#AACR17: Fresh from Mer­ck em­brace, fast-grow­ing In­cyte piv­ots in­to a PhI­II IDO1/Op­di­vo tie-up with Bris­tol-My­ers

PHO­TO: © AACR/Todd Buchanan 2017


Wash­ing­ton, DC — Two days af­ter In­cyte out­lined how it tied the knot with Mer­ck on a slate of six late-stage stud­ies com­bin­ing its check­point Keytru­da with the biotech’s IDO1 drug epaca­do­stat, ze­ro­ing in on front­line use, In­cyte has piv­ot­ed in­to a part­ner­ship on three stud­ies with Bris­tol-My­ers Squibb’s ri­val check­point Op­di­vo.

Like Mer­ck, Bris­tol-My­ers is look­ing for piv­otal da­ta on a front­line com­bo to tack­le non-small cell lung can­cer. And they’re adding a Phase III study that tack­les head and neck can­cer while ex­pand­ing an on­go­ing Phase I/II to in­clude an­ti-PD-1/PD-L1 re­lapsed/re­frac­to­ry co­horts of melanoma pa­tients.

Like its pact with Mer­ck, In­cyte $IN­CY is shar­ing the cost of the piv­otal work with Bris­tol-My­ers, look­ing to pen­e­trate a slate of can­cer mar­kets with lead­ers in the field. And as Mer­ck is tak­ing the lead on do­ing the re­search work on their pact, Bris­tol-My­ers is do­ing the same, In­cyte CEO Hervé Hop­penot tells me.

In­vestors loved the move in­to late-stage test­ing across a broad front, send­ing shares up 5% by late af­ter­noon on Mon­day.

Iron­i­cal­ly, In­cyte emerges from these back-to-back deals con­tin­u­ing to be close­ly al­lied with the two top play­ers in check­point in­hi­bi­tion. Mer­ck re­cent­ly seized the in­side track on non-small cell lung can­cer, leapfrog­ging a flail­ing Bris­tol-My­ers which was ham­mered — and not for the first time — as it re­cent­ly re­vealed that its com­bi­na­tion of Op­di­vo and the CT­LA-4 drug Yer­voy would not be head­ed to an ac­cel­er­at­ed re­view. And In­cyte is al­so al­ready en­gaged in pacts with As­traZeneca and Genen­tech on their check­points as well.

Hervé Hop­penot, In­cyte CEO

How about Baven­cio (avelum­ab), the new­ly ap­proved check­point from Mer­ck KGaA and Pfiz­er? I ask Hop­penot.

“We’re open to it,” he re­sponds with a ready smile.

In­cyte not on­ly has part­ner­ships with a line­up of key play­ers, it has its own check­point in de­vel­op­ment as well. (Just as Bris­tol-My­ers has its own IDO1 in ear­ly de­vel­op­ment.) The biotech is op­er­at­ing on the no­tion that epaca­do­stat has the po­ten­tial to be tied to a va­ri­ety of check­points for a list of dif­fer­ent can­cer types.

“I don’t think any­one knows how things will end up,” says Hop­penot, who views these de­vel­op­ment pacts as short term com­mit­ments. If the tri­als pan out as hoped, he says that the lead­ing IDO1 drug could be pre­scribed in com­bi­na­tions, a lu­cra­tive rev­enue source for the com­pa­ny. The deals do not in­clude com­mer­cial part­ner­ships.

In­cyte an­nounced the lat­est deal with Bris­tol-My­ers ear­ly Sun­day, as AACR was get­ting start­ed in Wash­ing­ton DC.

One of the rea­sons why IDO1 and check­points are so at­trac­tive, Hop­penot says, is that a tar­get­ed ther­a­py like an IDO1 — fo­cused on the tu­mor mi­croen­vi­ron­ment — could have a bet­ter shot at suc­cess with a check­point than, say, a PD-1 check­point and CT­LA-4 (like Yer­voy) where you’re adding a sys­temic drug that could trig­ger safe­ty is­sues for pa­tients.

The first one of these piv­otal com­bo stud­ies will be the Keytru­da/epaca­do­stat com­bo study that reads out in 2018, just around the cor­ner in R&D terms.

Leerink’s Sea­mus Fer­nan­dez en­thu­si­as­ti­cal­ly signed off on the lat­est Bris­tol-My­ers pact Mon­day morn­ing. He not­ed:

In our view, BMY’s de­ci­sion to fol­low MRK dra­mat­i­cal­ly re­duces the risk that Op­di­vo will be at risk even if the com­bi­na­tion with IDO is ul­ti­mate­ly deemed clin­i­cal­ly su­pe­ri­or to the com­bi­na­tion of CT­LA4 + PD1/PDL1. Fur­ther­more, as bio­mark­ers evolve and new treat­ment ap­proach­es evolve and emerge, it is like­ly that the PD1/PDL1 agents with the broad­est la­bels are most like­ly to ben­e­fit from this seg­men­ta­tion of the mar­ket. This “all com­ers” ap­proach to com­bi­na­tions high­lights what like­ly will con­tin­ue to be an ex­tra­or­di­nary cost of IO de­vel­op­ment and the race for lead­er­ship.

This is a crit­i­cal time for In­cyte, which is one of the biotechs most fre­quent­ly men­tioned as a like­ly takeover tar­get by over-caf­feinat­ed an­a­lysts ea­ger to pre­dict the next M&A deal. The staff of the Wilm­ing­ton, DE-based com­pa­ny has bro­ken past the 1,000 mark, with 850 in the US and the rest in Eu­rope — where In­cyte picked up the Ari­ad op­er­a­tions last May – well ahead of the Take­da buy­out in the US – for $140 mil­lion up front.

More than half of In­cyte’s staff is in R&D, with more than 200 sci­en­tists in the op­er­a­tion. And Hop­penot tells me he’s in­tent on build­ing a “flat” or­ga­ni­za­tion that is bro­ken in­to three dis­tinct re­gions: the US, Eu­rope and next in Japan.

“The ques­tion was how to be­come big with­out be­com­ing stu­pid,” says the CEO, a vet­er­an of the glob­al phar­ma gi­ant No­var­tis.

In­cyte now has 14 drugs in the clin­ic, a grow­ing top line with Jakafi sales, with rev­enue break­ing past the $1 bil­lion mark last year. These new and re­vamped pacts have helped dri­ve a big fo­cus on the pipeline.

Back in ear­ly 2015, In­cyte paid $60 mil­lion for an up­front and eq­ui­ty and promised up to $350 mil­lion in mile­stones to jump on board Agenus’s an­ti­body dis­cov­ery plat­form. That deal cov­ered a slate of check­point reg­u­la­tors that could be cru­cial to In­cyte’s fu­ture cov­er­ing GITR, OX40, LAG-3 and TIM-3. And a few weeks ago that 50/50 deal was re­jigged to leave In­cyte with the reins, with Agenus tak­ing cash and roy­al­ties in lieu of the split orig­i­nal­ly planned.

Late last year In­cyte em­braced Dutch biotech Merus and its bis­pe­cif­ic an­ti­body tech, agree­ing to buy in­to a new dis­cov­ery and de­vel­op­ment col­lab­o­ra­tion that start­ed with $200 mil­lion in an up­front and eq­ui­ty pay­ment and has the po­ten­tial to earn bil­lions more if it ma­tures in­to a co-com­mer­cial­iza­tion arrange­ment.

The key to mak­ing this all work, says Hop­penot, is to cre­ate sep­a­rate or­ga­ni­za­tions that can op­er­ate vir­tu­al­ly — though not en­tire­ly — in­de­pen­dent­ly, with­out a large hi­er­ar­chy over­see­ing every as­pect of de­vel­op­ment, slow­ing things down.

“We are a fast grow­ing com­pa­ny,” says Hop­penot. “That is not go­ing to change.”

And he isn’t about to guar­an­tee that every­thing now in the clin­ic will work.

“Some of it is go­ing to flop,” says the for­mer No­var­tis can­cer chief, who took the helm at In­cyte three-and-a-half years ago. It’s not tak­ing in­tel­li­gent, fo­cused risks that he finds a much big­ger threat. And so far, it’s all work­ing in his fa­vor.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.

The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 94,200+ biopharma pros reading Endpoints daily — and it's free.