AstraZeneca Acquires Remaining China Rights to AbelZeta’s GPC3 Armored CAR-T

Edited by Robert McTiernan··2 min read

AstraZeneca agreed to acquire AbelZeta Pharma’s remaining 50% stake in the China development and commercialization rights to C-CAR031, a glypican-3 (GPC3)-targeted armored chimeric antigen receptor T-cell (CAR-T) therapy, giving AstraZeneca full global control of the asset.

Under the agreement, AbelZeta is eligible to receive up to USD 630 million from AstraZeneca in total payment and milestone commitments tied to the GPC3 program in China. AstraZeneca already held ex-China rights through a 2023 co-development collaboration.

C-CAR031 (also known as AZD7003) is an autologous CAR-T therapy directed at GPC3, a cell surface protein overexpressed in hepatocellular carcinoma (HCC) and other solid tumors, and engineered using AstraZeneca’s armoring platform incorporating a dominant negative transforming growth factor-beta receptor II to enhance T-cell resilience in the immunosuppressive tumor microenvironment. The drug candidate is currently the subject of a Phase I/II trial in HCC being held in China.

The AllSci BriefSystematic R&D and deal news. Daily.

AbelZeta and AstraZeneca initially partnered in late 2023 on co-development of the GPC3 program, with AbelZeta manufacturing in China and AstraZeneca leading design and global development efforts outside China.

GPC3 and the competitive landscape

Glypican-3 (GPC3) is a validated oncofetal antigen highly expressed in HCC and select pediatric and adult solid tumors, but largely absent from normal adult tissues. This makes GPC3 an attractive target for a range of immunotherapeutic and targeted modalities, particularly in HCC where targetable surface antigens are scarce.

After initial efforts to target GPC3 using monoclonal antibodies, led by Roche’s GC33, failed to deliver meaningful clinical benefit, current clinical-stage development efforts include multiple modalities, including antibody-drug conjugates (ADCs), bi- and tri-specific antibodies, CAR-T cells, vaccines, and radiopharmaceuticals. Key examples (all in early-stage trials at present) include:

  • AstraZeneca: AZD9793 (trispecific T-cell engager)
  • Bayer: 225Ac-GPC3 (BAY 3547926), targeted alpha radiopharmaceutical
  • RayzeBio/Bristol Myers Squibb: RYZ801/RYZ811, peptide radiotherapeutics
  • Zymeworks: ZW251, GPC3-targeted ADC
  • SOTIO Biotech: BOXR1030, CAR-T
  • Eureka Therapeutics: ECT204, CAR-T
  • BeOne Medicines: BGB-B2033, bispecific antibody
  • CRISPR Therapeutics: RPCAR01, CAR-T