AstraZeneca Reshapes Cell Therapy Strategy, Discontinues Key Programs

AstraZeneca has announced a significant shift in its cell therapy portfolio, discontinuing three programs as part of a strategic prioritization effort. The move comes as the pharmaceutical giant continues to refine its approach to oncology and cell therapy development.

Neogene Acquisition Lead Candidate Dropped

AstraZeneca has halted development of NT-125, the lead candidate from its $200 million acquisition of Neogene Therapeutics in 2022. NT-125, designed to contain up to five distinct neoantigen-specific T-cell receptors per patient in a single cell product, was being evaluated in a phase 1 trial involving 42 patients with various cancers, including non-small cell lung cancer, colorectal adenocarcinoma, and head and neck squamous cell carcinoma.

The company cited "strategic portfolio prioritization" as the reason for ending the trial. This decision underscores AstraZeneca's focus on the broader potential of Neogene's TCR platform for solid tumors, rather than specific assets.

Armored CAR-T Programs Discontinued

In addition to NT-125, AstraZeneca has discontinued two armored CAR-T therapies:

1. AZD5851, a GPC3-directed CAR-T using AstraZeneca's transforming growth factor-beta receptor II (TGFβRII) dominant negative armouring platform. This therapy was being evaluated in a phase 1/2 study of 94 patients with GPC3-positive advanced or recurrent hepatocellular carcinoma.

2. AZD6422, a CLDN18.2-targeting CAR-T, which was undergoing a phase 1 study in 96 patients with advanced or metastatic CLDN18.2-positive gastrointestinal tumors. The company discontinued this program "due to efficacy" following data readout in the second quarter.

Continued Investment in Cell Therapy

Despite these setbacks, AstraZeneca remains committed to advancing its cell therapy pipeline. The company has made significant moves in the field, including:

• A $1 billion acquisition of EsoBiotec and its lentiviral vector platform, positioning AstraZeneca in the "off-the-shelf" cell therapy space.
• Opening a $300 million cell therapy manufacturing facility in Rockville, Maryland.
• Advancing a BCMA and CD19 dual-targeting CAR-T for multiple myeloma, acquired through the 2023 Gracell acquisition.

Susan Galbraith, Ph.D., AstraZeneca's executive vice president of oncology R&D, emphasized the company's broader cell therapy strategy, which encompasses traditional and next-generation CAR-Ts, as well as the potential for combining TCR technology with bispecific immune therapies to overcome T-cell exhaustion.

As AstraZeneca continues to refine its approach to cell therapy, the company remains focused on expanding its oncology portfolio and exploring innovative approaches to cancer treatment. The recent portfolio adjustments reflect the dynamic nature of pharmaceutical R&D and the ongoing quest to develop more effective therapies for patients with difficult-to-treat cancers.