NEWTON, Mass.--(BUSINESS WIRE)--Siamab Therapeutics, Inc., a biopharmaceutical company developing novel cancer immunotherapies, today announced the presentation of two posters featuring new preclinical data for its novel anti-Sialyl-Tn (STn) antibodies, antibody-drug conjugates (ADCs), and anti-STn, anti-CD3 bispecific antibodies at the American Association for Cancer Research (AACR) Annual Meeting 2017, being held April 1-5, 2017 in Washington, D.C. The findings highlight Siamab’s two-pronged approach to develop antibody therapeutics using both ADCs and bispecific antibodies to target STn, a tumor-associated carbohydrate antigen (TACA), and induce immune response to destroy tumor cells. The company’s lead program, ST1, is in late stage preclinical development and is expected to enter human clinical trials in 2018.
Siamab is leveraging its proprietary technology platform to discover and develop monoclonal antibody (mAb) therapeutics that bind to TACAs, a novel class of cancer-specific targets that are implicated in immune suppression, chemoresistance, and a cancer stem-cell phenotype. STn is an exciting TACA target with high cancer specificity, which is rarely expressed in normal tissues. STn is highly expressed in numerous human adenocarcinomas, including ovarian, pancreatic, prostate, colon, gastric, and breast cancers. STn expression has been linked to innate immune suppression, a chemoresistant stem-cell phenotype, invasion/metastasis, and poor prognosis. Myeloid-derived suppressor cells (MDSCs) are a population of immature myeloid cells that have undergone aberrant differentiation in the tumor and play a critical role in actively blocking T cell activation in the tumor microenvironment. Both myeloid and granulocytic MDSCs express STn antigens.
“We are pleased to present this new data at AACR highlighting our antibody drug development strategy using ADCs and bispecific antibodies to target STn, an intriguing cancer biomarker and therapeutic target,” said Jeff Behrens, president and chief executive officer of Siamab. “Our data show that manipulating STn biology in a variety of cancers offers the potential to generate significant immune re-engagement and anti-metastatic therapeutic benefits. In particular, we are very encouraged by our findings demonstrating that MDSCs express STn and therefore have the potential to be targeted with our antibody-based therapies to provoke an antitumor immune response. We are also encouraged by our proof-of-concept study data showing that our anti-STn, anti-CD3 bispecific antibodies are highly specific to both tumor and T cells and demonstrate strong efficacy in vitro.”
In a poster presentation titled, Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates (ADCs) demonstrate tumor specificity in vitro and in vivo antitumor efficacy (Abstract #36), Siamab reports new data for ST1 in ovarian and colorectal cancer models. The study shows that platinum resistant ovarian cancer samples are highly STn positive, and that anti-STn ADCs demonstrate in vivo efficacy and deplete STn expressing cells compared to the isotype ADC in an ovarian xenograft mouse model. The study also shows that STn is highly expressed both in colorectal cancer patient tumors and granulocytic MDSCs. Based on these findings, Siamab will explore targeting STn on MDSCs to reduce or eliminate this population and determine whether this approach can augment antitumor responses induced by checkpoint blockade antibodies.
In a poster presentation titled, Novel humanized anti-Sialyl-Tn, anti-CD3 bispecific antibodies demonstrate tumor and T-cell specificity for immune activation at the tumor site (Abstract #3640), Siamab describes proof-of-concept data for its novel bispecific antibody approach to target STn and CD3 on T cells. The study shows the promise of Siamab’s bispecific antibodies to selectively bind to multiple targets and engage T-cell mediated cytotoxicity to treat cancer. The poster describes data demonstrating the effective use of Siamab’s anti-STn, anti-CD3 bispecific antibodies for selectively binding T cells and STn+ tumor cells, activating T cells in the presence of STn+ tumor cells, and inducing tumor cell death. In addition, the poster highlights Siamab’s approach to screening bispecific antibodies with optimal tumor targeting using its proprietary glycan array to select candidates that are optimized for glycan-specificity and cancer-specific cytotoxicity. Siamab describes how it identified a relationship between sequence modification, glycan-binding promiscuity, and selective cytotoxicity using its glycan array.
The AACR 2017 poster presentations can be found online at the Siamab Therapeutics website.
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 late-stage preclinical studies for the treatment of solid tumors. Visit www.siamab.com to learn more about the company.