Keytru­da/epaca­do­stat com­bo crash­es in PhI­II melanoma study, rais­ing ques­tions about the fu­ture of IDO for In­cyte

A close­ly-watched Phase III study com­bin­ing Mer­ck’s PD-1 star Keytru­da with In­cyte’s IDO1 drug epaca­do­stat for metasta­t­ic melanoma has failed, cast­ing a pall over the fu­ture of this com­bi­na­tion ap­proach.

Ab­sent a sig­nif­i­cant im­prove­ment in pro­gres­sion-free sur­vival, as well as the like­ly fail­ure of the drug com­bi­na­tion to ex­tend over­all sur­vival, the in­ves­ti­ga­tors are halt­ing the study. In­cyte stuck with the top-line re­sults in their re­lease, promis­ing to roll out the full da­ta set lat­er. And they made it clear in a call with an­a­lysts this morn­ing that the ECHO-301 study fail­ure “has a neg­a­tive im­pact on the prob­a­bil­i­ty of suc­cess of the oth­er (com­bi­na­tion) stud­ies” — send­ing a shock wave through the I/O field.

In­cyte’s shares plunged 23% on the news, wip­ing out more than $3.5 bil­lion in mar­ket cap. The im­pli­ca­tions for oth­er IDO1 drugs al­so dam­aged oth­er com­pa­nies in the field, in­clud­ing NewLink $NLNK, down 44%, as well as Bris­tol-My­ers Squibb $BMY down 2.6%.

Steven Stein

Mer­ck is one of a slate of bio­phar­ma com­pa­nies to com­bine their check­points with In­cyte’s IDO drug, look­ing to im­prove pa­tients chances for liv­ing longer with can­cer. The fail­ure of this first late-stage test, af­ter stok­ing hopes for some ma­jor ad­vances, now leaves In­cyte’s drug $IN­CY in a pre­car­i­ous po­si­tion, cre­at­ing a cri­sis for CEO Hervé Hop­penot.

Epaca­do­stat was num­ber 3 on Eval­u­ate Phar­ma’s top 10 list of 2018 launch­es, with close to $2 bil­lion in pro­ject­ed peak sales es­ti­mates. And UBS an­a­lysts gave this study a 100% chance of suc­cess, not­ing the high ex­pec­ta­tions — and hype — fo­cused on this drug.

In­ves­ti­ga­tors tracked a haz­ard ra­tio of 1.00, which “leaves no doubt that in this study… the com­pound didn’t per­form,” said Steven Stein, the chief med­ical of­fi­cer, in the call. And there was no pos­i­tive glim­mer of hope seen in any sub­group analy­sis. “Giv­en those haz­ard ra­tios it is go­ing to be dif­fi­cult to dis­cern a sub­group with suf­fi­cient ef­fect.”

The fail­ure of the study al­so rais­es the chances that oth­er tri­als in the pro­gram may need to be ad­just­ed, he added, with pos­si­ble sta­tis­ti­cal and bio­mark­er mod­i­fi­ca­tions.

An­a­lysts had been en­cour­aged last sum­mer with the lat­est look at da­ta from a sin­gle-arm melanoma study, mak­ing this one of the most an­tic­i­pat­ed stud­ies of 2018. In­cyte faces a dif­fi­cult task now in re­build­ing hopes for a block­buster fu­ture as the field awaits a long string of read outs from com­bi­na­tion tri­als.

An­tic­i­pat­ing some big re­turns, a whole host of play­ers has dived in­to IDO. A re­cent study from the Can­cer Re­search In­sti­tute found that there were 18 IDOs in the pipeline. Epaca­do­stat was the most ad­vanced of them all, but there have been a num­ber of set­backs, in­clud­ing a pro­gram pur­sued by Genen­tech, which the com­pa­ny aban­doned af­ter see­ing weak re­sults. And a grow­ing line­up of fail­ures will boost fears that this is the wrong tar­get.

That woe­ful feel­ing didn’t help mat­ters at Bris­tol-My­ers, which has one of the most ad­vanced IDOs in the clin­ic af­ter In­cyte’s pro­gram. Bris­tol-My­ers paid $1.25 bil­lion to ob­tain their drug in the Flexus buy­out, which was im­pli­cat­ed in a suit In­cyte filed claim­ing that a for­mer staffer had stolen trade se­crets on their drug, hand­ing them off to Flexus. Sev­er­al an­a­lysts have out­lined rea­sons why they think that Bris­tol-My­ers has the bet­ter of the two drugs.

With the alarm bells ring­ing loud­ly all day Fri­day, NewLink re­spond­ed by putting out a re­lease as­sert­ing that its drug in­dox­i­mod had a “dif­fer­en­ti­at­ed mech­a­nism of ac­tion.” The biotech al­so said that it would do a re­view of its pro­grams in light of the set­back at In­cyte.

The failed study will help gain “un­der­stand­ing of the role of IDO1 in­hi­bi­tion in com­bi­na­tion with PD-1 an­tag­o­nists, and may in­form our broad­er epaca­do­stat clin­i­cal de­vel­op­ment pro­gram,” said Steven Stein, chief med­ical of­fi­cer, In­cyte. “We re­main ded­i­cat­ed to trans­form­ing the treat­ment of can­cer and will con­tin­ue to ex­plore how IDO1 in­hi­bi­tion and oth­er nov­el mech­a­nisms can po­ten­tial­ly im­prove out­comes for pa­tients in need.”


Im­age: Hervé Hop­penot, In­cyte CEO at an End­points News event, Jan­u­ary 2018. END­POINTS NEWS

Bio­gen shares spike as ex­ecs com­plete a de­layed pitch for their con­tro­ver­sial Alzheimer's drug — the next move be­longs to the FDA

Biogen is stepping out onto the high wire today, reporting that the team working on the controversial Alzheimer’s drug aducanumab has now completed their submission to the FDA. And they want the agency to bless it with a priority review that would cut the agency’s decision-making time to a mere 6 months.

The news drove a 10% spike in Biogen’s stock $BIIB ahead of the bell.

Part of that spike can be attributed to a relief rally. Biogen execs rattled backers and a host of analysts earlier in the year when they unexpectedly delayed their filing to the third quarter. That delay provoked all manner of speculation after CEO Michel Vounatsos and R&D chief Al Sandrock failed to persuade influential observers that the pandemic and other factors had slowed the timeline for filing. Actually making the pitch at least satisfies skeptics that the FDA was not likely pushing back as Biogen was pushing in. From the start, Biogen execs claimed that they were doing everything in cooperation with the FDA, saying that regulators had signaled their interest in reviewing the submission.

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Nick Galakatos, Blackstone global head of life sciences

Nick Galakatos and the Black­stone team now have a record $4.6B to in­vest in bio­phar­ma, with a big fo­cus on push­ing com­pa­nies over the top

Nick Galakatos and his team at Blackstone Life Sciences have seen their biggest opportunities swell up in mostly established players who don’t have all the money they need to accomplish everything on the to-do list. And right now, with the industry booming, that’s a long list with some hefty needs.

The Blackstone team has neatly tied up the largest private fund ever raised in life sciences for making big dreams come true in biopharma. Late Thursday, Blackstone put out word that they had closed their highly anticipated fund with the projected $4.6 billion all in.

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Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Gilead boasts of pos­i­tive remde­sivir da­ta on mor­tal­i­ty — but their analy­sis pro­vokes the skep­tics

Gilead is surging again off data that suggest its antiviral remdesivir might improve survival.

The new data come from an analysis Gilead conducted comparing the death rate and recovery time of patients in one of its remdesivir trials to a group of 800 patients “with similar baseline characteristics and disease severity” who received only standard-of-care around the same time. The result, they said, suggested that patients who received remdesivir had a 62% better chance at surviving than those who did not.

Andrew Kruegel, Kures president and co-founder (Columbia Tech Ventures via Vimeo)

Af­ter psilo­cy­bin and ke­t­a­mine, a new biotech comes along de­vel­op­ing a drug Scott Got­tlieb fought

Andrew Kruegel was six years into his chemistry work at Columbia University, when, one day in August 2016, he learned he might have only 30 days before the government made him destroy his research.

Kruegel had been studying kratom, a leaf long used in Southeast Asia as a stimulant or for pain. It had opioid-like properties, he found, but seemed to offer pain relief without the addictive potential or respiratory side effects of traditional opioids — a riddle that might help illuminate how human opioid receptors work.

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The home run count: The $100M+ mega-round boom in biotech in­spired a $7.3B feed­ing fren­zy — so far this year

Over the last 6 months there’s been a blizzard of money piling up drifts of the green stuff through the biotech landscape. And the forecast calls for more cash windfalls ahead.

Even as a global pandemic has killed more than half a million people, blighted economies and divided nations over the proper response, it’s also helped ignite an unprecedented burst of big-time investing. And not just in Covid-19 deals, as we’ve looked at before.

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Atul Deshpande, Harbour BioMed chief strategy officer & head, US operations (Harbour BioMed)

An­oth­er biotech IPO set-up? Multi­na­tion­al biotech leaps from round to round, scoop­ing up cash at a blis­ter­ing pace

A short four months after announcing a $75 million haul in Series B+ fundraising, the multinational biotech Harbour BioMed pulled in another round of investments and eclipsed the nine-digit mark in the process.

Harbour completed its Series C financing, the company announced Thursday morning, raising $102.8 million and bringing its total investment sum to over $300 million since its founding in late 2016. The biotech plans to use the money to transition early-stage candidates from the discovery phase, fund candidates already in the clinic, and prep late-stage candidates for commercialization.

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Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

A new study points to $6.5B in pub­lic sup­port build­ing the sci­en­tif­ic foun­da­tion of Gilead­'s remde­sivir. Should that be re­flect­ed in the price?

By drug R&D standards, Gilead’s move to repurpose remdesivir for Covid-19 and grab an emergency use authorization was a remarkably easy, low-cost layup that required modest efficacy and a clean safety profile from just a small group of patients.

The drug OK also arrived after Gilead had paid much of the freight on getting it positioned to move fast.

In a study by Fred Ledley, director of the Center for Integration of Science and Industry at Bentley University in Waltham, MA, researchers concluded that the NIH had invested only $46.5 million in the research devoted to the drug ahead of the pandemic, a small sum compared to the more than $1 billion Gilead expected to spend getting it out this year, all on top of what it had already cost in R&D expenses.

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Hal Barron, GSK

Win or lose on the mar­ket­ing OK, the FDA just gunned down GSK’s bright hopes for their BC­MA ther­a­py

The FDA’s ODAC — the Oncologic Drugs Advisory Committee — has a well-known bias in favor of adding new cancer drugs to the market, even if efficacy is at best marginal and serious safety issues demand careful management.

Doctors want as many arrows in their quiver as they can get. And when patients are dying after failing multiple drugs, why not give it a go one more time?

GlaxoSmithKline, though, is about to test out how their new BCMA antibody drug conjugate belantamab mafodotin can do after being mauled in an in-house FDA review, ahead of the Tuesday expert panel discussion. Even if the agency goes ahead with an expected green light, this drug will likely be constrained to a small niche — icing any plans they may have for making waves in oncology anytime soon.

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