Kelli Luginbuhl and Ashutosh Chilkoti

Start­up sets out to tack­le the gene ther­a­py man­u­fac­tur­ing cri­sis

Af­ter Kel­li Lug­in­buhl fin­ished her PhD, her ad­vi­sor, Duke bio­engi­neer and Phase­Bio co-founder Ashutosh Chilkoti, sat her down and asked if she want­ed to launch and then run a com­pa­ny. Chilkoti had a once-ob­scure tech­nol­o­gy he and the ven­ture cap­i­tal­ist Joe McMa­hon thought could form the ba­sis of his sec­ond com­pa­ny and fi­nal­ly pay huge div­i­dends. Lug­in­buhl knew the tech from years in his lab and was al­ready look­ing for biotech jobs. It all added up.

Three years, some strate­giz­ing, and 10 or so pitch meet­ings lat­er, the trio is launch­ing Isol­ere Bio, with $7 mil­lion in seed fund­ing led by North­pond Ven­tures and tech­nol­o­gy they be­lieve can al­low gene ther­a­py com­pa­nies to vast­ly in­crease the num­ber of dos­es they can pro­duce. It’s one po­ten­tial so­lu­tion to a slow-boil­ing cri­sis that has be­come in­creas­ing­ly acute, as new com­pa­nies strug­gle to get the ma­te­ri­als they need for tri­als and some com­mon dis­eases re­main the­o­ret­i­cal­ly un­fix­able by gene ther­a­py, be­cause com­pa­nies would nev­er be able to make enough dos­es for that many pa­tients.

The prob­lem is par­tial­ly that the fa­cil­i­ties don’t yet ex­ist to pro­duce this much of gene ther­a­py. Ex­perts, how­ev­er, al­so point to an­ti­quat­ed man­u­fac­tur­ing process­es.

“In gene ther­a­py, man­u­fac­tur­ing has a lot of in­ef­fi­cien­cies to over­come, which our tech­nol­o­gy is unique­ly po­si­tioned to ad­dress,” Lug­in­buhl, who serves as CEO, told End­points News.

Large phar­ma com­pa­nies and CD­MOs have known about the gene ther­a­py man­u­fac­tur­ing short­fall for a few years, spend­ing bil­lions to retro­fit old drug-mak­ing fa­cil­i­ties or build new ones to as­sure ca­pac­i­ty for a fu­ture where hun­dreds of gene ther­a­pies are in clin­i­cal tri­als and dozens are on the mar­ket (cur­rent­ly on­ly two are ap­proved in the US, both for rare dis­eases). More re­cent­ly, though, a small hand­ful of star­tups have tried to not on­ly build new fac­to­ries but rein­vent how gene ther­a­pies are made, turn­ing a large­ly aca­d­e­m­ic process in­to an in­dus­tri­al one. That in­cludes the George Church spin­out 64xBio and the mon­strous­ly backed Bob Nelsen start­up Re­silience.

Like Re­silience and 64x, Isol­ere is try­ing to boost the pro­duc­tion of AAV, the non-dis­ease caus­ing virus that most gene ther­a­py com­pa­nies use to de­liv­er healthy or func­tion­al re­place­ment genes in­to pa­tients. They’re do­ing so by chang­ing one ob­scure process in the man­u­fac­tur­ing chain: how AAV is fil­tered out of the huge bags of cells used to pro­duce the virus.

AAVs are large, 20-sided par­ti­cles, but cur­rent­ly man­u­fac­tur­ers fil­ter the virus­es out with the same decades-old pro­ce­ses they would use for much small­er mol­e­cules: chro­matog­ra­phy columns, ver­ti­cal tubes where you mix a so­lu­tion from the cells with beads that bind to and pre­vent the AAV from pass­ing through ini­tial­ly, while every­thing else flush­es out. It’s high­ly in­ef­fi­cient, though, Lug­in­buhl said. Among oth­er is­sues, the columns have low ca­pac­i­ty. Be­tween 70% and 80% of the so­lu­tion is gen­er­al­ly lost, Lug­in­buhl said.

Chilkoti’s lab is known for its work on bio­ma­te­ri­als, the ones he put to use found­ing Phase­Bio, hop­ing to build drugs that float­ed through the body dif­fer­ent­ly and en­abled more pa­tient-friend­ly dos­ing reg­i­mens. The bio­ma­te­ri­als Isol­ere is bring­ing for­ward bind to the AAV and form the same kind of liq­uid-liq­uid sep­a­ra­tion as you see in oil in wa­ter emul­sions — like a pro­tec­tive bub­ble around AAV, sep­a­rat­ing it from the rest of the so­lu­tion.

That ma­te­r­i­al can shep­herd the AAV through the fil­tra­tion process, Lug­in­buhl said. The goal is to im­prove yields by 50%.

It’s “a huge pain point in AAV man­u­fac­tur­ing that we’re po­si­tioned to ad­dress,” she said.

Lug­in­buhl said their tech­nol­o­gy can work on any AAV and added, rel­a­tive­ly seam­less­ly, in­to ex­ist­ing man­u­fac­tur­ing process­es. So far, they’ve on­ly test­ed it on 2 liter tanks, but she said they’ve been work­ing with ma­jor gene ther­a­py com­pa­nies and hope to sign a co-de­vel­op­ment deal that would let them scale up the process.

The goal is to get to the mar­ket in 16 months. A Se­ries A is in the works, she said, but of less­er con­cern. For now, they have the run­way, she said, and the field is in dire need of new tech­niques.

“You hear that quote that we’re train­ing chil­dren for jobs that don’t ex­ist to­day,” she said. “The med­i­cines of the fu­ture are modal­i­ties we may not even know ex­ist to­day. And so it’s im­por­tant to be ready to man­u­fac­ture the next gen­er­a­tion of med­i­cines.”

“To do that we need new ideas and new in­no­va­tions in man­u­fac­tur­ing,” she added. “The down­stream pu­rifi­ca­tion field had re­al­ly re­mained quite stag­nant.“

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Janet Woodcock, acting FDA commissioner (Al Drago/Bloomberg via Getty Images)

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An­oth­er busy week for IPOs be­gins with an off-the shelf cell ther­a­py play­er sniff­ing around uni­corn sta­tus

Editor’s note: Interested in following biopharma’s fast-paced IPO market? You can bookmark our IPO Tracker here.

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