Siamab Therapeutics is a biopharmaceutical company developing therapies targeting abnormal carbohydrates found only on cancer cells. These tumor associated carbohydrate antigens (TACAs) are present in the majority of solid tumors, and are exploited by tumor cells to hijack glycan-dependent biological processes to their advantage, thus ensuring tumor growth and dissemination. Therefore, therapeutic antibodies targeting TACAs have the potential to not only kill cancer cells but also inhibit critical biological functions in cancer progression.
Siamab Therapeutics has developed a platform of technologies that enable the discovery and development of highly specific, high affinity, anti-TACA therapeutic antibodies. Siamab’s core technologies were licensed from the laboratory of Dr. Ajit Varki (UCSD), a world expert in glycobiology and sialic-acid biochemistry. Siamab has brought together a world-leading team of scientists and advisors in oncology, glycoimmunology, and antibody engineering to support our anti-TACA antibody discovery and development programs.
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.
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.
Siamab Corporate Headquarters
55 Chapel Street, Newton, MA 02458
Siamab Scientific Headquarters
3210 Merryfield Row, San Diego, CA 92121
Jeff Behrens, MS, MBA – President and CEO, Board of Directors
Julie Hermann, MS, MBA – Senior Director, Corporate Development
Kristan Meetze, PhD – Senior Director, R&D
Ana Paula Galvao da Silva, PhD – Senior Research Scientist
Mai Zhang, MD, PhD – Senior Research Scientist
$6 million – Series B
Ajit Varki, MD
Co-Founder, Board of Directors
Distinguished Professor of Medicine and Cellular & Molecular Medicine
School of Medicine