AstraZeneca's Ambitious Oncology Strategy: From ADCs to Radiopharmaceuticals

AstraZeneca is making significant strides in its oncology pipeline, leveraging a diverse array of cutting-edge technologies to potentially redefine cancer care. The pharmaceutical giant's recent investments and clinical progress span antibody-drug conjugates (ADCs), radiopharmaceuticals, bispecific antibodies, and cell therapies, positioning the company at the forefront of next-generation cancer treatments.

ADCs and Radiopharmaceuticals: A Two-Pronged Approach

AstraZeneca's oncology strategy heavily emphasizes ADCs and radiopharmaceuticals, two modalities showing promise in targeted cancer therapy. The company has already achieved success with ADCs like Enhertu and Datroway, both developed in collaboration with Daiichi Sankyo. Building on this foundation, AstraZeneca is now focusing on its internal ADC pipeline.

Puja Sapra, Ph.D., AstraZeneca's senior vice president for biologics engineering and oncology target discovery, highlighted the company's progress: "We have deliberately made investment in the next-generation technologies which we believe will redefine oncology care, like ADCs [and] radioconjugates."

The company's in-house ADC pipeline includes six clinical-stage candidates targeting various solid tumors and hematological malignancies. Two notable candidates, AZD5335 and AZD8205, have shown encouraging results in recent clinical trials. AZD5335, a folate receptor α (FRα)-targeted ADC, is in phase 2 trials for ovarian cancer and lung adenocarcinoma, while AZD8205, a B7-H4–directed topoisomerase I inhibitor ADC, is being evaluated in solid tumors.

In the radiopharmaceuticals space, AstraZeneca's acquisition of Fusion Pharmaceuticals has bolstered its capabilities. The company is now advancing FPI-2265, a PSMA-directed radioconjugate, in a phase 2 prostate cancer trial. Additionally, an EGFR-cMET targeted radioconjugate is undergoing phase 1 testing.

Bispecific Antibodies and Cell Therapies: Expanding the Arsenal

AstraZeneca is also making significant investments in bispecific antibodies and cell therapies. The company's bispecific antibody portfolio includes rilvegostomig, a PD-1/TIGIT bispecific, and volrustomig, which targets CTLA-4 and PD-L1. These candidates are currently being evaluated in a total of nine phase 3 trials.

Sapra emphasized the unique design of these bispecifics, stating, "They are very different designs. They go after different population settings and that's why we are trying to maximize and put [them] in different settings."

In the cell therapy arena, AstraZeneca has seven programs in clinical development. The company's recent acquisition of EsoBiotec has added "in vivo" capabilities to its cell therapy portfolio. This move underscores AstraZeneca's long-term commitment to the space, despite other pharmaceutical companies scaling back their cell and gene therapy efforts.

"We have made broad commitments to cell therapy, and that's clear from EsoBiotec, but other things also," Sapra explained. "We have gone from autologous to building the allogeneic [and] now thinking about in vivo. So this is a long-term vision to be in this space."

AstraZeneca's diverse oncology portfolio reflects a deliberate strategy to explore multiple avenues in cancer treatment. As Sapra concluded, "That's by design, which we are very proud of. It has been built on solid, binary scientific foundations." With its wide-ranging investments and promising clinical progress, AstraZeneca is positioning itself as a major player in the future of oncology care.