Thomas Lynch

When Tom Lynch took the top R&D job at Bris­tol-My­ers Squibb, he got one of the best — and at the same time, one of the hard­est — jobs in biotech.

It was one of the best be­cause Bris­tol-My­ers built what is wide­ly con­sid­ered one of the most in­no­v­a­tive re­search groups for a bio­phar­ma of its size, in a heavy­weight class not known for home­made break­throughs. It was one of the hard­est be­cause the group had just de­railed, giv­ing up its first-place po­si­tion in im­muno-on­col­o­gy in a hard fall on a mis­guid­ed late-stage ef­fort on lung can­cer.

That’s how Lynch end­ed up with the job.

Dur­ing yes­ter­day’s Q1 call with an­a­lysts, Lynch — who made an un­usu­al move from the board to head of R&D — out­lined his strat­e­gy for what comes next. How can Bris­tol-My­ers re­trieve its lead po­si­tion?

As Lynch not­ed to a group that in­clud­ed some ex­pe­ri­enced skep­tics, his board­room po­si­tion gave him a bird’s eye view of the com­pa­ny’s op­er­a­tions. For a first in­ter­view with an­a­lysts, he pro­vid­ed an im­pres­sive, de­tailed strat­e­gy out­line, rec­og­niz­ing the weak­ness­es in Bris­tol-My­ers’ I/O ef­forts and of­fer­ing ways to deal with those weak­ness­es in the clin­ic.

Lynch’s game plan cen­ters on the com­pa­ny’s work on next-gen com­bos, look­ing to build on Op­di­vo (PD-1) and Yer­voy (CT­LA-4) — with all its faults — with new com­bos and less tox­ic al­ter­na­tives now in the clin­ic.

In Lynch’s words, here’s the strat­e­gy:

— (F)irst, ac­cel­er­at­ing the de­liv­ery of our next wave of I-O as­sets like IDO, which we re­cent­ly pre­sent­ed da­ta on at AACR. We’ll al­so be pre­sent­ing ear­ly re­sults for LAG-3, GITR, and the In­cyte IDO at AS­CO this year.

— Sec­ond, un­der­stand­ing the bi­ol­o­gy of I-O re­sis­tance, both in­trin­sic re­sis­tance and ac­quired, and bring­ing a laser-like fo­cus to over­com­ing this. We will fo­cus on ex­pand­ing in­to tu­mor types where I-O hasn’t had a broad im­pact yet, tu­mors like breast can­cer, col­orec­tal can­cer, and prostate can­cer. We will use our next-wave as­sets to cre­ate op­tions for pa­tients who progress on their ini­tial I-O ther­a­py.

— Third, we will con­tin­ue to de­vel­op com­bi­na­tion reg­i­mens, in­clud­ing I-O/I-O com­bi­na­tions, I-O/tar­get­ed com­bi­na­tions, and I-O/chemother­a­py com­bi­na­tions where these make sense.

— And fourth, we will ac­cel­er­ate the de­vel­op­ment of our most promis­ing as­sets in the car­dio­vas­cu­lar, im­muno-sci­ence, and fi­bro­sis pipeline. As [CEO] Gio­van­ni [Caforio] men­tioned, we re­cent­ly pre­sent­ed promis­ing Phase II da­ta on our FGF21 as­set in pa­tients with NASH at the In­ter­na­tion­al Liv­er Con­gress. The re­sults showed an im­prove­ment across mul­ti­ple as­pects of NASH, in­clud­ing a sig­nif­i­cant re­duc­tion in liv­er fat ver­sus place­bo.

He fol­lowed up by cit­ing an ex­pand­ed re­la­tion­ship with Cy­tomX to build a less tox­ic CT­LA-4, a move that could even­tu­al­ly have ma­jor im­pli­ca­tions for con­tenders like As­traZeneca, and all the big ri­vals cur­rent­ly in the mar­ket, from Mer­ck to Roche and Pfiz­er/Mer­ck KGaA. IDO com­bi­na­tions will play a role here as well.

Ge­off Meacham at Bar­clays ob­serves that it seems that the biggest op­por­tu­ni­ty is in “cold tu­mors, breast, ovar­i­an, colon, et cetera. To fol­low up on the ear­li­er com­ment, CT­LA-4 com­bos, do you guys feel, at this point, CT­LA-4 com­bos plus a PD-L1 is go­ing to be a com­po­nent of that?”

Lynch:

So we think we have mul­ti­ple op­por­tu­ni­ties to look at com­bi­na­tions of I-O/I-O agents in these cold tu­mors. We pre­sent­ed da­ta with our IDO as­set, as you men­tioned, and we al­so will be pre­sent­ing ini­tial da­ta at AS­CO this year with our GITR com­pound, which could be the type of agent that might play a role in the cold tu­mor space.

Tim An­der­son at Bern­stein al­so ze­roed in on grow­ing ques­tions about the fu­ture of PD-1, CT­LA-4 com­bos. “A bear’s point of view could say that this fore­tells prob­lems with Yer­voy and Op­di­vo, specif­i­cal­ly in front-line lung.”

Lynch:

I think the first is that again, just em­pha­siz­ing how com­plex and dif­fi­cult a dis­ease lung can­cer is to treat, it’s high­ly un­like­ly that there’s go­ing to be one ap­proach that’s go­ing to fit every pa­tient who presents in first-line. We be­lieve strong­ly that Yer­voy/Op­di­vo is cer­tain­ly one of the op­tions that needs to be pur­sued and de­vel­oped, and we’re look­ing at that in first-line lung can­cer. And we’re al­so look­ing at it in the set­ting of what ap­pro­pri­ate bio­mark­ers might be im­por­tant in eval­u­at­ing the po­ten­tial for this com­bi­na­tion and for re­al­ly all of our drugs in first-line lung can­cer.

Fi­nal­ly, on new R&D in­vest­ments:

“(W)e’ve got to ex­e­cute our pipeline. We’ve got to de­vel­op our next-gen­er­a­tion drugs. And to do that, we’re go­ing to need to in­vest in tu­mor bi­ol­o­gy and trans­la­tion­al med­i­cine as well as da­ta and an­a­lyt­ics.”

So there’s the plan. Tak­ing over at R&D now is like jump­ing on a rolling truck at Bris­tol-My­ers, which spent $5 bil­lion on re­search last year. You can grab the wheel, but then you have to man­age the mo­men­tum. That won’t be easy.