At­las and Or­biMed back Boston's Kyn in $49M round to pur­sue im­munome­tab­o­lism ther­a­pies

Boston biotech Kyn Ther­a­peu­tics has raised $49 mil­lion in a Se­ries A round to ad­vance its im­munome­tab­o­lism ther­a­pies to treat can­cer.

The mon­ey comes from At­las Ven­ture and Or­biMed — both re­peat in­vestors who first fund­ed the com­pa­ny dur­ing its launch last March.

Mark Man­fre­di

Kyn is led by an At­las en­tre­pre­neur-in-res­i­dence Mark Man­fre­di, who was pre­vi­ous­ly chief sci­en­tif­ic of­fi­cer at Raze Ther­a­peu­tics (al­so an At­las-fund­ed start­up). Raze raised a $24 mil­lion Se­ries A in 2014, but the com­pa­ny ap­pears to have wound down pret­ty quick­ly. The web­site is no longer ac­tive, and Man­fre­di said Raze still has some as­sets and col­lab­o­ra­tions, but no longer em­ploys any­one. At­las’ Bruce Booth says the un­der­ly­ing can­cer me­tab­o­lism bi­ol­o­gy was too com­pli­cat­ed to war­rant fur­ther in­vest­ment. Be­fore Raze, Man­fre­di was VP of on­col­o­gy bi­ol­o­gy at Take­da.

Now as CEO of Kyn, Man­fre­di is once again lead­ing a com­pa­ny fo­cused on im­munome­tab­o­lism to treat can­cer, a grow­ing area of im­muno-on­col­o­gy. The field lever­ages meta­bol­ic path­ways and the bro­ken-down mol­e­cules that re­sult from me­tab­o­lism (called metabo­lites). Kyn has an undis­closed num­ber of pre­clin­i­cal pro­grams de­signed to re­verse the ef­fects of metabo­lites pro­mot­ed by can­cer cells.

First, the com­pa­ny is tar­get­ing the IDO and TDO path­ways. IDO and TDO are meta­bol­ic en­zymes over­ex­pressed in many can­cers that con­vert tryp­to­phan to kynure­nine. Kynure­nine ac­cu­mu­lates in and around the tu­mor where it en­ters im­mune cells and binds the aryl hy­dro­car­bon re­cep­tor. This trig­gers the broad sup­pres­sion of the im­mune sys­tem, Man­fre­di said.

Kyn’s plan is to de­grade kynure­nine and/or an­tag­o­nise the aryl hy­dro­car­bon re­cep­tor.

The IDO path­way is al­ready be­ing eyed up by oth­er com­pa­nies, in­clud­ing In­cyte, Bris­tol-My­ers, and NewLink Ge­net­ics. But Man­fre­di tells me he thinks it’s im­por­tant to tar­get TDO, as well.

“The in­hibitors out there on­ly in­hib­it IDO,” Man­fre­di said. “Some tu­mors ex­press IDO, but oth­ers ex­press TDO as well, which al­so pro­duces the sup­pres­sive metabo­lite kynure­nine. We think if we go af­ter that metabo­lite specif­i­cal­ly, it will be more ef­fec­tive.”

Kyn plans to test their prod­uct can­di­dates as sin­gle agents, as well as in com­bi­na­tion stud­ies with check­point in­hibitors.

Of the com­pa­ny’s new $49 mil­lion, $28 mil­lion is go­ing to fu­el these pro­grams. Man­fre­di said the com­pa­ny isn’t dis­clos­ing which can­cers it’s tack­ling.

The rest of the cash is go­ing to Kyn’s af­fil­i­ate called Ar­rys Ther­a­peu­tics, which has ex­clu­sive­ly con­tract­ed Kyn to de­vel­op ARY-007. This pro­gram does not tar­get IDO/TDO, but is still in the im­munome­tab­o­lism field. The prod­uct can­di­date blocks the EP4 re­cep­tor, which is in­volved in the prostaglandin E2 path­way. ARY-007 has al­ready shown fa­vor­able ther­a­peu­tic char­ac­ter­is­tics in hu­man tri­als for os­teoarthrit­ic pain, Man­fre­di said.

The com­pa­ny is jump­ing in­to Phase Ib stud­ies in 2018.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

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

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