AstraZeneca Withdraws Three Cell Therapy Candidates Amid Industry-Wide Strategic Reassessment

The clinical trial appendix released by AstraZeneca shows that three products in the cell therapy pipeline, NT-125, AZD5851, and AZD6422, have been removed. These products that have been suspended are highly innovative. However, behind their technological advancement lies the complex reality of clinical translation and industrial implementation: long R&D cycles, complicated manufacturing processes, uncontrollable costs, and low standardization levels.

Notably, AstraZeneca is not alone. Globally, a group of pharmaceutical companies, including BMS, Astellas, CARGO, and Adaptimmune, have gradually begun to "streamline and focus" their cell therapy pipelines, concentrating resources on more platform-valuable, universal, and scalable pathways.

"Under the 'collective cooling-off period,' the cell therapy industry is gradually entering the deep waters of 'from the Great Leap Forward to refined operations.'"

01.

Three Major Projects Rational Retreat

Pharmaceutical Companies Collectively Enter the "Calm Period" of Cell Therapy

Among the three terminated products, the most notable is NT-125, developed by Neogene Therapeutics. This therapy is a fully individualized, multispecific TCR-T therapy targeting neoantigens in cancer, capable of integrating up to five different neoantigen-specific TCRs in a single cell product, thereby reducing the likelihood of tumor antigen escape. Subsequently, AstraZeneca initiated a Phase I clinical trial involving 42 patients, including those with non-small cell lung cancer, colorectal adenocarcinoma, and squamous cell carcinoma of the head and neck, among other solid tumors, to evaluate the efficacy of NT-125.

As one of the core assets when AstraZeneca acquired Neogene for nearly $2 billion in 2022, despite the termination of the NT-125 pipeline, Chief Financial Officer Aradhana Sarin still stated that this deal was "absolutely worth it." She added during the earnings call on Tuesday morning: "Beyond these assets, we have also brought in key talent and manufacturing capabilities through Neogene."

The cell pipelines halted together with NT-125 are two "armored CAR-T" products, AZD5851 and AZD6422, targeting GPC3 and Claudin18.2 respectively, both equipped with a dominant-negative TGFβRII structure to enhance resistance to inhibition. AZD5851 entered clinical trials at the end of 2023, and the 2024 ASCO report showed that its derivative product, C-CAR031, achieved an ORR of 56.5% in Chinese patients with advanced liver cancer, demonstrating good safety; however, the official website indicates the project was terminated for strategic reasons. AZD6422 conducted IIT in collaboration with AbelZeta, showing positive results in early animal experiments, but was also abandoned due to efficacy concerns.

Correlation analysis shows that NT125, as a highly individualized TCR-T product, theoretically has an advantage in precision but falls slightly behind universal cell therapies in mass production, commercial standardization, and cost control. Both AZD5851 and AZD6422 are armored CAR-T products designed to enhance the tolerance and killing ability of immune cells in the solid tumor microenvironment through modifications such as the introduction of TGF-β inhibition mechanisms. While significantly improving efficacy, these innovations bring with them complex production processes and increased costs.

Overall, AstraZeneca has determined that the commercialization priority of these three products at the current stage is lower than other ongoing cell therapy pipeline projects. In an environment where the cell therapy field has yet to establish unified industry standards and differentiation barriers are blurred, fully advancing high-cost, high-uncertainty products could very likely face the dilemma of an insufficient benefit-risk ratio.

Therefore, AstraZeneca's strategic abandonment of these three products this time is very likely a resource reallocation decision made after prudently weighing the clinical prospects, manufacturing costs, and market competition landscape, aiming to focus investment on cell therapy projects with greater feasibility and return potential.

AstraZeneca is not an isolated case. In recent years, the entry of cell therapy into a "rational adjustment moment" has become a common state for pharmaceutical companies.

In 2024, Bristol-Myers Squibb (BMS) will close its Tumor Microenvironment and Cell Therapy Research Center located in Redwood City, California, to streamline early-stage R&D teams and implement a strategic downsizing, focusing efforts on the most promising areas to maximize the utilization of existing assets.

In January 2025, AstraZeneca announced the termination of an early-stage CAR-T therapy, ASP2802, an autologous cell therapy targeting CD20-positive B-cell lymphoma currently in Phase I clinical trials. This pipeline was acquired by AstraZeneca through its 2019 purchase of Xyphos Bioscience. The company stated that the decision to halt the program was based on "evaluating how to streamline operations and prioritize resource allocation."

In addition to large pharmaceutical companies, biotech firms in the cell therapy sector also face challenges.

In March 2025, CARGO Therapeutics announced the suspension of the development of its core project, CRG-023. The product had previously showcased preclinical study results at the 66th American Society of Hematology (ASH) Annual Meeting in 2024, demonstrating high activity and significant tumor-killing capability. However, the company ultimately terminated the development citing "insufficient benefit-to-risk ratio" and stated that it is actively advancing new strategic alternatives.

In July of the same year, Adaptimmune Therapeutics, a company headquartered in the UK, planned to cut 62% of its workforce after completing the sale of four cell therapy assets to US WorldMeds.

02.

Cell Therapy Strategy "Reordered"

Platform Builds New Paradigm

Notably, although AstraZeneca has terminated the development of three cell therapy products this time, its layout in the field of cell therapy has not slowed down.

According to public statements, Susan Galbraith, Head of Oncology R&D at AstraZeneca, pointed out that AstraZeneca "remains optimistic about the potential of cell therapy," and this adjustment reflects more of "a reprioritization based on pipeline maturity and platform capabilities."

The semi-annual report shows that AstraZeneca currently has several CAR-T and TCR-T products steadily advancing, maintaining a positive pace in the R&D of the cell therapy sector.

In fact, the "industrial product model" for cell therapy has not yet matured. Each treatment product is almost custom-made for a single patient, including cell collection, genetic engineering modification, expansion, quality testing, and reinfusion. While personalization provides precision, it also means complex processes, difficulty in standardization, poor batch stability, and long production cycles. This model is commercially unsustainable. The core challenge for industrialization is how to build cell products that can be mass-produced, have controllable quality, affordable costs, and are acceptable to payment systems, all while ensuring efficacy.

Therefore, the trend of shifting from "individual target breakthrough" to "building a platform-based technology system" is quietly becoming the "second curve" consensus in the global cell therapy field: after the traditional single-product orientation encounters technical and industrial bottlenecks, only by "platformizing" cell therapy capabilities can we bridge the three gaps of validation, implementation, and commercialization.

In March 2025, AstraZeneca announced the acquisition of Belgian biotech startup EsoBiotec for up to $1 billion. EsoBiotec has developed an "in-vivo CAR-T" platform capable of delivering genes to T cells via intravenous injection and completing the modification within the body. The technology, which enables "in vivo cell modification" through a simple injection, is expected to revolutionize the treatment model of cell therapy, making it more cost-effective, readily available, and significantly reducing manufacturing time and costs.

Currently, several companies, including Interius, Umoja, Astellas, Jiyin Bio, and Unicar-Therapy, are conducting research and development around in vivo CAR-T. AstraZeneca's investment trends also indicate that it has high hopes for this direction.

This also means that moving towards a "platform-led" approach is becoming a new paradigm for the development of cell therapy. In this paradigm, companies no longer chase the quick market opportunities of one or two popular targets. Instead, they focus on key areas such as delivery methods, cell engineering modules, gene regulation technologies, and immune tolerance mechanisms to form a scalable, replicable, and licensable technology foundation.

In addition, in July 2025, AstraZeneca announced a planned investment of $50 billion in the United States, which will be used to fund the expansion of a factory in Virginia across multiple states, enhancing R&D and production capabilities, and driving manufacturing capacity to become the next moat in the development of cell therapy.

Multiple enterprises with strong R&D backgrounds have scaled back their operations in the CAR-T/TCR-T field. This is not only a localized adjustment but also a profound footnote for the entire cell therapy industry—industrialization is not merely a technological competition but a systemic challenge that balances the "efficacy-cost-sustainability triangle." Any company wishing to establish itself in the cell therapy sector will ultimately face the full-chain test of moving from "laboratory feasibility" to "clinical accessibility" and then to "market affordability." Conducting cross-evaluations of commercial feasibility and clinical data at every stage of R&D, while promptly eliminating redundant or underperforming projects, may become the future trend in cell therapy research and development.