Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.
MDX-124 therefore provides an innovative approach to cancer therapy. Medannex initiated a First-In-Human study in Q4 2021 to evaluate MDX-124 in solid malignancies known to overexpress ANXA1.
MDX-124 binds to secreted and extracellular ANXA1 disrupting interactions with FPR1/2. This results in altered expression levels of several key cancer-related proteins preventing the activation of oncogenic signaling pathways that promote cancer progression. MDX-124 has demonstrated anti-cancer activity in several TNBC cell line and mouse models, as both a single agent and in combination with other drugs, including anti-PD-1 immunotherapy.
Incubation of a panel of cell lines representing several histological cancer subtypes with MDX-124 for 72h resulted in a statistically significant dose-dependent reduction in cell viability compared to control. ANXA1 expression in the subcellular compartments (nucleus, cytoplasm and membrane) was quantified in a panel of cancer cell lines via imaging flow cytometry and the anti-proliferative effect of MDX-124 was shown to correlate with membrane ANXA1 expression. Using a transwell assay, TNBC and acute myeloid leukemia cell lines exposed to MDX-124 exhibited a statistically significant reduction in migration compared to untreated controls.