Daiichi Sankyo Submits IND Application in China for DS-3939a, a Novel TA-MUC1-Targeting ADC, Entering Clinical Development for Solid Tumors

Dec 19, 2024 09:48 CST Updated 09:48

Daiichi-Sankyo

Pharmaceutical R&D Developer

▎WuXi AppTec Content Team Report

Today (December 19), the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced,The clinical trial application for DS-3939a, a Class 1 new drug submitted by Daiichi Sankyo, has been accepted.Public information shows,DS-3939a is an antibody-drug conjugate (ADC) targeting TA-MUC1., which is currently in Phase 1/2 clinical trials globally. According to the CDE official website, this is the first clinical application for this product in China.

Screenshot Source: CDE Official Website

MUC1 is an emerging target for cancer immunotherapy.MUC1 is a highly glycosylated transmembrane protein that plays a crucial role in the lubrication and protection of normal epithelial cells. MUC1 undergoes hypoglycosylation due to alterations in the expression patterns of certain sialyltransferases, exposing new epitopes on MUC1 in tumors, referred to as tumor-associated MUC1 (TA-MUC1).It is highly expressed in various human epithelial cancers, making it an attractive target for cancer therapy.

DS-3939a is an ADC targeting TA-MUC1, composed of a humanized anti-TA-MUC1 antibody, an enzymatically cleavable tetrapeptide linker, and a DNA topoisomerase I inhibitor (DXd) with a high drug-to-antibody ratio (DAR).

▲Introduction to DS-3939a (Screenshot source: Daiichi Sankyo 2024 R&D Day Materials)

According to the research results published by researchers at the 2024 American Association for Cancer Research (AACR) Annual Meeting, DS-3939a inhibited in in vitro experiments.TA-MUC1The growth of positive cancer cells, whileTA-MUC1Negative cancer cells have no inhibitory effect.In vitro studies have shown that DS-3939a exhibits TA-MUC1-dependent cell growth inhibition through DXD-mediated cytotoxic effects.In addition, DS-3939a demonstrated significant antitumor effects in several TA-MUC1-positive cancer cell line-derived xenograft models and various PDX models. In several xenograft models, DS-3939a induced strong tumor regression even after treatment with other cytotoxic ADCs.

Currently, Daiichi-Sankyo is conducting a Phase 1/2, first-in-human, open-label, multicenter, two-part, dose-escalation and dose-expansion study to evaluateDS-3939aA Phase 1/2 Clinical Study on the Safety, Tolerability, and Efficacy in Patients with Advanced Solid Tumors. This studyPlan to recruit up to 430 adult patients, the first part (dose escalation) includes patients with locally advanced, metastatic, or unresectable urothelial carcinoma, non-small cell lung cancer, breast cancer, ovarian cancer, biliary tract cancer, or pancreatic cancer, and the second part (dose escalation) includes various advanced solid tumors.TA-MUC1Expressing tumor patients.

References:

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Dec 16, 2024, from https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2] Abstract 6579: DS-3939a, a novel TA-MUC1-targeting antibody-drug conjugate (ADC) with a DNA topoisomerase I inhibitor DXd, exhibits potent antitumor activity in preclinical models . Retrieved Mar 22, 2024 from https://aacrjournals.org/cancerres/article/84/6_Supplement/6579/738363/Abstract-6579-DS-3939a-a-novel-TA-MUC1-targeting

[3] Daiichi Sankyo Official Website. From https://www.daiichisankyo.com/investors/library/materials/

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