ATYR2810 is the first Investigational New Drug (IND) candidate to arise from our in-house research program designing monoclonal antibodies to selectively target the Neuropilin-2 (NRP2) receptor and its associated signaling pathways. ATYR2810 is a fully humanized monoclonal antibody that specifically and functionally blocks the interaction between NRP2 and one of its primary ligands, VEGF. ATYR2810 is currently in preclinical development for cancer.

Target Relevance in Cancer

NRP2 is highly expressed in certain tumors, the lymphatic system and on key immune cells implicated in cancer progression. Increased NRP2 expression is associated with worse outcomes in many cancers, including resistance to targeted therapies, metastasis and overall survival. The role of NRP2 and VEGF signaling in the tumor microenvironment and its importance in the progression of certain aggressive cancers, such as breast cancer, renal cell carcinoma and lung cancer, is becoming increasingly validated.

Preclinical Development

Preclinical data suggest that ATYR2810 could be effective against certain types of solid tumors, including highly aggressive tumors such as triple-negative breast cancer. There is a strong body of evidence that expression of NRP2 is enriched in treatment-resistant, dedifferentiated cancer cells expressing mesenchymal markers. Furthermore, NRP2/VEGF signaling is implicated in enhanced tumor metastasis promoted by the process of epithelial-to-mesenchymal transition (EMT) in breast cancer. ATYR2810 blocks binding of VEGF to NRP2 and demonstrates tumor inhibitory effects and increased sensitivity to chemotherapy in human-derived organoids and other in vitro models of triple-negative breast cancer. These findings suggest that targeting the NRP2/VEGF pathway may be an effective therapeutic strategy for breast cancer and potentially other aggressive solid tumors where many patients remain unresponsive to currently available treatments.

ATYR2810 is currently undergoing IND-enabling studies.