AstraZeneca has dropped the lead candidate from its $200 million buyout of Neogene Therapeutics as part of a wider cell therapy clearout.
When AstraZeneca scooped up the company back in 2022, Neogene’s most advanced asset was NT-125, which was designed to contain up to five distinct neoantigen-specific T-cell receptors per patient in a single cell product. The theory was that this approach could cut the risk of antigen escape and trigger deep, durable clinical responses.
AstraZeneca has since been evaluating NT-125 in a phase 1 trial of 42 patients with various cancers, including non-small cell lung cancer, colorectal adenocarcinoma, and head and neck squamous cell carcinoma. But the company revealed in its second-quarter earnings release that it has ended the trial “due to strategic portfolio prioritization.”
In fairness to AstraZeneca, the company made no secret of the fact that the biggest prize from the Neogene acquisition was the biotech’s TCR platform and its potential for solid tumors rather than any specific assets.
In an interview with Fierce Biotech a month after the Neogene deal, AstraZeneca’s executive vice president of oncology R&D Susan Galbraith, Ph.D., positioned the acquisition as part of a broader cell therapy strategy that also encompasses traditional and next-generation CAR-Ts.
Incorporating TCR technology “increases the spectrum of cancers that can then be targeted,” Galbraith said in the 2022 interview. “You probably need to put that together with armoring and maybe in combination with some of our bispecific immune therapies to help overcome the potential for exhaustion,” she added.
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While Gabraith may have name-checked armored CAR-Ts—a term for CAR-Ts engineered to express additional proteins alongside the chimeric antigen receptor—as another key part of AstraZeneca’s cell therapy arsenal, it hasn’t stopped the company from discontinuing two of these therapies alongside NT-125 this morning.
One of these is AZD5851, a GPC3-directed CAR-T that uses AstraZeneca’s transforming growth factor-beta receptor II (TGFβRII) dominant negative armoring platform. The company had been evaluating AZD5851 in a phase 1/2 study of 94 patients with GPC3-positive advanced or recurrent hepatocellular carcinoma, but it sounds like the therapy has fallen victim to the same portfolio prioritization.
The final med thrown on the cell therapy scrap heap this morning is another armored CAR-T called AZD6422. That therapy, which targets CLDN18.2, was being tested in a phase 1 study of 96 patients with advanced or metastatic CLDN18.2-positive gastrointestinal tumors.
Data from the trial read out in the second quarter, according to AstraZeneca’s documents. It doesn’t sound like the results were good enough, with the company explaining that it has discontinued the program “due to efficacy.”
While AstraZeneca may have relieved itself of three cell therapies today, the company’s wider push into the space shows no signs of slowing down. So far this year, the pharma has become an “off-the-shelf” cell therapy player via a $1 billion deal to acquire EsoBiotec and its lentiviral vector platform as well as by opening a $300 million cell therapy manufacturing facility in Rockville, Maryland.
The pharma’s current cell therapy pipeline is led by a BCMA and CD19 dual-targeting CAR-T for multiple myeloma acquired as part of 2023’s Gracell acquisition, and AstraZeneca name-checked cell therapies along with radioconjugates in this morning’s earnings release as examples of the R&D areas it has been specifically investing in.
