AstraZeneca goes all-in on AbelZeta’s Car

AstraZeneca securing China rights to AbelZeta’s anti-GPC3 Car-T therapy C-CAR031/AZD7003, as announced on Sunday, locks in global ownership for the UK company of one of the industry's most promising solid tumour cell therapies.

While the move might at this point be seen as a mere formality, it brings to a close a period of over five years during which the two companies worked on GPC3-targeting Car-T projects, at first somewhat loosely. That gave rise to two Car-T projects differing only in the way they were manufactured, and Astra locking in AZD7003 comes after work on the other, AZD5851, was scrapped last year.

Until Sunday Astra held China co-development rights, as well as ex-China rights, to AZD7003 under a cross-licensing arrangement with AbelZeta that had formally been signed back in December 2023. The new deal gives Astra all the rights AbelZeta had previously held, meaning primary responsibility in China. 

The up-front terms of neither the new deal nor the original transaction have been made public. The new arrangement is said to involve Astra paying AbelZeta up to $630m, including an up-front fee plus development, regulatory and sales milestone payments for AZD7003 in China, thus adding to Astra’s earlier obligation to pay milestones and royalties on ex-China sales.

How did we get here?

The original alliance might have been announced in late 2023, but the two companies had actually worked together for rather longer, dating back to when AbelZeta was still known as Cellular Biomedicine Group (CBMG).

Indeed, Astra’s first-quarter 2023 financials deck listed C-CAR031, and said this was "designed by AstraZeneca and manufactured and developed in China by CBMG". An early clinical abstract on C-CAR031 presented at AACR in April 2023 listed as co-author Mark Cobbold – Astra’s head of immuno-oncology, discovery and oncology cell therapy.

In a mid-2022 story in Fierce Biotech Astra’s vice-president of oncology R&D, Susan Galbraith, cited "an agreement with CBMG" covering an autologous armoured anti-GPC3 Car. And in 2021, when CBMG delisted from Nasdaq, the AstraZeneca-CICC Fund co-led a $120m series A raise.

Having spoken to people close to the collaboration ApexOnco understands that the anti-GPC3, dnTGFbRII-armoured construct used in CAR031/AZD7003 and AZD5851 is identical, and that Astra developed it in collaboration with the Fred Hutchinson Cancer Center. Back then the UK group had no cell therapy manufacturing, but obtained this through CBMG, which did have such expertise.

For reasons that are unclear CBMG then assigned its own code (C-CAR031) to the Astra construct, AZD5851, packaged in CBMG’s vector. Perhaps to avert any litigation between the companies, the December 2023 deal tidied up this arrangement, giving Astra co-development rights to C-CAR031/AZD7003, and granting AbelZeta a milestone and royalty stake in AZD5851.

ASCO splash

It was only at ASCO in 2024 that the importance of all this work became apparent, when C-CAR031/AZD7003 yielded stunning early data in liver cancer, representing one of the most impressive clinical datasets ever reported for a cell therapy in a solid tumour. This subsequently triggered numerous other biotechs to develop anti-GPC3 Car-T assets.

Last year Astra announced the discontinuation of AZD5851, deciding instead to put all its eggs in the AZD7003 basket. ApexOnco understands that this was something of a pragmatic move, driven mostly by a desire to take forward the asset with the more advanced data; obviously the discontinuation made irrelevant the rights AbelZeta had over AZD5851.

With the focus now on AZD7003 the next move is for Astra to start its own, global, study to confirm AbelZeta’s success. This has yet to materialise, but perhaps the latest deal will enable it to happen soon.