they ex­pect to see more re­spons­es with time. And they have rea­son to be­lieve that, af­ter track­ing a 46% ORR in RCC at SITC that has now grown to 71% at AS­CO.

“You’ll see the ORR go­ing up,” says Tagli­a­fer­ri, as they have a chance to col­lect mul­ti­ple scans on the sec­ond-stage pa­tients. “It s a lit­tle frus­trat­ing that peo­ple aren’t un­der­stand­ing that.”

Al­so im­por­tant, they say, is clear ev­i­dence that the com­bi­na­tion of NK­TR-214 is do­ing what they re­al­ly want­ed: Spark­ing re­spons­es in PD-L1 neg­a­tive tu­mors where Op­di­vo is not suc­cess­ful. If that all plays out in the am­bi­tious piv­otal pro­gram now un­der­way, it will eas­i­ly jus­ti­fy Bris­tol-My­ers’ record $3.6 bil­lion wa­ger.

If not….

In melanoma, re­searchers saw 5 out of 11 PD-L1 neg­a­tive pa­tients re­spond; in kid­ney can­cer it was 9 out of 17, or 53%. Those num­bers are fine.

Right now, though, they’ve cre­at­ed an at­mos­phere of doubt that will make every turn of da­ta a cat­a­lyst for the gam­blers now lin­ing up their bets for and against the com­bi­na­tion. That will ei­ther help or hurt these com­pa­nies, which are now bet­ting heav­i­ly that step 2 will ul­ti­mate­ly play out in their fa­vor.

We’ll find out more at the next SITC con­fer­ence in No­vem­ber, Tagli­a­fer­ri adds, with ab­stracts due in Au­gust.

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)

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

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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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Angela Merkel (AP Photo/Michael Sohn)

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

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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.

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The European Medicines Agency’s safety committee said Friday that it’s aware of cases of inflammation of the heart muscle and inflammation of the membrane around the heart, mainly reported following vaccination with Pfizer’s Covid-19 vaccine, known in Europe as Comirnaty.

“There is no indication that these cases are due to the vaccine,” the EMA’s Pharmacovigilance Risk Assessment Committee said.

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Ron DePinho (file photo)

A 'fly­over' biotech launch­es in Texas with four Ron De­Pin­ho-found­ed com­pa­nies un­der its belt

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“If it doesn’t come out of MGH or MIT or Harvard, probably not that interesting,” he said of the mindset.

Now, he and some well-known industry players are looking to change that, and they’ve reeled in just over $38 million to do it.

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