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.

Zo­genix plans quick re­turn to the FDA with their spurned ap­pli­ca­tion on Dravet syn­drome drug — shares spike

Zo­genix shares are claw­ing back some of the val­ue they lost 2 months ago af­ter the FDA hit the biotech with a refuse-to-file no­tice on their ex­per­i­men­tal ther­a­py for Dravet syn­drome. 

Com­pa­ny ex­ecs said this morn­ing that they worked out reg­u­la­tors’  is­sues with the ap­pli­ca­tion for Fin­tepla, which cen­tered on a pair of big prob­lems: the ab­sence of non-clin­i­cal stud­ies need­ed to al­low as­sess­ment of the chron­ic ad­min­is­tra­tion of fen­flu­ramine and the in­clu­sion of an in­cor­rect ver­sion of a clin­i­cal dataset. Now they plan to re­sub­mit in Q3 af­ter get­ting off the hook on both scores — which trig­gered a sigh of re­lief among in­vestors.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Turned back at the FDA, Im­muno­Gen is ax­ing 220 staffers, sell­ing pro­grams and hun­ker­ing down for a new PhI­II gam­ble

After being stymied by FDA regulators who were unconvinced by ImmunoGen’s $IMGN desperation shot at an accelerated OK based on a secondary endpoint, the struggling biotech is slashing its workforce, shuttering R&D projects and looking for buyers to pick up some of its experimental cancer assets as it goes back into a new Phase III with the lead drug.

We found out last month that the FDA had batted back their case for an accelerated approval of their antibody-drug conjugate mirvetuximab soravtansine, which had earlier failed a Phase III study for ovarian cancer. Now the other shoe is dropping.

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Novavax site in Gaithersburg, MD. Novavax

Beef­ing up its new gene ther­a­py unit, Catal­ent inks $18M deal to snap up No­vavax fa­cil­i­ties

Catal­ent’s hunt for rapid growth on the gene ther­a­py front — ce­ment­ed with a $1.2 bil­lion ac­qui­si­tion of Paragon Bio­sciences two months ago — has led them to the vac­cine mak­ers at No­vavax.

With an $18 mil­lion pay­ment, Paragon is tak­ing over two No­vavax sites in Gaithers­burg, MD, in­clud­ing more than 100 of the em­ploy­ees al­ready work­ing there. That’s in ad­di­tion to a sig­nif­i­cant re­duc­tion in op­er­at­ing costs, says the com­pa­ny, as No­vavax shifts to re­ly on Paragon for GMP ma­te­ri­als in clin­i­cal tri­als and, even­tu­al­ly, com­mer­cial sup­ply of their prod­ucts.

As­traZeneca chal­lenges Roche on front­line SCLC af­ter seiz­ing an in­ter­im win — and Mer­ck may not be far be­hind

The crowded playing field in the PD-1/L1 marketing game is about to get a little more complex.

This morning AstraZeneca reported that its CASPIAN study delivered a hit in an interim readout for their PD-L1 Imfinzi combined with etoposide and platinum-based chemotherapy options for frontline cases of small cell lung cancer, a tough target which has already knocked back Bristol-Myers’ shot in second-line cases. The positive data  — which we won’t see before they roll it out at an upcoming scientific conference — give AstraZeneca excellent odds of a quick vault to challenging Roche’s Tecentriq-chemo combo, approved 3 months ago for frontline SCLC in a landmark advance.

“This is the first trial offering the flexibility of combining immunotherapy with different platinum-based regimens in small cell lung cancer, expanding treatment options,” noted AstraZeneca cancer R&D chief José Baselga in a statement.

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Bridge­Bio takes crown for biggest biotech IPO of 2019, as fel­low uni­corn Adap­tive rais­es of­fer­ing size and price

Bridge­Bio Phar­ma and Adap­tive Biotech­nolo­gies have not just up­sized IPO of­fer­ings — the pair of uni­corns have al­so raised their of­fer­ing prices above the range, haul­ing in a com­bined $648.5 mil­lion.

Neil Ku­mar’s Bridge­Bio Phar­ma, found­ed in 2015, has a sta­ble of com­pa­nies fo­cused on dis­eases that are dri­ven by de­fects in a sin­gle gene — en­com­pass­ing der­ma­tol­ogy, car­di­ol­o­gy, neu­rol­o­gy, en­docrinol­o­gy, re­nal dis­ease, and oph­thal­mol­o­gy — and can­cers with clear ge­net­ic dri­vers. The start­up mill birthed a pletho­ra of firms such as Ei­dos, Navire, QED Ther­a­peu­tics and Pelle­Pharm, which func­tion as its sub­sidiaries.

Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.