NEWTON, Mass.--(EON: Enhanced Online News)--Siamab Therapeutics, Inc., a biopharmaceutical company developing novel cancer immunotherapies, today announced the publication of new preclinical data describing its novel ST1 antibodies targeting, with high affinity and specificity, the Sialyl-Thomasen-nouveau antigen (STn), a tumor-associated carbohydrate antigen (TACA). As antibody drug conjugates (ADCs), these selective anti-STn antibodies possess potent anti-tumor activity in in vitro and in vivo preclinical cancer models. The paper, titled “Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity,” was published online in the journal mAbs and will be available in the May/June issue.
“Targeted therapies that can reliably differentiate between normal and malignant tumor cells represent an ideal profile for cancer treatment”
Siamab uses its proprietary technology platform to discover and develop monoclonal antibody (mAb) therapeutics that bind to TACAs, a new class of cancer-specific targets. ST1, the Company’s lead program, is in late stage preclinical development and is expected to enter human clinical trials in 2018.
“The paper describes the promise of our platform to unlock this exciting class of cancer targets and highlights our unique approach to develop highly specific anti-TACA therapeutic antibodies and antibody drug conjugates that have the potential to not only eradicate cancer cells, but also re-engage the immune system and overcome chemo-resistance,” said Jeff Behrens, president and chief executive officer of Siamab Therapeutics. “We are encouraged by the efficacy and safety findings for ST1 in breast and colorectal cancer models, which add to our ovarian cancer data presented last year at AACR and show we can have a significant effect in vivo across a range of indications. We continue to advance our ST1 program and plan to launch our first Phase 1 clinical trial for this program next year.”
TACAs, resulting from abnormal glycosylation, have been implicated in an array of human diseases and are a common feature of cancer cells. They are present in the majority of solid tumors including ovarian, pancreatic, prostate, colon, gastric, and breast, and are exploited by tumor cells to suppress innate immune function, enable tissue invasion and metastasis, resist chemotherapy, and promote a stem-cell phenotype.
Siamab has identified novel antibodies that specifically target the STn antigen with high affinity, and bind to STn independent of its carrier protein. This discovery may lead to the identification of a wider array of cancer-specific, abnormally sialylated proteins. The targeted epitopes are glycan-specific and are present on multiple glycosylated proteins on cancer cells. STn is expressed in numerous human adenocarcinomas, including ovarian, pancreatic, prostate, colon, gastric, and breast cancers. A STn-specific ADC offers significant therapeutic potential.
ADCs utilize antibodies as targeting tools for delivering potent cytotoxic payloads specifically to cancer cells. ADCs enable dosing of highly cytotoxic chemotherapeutics at safe, therapeutic concentrations by delivering the chemotherapeutic directly to the tumor. ADCs also have been reported to stimulate immune system responses. To enable patient selection, Siamab is also developing a companion diagnostic to identify patients most likely to benefit from therapy.
The paper describes the power of Siamab’s technology platform to access this new class of cancer targets and highlights the Company’s novel approach to developing mAb therapeutics that target STn with demonstrated high affinity, specificity and anti-tumor activity in vitro and in vivo. Siamab scientists and collaborators generated a panel of murine monoclonal anti-STn therapeutic antibodies and characterized their binding specificity and efficacy in in vitro and in vivo murine cancer models. The manuscript explains the capabilities of Siamab’s glycan array to enable the screening and development of highly specific antibodies, and illustrates how Siamab’s internally generated anti-STn mAb selectively binds to STn, but not to related structures. The scientists and collaborators used a subset of these antibodies to generate ADCs consisting of anti-STn mAbs, conjugated to monomethyl auristatin E (MMAE). The findings show that these ADCs demonstrate in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in vivo in STn-expressing tumor xenografts—both human breast and colon cancer models—with no evidence of overt toxicity. In the subcutaneous human breast cancer xenograft model, Siamab’s anti-STn ADCs generated a dramatic reduction in tumor volume to 3.6% and 3.0%, respectively (both p<0.001), and sustained tumor inhibition for a period of nearly four weeks post treatment.
“Targeted therapies that can reliably differentiate between normal and malignant tumor cells represent an ideal profile for cancer treatment,” said Bo Rueda, Ph.D., director of the Vincent Center for Reproductive Biology, in the Department of Obstetrics and Gynecology at Massachusetts General Hospital and senior author of the paper. “STn is expressed by more than 80% of ovarian carcinomas and until now has been a very challenging target to access. The preclinical findings are encouraging as we continue to study anti-STn antibody drug conjugates.”
About Siamab Therapeutics, Inc.
Siamab Therapeutics, Inc. is a biopharmaceutical company developing novel cancer immunotherapies targeting cancer-specific carbohydrate antigens seen in multiple solid tumors. Siamab has developed a platform that enables the rapid discovery and development of therapeutic antibodies that bind with unprecedented specificity and affinity to this novel class of carbohydrate antigens present on cancer cells called tumor associated carbohydrate antigens (TACAs). TACAs are an exciting cancer target class due to their cancer specificity, association with a chemoresistant phenotype, and ability to suppress immune function in the region of solid tumors. The Company’s lead program, ST1, targets Sialyl-Tn (STn), a tumor specific antigen seen in multiple solid tumors including ovarian, pancreatic, prostate and colon cancers. ST1 is in preclinical studies for the treatment of solid tumors. Visit www.siamab.com to learn more about the Company.