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.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Israel Lowy (Regeneron)

#ES­MO20: 'As good as any PD-1 out there': Re­gen­eron flash­es PD-(L)1 lung can­cer da­ta to ri­val Mer­ck

Regeneron entered the PD-(L)1 game late, so they devised a two-pronged strategy to catch up with Big Pharma rivals: They would push it into cancers where PD-1s had yet been tested, and they would prove that it’s as powerful in the big indications as any other on the market.

They cleared a hurdle on the first goal Friday, showing a 31% response in patients with the rare skin cancer basal cell carcinoma. And with the data they’re rolling out Monday, Regeneron cancer chief Israel Lowy is ready to declare success on the second.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Donald Trump, AP

Covid-19 roundup: Trump sug­gests Pfiz­er vac­cine could be first ap­proved; VBI Vac­cines inks de­vel­op­ment deal with Cana­da

President Donald Trump commented Monday morning that Pfizer’s Covid-19 vaccine candidate could be the first to win approval by regulators.

During an interview on a Fox News’ morning show, the president said Pfizer was doing “very well” when asked which candidate could be approved, according to a Reuters report. He added that J&J could follow up afterward, saying “they’ll probably be a little later.”

Is­raeli biotech rais­es $57M to go where cur­rent BRAF in­hibitors can't, with back­ing from No­var­tis, SR One

For the blockbuster potential of Novartis’ Tafinlar and Pfizer’s Braftovi, all the BRAF inhibitors on the market so far only target V600 mutations — which accounts for roughly 50% of patients.

Israeli biotech Novellus now has $57 million to develop a drug that they say can help the other 50% who have everything else.

The Series C will fund a Phase II trial for PLX-8394, a “paradox breaker” that could block RAF without activating MAPK signaling. In a Phase I trial, a patient with a BRAF fusion saw their tumor go away after taking the drug, allowing Novellus to hit the ground running.