Unum’s second halt puts CD20 targeting under the spotlight


Unum Therapeutics’ clinical hold, revealed on Tuesday, is clearly bad news for the company, but the broader question is what it means for other companies trying to take CD20 targeting a stage further. Toxicity is clearly manageable in the setting of a naked anti-CD20 antibody like Rituxan, but when combined with Unum’s ACTR087, which is akin to a modular CAR-T approach, it is unacceptable. ACTR087’s phase I study has been put on hold owing to neurotoxicity, cytomegalovirus infection and respiratory distress; in December 2017 the same trial had been halted for two months because of serious adverse events that led to protocol and dosing changes. Cell therapies cause more potent T-cell recruitment than naked antibodies, so toxicities tend to be more pronounced, and clinicaltrials.gov reveals 19 studies of CD20-directed CAR-T therapies, mostly in China. Unum stressed that it had already deprioritised ACTR087 in favour of ACTR707, but crucially this second construct still relies on Rituxan to direct T cells to tumours. The company, now trading 80% below last year’s IPO price, is therefore refusing to give up on CD20 targeting, hoping instead to ameliorate matters by modifying the way its approach stimulates T cells.

CAR-T compared with Unum's modular approach.

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