Claudin18.2 ADC Development Part 0: Series Introduction

This series provides an in-depth review of the current landscape of Claudin18.2 (CLDN18.2)-targeted antibody–drug conjugates (ADCs) in gastric and gastroesophageal junction (GEJ) cancers. Structured into five parts, it covers pivotal clinical trials, drug design strategies, comparative analyses, and global development trends. In this introductory article (Part 0), we outline the rationale for CLDN18.2 targeting and the scope of the series.

Why CLDN18.2 Matters

Gastric and GEJ cancers remain among the leading causes of cancer mortality worldwide. Although HER2-targeted therapies and immune checkpoint inhibitors have improved outcomes for subsets of patients, many still face poor prognoses.

CLDN18.2 is selectively expressed in gastric mucosa and exposed on the tumor cell surface during malignant transformation, making it an attractive therapeutic target. The monoclonal antibody zolbetuximab, approved by the FDA in 2024, validated this approach, but its benefits are modest. This has fueled growing interest in ADCs, which deliver potent cytotoxic payloads directly to tumor cells.

Series Structure

The series is organized as follows:

1. Part 1: Phase 1 trial results and clinical implications of SHR-A1904 (Nature Medicine, 2025)
2. Part 2: Phase 1 trial results and molecular innovations of IBI343 (Nature Medicine, 2025)
3. Part 3: Comparative analysis of SHR-A1904 and IBI343, including safety, efficacy, and positioning
4. Part 4: Global CLDN18.2 ADC development landscape (CMG901, EO-3021, XNW27011, and more)

With this Part 0 introduction, readers can navigate the series systematically, gaining both context and continuity.

Significance of the Series

This series goes beyond summarizing trial data: it integrates clinical trial design, structural engineering, toxicity profiles, resistance mechanisms, and development strategies. Each part concludes with the author’s perspective, offering insights into the clinical and translational trajectory of CLDN18.2 ADCs.

What Comes Next

Part 1 will focus on SHR-A1904, examining the details of its phase 1 trial and clinical significance. The series then progresses to IBI343 (Part 2), a comparative analysis of both ADCs (Part 3), and a global overview of development efforts (Part 4).

MorningGlorySciences is provided a series of life science and therapeutics news.

世界最先端の治療薬を創る〜製薬会…

ADC Series – Bonus Chapter: Breakthroughs and the Fierce Global Race for Next-Generation Antibody-Dr… Over the past few years, the landscape of Antibody-Drug Conjugates (ADCs) has undergone a dramatic transformation, shifting from a niche therapeutic approach

世界最先端の治療薬を創る〜製薬会…

Beginner-Friendly Intro Series – Create the Most Advanced Therapeutics ~ Pharmas, Biotech Ventures, … Welcome to Part 1 of our Summer Special Beginner Series Vol.2 on Morningglorysciences.This time, we’ll explore the technology behind ADCs—Antibody-Drug

世界最先端の治療薬を創る〜製薬会…

Part 2: Basic Structure and Components of ADCs — Understanding the Role of Antibody, Linker, and Pay… Antibody-drug conjugates (ADCs) are next-generation therapeutics gaining attention, especially in oncology. In this second part, we introduce the three

世界最先端の治療薬を創る〜製薬会…

ADC Series Part 3: Antibody Structure and Target Recognition — The Role of the Variable Region – Cre… In Antibody-Drug Conjugates (ADCs), antibodies serve as targeting agents that deliver drugs to cancer cells. This article focuses on the “Variable Region,”

世界最先端の治療薬を創る〜製薬会…

ADC Series Part 4: Mechanism of Drug Release and Intracellular Action in Tumor Cells – Create the Mo… Antibody-drug conjugates (ADCs) deliver highly potent cytotoxic agents specifically to cancer cells, representing a breakthrough in targeted therapy.

世界最先端の治療薬を創る〜製薬会…

Biotech Investment News: Major Pharmaceutical Deals of Daiichi Sankyo (2015–2025) – Create the Most … Daiichi Sankyo has built a strong global presence through its antibody-drug conjugate (ADC) platform. While previous partnerships with AstraZeneca and Seagen

世界最先端の治療薬を創る〜製薬会…

How Did Japanese Pharma Choose and Compete Globally? — A 2015–2025 Strategic Overview – Create the M… Over the past decade, major Japanese pharmaceutical companies have undergone significant evolution amidst global competition. Daiichi Sankyo, Takeda, Otsuka,

世界最先端の治療薬を創る〜製薬会…

2025 Therapeutics Trend – Create the Most Advanced Therapeutics ~ Pharmas, Biotech Ventures, and Inv… The presence of obesity drugs in the market will continue to grow as it did last year. The market is estimated to be worth 10 trillion yen worldwide.

This article was edited by the Morningglorysciences team.