RESEARCH

Our lead candidate is a novel, first-in-class monoclonal antibody that binds to Nodal and blocks the interaction with its receptor.

Nodal, an embryonic morphogen belonging to the TGF-β superfamily, is an important cell signaling regulator in embryonic stem cells. The re-emergence and high expression level of Nodal has recently been reported in patients with aggressive tumor progression, such as melanoma, breast cancer, pancreatic cancer and hepatocellular carcinoma. These results support Nodal as a prognostic biomarker for cancer, where Nodal plays a critical role in promoting tumor growth, in addition to vasculogenic mimicry (VM). Nodal is a secreted protein and can be detected in cancer patient serum. A diagnostic kit for Nodal is also under development as a companion tool for the selection of patients for antibody therapy. Nodal is a promising cancer target, especially for those cancer patients who have failed standard-of-care  therapy.

Lefty protein is an antagonist of Nodal, and specifically inhibits the Nodal signaling pathway by binding directly to Nodal or Cripto-1 to prevent the assembly of the Nodal/Cripto-1/receptor complex, blocking the subsequent signaling cascade. Current results show that human Lefty can inhibit cancer cell proliferation and invasion, as well as promote cancer cell apoptosis. Thus, in addition to the potential antibody drug targeting Nodal, the second project focuses on the  development of a functional recombinant Lefty for topical application in treating melanoma and dysplastic nevi.

There are presently no approved drugs or treatment regimens that target Nodal and Lefty signaling. The unique development of these two products will offer new treatment opportunities to patients who become resistant to current cancer therapy.