ANG4043

Proof-of-concept in neuro-oncology

In order to perform proof-of-concept for mAbs in CNS disease, Angiochem has embarked on internal programs designed to demonstrate that the technology can create brain-penetrant monoclonal antibodies.

Currently, Angiochem has created ANG4043, a Peptide-Antibody Conjugate of anti-HER2 for neuro-oncology indications. ANG4043 crosses the BBB while maintaining binding affinity, cytotoxicity and a half-life similar to that of Herceptin^®.

Via a series of in vivo experiments in mice, Angiochem demonstrated that ANG4043:

1. Reaches the brain and targets HER2+ tumors
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2. Induces intracranial tumor shrinkage
3. Increases survival in mice that have been intracranially implanted with HER2+ tumor cells

ANG4043 induces tumor shrinkage

Protocol Overview

Mice implemented with BT-474 cells, which were preloaded with DiR, a lipophilic dye that emits fluorescence, received treatment twice a week starting on day 12. Imaging was performed before the first and after the fifth treatments. Results showed a tumor fluorescence reduction of 75% in the ANG4043 treated group (see figure below) as compared to an increase of 19% in the brains of the control treated group; demonstrating that ANG4043 crosses the BBB and reaches the target tumor at therapeutic concentrations inside the brain.