At­las Ven­ture-backed Unum, which once har­bored am­bi­tions to ri­val the two CAR-T ther­a­pies Kym­ri­ah and Yescar­ta, is pay­ing the price for a laun­dry list of set­backs.

Seth Et­ten­berg Unum

On Mon­day, the Cam­bridge, Mass­a­chu­setts-based com­pa­ny said it was cut­ting its work­force by 43 em­ploy­ees (rough­ly 60% of the to­tal head­count) to fo­cus its ef­forts on a pre­clin­i­cal pro­gram. It al­so dis­closed the de­par­ture of its chief sci­en­tif­ic of­fi­cer, Seth Et­ten­berg, as it ceas­es the de­vel­op­ment of tri­als har­ness­ing its maid­en tech­nol­o­gy: AC­TR.

The tri­als shelved in­clude an ear­ly-stage lym­phoma pro­gram test­ing the ex­per­i­men­tal drug, AC­TR707, in com­bi­na­tion with rit­ux­imab (Roche’s MabThera), as well as a Phase I sol­id tu­mor tri­al eval­u­at­ing the com­bi­na­tion of AC­TR707 and trastuzum­ab (Roche’s Her­ceptin).

Cell ther­a­pies un­der the plat­form were en­gi­neered to arm a pa­tient’s T cells with the ar­se­nal to launch a dou­ble at­tack on can­cer cells. First, the cells are de­signed to ex­press AC­TR — a chimeric pro­tein made out of com­po­nents from T cells and nat­ur­al killer cells — and then are com­bined with the tu­mor-tar­get­ing abil­i­ty of co-ad­min­is­tered an­ti­bod­ies.

The plat­form has seen fail­ure af­ter fail­ure. Back in 2018, in its IPO fil­ing, the com­pa­ny dis­closed that two out of nine pa­tients in the high-dose arm of a clin­i­cal tri­al for their then-lead cell ther­a­py — AC­TR087 — had died, forc­ing the FDA to im­pose a clin­i­cal hold that was lift­ed just ahead of their bid to go pub­lic. While it broke no laws, the com­pa­ny’s ap­proach to trans­paren­cy didn’t win it any plau­dits — the IPO was priced at the bot­tom of the range.

Then, last year, things got worse. Ex­ec­u­tives in Ju­ly re­vealed that the FDA had slapped an­oth­er clin­i­cal hold on AC­TR087,  af­ter a pa­tient in the safe­ty co­hort of a Phase I study ex­pe­ri­enced a raft of se­ri­ous ad­verse events. By this time, Unum — which is al­so backed by F-Prime Cap­i­tal — had repri­or­i­tized its pipeline to fo­cus on AC­TR707.

Come No­vem­ber, AC­TR087 was for­mal­ly aban­doned amid a broad­er shift from hema­tol­ogy to sol­id tu­mors. The com­pa­ny’s oth­er tech plat­form, BOXR, hit the spot­light.

The tu­mor mi­croen­vi­ron­ment in many sol­id tu­mor can­cers is deeply im­muno­sup­pres­sive, block­ing T cells from func­tion­ing nor­mal­ly. Unum’s Bolt-on Chimeric Re­cep­tor (BOXR) is de­signed to “bolt-on” trans­genes to boost in­trin­sic T cell func­tion­al­i­ty to con­quer that im­muno­sup­pres­sion.

In Unum’s lat­est up­date, it looks like AC­TR707 has al­so made the scrap heap — leav­ing pre­clin­i­cal BOXR1030 as the sole fo­cus. The com­pa­ny’s shares $UM­RX wad­ed deep­er in­to pen­ny stock ter­ri­to­ry, dip­ping slight­ly pre­mar­ket to 54 cents.

Re­gen­er­a­tive stem cell play­er Blue­Rock Ther­a­peu­tics, mean­while, has scored the ser­vices of Unum’s erst­while CSO Et­ten­berg.

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.