That $1.25B Bris­tol-My­ers IDO1 drug? In­cyte claims a for­mer staffer stole it

Ter­ry Rosen

When Bris­tol-My­ers Squibb agreed to pay up to a jaw-drop­ping $1.25 bil­lion to ac­quire the fledg­ling biotech Flexus back in ear­ly 2015 for the sole pur­pose of gain­ing con­trol of a pre­clin­i­cal IDO1 drug, the math seemed to de­fy every known stan­dard on overnight biotech wind­falls.

The 18-month-old biotech had just lined up a $38 mil­lion round from Klein­er Perkins, Cel­gene and The Col­umn Group. In a world where a 10X pay­off af­ter a few years is con­sid­ered a home run, Bris­tol-My­ers’ $800 mil­lion up­front, with $450 mil­lion in ear­ly-stage mile­stones, for a drug that had yet to go in­to hu­mans was done on a whole new lev­el.

“We had a da­ta set that sug­gest­ed it has the po­ten­tial to be best-in-class, with the abil­i­ty for a part­ner to com­bine it with many oth­er as­sets,” Flexus co-founder Ter­ry Rosen told me at the time. “If you look at any com­pa­ny work­ing in on­col­o­gy, it can po­ten­tial­ly in­crease the val­ue of a whole port­fo­lio of as­sets. It could be mul­ti­plica­tive and that cre­ates a big val­u­a­tion.”

What went large­ly (though not en­tire­ly) un­no­ticed at the time was that a fu­ri­ous In­cyte — the wide­ly rec­og­nized leader in IDO1 now in late-stage test­ing with one of the most close­ly-watched pro­grams in on­col­o­gy — quick­ly went to war over the deal.

The com­pa­ny claimed that Jor­dan Frid­man, a sci­en­tist in its ranks, had sys­tem­at­i­cal­ly lift­ed its IDO1 se­crets be­fore mak­ing his way to Flexus. In a law­suit filed against Rosen and Juan Jaen seek­ing more than a bil­lion dol­lars in dam­ages, In­cyte claimed that Frid­man had been de­mand­ing in­for­ma­tion on their IDO1 work in the three months he re­mained at In­cyte af­ter giv­ing no­tice.

Lat­er in 2014, ac­cord­ing to a law­suit In­cyte filed against Flexus, Frid­man “false­ly told In­cyte’s em­ploy­ees that Flexus did not have an IDO-1 in­hibitor project and that he was no longer work­ing on IDO-1 in­hibitors.” But then he al­leged­ly ad­mit­ted his in­volve­ment lat­er that year.

The News Jour­nal in Delaware cov­ered the case in a big fea­ture to­day, which is like­ly to re­fo­cus con­sid­er­able at­ten­tion on Bris­tol-My­ers’ IDO1 work on BMS-986205, which is now be­ing stud­ied in com­bi­na­tion with its big check­point in­hibitor Op­di­vo. Ac­cord­ing to the re­port, the case is head­ed to court next year.

Lawyers for Rosen and Jaen de­nied the claims and seem ready to fight it out in front of a judge.

In an ab­stract post­ed at AACR last April, Bris­tol-My­ers — which like its ri­vals is part­nered with In­cyte’s IDO1 epaca­do­stat — boast­ed about the clear po­ten­tial they were see­ing in their ear­ly-stage in-house pro­gram. Ac­cord­ing to their ab­stract:

Ev­i­dence of sub­stan­tial serum kyn re­duc­tion was ob­served at dos­es as low as 25 mg QD; in­hi­bi­tion at 100 and 200 mg QD ap­pears greater than that re­port­ed for oth­er in-class com­pounds. In ad­di­tion, we have pre­sent­ed the first ev­i­dence of in­tra­tu­moral kyn re­duc­tion by an IDO1 in­hibitor. These da­ta sug­gest the po­ten­tial of BMS-986205 as an IDO1 in­hibitor with su­pe­ri­or PD prop­er­ties and sup­port fur­ther eval­u­a­tion in com­bi­na­tion with ni­vo.

Ever­cor­eISI’s Umer Raf­fat just days ago put out a note say­ing that he thinks the Bris­tol-My­ers drug could be bet­ter than In­cyte’s — with one cru­cial dif­fer­ence. He wrote: “(R)ather than sim­ply pre­vent the en­zyme’s sub­strate from bind­ing, BMY’s in­hibitor wrecks the whole struc­ture of the ac­tive site, form­ing the ba­sis for a po­ten­tial­ly ir­re­versible in­hibitor.”

The Bris­tol-My­ers drug is now in three dif­fer­ent stud­ies, ac­cord­ing to the list­ings on clin­i­cal­tri­, in­clud­ing a Phase II rapid-fire set of com­bi­na­tion tests for non-small cell lung can­cer. And Phase I/II da­ta is due at the up­com­ing SITC con­fer­ence in ear­ly No­vem­ber.

Frid­man, who’s not a named par­ty in the law­suit, went on to join an­oth­er Klein­er Perkins start­up called FLX Bio as the CSO. A spokesper­son for the com­pa­ny, though, says he’s left the biotech.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Deborah Dunsire

The fourth CGRP mi­graine drug is here. Time for Lund­beck to prove it's worth $2B

They may be late, but Lundbeck is now officially in the game for preventing migraine with CGRP drugs.

The FDA has OK’d eptinezumab, the prize in Lundbeck’s $2 billion acquisition of Alder. Like rival offerings from Amgen/Novartis, Eli Lilly and Teva, the antibody blocks the calcitonin gene-related peptide, which is believed to dilate blood vessels in the brain and cause pain.

It will now be sold as Vyepti. The company has yet to announce a price. Amgen and Novartis had set the wholesale acquisition cost of their pioneering Aimovig at $6,900 for a year’s supply before raising it slightly this year; Lilly and Teva had followed suit with Emgality and Ajovy.

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Special report

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

“We’re kind of like the old comfortable shoe,” Esperion’s chief commercial officer Mark Glickman remarked in an interview with Endpoints News ahead of the decision date. “It’s an oral product, once-daily and nontitratable — these are things that just resonate so true with patients and physicians and I think we’ve kind of forgotten about that.”

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

As it stands, the antibiotic market is cursed — it harbors the stink of multiple bankruptcies, a dearth of innovation, and is consequently barely whetting the voracious appetites of big pharma or venture capitalists. Enter artificial intelligence — the biopharma industry’s cure-all for the pesky process of making a therapeutic, including data mining, drug discovery, optimal drug delivery, and addressable patient population.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

Gilead sustained two more losses in their efforts to rid themselves of an activist-backed patent lawsuit from the US government over a best-selling HIV pill.

Urged on by activists seeking to divert a portion of Gilead’s revenue to clinics and prevention programs, the Department of Health and Human Services made a claim to some of the patents for the best-selling HIV prevention drug, Truvada, also known as PrEP. Gilead responded by arguing in court that HHS’s patents were invalid.

Today, the US Patent and Trademark Office ruled that Gilead was likely to lose the last two of those challenges as well. The USPTO ruled against Gilead on the first two patents earlier this month.

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Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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