As co-di­rec­tor of an ex­per­i­men­tal cel­lu­lar ther­a­py process de­vel­op­ment and man­u­fac­tur­ing group at UCSF spe­cial­iz­ing in T cell ther­a­pies for au­toim­mune con­di­tions, Jonathan Es­en­sten has learned a lot about the chal­lenges in­volved when his group hand-fash­ions a cell ther­a­py. Es­en­sten — who was a post­doc in Wen­dell Lim’s lab and counts the leg­endary Jef­frey Blue­stone as a men­tor — gives them all high marks at be­ing great at what they do, but time and again there are vari­a­tions in the treat­ments they con­struct.

And that’s a prob­lem.

Jonathan Es­en­sten

Es­en­sten can’t of­fer any da­ta, and these are high­ly trained in­di­vid­u­als we’re talk­ing about, but “my in­tu­ition is that small dif­fer­ences in tech­nique can make a dif­fer­ence in the out­come of a cell ther­a­py man­u­fac­tur­ing run,” he says.

As any­one in bio­phar­ma can tell you, vari­a­tions in ther­a­peu­tic out­put are not OK. You want to set a stan­dard and hit it every time.

So when Fred Pari­et­ti came in a cou­ple of years ago to take a first-hand look at what they were do­ing at UCSF and see for him­self what cell ther­a­py man­u­fac­tur­ing was all about, they got to talk­ing.

It wasn’t just that there were vari­a­tions in the prod­uct, Es­en­sten says. It’s ex­pen­sive to get a trained group to­geth­er. Hard­er to pre­vent them from be­ing raid­ed by the grow­ing mul­ti­tude of biotechs in the area, who find it easy to beat a uni­ver­si­ty salary.

For Pari­et­ti, who joined a band of MIT grads and jour­neyed to the Bay Area to launch a ro­bot­ics up­start called Mul­ti­ply Labs, it was an eye-open­ing ex­pe­ri­ence, and one that led to a unique al­liance. Now Pari­et­ti’s start­up is fund­ing work in Es­en­sten’s group to de­vel­op a ro­bot­ic sys­tem to do that work — an ap­proach that he feels has near-term com­mer­cial po­ten­tial.

And af­ter rais­ing $5 mil­lion in seed cash to get them go­ing, he’s won over some key con­verts. The team at Mul­ti­ply can now boast of a $20 mil­lion fol­lowup round to get the prod­uct through test­ing and in­to the hands of an in­dus­try he feels is ripe for this kind of pre­ci­sion man­u­fac­tur­ing tech as cell ther­a­pies boom.

Cas­din Cap­i­tal led the round, with new in­vestors Lux Cap­i­tal and Pathfind­er, Founders Fund’s ear­ly stage in­vest­ment ve­hi­cle, al­so par­tic­i­pat­ing along with seed in­vestors Fifty Years and Garage Cap­i­tal.

Fred Pari­et­ti

Mul­ti­ply got start­ed man­u­fac­tur­ing a ro­bot­ics sys­tem that can make cus­tom de­signed pills, of­ten us­ing spe­cif­ic com­bos — a grow­ing fea­ture in the man­u­fac­tur­ing world. Once they get their new sys­tem set up for cell ther­a­pies, Pari­et­ti al­so be­lieves that there are a num­ber of play­ers in the cell ther­a­py field that can see the ad­van­tage of us­ing ro­bots in place of peo­ple, work­ing 24/7, with­out any vari­a­tions in tech­nique. With no pen­chant for mak­ing mis­takes. And no new salary de­mands.

“Es­sen­tial­ly the cell ther­a­py process­es are all lab process­es adapt­ed for GMP, but they were nev­er cre­at­ed to scale … ,” he says. “Peo­ple make mis­takes. That’s the de­f­i­n­i­tion of peo­ple.”

“The peo­ple are the biggest dan­ger for the drug,” Pari­et­ti adds. “In cell ther­a­py you want to pro­tect the drug from the peo­ple, not the peo­ple from the drug … Our job is to make stuff ef­fi­cient and au­to­mat­ed.”

It’s al­so a ques­tion of ef­fi­cien­cy, which re­volves around what Pari­et­ti calls par­al­lelism. With au­to­mat­ed sys­tems, you can con­tin­u­ous­ly use mul­ti­ple biore­ac­tors in par­al­lel. With peo­ple, or the al­ter­na­tive sys­tems on the mar­ket that Es­en­sten points to, biore­ac­tors have to be seg­re­gat­ed in in­di­vid­ual spaces to avoid cross con­t­a­m­i­na­tion.

That’s a big job, but Mul­ti­ply is still small, with 10 peo­ple plus an­oth­er 5 con­sul­tants. That should grow sig­nif­i­cant­ly with the cur­rent ven­ture round.

The in­spi­ra­tion for the team start­ed at MIT, where Pari­et­ti, who was work­ing on ex­oskele­tons in the ro­bot­ics group, met up with Al­ice Me­loc­chi, who was de­vot­ed to health­care sys­tems. To­geth­er, they built a team that tar­get­ed man­u­al drug man­u­fac­tur­ing, get­ting a foothold with their cap­sule tech. Now they feel equipped to go af­ter a much more am­bi­tious tar­get in cell ther­a­pies.

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

As Ireland continues to see more investments and building projects from pharma companies, another contender is looking to place more investment in the Emerald Isle.

According to a report from The Irish Times on Friday, Abbott Laboratories is investing €440 million, or about $451 million, to build a new manufacturing plant in Kilkenny, located in the country’s southeast, to make more of its glucose monitors.