The recent FDA decision to investigate the serious risk of patients developing new cancers after treatment with CAR-T therapies may have created some bad press around cell and gene therapies, but AstraZeneca has continued to consolidate its ambitions in the area with the acquisition of China-based cell therapy biotech, Gracell Biotechnology, for some USD 1.2 billion.


FDA Red Flag

Last November, following reports of T-cell malignancies among patients who received BCMA- or CD19-directed CAR-T cell immunotherapies, the FDA announced that it would be investigating the serious risk of T-cell malignancy linked to these therapies. The reports came from clinical trials and post marketing adverse event (AE) data, and, according to the agency, some of the patients involved have been hospitalised, or have died.

Regardless of the FDA’s announced probe into CAR-T cell therapies, the agency apparently still believes that the benefits of these treatments outbalance their risks and for the time being there are no plans to withdraw the approvals of any existing drugs.

CAR-T has represented a major breakthrough in the treatment of a number of blood cancers in recent years and big pharma companies, including Novartis, Johnson & Johnson, and Gilead, have been quick to jump into the race to advance new therapies. CAR-T treatments have indeed presented impressive results with Gilead’s Yescarta reducing disease progression and death by 60.2 percent for large B-cell lymphoma and J&J’s Carvykti demonstrating a 74 percent benefit in delaying tumor progression compared to standard combination therapy in patients with multiple myeloma.

However, challenges remain in CAR T-cell therapy with respect to solid tumors, CAR-T treatment is extremely costly, and therapies are time-consuming to produce.


AstraZeneca: Building a Cell Therapy Portfolio

An important player in the oncology space, with a portfolio in the field that accounted for more than a third of its revenues in 2022, AstraZeneca has not taken part in big pharma’s initial cell therapy rush. However, the Anglo-Swedish company has been working on building its capabilities in the area for some time.

In a recent deal with US and China-based AbelZeta Pharma, the company agreed to jointly develop the autologous, armoured GPC3-targeting chimeric antigen receptor CAR-T therapy, C-CAR031, to treat hepatocellular carcinoma (HCC). AstraZeneca also acquired Neogene Therapeutics last year for USD 320 million, bringing onboard its next-generation T-cell receptor therapies (TCR-Ts) that look to target DNA mutations specific to tumours.

The new acquisition will enhance AstraZeneca’s cell therapy pipeline with Gracell’s GC012F, FasTCAR-enabled BCMA and CD19 dual-targeting autologous chimeric antigen receptor CAR-T that is being tested in a phase 1b/2 trial for multiple myeloma. “The proposed acquisition of Gracell will complement AstraZeneca’s existing capabilities and previous investments in cell therapy, where we have established our presence in CAR-T and T-cell receptor therapies (TCR-Ts) in solid tumors,” said Susan Galbraith, EVP of Oncology R&D.

Not only will AstraZeneca get the candidate, it will also obtain Gracell’s FasTCAR platform that was used to develop it, a platform designed to reduce manufacturing time and enhance T-cell fitness to potentially improve efficacy. AstraZeneca suggested that it may use the platform for further applications. “GC012F will accelerate our cell therapy strategy in hematology, with the opportunity to bring a potential best-in-class treatment to patients living with blood cancers using a differentiated manufacturing process,” Galbraith added.

In a 2029 PharmaBoardroom interview, the founder, chairman & CEO of Gracell, William (Wei) Cao, said that the biotech was looking to tackle the “pain points” relating to CAR-T, including its elevated cost and the length of manufacturing.  “Our novel FasT-CAR platform … seeks to deal with both the high cost and the length of the manufacturing process,” he said. “At the moment, the industry average manufacturing time is around two weeks. Our technology allows for manufacturing to be done overnight – the shortest in the industry so far.”


AZ’s Long-term Cancer Strategy

AstraZeneca’s pursuit of cell therapies has not been limited to M&A and as Dave Fredrickson, executive VP of the firm’s oncology business claimed in 2022, “building our own cell therapy expertise” is a key part of AstraZeneca’s longer-term cancer strategy. “We don’t see that we have to go pursue M&A in order to compensate for a pipeline that isn’t delivering organically,” Fredrickson claimed. “We’ve got our own R&D that we’re really enthusiastic about, but we’re always looking outside to make sure that we’re not missing a trick.”

The drugmaker is avidly investigating cell therapy for solid tumours, and what are known as “off-the-shelf,” therapies. Instead of using the patient’s own cells to create the treatment, these therapies would collect them from healthy donors and manufacture doses that could be stored for use as needed, thus reducing costs and timelines.