Mi­cro­bio­me up­start Vedan­ta teams up with NYU Lan­gone sci­en­tist on check­point drugs

Aca­d­e­m­ic col­lab­o­ra­tions have been cen­tral to the de­vel­op­ment of new im­muno-on­col­o­gy drugs. And now the mi­cro­bio­me start­up Vedan­ta Bio­sciences is fol­low­ing the same sci­en­tif­ic trail in ad­vanc­ing a new set of ther­a­pies that could one day play a role in the hot check­point in­hibitor field.

Build­ing on the work of Vedan­ta sci­en­tif­ic co­founder Kenya Hon­da at Keio Uni­ver­si­ty, the biotech will work with a team of in­ves­ti­ga­tors head­ed by Jef­frey S. We­ber, M.D., Ph.D., deputy di­rec­tor of the Lau­ra and Isaac Perl­mut­ter Can­cer Cen­ter at NYU Lan­gone Med­ical Cen­ter. They’ll fo­cus on bac­te­r­i­al strains that have shown signs of ac­ti­vat­ing im­mune cells in the gut to amp up the ef­fi­ca­cy of check­points like Op­di­vo and Keytru­da, which have roiled the on­col­o­gy drug mar­ket.

“Dr. We­ber is a pi­o­neer in trans­la­tion­al re­search, par­tic­u­lar­ly in im­munother­a­py and the de­vel­op­ment of check­point in­hibitors,” said Dr. Bruce Roberts, the CSO of Vedan­ta.

Bernat Olle, Vedan­ta

Vedan­ta is one of a group of biotech up­starts look­ing to make drugs from bugs, so to speak. In­spired by the abil­i­ty of fe­cal trans­plants to re­boot the bal­ance of healthy mi­crobes need­ed in the gut to re­store health, Vedan­ta has been de­vel­op­ing treat­ments out of tai­lored pack­ages of bac­te­r­i­al strains de­signed to spur spe­cif­ic ther­a­peu­tic re­spons­es. I asked Vedan­ta CEO Bernat Olle a cou­ple of ques­tions by email. Here’s the ex­change:

JC: Giv­en the com­plex­i­ty of mi­cro­bio­me work, is this some­thing you see as painstak­ing, nit­ty grit­ty re­quir­ing years of pre­clin­i­cal work, or are we clos­er to the clin­ic than that?

BO: The ap­proach we are in­ter­est­ed in ex­plor­ing first is com­bin­ing oral­ly ad­min­is­tered con­sor­tia of live bac­te­ria with check­point in­hibitors. The goal is to en­hance the an­ti-tu­mor ac­tiv­i­ty of check­point in­hibitors by ad­min­is­tra­tion of bac­te­ria that can col­o­nize the gut and ac­ti­vate ef­fec­tor cells. (So not CAR-T as part of this col­lab­o­ra­tion but I rec­og­nize this is a po­ten­tial fu­ture av­enue).  I would pre­fer not to ven­ture a time­line to the clin­ic. I’d like to point out though, a dis­tinct ad­van­tage of work­ing with com­men­sal bac­te­ria that have not been re­com­bi­nant­ly mod­i­fied is that we know they can safe­ly col­o­nize hu­mans in large dos­es, for life, so the like­li­hood that we are sur­prised by a com­plete­ly un­ex­pect­ed safe­ty sig­nal is rel­a­tive­ly low, in my view, com­pared to oth­er ther­a­peu­tic modal­i­ties that en­tail in­tro­duc­ing new chem­i­cal en­ti­ties that the hu­man body has nev­er seen be­fore. And that is the pri­ma­ry con­cern when you are go­ing in­to the clin­ic for the first time. Mul­ti­ple fe­cal trans­plan­ta­tion tri­als have moved for­ward in the mi­cro­bio­me field quite quick­ly, in both C. diff and IBD, de­spite the fact that the com­plex­i­ty of this ap­proach is not well un­der­stood. In my opin­ion that is an ac­knowl­edge­ment that mod­i­fy­ing the mi­cro­bio­ta with na­tive species is an ap­proach with an at­trac­tive safe­ty pro­file (of course risk/ben­e­fit con­sid­er­a­tions are dif­fer­ent for each in­di­ca­tion). That doesn’t mean what we’re do­ing is easy and lin­ear – it’s not. There’s a lot to learn around mech­a­nisms in­volved in how the mi­cro­bio­ta in­ter­acts with the host. We’re fo­cus­ing a lot of our ef­forts there, mak­ing sure there is a ra­tio­nal cri­te­ria be­hind the de­ci­sions of what mi­crobes we pick to in­clude in our drug can­di­dates. Da­ta from col­lab­o­ra­tions like the one we are start­ing with our NYU col­leagues is a valu­able in­put to our de­vel­op­ment process be­cause it can help us de­ter­mine if the ef­fects we see in pre­clin­i­cal mod­els are rel­e­vant to the hu­man pop­u­la­tions that we want to tar­get.

JC: Giv­en the re­cent set­back at Seres (where a Phase II ef­fort re­cent­ly failed), I was struck again how a set­back in a new tech­nol­o­gy at one com­pa­ny can be au­to­mat­i­cal­ly at­trib­uted to every­one else (doesn’t re­al­ly play out, though, as we’re see­ing in gene ther­a­py, where com­pa­nies dis­tin­guish them­selves in one way or an­oth­er.) What are your thoughts on that?

BO: The sci­en­tif­i­cal­ly hon­est thing to say is that un­til they have com­plet­ed their root cause analy­sis and de­ter­mine what caused the fail­ure, it’s hard to make any con­clu­sion on what that means to the field.

That be­ing said, our ap­proach is quite dif­fer­ent from SER109. They used a pro­ce­dure in­volv­ing a mod­i­fied form of fe­cal trans­plan­ta­tion, get­ting fe­cal ma­te­r­i­al di­rect­ly from a donor, pro­cess­ing the sam­ples and then giv­ing the processed frac­tion to the pa­tient. We have been fo­cused on ra­tio­nal­ly se­lect­ing pure strains based on mech­a­nis­tic in­sights, and grow­ing them start­ing from cell banks via fer­men­ta­tion, so we can con­trol ex­act­ly the com­po­si­tion of the prod­uct.

And I think the con­text of the ac­cu­mu­lat­ed clin­i­cal da­ta in the field is use­ful too: there have been mul­ti­ple suc­cess­ful ran­dom­ized con­trolled tri­als with fe­cal mi­cro­bio­ta trans­plan­ta­tion (FMT), with re­port­ed cure rates in C diff. in the 80-90% range (Van Nood et al, NE­JM, 2013; Young­ster et al, 2014; oth­ers) and the util­i­ty of mi­cro­bio­me mod­u­la­tion is ex­pand­ing to oth­er clin­i­cal ap­pli­ca­tions in­clud­ing IBD, with two re­cent place­bo-con­trolled tri­als show­ing suc­cess­ful in­duc­tion of re­mis­sion (Moayye­di et al, 2016; Paramsothy et al, 2015). This pos­i­tive clin­i­cal da­ta is re­in­forced by a ro­bust body of ba­sic re­search in the field that is both iden­ti­fy­ing new po­ten­tial ap­pli­ca­tions of mi­cro­bio­me mod­u­la­tion and in­creas­ing­ly mov­ing to­wards a more de­tailed un­der­stand­ing of the mech­a­nisms in­volved in host-mi­cro­bio­me in­ter­ac­tions that was miss­ing from FMT ap­proach­es. So I re­main op­ti­mistic of the po­ten­tial of the field.

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