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.

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At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

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He went on to assure everyone that he hadn’t misrepresented the CRL.

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Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

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Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.