AstraZeneca Unveils Promising Phase I Data for CD19/CD3 Bispecific T-Cell Engager AZD0486 in B-Cell Malignancies

Recently,AstraZenecaInAnnual Meeting of the American Society of HematologyPresented the first Phase I clinical data of its CD3/CD19 bispecific antibody (AZD0486) for the treatment of B-cell malignancies.

The study tested four dose levels. The results showed that in 27 patients with follicular lymphoma treated with the three highest doses of AZD0486, the ORR was 96%.CRFor85%。

Moreover, at two medium dose levels, 17 of 19 patients had undetectable minimal residual disease after 12 weeks.

But forDiffuse Large B-Cell Lymphoma (DLBCL）This more difficult-to-treat disease has a poorer treatment outcome.According to last month's summary, at the dose expected to enter further studies, 9 of 19 patients (47%) responded, and 8 of 19 patients (42%) achieved complete remission.

Susan Galbraith, Executive Vice President of Oncology R&D at AstraZeneca, stated: "The most promising aspect of these data is that responses are being seen even in patients who have previously received CAR-T or anti-CD20 therapies."

For patients who experience disease progression after receiving CAR-T therapy, treatment options are extremely limited.

About AZD0486

AZD0486 is a bispecific T-cell engager (TCE) targeting CD19/CD3, originally developed by TeneoTwo. In 2022, AstraZeneca acquired TeneoTwo for $1.265 billion, gaining the rights to its clinical-stage drug TNB-486 (AZD0486）。

According to publicly available data, AZD0486 can bind to CD19 on the surface of B lymphocytes and CD3 receptors on the surface of T lymphocytes, thereby initiating an immune response in T lymphocytes.

On February 28, AZD0486 was approved for clinical use in China, with the indication being relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Market Prospects

Currently, globally, only Amgen's blinatumomab (Blincyto), a CD19/CD3 bispecific antibody, was approved by the U.S. FDA at the end of 2014 for the treatment of Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia (ALL). Clinical results show it can significantly improve patient survival.

After its market launch, Blincyto's global sales have been on a steady rise, reaching $379 million in 2020 and increasing to $583 million in 2022. According to Amgen's 2023 financial report, Blincyto's sales grew by 48% year-over-year to $861 million.

The surge in Blincyto's sales has led many pharmaceutical companies to see a broad potential market prospect. In recent months, there have been several transactions related to CD19 bispecific antibodies.

On August 9, Merck announced that it had reached a final agreement with Tongrun Bio to acquire CN201, a CD3/CD19 bispecific antibody, through its subsidiary. Merck plans to evaluate CN201 as a treatment for B-cell malignancies and explore its potential to provide new scalable options for autoimmune disease therapy.

On October 30, GSK reached an agreement with Enmu Biotech to acquire its CD19/CD20 bispecific antibody CMG1A46 for a total of $550 million. GSK plans to develop and commercialize CMG1A46 for the treatment of B cell-driven autoimmune diseases such as systemic lupus erythematosus (SLE) and lupus nephritis (LN).