Chinese Biopharma Leads the Race: CDH17 Emerges as a Hot ADC Target with 9 Candidates in Clinical Trials

Interestingly enough, in the same week,MabwellAnnouncing that the clinical trial application for its CDH17-targeted ADC innovative drug 7MW4911 has been approved by the NMPA;ZAIMINGThe CDH17 ADC drug SIM0609 also received clinical approval from China's NMPA and the U.S. FDA in September.

CDH17, once an obscure target, quickly captured widespread attention in the industry.

CDH17(Cadherin 17), a calcium-dependent transmembrane glycoprotein, primarily mediates cell-cell adhesion.

▲ Structure of CDH17: Extracellular amino-terminal (NH2) with seven cadherin repeats (EC1-EC7), a transmembrane region, and a short cytoplasmic domain at the carboxyl-terminal (COOH).

CDH17 stands out from numerous potential targets, primarily due to its highly specific expression pattern. Research has shown that this protein is restricted to epithelial cells in the intestines, pancreas, and other tissues in normal human physiology, whileHighly expressed in a variety of gastrointestinal tumors, such as gastric cancer, colorectal cancer, pancreatic cancer, etc.

In terms of mechanism of action, CDH17 promotes tumor development through various signaling pathways. In gastric cancer, for example, CDH17 stabilizes integrin activity, upregulates Cadherin-Integrin signaling, and subsequently activates the Ras/Raf/MEK/ERK pathway, affecting cell proliferation, migration, adhesion, and apoptosis, thereby promoting tumor progression.

The expression location of CDH17 in tumor cells also makes it an ideal drug target. In normal cells, CDH17 is highly restricted to the basolateral membrane of intestinal epithelial cells and is covered by tight junction structures, making it difficult for drugs in the blood to access; whereas in cancer, the upregulation of CDH17 leads to its exposure on the surface of cancer cell membranes. ThisNormal Concealment, Tumor ExposureThe unique expression differences provide an ideal "window" for drug design.

However, despite the discovery of CDH17 nearly 20 years ago, early monoclonal antibody drug development repeatedly encountered setbacks due to insufficient penetration in solid tumors and limited killing efficacy. It was not until the maturation of ADC technology that the potential of this target was truly unleashed.

As the potential of the CDH17 target continues to emerge, pharmaceutical companies worldwide are actively entering this field. Currently, there are no approved drugs targeting CDH17, and almost all research pipelines are in preclinical or early clinical stages.

According to incomplete statistics, currently globally there are alreadyAt Least 9 ProductsCDH17-Targeted ADC Drugs Enter Clinical Stage, Almost All from Chinese Enterprises. The table below shows some representative CDH17 ADC pipelines currently in the clinical stage.(The order is not ranked)。

▲ CDH17 ADC Represents the Pipeline

From the above pipeline, it can be seen that CDH17 ADCs currently in clinical stages exhibit three significant characteristics:

FirstlyIndications Highly Concentrated in Gastrointestinal Tumors, which is consistent with the specific expression of CDH17; secondly, the clinical stage is based onEarly Exploration Oriented, reflecting that the core goals in this field currently remain focused on safety and preliminary efficacy verification; third isChinese Enterprises Occupy an Absolute Dominant PositionA group of Chinese pharmaceutical companies have taken over all clinical-stage pipelines, highlighting China's global leading advantage in CDH17 ADC research and development.

Recently, the commercial potential in this field has been further validated through multiple BD deals. In addition to the previously mentioned $1.53 billion licensing agreement between Hansoh Pharma and Roche, Lepu Biopharma also successfully completed an overseas deal for its CDH17 ADC. These transactions not only reflect the positive outlook of international giants on the CDH17 target but also affirm the R&D capabilities of Chinese pharmaceutical companies.

In the future, once relevant pipelines enter the late-stage clinical validation phase, it will undoubtedly drive this field to become a new growth point in the ADC track. The early layout by international giants is undoubtedly also a strategic positioning.

The editor will introduce the pipeline R&D updates of the aforementioned companies one by one.

MRG007 is a novel humanized IgG1 antibody conjugated with the cytotoxin Exatecan through site-specific conjugation, featuring a balanced drug-to-antibody ratio.（DAR）. Currently, the drug is in Phase 1/2 clinical trials for solid tumor indications. Preclinical studies have shown that MRG007 exhibits potent antitumor activity in various preclinical models of gastrointestinal cancers.

Previously, in January 2025, Mabwell$47 Million, Up to $1.16 BillionGlobal Development of MRG007(Excluding Greater China)Rights Granted to ArriVent.

Lixun Pharmaceuticals(Has been acquired by China Biologic Products)The LM350 is based on the new generation antibody-drug conjugate platform LM-ADC™Developed with the IgG1 wild-type configuration, it possesses ADCC activity. Currently, the drug is in Phase 1/2 clinical trials for the indication of solid tumors. Preclinical data show that LM350, when used at doses of 3 or 6 mg/kg, can significantly inhibit tumor growth or lead to its regression.Tumor growth inhibition rate ranges from 70% to 129%.。

7MW4911, developed by Mabwell based on its IDDC™ antibody-drug conjugate technology platform, targets gastrointestinal cancers such as colorectal cancer and has currently been approved for clinical trials in both China and the United States. The drug adoptsHighly Engineered Design, including those with rapid internalization properties and cross-species(Human/Monkey)CDH17 High-Specificity Monoclonal Antibody Mab0727 with Moderate Affinity, a Novel Cleavable Linker, and a Proprietary DNA Topoisomerase I Inhibitor MF-6 Payload Designed to Overcome Multidrug Resistance Mechanisms. Among these, MF-6 significantly enhances antitumor activity through excellent plasma stability, controlled drug release, and a potent bystander effect.

CM518D1 is currently in Phase 1/2 clinical trials for the indication of solid tumors.

Preclinical studies have shown that CM518D1 exhibits strong direct cytotoxic effects and a "bystander effect," possesses good plasma stability, and demonstrates excellent anti-tumor activity in various solid tumor animal models.

SIM0609 is composed of a humanized monoclonal antibody conjugated with ZAIMING's independently developed novel topoisomerase I inhibitor through Simcere’s proprietary novel water-soluble cleavable linker. Currently, the drug has successively obtained clinical trial approvals from China’s NMPA and the U.S. FDA, with the indication being solid tumors.

YL217 is currently in international multicenter Phase 1 clinical trials for gastrointestinal tumors. The drug utilizes a novel toxin linker platform technology developed by Mabwell, which is activatable in the tumor microenvironment.（TMALIN^®）Developed. Preclinical pharmacokinetic studies have shown that YL217 is highly stable,Less than 1% of the payload is released into the bloodstream(Molar Ratio)。

Based on TMALIN^®Technologically, Yilian Bio has already received clinical approval from both China and the U.S. for twelve ADC products and has initiated clinical research.

AMT676 is Mabwell's CDH17 ADC project, utilizing a TOPOi-type payload with a DAR of 4. Currently, the drug is in Phase 1 clinical trials for the indication of solid tumors. Preclinical studies of AMT676 have shown significant anti-tumor activity in various gastrointestinal cancer models and demonstrated high tolerability in safety studies.

At the 2025 ASCO Annual Meeting, AMT676's first-in-human trial abstract and protocol were presented by ZAIMING.

HS20110 is composed of an anti-CDH17 monoclonal antibody linked to a TOPOi payload through a covalent bond. According to the official press release, this drug is currently undergoing a global Phase 1 clinical trial in China and the United States for the treatment of colorectal cancer and other solid tumors.

On October 17, 2025, Hansoh Pharma$80 million upfront payment and up to $1.45 billionMilestone payment for granting Roche the global exclusive license (outside Greater China) for HS-20110.

HDM2017, a conjugate of an anti-CDH17 monoclonal antibody and a topoisomerase I inhibitor linked via a cleavable linker with a DAR of 4, has been approved for clinical trials by China's NMPA and the U.S. FDA for the indication of advanced malignant solid tumors.

Preclinical study results show that HDM2017 has good druggability, safety, and efficacy. HDM2017 demonstrated potent anti-tumor effects in efficacy models of target-positive colorectal cancer, pancreatic cancer, and gastric cancer, with good tolerability in animal studies.

Overall, CDH17 ADC represents one of the faster-progressing and more concentrated pipelines in the development of drugs targeting this site. Chinese companies have formed the first tier through intensive early clinical stage layouts. Additionally, other pathways are being explored for CDH17-targeted drug development, such as CAR-T cell therapy and TCE bispecific antibodies. However, progress in these areas currently lags behind ADC, which remains the main focus of research and development for this target.

In the future, with the further disclosure of clinical data, the advancement of differentiated pipelines, and the exploration of combination therapy strategies, CDH17 is expected to become one of the breakthrough targets in the treatment of gastrointestinal tumors.

Editorial Director | Xuan Xiao

Proofread by | Xuan Xiao

References:

1.Official Websites and Official WeChat Accounts of Various Companies

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