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.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

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Cy­to­ki­net­ics’ ALS drug fails PhI­II, leav­ing the biotech with a sin­gle late-stage prospect

Cytokinetics’ candidate for the muscle disease amyotrophic lateral sclerosis, or ALS, failed a Phase III trial, the Bay Area biotech announced Friday morning.

At a second interim analysis of the trial, an independent review committee recommended that Cytokinetics discontinue its COURAGE-ALS trial for reldesemtiv, as it “found no evidence of effect” compared to placebo on the primary or key secondary endpoints.

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CHMP gives thumbs-up for We­govy use in ado­les­cents, along with nine new drug rec­om­men­da­tions

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) recommended nine drugs for approval this week while also giving thumbs up for six expanded indications, including Novo Nordisk’s approved obesity medication Wegovy for younger people. Wegovy is already approved as an obesity treatment in the EU for adults, and the new indication would allow prescriptions for adolescents aged 12 and older.

Austin biotech Mol­e­c­u­lar Tem­plates lays off more than 100 staffers as pipeline nar­rows

Molecular Templates is ridding itself of a Phase I HER2 asset and fine-tuning its pipeline to focus on three programs and a preclinical Bristol Myers Squibb collaboration. With the narrowed scope on its so-called engineered toxin bodies, the Austin, TX biotech is laying off about half of its staff.

That’s a little more than 100 employees, per an SEC filing. Molecular’s layoffs, approved by its board Wednesday, add to the dozens of pullbacks in the industry in the first three months of 2023.

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Green­Light re­ceives buy­out of­fer; Apol­lomics com­pletes SPAC merg­er

RNA biotech GreenLight Biosciences has been handed an offer for potential acquisition.

GreenLight said in a release that it has received a non-binding “indication of interest” from Fall Line Endurance Fund to acquire GreenLight’s capital stock for $0.60 per share in cash. The release said any potential agreement between the two parties would depend on certain conditions.

Through a special committee, the biotech will evaluate the offer but added there’s no certainty a deal will go forward. GreenLight will also not make any more announcements until a deal comes through or “otherwise determines” a statement is necessary.

TScan Therapeutics' departing CEO David Southwell and CSO/COO Gavin MacBeath

TCR up­start an­nounces CEO ex­it, with CSO now act­ing re­place­ment

A public T cell biotech’s chief executive has decided to leave the company.

TScan Therapeutics said Friday morning that CEO David Southwell stepped down earlier this week, leaving both his chief executive and board member roles. Filling in is Gavin MacBeath, the company’s CSO and COO. He became the acting CEO on Tuesday, and will continue to remain CSO and COO, TScan’s announcement read.

Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Aptinyx eval­u­ates fu­ture of the com­pa­ny fol­low­ing two failed tri­als, 60% lay­offs

This year has been tough for Aptinyx — two failed trials, a 60% cut in its workforce, and now the company has brought on a firm to help evaluate the future of the company.

The press release noted it’s working with the firm Ladenburg Thalmann as its financial advisor to assist in exploring and evaluating “strategic alternatives” — a process that a growing group of struggling biotechs has embarked on, sometimes ending in a merger, asset sale or wind-down.

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Sar­to­rius to ac­quire French man­u­fac­tur­er for $2.6B+ in cell and gene ther­a­py play

The German life science group Sartorius will be picking up French contract manufacturer Polyplus for the price of €2.4 billion, or $2.6 billion.

On Friday, Sartorius announced the acquisition through its French subgroup, Sartorius Stedim Biotech, which will be acquiring Polyplus from private investors ARCHIMED and WP GG Holdings IV. Polyplus has 270 employees and produces materials and components that go into making viral vectors that are used in cell and gene therapies. This includes DNA/RNA reagents as well as plasmid DNA. Polyplus has locations in France, Belgium, China and the US.