Mabwell’s self-developed CDH17-targeting ADC has received IND clearance from the U.S. Food and Drug Administration (FDA).
The clearance enables the initiation of a phase I/II study of 7MW4911 to evaluate the safety, pharmacokinetics, and efficacy in patients with advanced colorectal cancer and other advanced gastrointestinal tumours.
7MW4911 is an investigational CDH17-targeting ADC developed using Mabwell’s IDDC platform. Its structure integrates three key elements:
Mab0727: A highly specific CDH17 monoclonal antibody with rapid internalization properties, cross-species (human/monkey) moderate affinity, and minimal off-target binding.
Novel cleavable linker: Ensures precise payload release in tumour tissues.
MF-6 payload: A proprietary DNA topoisomerase I inhibitor designed to overcome multidrug resistance (MDR), exhibiting superior plasma stability, controlled drug release, and potent bystander effects.
In July 2025, Mabwell published preclinical data in Cell Reports Medicine (Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor), demonstrating 7MW4911’s tumour-selective cytotoxicity via CDH17-mediated internalization.
Key advantages include:
Optimised molecular design: Homogeneous drug-to-antibody ratio (DAR=4, >95%) and stable linker confer exceptional plasma stability, while membrane-permeable MF-6 drives potent bystander killing.
Broad anti-tumour efficacy: Demonstrates robust tumour regression in colorectal, gastric, and pancreatic cancer PDX/CDX models, including tumours with RAS/BRAF mutations and diverse consensus molecular subtypes (CMS).
MDR resistance: Outperforms MMAE/DXd-based ADCs in ABC transporter-mediated MDR models and reverses tumour progression post-ADC treatment.
Target versatility: Active even in tumours with low-to-moderate CDH17 expression, expanding potential patient eligibility.
Favorable safety profile: Limited tissue distribution in mice, controllable pharmacokinetics (moderate half-life, no accumulation), and a wide therapeutic window in cynomolgus monkeys, with no significant toxicity signals.
The company said 7MW4911 is a promising therapeutic candidate for advanced gastrointestinal cancers.
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