Siamab's first program -- ST1 -- targets a tumor associated carbohydrate antigen ("TACA1") present in the majority of solid tumors but rarely expressed in normal tissue. Expression of TACA1 in tumors is correlated with metastatic disease, poor prognosis, decreased survival, and lack of response to chemotherapy. De novo expression of TACA1 can modulate carcinoma cells, suppress local immune function, change the malignant phenotype, and lead to more aggressive cell behaviors. As such, TACA1 is not only an interesting biomarker and cancer target, but interfering with its function offers the intriguing potential to have significant immunologic and anti-metastatic therapeutic benefits. Therefore, multiple complementary mechanisms are possible with Siamab's ST1 program:

• Re-enable immune regulation dampened by TACA1
• Tumor cell killing of naked antibody by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC)
• Prevent TACA1-mediated proliferation and metastasis
• Impair function of TACA1-bearing proteins
• Internalization and cell-killing as an antibody-drug conjugate (ADC)

Siamab Therapeutics has generated and characterized a panel of highly specific monoclonal antibodies targeting TACA1. The targeted epitopes are within the glycan itself, not a particular glycopeptide or carrier protein, which should offer the broadest potential to bind to multiple glycosylated proteins on cancer cell surfaces. These antibodies have been shown to bind with high affinity as well as demonstrate protein internalization in cancer cell lines, and were able to significantly inhibit the growth of tumors in in vivo studies. These antibodies are currently being developed for the treatment of solid tumors.