#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.

Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Mi­rati preps its first look at their KRAS G12C con­tender, and they have to clear a high bar for suc­cess

If you’re a big KRAS G12C fan, mark your calendars for October 28 at 4:20 pm EDT.

That’s when Mirati $MRTX will unveil its first peek at the early clinical data available on MRTX849 in presentations at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Mirati has been experiencing the full effect of a rival’s initial success at targeting the G12C pocket found on KRAS, offering the biotech some support on the concept they’re after — and biotech fans a race to the top. Amgen made a big splash with its first positive snapshot on lung cancer, but deflated sky-high expectations as it proved harder to find similar benefits in other types of cancers.

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The FDA will hus­tle up an ex­pe­dit­ed re­view for As­traZeneca’s next shot at a block­buster can­cer drug fran­chise

AstraZeneca paid a hefty price to partner with Daiichi Sankyo on their experimental antibody drug conjugate for HER2 positive breast cancer. And they’ve been rewarded with a fast ride through the FDA, with a straight shot at creating another blockbuster oncology franchise.

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Sean Parker, AP

Sean Park­er helps cre­ate a CRISPRed cell ther­a­py 2.0 play — and he’s got a high-pro­file set of lead­ers on the team

You can rack up one more high-profile debut effort in the wave of activity forming around cell therapy 2.0. It’s another appealing Bay Area group that’s attracted some of the top hands in the business to a multi-year effort to create a breakthrough. And they have $85 million in hand to make that first big step to the clinic.

Today it’s Ken Drazan and the team at South San Francisco-based ArsenalBio that are coming from behind the curtain for a public bow, backed by billionaire Sean Parker and a collection of investors that includes Beth Seidenberg’s new venture investment operation based in LA.
Drazan — a J&J Innovation vet with a long record of entrepreneurial endeavors — exited the stage in 2018 when his last mission ended as he stepped aside as president of Grail. It wasn’t long, though, before he was helping out with a business plan for ArsenalBio that revolved around the work of a large group of interconnected scientists supported by the Parker Institute for Cancer Immunology.
The biotech started by putting together an “arsenal” of technologies aimed at making cell therapies for cancer much, much better than the rather crude first-generation drugs that hit the market from Novartis and Kite.
Their drugs have become the baseline against which all others are being measured.
“The technology set we’re developing is independent of the chassis,” Drazan tells me. “It doesn’t have to be autologous (extracted from the patient) or allogeneic (off the shelf). It doesn’t have to be a T cell, it could be a B cell.” But they are starting out on the autologous side, where they have the most knowledge and insight into manufacturing techniques.
It also doesn’t have to be close to the clinic.
Drazan expects the biotech will be working its way through preclinical operations for “a few years,” with enough money from the $85 million launch round to get into humans.
By today’s superheated fundraising standards, that’s not a huge amount of cash. Lyell, another cell therapy 2.0 startup we featured last week, raised $600 million in a year, including a big chunk of cash from GlaxoSmithKline. Drazan is interested in dealmaking as well, but he also knows he has the cash necessary to support the company for a good run — a key part of what it takes to bring together a stellar team of top players.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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UCB tries to win some re­spect in the crowd­ed pso­ri­a­sis mar­ket with a dual IL-17 ap­proach — and it won't be easy

For a pharma company with about $5 billion in revenue, a couple of respectably sized blockbuster drugs on the market and some high-profile partners like Amgen, Belgium’s UCB has kept an unusually low profile on the pipeline side of things over the years.
Until now.
Just days after striking a $2.1 billion deal to buy Ra Pharmaceuticals and its C5 rival to Soliris, UCB is posting positive top-line Phase III results for a dual IL-17 inhibitor that it’s steering into one of the most competitive commercial spaces in the industry. And despite plenty of obvious challenges as they struggle to roll out Evenity with Amgen and patent expirations loom on its franchise drugs, including Cimzia, the company just may be ready to tackle some of the biggest players on the planet.
In their first of 3 Phase III studies for bimekizumab, researchers touted top-line wins on statistically significant results on clearing plaque psoriasis, including a victory over J&J’s IL-23 contender Stelara on key endpoints. The drug targets both IL-17A and IL-17F, a modification on the IL-17A strategy laid out for Taltz (Eli Lilly) and Cosentyx (Novartis). And the new group also includes J&J’s Tremfya and AbbVie’s Skyrizi.
We don’t know the PASI90 and IGA scores — but UCB knows that with the kind of heavyweight competition it faces with Novartis and others, marginal gains for patients won’t stack up. So we’ll be watching for the hard numbers. And there’s another head-to-head with Cosentyx that will play a big role in pushing up analysts’ projections on peak sales, which currently fall well short of blockbuster status.
UCB hasn’t exactly been in the spotlight for the last few years, but it’s in a position now that the company has to win some respect in R&D, with blockbuster projects that can keep investors’ attention at a time the industry is experiencing booming R&D development efforts around the planet.
It hasn’t been easy. There was a setback on a lupus drug partnered with Biogen. But there have been some advances, with a deal to buy Proximagen’s NDA-ready nasal spray therapy USL261, designed as a rescue therapy for acute repetitive seizures, for $150 million in cash and another $220 million in sales and regulatory milestones. There was even a report that the company was kicking the deflated tires at Acorda, though nothing came of that.
Late last year UCB also committed to spend up to £200 million on a new R&D hub in the UK.
That may not translate into a lot of excitement right now, but they’re trying. And there’s a subtle promise that more deals may be in the works.

Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

Swamy Vijayan. Plexium

San Diego up­start de­buts dis­cov­ery en­gine that puts a twist to pro­tein degra­da­tion

For years, the idea of protein degradation — utilizing the cell’s natural garbage disposal system to mark problematic proteins for destruction — remained an elegant but technically difficult concept. But now established as a promising clinical strategy, with major biopharma players such as Bayer, Gilead and Vertex trying to grab a foothold via partnership deals, a San Diego startup is looking to exploit it and push its limits.

CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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