IDO rout: Piv­otal tri­als with Bris­tol-My­ers, Mer­ck and As­traZeneca dumped in wake of In­cyte's PhI­II im­plo­sion

The IDO R&D pipeline is in dan­ger of be­ing ex­ter­mi­nat­ed.

In the wake of a piv­otal fail­ure of In­cyte’s $IN­CY lead IDO drug epaca­do­stat, Bris­tol-My­ers Squibb $BMY be­came the third play­er forced to re­trench in that im­muno-on­col­o­gy field, drop­ping three late-stage stud­ies of a ri­val drug it bagged in a $1.25 bil­lion buy­out. But that was just the start of a rout.

In­cyte re­port­ed this morn­ing that its wide-rang­ing col­lab­o­ra­tions with Big Phar­ma play­ers are com­ing un­done. In their Q1 an­nounce­ment, echo­ing the fail­ure of ECHO-301, the com­pa­ny not­ed:

En­roll­ment will be dis­con­tin­ued in the four ad­di­tion­al piv­otal tri­als of epaca­do­stat in com­bi­na­tion with pem­brolizum­ab (Mer­ck’s Keytru­da), and in the two piv­otal tri­als of epaca­do­stat in com­bi­na­tion with nivolum­ab (Bris­tol-My­ers’ Op­di­vo); each of these stud­ies will be amend­ed to en­able pa­tients and their physi­cians to con­sid­er al­ter­na­tive ther­a­peu­tic op­tions. The piv­otal tri­al in com­bi­na­tion with dur­val­um­ab (As­traZeneca’s Imfinzi) in Stage 3 lung can­cer will not be ini­ti­at­ed.

A spokesper­son for As­traZeneca al­so tells me that there is “an­oth­er Phase II (com­bi­na­tion study) in sol­id tu­mors and we’re go­ing to stop en­roll­ment there too.” That will be all for the ECHO-203 study — epaca­do­stat plus dur­val­um­ab again. “In­cyte did present some da­ta from ECHO-203 at AACR: 15 pa­tients with pan­cre­at­ic can­cer were en­rolled across mul­ti­ple dose lev­els, no clin­i­cal ac­tiv­i­ty was ob­served.”

In ad­di­tion, In­cyte said that it is “sig­nif­i­cant­ly down­siz­ing the epaca­do­stat de­vel­op­ment pro­gram,” sig­nal­ing a painful re­treat for a one-time star drug that com­mand­ed pro­jec­tions of block­buster peak sales.

Ac­cord­ing to clin­i­cal­tri­als.gov, in­ves­ti­ga­tors for the big biotech to­day ter­mi­nat­ed a Phase III study of BMS-986205 in com­bi­na­tion with Bris­tol-My­ers’ Op­di­vo for front­line head and neck can­cer. An­oth­er Phase III study for front­line Stage IV or re­cur­rent non-small cell lung can­cer us­ing BMS-986205 and Op­di­vo with or with­out chemo ver­sus chemo alone was with­drawn. And there’s a third study for melanoma that’s now ac­tive but not re­cruit­ing af­ter en­list­ing 72 pa­tients.

A spokesper­son for Bris­tol-My­ers told us Mon­day night:

Based on emerg­ing da­ta on the IDO path­way, we closed reg­is­tra­tional stud­ies of our IDO in­hibitor, BMS-986205, in melanoma, SC­CHN and NSCLC. We re­main com­mit­ted to con­tin­ued re­search of BMS-986205-based com­bi­na­tions in an in­formed and sci­en­tif­i­cal­ly ro­bust man­ner. We will con­tin­ue to eval­u­ate BMS-986205-based com­bi­na­tions in our Phase 1/2 study, CA017-003.

Sep­a­rate­ly, we are work­ing quick­ly with In­cyte to as­sess our pro­gram un­der the col­lab­o­ra­tion.

NewLink $NLNK was the first to over­haul its ap­proach on IDO fol­low­ing the In­cyte dis­as­ter.  The biotech scrapped a melanoma study that would have eval­u­at­ed in­dox­i­mod in com­bi­na­tion with check­point in­hibitors Keytru­da or Op­di­vo in 600 pa­tients. In a press re­lease, NewLink ex­plained the de­ci­sion was made “in the con­text of the fail­ure of a com­peti­tor’s tri­al of its en­zy­mat­ic IDO in­hibitor in a sim­i­lar clin­i­cal set­ting.

Bris­tol-My­ers’ de­ci­sion — first re­port­ed by Xcon­o­my — un­der­scores a grow­ing be­lief that In­cyte’s fail­ure was as much a fail­ure of the class as an in­di­vid­ual ther­a­py, po­ten­tial­ly tor­pe­do­ing a wide swath of clin­i­cal tri­als now in the pipeline.

In­cyte frankly con­ced­ed that its piv­otal fail­ure raised doubts about its en­tire ef­fort, which in­cludes a host of com­bi­na­tion stud­ies with check­point lead­ers like Mer­ck and As­traZeneca. In this case, Bris­tol-My­ers is cut­ting back on a drug that it ac­quired in a block­buster deal to ac­quire Flexus 3 years ago. In­ves­ti­ga­tors have re­peat­ed­ly tout­ed the drug as a po­ten­tial lynch­pin in im­muno-on­col­o­gy, fo­cus­ing on an en­zyme that sup­press­es the im­mune cells Op­di­vo and a whole new class of PD-1/L1 check­points are de­signed to un­leash in an at­tack on can­cer cells.

Iron­i­cal­ly, In­cyte has been pur­su­ing lit­i­ga­tion against one of its for­mer sci­en­tists, claim­ing he de­fect­ed to Flexus with IDO trade se­crets in hand, well be­fore the buy­out. Bris­tol-My­ers, though, has stead­fast­ly as­sert­ed — with some sup­port from an­a­lysts — that it had the bet­ter IDO that could leapfrog epaca­do­stat. The leap­ing in IDO, though, has stopped. At least for now.

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On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

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Michel Vounatsos, Biogen CEO (via YouTube)

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Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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In­novent and Eli Lil­ly chal­lenge Mer­ck­'s mega-block­buster Keytru­da in non-small cell lung can­cer field

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Anap­tys­Bio's etokimab pro­vides more dis­ap­point­ing re­sults, rais­ing ques­tions about com­pound's fu­ture

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Etokimab, an IL-33 inhibitor, did not achieve statistically significant improvement in a Phase II trial for patients suffering from chronic rhinosinusitis with nasal polyps. Researchers measured the individuals’ bilateral nasal polyps score and sino-nasal outcome test, finding that neither improved upon a placebo after both four- and eight-week time markers, though they did demonstrate improvement over baseline levels of the examinations.

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When CureVac initially jotted down $100 million for its IPO raise a couple of weeks ago, it seemed small. The German mRNA player, after all, had jumped into a Covid-19 race that swelled the sails of Moderna and BioNTech by tens of billions. And after raising $640 million in a slate of deals, $100 million in a hot market like this seemed like a pittance in the bigger scheme of things.

Today, we got a look at a figure that probably comes closer to the game-changing number the top execs probably have in mind. Selling 15.3 million shares at the high end of their $14 to $16 range would net a $243 million bounty. Majority owner Dietmar Hopp is putting in another €100 million, bringing the total to around $350 million. And what are the chances they want to do even better than that?

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Warren Huff, Reata CEO

Rea­ta sug­gests Friedre­ich's atax­ia pro­gram could be de­layed, send­ing stock plung­ing

Reata Pharmaceuticals $RETA made waves last October when its drug omaveloxolone produced positive trial results in treating a rare neurological disorder, but the candidate’s path forward became much murkier Monday.

In a report of quarterly earnings, the biotech divulged that the FDA is considering delaying omaveloxolone’s NDA pending completion of a second trial. That could push back approval by at least a year given that the target population, individuals with Friedreich’s ataxia, is limited and progression of the hard-to-treat illness is notoriously slow. The Covid-19 pandemic would also hinder Reata’s ability to complete an additional trial.