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.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Janet Woodcock (AP Images)

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Michelle McMurry-Heath, BIO CEO (BIO via YouTube)

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Janet Woodcock and Joshua Sharfstein (AP, Images)

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