Differentiation between normal and malignant tumor cells represents the gold standard for the development of highly specific cancer diagnostics and targeted therapies. Aberrant glycosylation forms have been described in numerous human cancers, identifying tumor associated carbohydrate antigens (TACAs) as an entire class of cancer-specific cell surface molecules suitable for tumor targeting.

TACAs are exploited by tumor cells to hijack glycan-dependent biological processes to their advantage, thus ensuring tumor growth and dissemination. Expression of TACAs frequently correlates with invasiveness, metastasis and tumor grade. Further, TACAs play important functional roles in immune suppression, tumor migration, cell adhesion, and metastasis; therefore, therapeutic antibodies targeting TACAs have the potential to not only kill cancer cells but also inhibit critical biological functions in cancer progression.

A number of TACAs have been well described in the scientific literature, but TACAs historically have been difficult targets against which to develop therapeutic antibodies for a number of reasons:

• Many TACA epitopes are not immunogenic in mice or humans
• Potent anti-TACA antibodies require high affinity, avidity, and specificity to ensure safety
• Fine binding specificity has been hard to assay but essential to achieve (particularly for ADCs)
• Reagents (synthetic carbohydrates) are difficult to synthesize
• Many protocols require significant modifications to detect, preserve, and assay glycans

Siamab's unique platform allows for the rapid discovery of therapeutic anti-TACA antibodies. We have developed a patented platform of tools to identify and precisely assay anti-TACA antibodies -- enabling rapid discovery and screening of candidate antibodies as well as characterization of binding epitopes.

Siamab's platform enables fine tuning of anti-TACA antibody binding specificity, including:

• binding that is dependent on a specific protein backbone, or binding to the carbohydrate antigen that is protein independent
• sialylation-state specific binding
• precise, microarray-based carbohydrate epitope mapping

Siamab's platform is up and running today, and has enabled the discovery and characterization of a panel of anti-TACA antibodies for Siamab's first development program -- ST1.

Siamab's core technologies were licensed from the laboratory of Dr. Ajit Varki (UCSD), a world expert in glycobiology and sialic-acid biochemistry.