AstraZeneca Submits IND Application in China for AZD9829, a Novel CD123-Targeting ADC for Hematologic Malignancies

Dec 25, 2023 17:24 CST Updated 17:24

AstraZeneca

Biopharmaceutical Manufacturer

▎WuXi AppTec Content Team Report

On December 25, the official website of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China announced,AstraZeneca submitted a clinical trial application for the new drug AZD9829 (Class 1) and received approval. According to publicly available information,This is a CD123-targetedTopoisomerase 1 Inhibitor (TOP1i)-Antibody-drug conjugates (ADCs) are currently in Phase 1/2 clinical trials in the United States.

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) PayloadThe ADC formed by connection, itsThe main mechanism of action is to deliver the TOP1i payload to cancer cells expressing CD123, resulting in DNA damage and apoptosis.

November 2023,BloodJournalPublished for the first timeAZD9829Preclinical study data. The study shows that AZD9829 demonstrates 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 diseases 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 reduction of 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 to evaluate AZD9829 as a monotherapy or in combination therapy.Patients with CD123-positive hematologic malignanciesSafety, tolerability, pharmacokinetics, and preliminary antitumor activity.

References:

[1]Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Dec 25, 2023, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

[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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