Radek Špíšek, Sotio CEO

Sold for pen­nies, Unum gets one last shot at re­demp­tion

Unum Ther­a­peu­tics’ cell ther­a­py tech is get­ting one last lease on life af­ter a Czech biotech was able to pick up the core of a once-bal­ly­hooed com­pa­ny for the cost of spare parts.

For $8.1 mil­lion up­front and just $3.4 mil­lion in mile­stones, Prague-based cell ther­a­py start­up So­tio bought out the pre­clin­i­cal “BOXR” CAR-T plat­form that Unum said they would turn to in March, af­ter a third round of safe­ty is­sues in as many years proved the fi­nal straw for their lead pro­gram.

That nev­er quite hap­pened. In­stead, with their re­serves dwin­dling, their CSO de­part­ing and the stock strug­gling to stay above $0.50 cents, chair­man Bruce Booth and the board or­ches­trat­ed a deal to ef­fec­tive­ly emp­ty out Unum and re­place its core with ki­nase-tar­get­ing tech from a small Cam­bridge biotech called Kiq. It was an ad­mis­sion of de­feat for a com­pa­ny that had A-list in­vestors and sought to bring the “next-gen­er­a­tion” of CAR-T. They start­ed ac­tive­ly look­ing to sell-off BOXR.

So­tio CEO Radek Špíšek ac­knowl­edged he paid a rel­a­tive­ly mea­ger price for BOXR, but he says that re­flect­ed Unum’s rep­u­ta­tion more than the mer­its of the new ap­proach. He not­ed that the pre-clin­i­cal plat­form is dis­tinct from the AC­TR ap­proach that led to mul­ti­ple pa­tient deaths and clin­i­cal holds.

“I think they were very much pun­ished by the mar­ket,” he told End­points News, adding of the BOXR plat­form: “It’s very much dif­fer­ent — it’s ac­tu­al­ly to­tal­ly con­cep­tu­al­ly dif­fer­ent than the pre-ex­ist­ing pro­grams that had the reg­u­la­to­ry prob­lems.”

The plat­form re­mains pre­clin­i­cal, so the odds of fail­ure are nat­u­ral­ly high. Still, one in­de­pen­dent cell ther­a­py ex­pert who re­viewed their pre­clin­i­cal work said the ap­proach made mech­a­nis­tic sense and looked promis­ing. Es­sen­tial­ly, it in­volves tak­ing T cells, adding CARs to di­rect them to­ward tu­mors and then al­so adding oth­er trans­genes that will al­low the cells to en­ter and per­sist in the mi­cro-en­vi­ron­ment around sol­id tu­mors.

The idea is one of many now be­ing test­ed to bring CAR-T’s ben­e­fits to sol­id tu­mors. The lead pro­gram with­in BOXR in­volves CARs that tar­get GCPR3, a gene of­ten over-ex­pressed in liv­er and oth­er can­cers. In ad­di­tion to the CAR, re­searchers add to the T cells a gene that reg­u­lates cell me­tab­o­lism called GOT2.

Christo­pher Rudd

“It could be ef­fec­tive to all tu­mors, not just those who are re­sis­tant to CAR ther­a­py,” Christo­pher Rudd, di­rec­tor of im­muno-on­col­o­gy at the Uni­ver­si­ty of Mon­tre­al, told End­points . For “those that are af­fect­ed by CAR ther­a­py, it could make [the ther­a­py] even more ef­fi­cient.”

He added there were still ques­tions about how it would pre­vent T cells from ex­haust­ing and pro­mot­ing cy­tokines — im­mune sig­nals — with­in the tu­mor. Safe­ty is al­ways a con­cern with im­muno-on­col­o­gy, he said, but noth­ing stood out with this ap­proach.

So­tio is hop­ing to file an IND for he­pa­to­cel­lu­lar car­ci­no­ma be­fore the end of next year, but Špíšek said the com­pa­ny had larg­er goals with the old Unum out­fit than a sin­gle pro­gram.

Over the last decade, they’ve built up a cell ther­a­py lo­gis­tics and man­u­fac­tur­ing base in the Czech Re­pub­lic, while ex­pand­ing in­to Chi­na and Basel. Now, they’ll try to turn the new ac­qui­si­tion in­to a re­search base in­side Cam­bridge, which they’re call­ing “A T cell ther­a­py R&D Cen­ter of Ex­cel­lence.” It will be led at first with a man in­ti­mate­ly ac­quaint­ed with the BOXR plat­form and the promise and pit­falls of cell ther­a­py: long­time Unum CTO Ge­off Hodge, whose cell ther­a­py ex­per­tise like­ly be­came ex­tra­ne­ous when Unum piv­ot­ed to ki­nas­es.

Ge­off Hodge

Špíšek is hop­ing their GMP cell ther­a­py fa­cil­i­ties will let them progress the plat­form faster than oth­ers could. They will al­so look to com­bine the BOXR CAR-Ts with their pre-ex­ist­ing drugs, in­clud­ing an en­gi­neered IL-15 that might stim­u­late the T cells fur­ther.

So far, he said, there have been no safe­ty sig­nals. But he added it was still quite ear­ly.

“Of course, this needs to be de­vel­oped very cau­tious­ly in the clin­ic,” he said.

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