A manufacturing delay is stymying progress of a clutch of Autolus’ CAR-T programs. Autolus revealed the setbacks alongside news that it is dumping the first-generation version of AUTO2 in the face of tough competition in the BCMA space.
The manufacturing issue, which is affecting three Autolus’ programs, relates to a five-month delay in the timeline for qualifying the U.K.’s Cell Therapy Catapult. Autolus’ clinical trial manufacturing site at Catapult was licensed in March and has supplied materials to studies since then. But the ramp-up of output has been slowed by delays at the broader Catapult complex.
“The Cell Therapy Catapult site is a brand-new facility. And the challenge that we're seeing with the facility is a delay on the construction and qualification of the main facility. That actually basically resulted in a situation where the delay in the buildup and the construction of facility had a knock-on effect on our own ability to get our own suite that we're operating fully licensed and operational,” Autolus CEO Christian Itin said on a second-quarter results conference call with investors.
Those delays pushed back overall qualification of the Catapult by five months. Itin said Autolus was able to claw back some of the lost time but still faces delays to multiple clinical trials programs.
Autolus now plans to start the phase 2 portion of a trial of CD19xCD22 dual-CAR-T therapy AUTO3 in the second quarter of 2020. The phase 2 was due to get underway before the end of 2019.
AUTO4 and AUTO5 have suffered similar delays. Autolus pushed back initial phase 1 data on AUTO4, a TRBC1-targeting CAR-T, from the first quarter of 2020 into the second half of the year. AUTO5 is now due to enter the clinic in the second half of 2020.
Autolus’ plans for AUTO2 were pushed back by a different problem. Faced with clinical data that Itin said showed AUTO2 “may not be differentiated from more advanced competitor programs,” Autolus has scrapped development of the current version of the BCMAxTACI-targeted CAR-T therapy in favor of a next-generation successor that is due to start testing in humans next year.
The decision reflects the number of companies with BCMA assets in the clinic. Bluebird bio, Celgene and Johnson & Johnson all have anti-BCMA CAR-T therapies in the clinic and a clutch of other drug developers are going after the target via other modalities. Those competitive considerations played a role in Gilead’s decision to drop KITE-585 earlier this year.
Another strategic decision lay behind the final delay disclosed by Autolus in its results. Autolus is switching its focus in pediatric acute lymphoblastic leukemia (ALL) from AUTO3 to a next-generation version of AUTO1.
“This new program leads to a one-year delay for [Autolus] to enter the pediatric ALL market with initial Ph1 data to be expected in H2 '20,” analysts at Jefferies wrote in a note to investors.
The delays shaved a little more value off Autolus’ already depressed stock price, which is down around 70% from the high it hit last year.