Our lead program SECN-15 is a potential first-in-class antisense oligonucleotide (ASO) targeting Neuropilin 1 (NRP1).

NRP1 is a protein which is involved in various tumor-promoting functions such as angiogenesis, suppression of effector immune responses, cancer cell migration and metastasis. In particular, NRP1 contributes to the suppressive capacity of tumor-associated macrophages and regulatory T cells, both cell types that can be efficiently targeted with ASOs. 

Due to pharmacokinetic hurdles posed by its soluble and endothelium-bound forms, NRP1 is a challenging target for approaches that bind directly to the target protein such as antibodies, peptides or small molecules. These hurdles do not apply to modalities that don’t bind to the target protein such as antisense oligonucleotides. Furthermore, different functions of NRP1 are mediated by different domains that cannot be blocked simultaneously by modalities that bind to the target protein; however, unlike these modalities, oligonucleotides prevent protein production by targeting the NRP1 RNA and therefore are able to simultaneously block all functions of NRP1.

SECN-15 selectively and with high potency suppresses NRP1 protein production in relevant immune cell types of the tumor microenvironment, translating into highly potent single agent and synergistic anti-tumor activity in combination with PD1/PD-L1 checkpoint inhibitors in in vivo disease models, including PD-1 checkpoint inhibitor resistant models.

SECN-15 has the potential to break resistance to checkpoint therapy in cancer patients and is promising in a range of solid tumors.