Mabwell's CDH17-Targeting ADC 7MW4911 Receives Dual IND Acceptance from FDA and NMPA

Key Insights

• Mabwell's investigational antibody-drug conjugate 7MW4911 has received IND application acceptance from both the FDA and China's NMPA, marking a significant regulatory milestone for this CDH17-targeting therapy.
• The ADC demonstrates superior efficacy against multidrug-resistant gastrointestinal cancers, outperforming existing MMAE/DXd-based ADCs in preclinical models of colorectal, gastric, and pancreatic cancers.
• 7MW4911 features an optimized molecular design with a homogeneous drug-to-antibody ratio of 4 and incorporates a proprietary DNA topoisomerase I inhibitor payload designed to overcome treatment resistance.

Mabwell (688062.SH) announced that its proprietary CDH17-targeting antibody-drug conjugate (ADC), 7MW4911, has received Investigational New Drug (IND) application acceptance from both China's National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA). This dual regulatory milestone positions the investigational therapy for clinical evaluation in advanced gastrointestinal cancers.

Novel ADC Platform Targets Multidrug Resistance

7MW4911 was developed using Mabwell's proprietary IDDC™ platform and integrates three key components designed to overcome treatment resistance. The ADC features Mab0727, a highly specific CDH17 monoclonal antibody with rapid internalization properties and minimal off-target binding. The therapy incorporates a novel cleavable linker that ensures precise payload release in tumor tissues, coupled with MF-6, a proprietary DNA topoisomerase I inhibitor designed to overcome multidrug resistance (MDR).

The optimized molecular design achieves a homogeneous drug-to-antibody ratio of 4 with greater than 95% purity. The membrane-permeable MF-6 payload exhibits superior plasma stability, controlled drug release, and potent bystander effects that extend therapeutic activity beyond directly targeted cells.

Preclinical Efficacy Across Multiple Cancer Types

In July 2025, Mabwell published preclinical data in Cell Reports Medicine demonstrating 7MW4911's tumor-selective cytotoxicity via CDH17-mediated internalization. The study showed robust tumor regression across colorectal, gastric, and pancreatic cancer patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models, including tumors harboring RAS/BRAF mutations and diverse Consensus Molecular Subtypes (CMS).

Notably, 7MW4911 outperformed MMAE/DXd-based ADCs in ABC transporter-mediated multidrug resistance models and demonstrated the ability to reverse tumor progression following previous ADC treatment. The therapy maintained activity even in tumors with low-to-moderate CDH17 expression, potentially expanding the eligible patient population beyond those with high target expression.

Favorable Safety Profile Supports Clinical Development

Preclinical safety studies revealed limited tissue distribution in mice and controllable pharmacokinetics characterized by moderate half-life without accumulation. In cynomolgus monkey studies, 7MW4911 demonstrated a wide therapeutic window with no significant toxicity signals, supporting its advancement into human clinical trials.

CDH17 as Therapeutic Target

CDH17 represents a validated pan-cancer target with restricted expression in normal intestinal epithelium but marked overexpression in gastrointestinal cancers, including colorectal, gastric, and pancreatic malignancies. The protein's aberrant expression correlates with tumor metastasis and poor prognosis, making it an attractive therapeutic target for ADC development.

The dual regulatory acceptance enables Mabwell to initiate clinical studies evaluating 7MW4911's safety and efficacy in patients with advanced gastrointestinal cancers, representing a potential new treatment option for a patient population with significant unmet medical needs.