Axcynsis Therapeutics has announced that the FDA has cleared its Investigational New Drug (IND) application for AT03-65, an antibody-drug conjugate (ADC) designed to target CLDN6-positive solid tumors. The company plans to initiate a Phase 1 multicenter clinical trial in the United States in the first quarter of 2025.
AT03-65 is the first program to utilize Axcynsis' AxcynDOT™ technology, a proprietary payload with a differentiated mechanism of action. The ADC selectively binds to CLDN6, a protein overexpressed in various cancers, including lung, ovarian, endometrial, uterine, testicular, and gastric cancers, while exhibiting minimal expression in normal tissues. The therapy is designed to deliver targeted treatment to patients with advanced or metastatic CLDN6-positive cancers, potentially improving patient outcomes.
Differentiated Mechanism of Action
AT03-65 consists of a recombinant anti-CLDN6 monoclonal antibody conjugated to AxcynDOT™, a payload developed by Axcynsis. The AxcynDOT™ payload incorporates a derivative of an approved oncology therapeutic with unique mechanism of action and broad anti-tumor activity, coupled with a cleavable and hydrophilic proprietary linker. Preclinical studies suggest that AT03-65 not only directly kills CLDN6-positive tumor cells but also exhibits a bystander killing effect, targeting neighboring CLDN6-negative tumor cells to enhance its anti-tumor efficacy. AT03-65 has demonstrated promising anti-tumor activities in multiple tumor mouse models and a favorable safety profile in non-human primates.
Clinical Trial Details
The Phase 1 clinical trial will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AT03-65 in patients with advanced CLDN6-positive solid tumors. The trial will be conducted across multiple centers in the United States.
Axcynsis' Perspective
"This is a transformational event for Axcynsis and a significant milestone for our proprietary ADC platform using AxcynDOT™," said Dr. Zou Bin, CEO of Axcynsis. "We are pleased that FDA has cleared AT03-65 which leverages our AxcynDOT™ technology for this first-in-human study. We are very excited with the potential of offering a transformative therapeutic option for patients with CLDN6-positive tumors as well as advancing our pipeline with differentiated and effective ADCs using AxcynDOT™ to improve the lives of cancer patients worldwide".
About AxcynDOT™
AxcynDOT™ is a proprietary payload developed by Axcynsis. It is a derivative of trabectedin, an approved chemotherapy in the United States, Europe and selected Asian countries, with a unique mechanism of action that is differentiated from other DNA alkylating payloads. AxcynDOT™ is optimized with enhanced potency and improved safety profile compared to trabectedin.
