AstraZeneca's Novel CD123-Targeting ADC AZD9829 Granted Clinical Trial Approval in China

Mar 06, 2024 14:22 CST Updated 14:23

AstraZeneca

Biopharmaceutical Manufacturer

▎WuXi AppTec Content Team Report

On March 5, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,AstraZeneca's Class 1 new drug AZD9829 has received clinical trial implied permission, intended for development to treatCD123-positive malignant hematological diseases. Public information shows,AZD9829Is a CD123-targetedTopoisomerase 1 Inhibitor (TOP1i)-Antibody-Drug Conjugates (ADC).

Screenshot source:CDE Official Website

According to literature reports, CD123 is a cell surface protein that is overexpressed in several hematologic malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and its expression is restricted in normal hematopoietic stem cells. Compared with other AML-related targets such as CD33, the characteristic of CD123 is thatHighly expressed in the bone marrow of AML patients, but with limited expression in the bone marrow of healthy donors.

AZD9829 is an antibody targeting CD123.With AstraZeneca's proprietaryTopoisomerase 1 Inhibitor (TOP1i) PayloadADC formed by connection. The drug'sThe main mechanism of action is to deliver the TOP1i payload to cancer cells expressing CD123, resulting in DNA damage and apoptosis.

November 2023,BloodMagazinePublished for the first timeAZD9829Preclinical study data. Studies have shown that AZD9829 exhibits potent killing ability against CD123-positive AML cell lines in vitro.The anti-tumor activity of this product was also observed in 13 patient-derived xenograft (PDX) models from AML patients, representing the heterogeneity of AML with different mutation statuses, disease stages, prior treatment responses, and CD123 expression levels.In addition, AZD9829 demonstrated sustained reduction of leukemia blasts on Day 28 after the first dose, including reductions in leukemia blasts in both blood and bone marrow. Safety studies in cynomolgus monkeys support the clinical development of AZD9829.

According toClinicalTrialsAccording to the official website, AstraZeneca is conducting a Phase 1/2 clinical study in the United States to evaluate AZD9829 as a monotherapy or in combination therapy.Patients with CD123-positive hematologic malignanciesThe safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity. The product's recent implied clinical trial approval in China indicates that clinical research will also be conducted in China.

References:

[1]Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Mar 05, 2024, from https://www.cde.org.cn/main/xxgk/listpage/2f78f372d351c6851af7431c7710a731

[2]Dipannita Dutta.(2023) First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors.Blood.doi:https://doi.org/10.1182/blood-2023-187642

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