On October 3, 2017 Siamab Therapeutics, Inc., a biopharmaceutical company developing novel cancer immunotherapies, reported the presentation of new preclinical data for its novel anti-Sialyl-Tn (STn) antibodies and antibody drug conjugates (ADCs) that show inhibition of tumor progression in in vivo and in vitro patient derived xenograft (PDX) ovarian cancer models with complete regression in some treatment arms (Press release, Siamab Therapeutics, OCT 3, 2017, View Source [SID1234520772]). The data were presented in a poster presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Addressing Critical Questions in Ovarian Cancer Research and Treatment Meeting, held October 1-4, 2017 in Pittsburgh, Pennsylvania. ST1, Siamab’s lead antibody program targeting STn, is in late stage preclinical development for the treatment of solid tumors.

Siamab is developing monoclonal antibody (mAb) therapeutics that target cancer cell surface glycans called tumor-associated carbohydrate antigens (TACAs), a novel class of cancer-specific antigens found on the cell surface of many solid tumors. TACAs are implicated in immune suppression, chemoresistance, and a cancer stem cell (CSC) phenotype. The elevated presence of STn, a key TACA observed in the majority of ovarian tumors, is associated with metastatic disease, poor prognosis, and reduced overall survival. Elevation of STn expression is linked to chemotherapy resistance and enables tumors to evade the host immune system. Siamab has also identified the presence of STn on myeloid-derived suppressor cells, which are major regulators of immune response in cancer and influence the tumor microenvironment by suppressing T cells. STn is a major reported constituent of two established CSC biomarkers, CD44 and MUC1, which reside on both CSCs and mature malignant cells in some cancer types.

In the poster presentation, titled Targeting the Tumor-Associated Carbohydrate Antigen STn with Humanized anti-Sialyl-Tn Monoclonal Antibody-drug Conjugates Inhibits Ovarian Cancer Tumor Growth in vitro and in vivo,” Siamab scientists and collaborators reported data demonstrating anti-tumor effect in vitro utilizing humanized anti-STn ADCs as well as inhibition of tumor progression in vivo in both cell line- and PDX ovarian cancer models with complete regressions observed in some treatment groups. In a chemo-naïve ovarian PDX model, 75% of animals given ST1 are completely tumor free at 52 days post treatment as compared to control-treated animals. In a chemoresistant ovarian PDX model, tumors regressed by more than 50% in 75% of the animals in the ST1 group as compared to control-treated animals. No significant weight loss was observed for any of the treatment groups, indicating the therapy was well tolerated by all the groups. A decrease in STn expression was noted in the tumors following treatment, indicating that Siamab’s anti-STn ADC was depleting the mAb-targeted STn+ tumor cells. In addition, researchers utilized the STn-selective antibodies to develop both tissue- and serum-based biomarker assays with the potential to become companion diagnostics.

“Our research findings show that tumor-associated carbohydrate antigens, and in particular STn, have the potential to offer a unique approach to targeting cancer cells,” said Jeff Behrens, president and chief executive officer of Siamab. “STn is not only an intriguing cancer biomarker and therapeutic target, but

manipulating STn biology offers the potential to have significant immune re-engagement and anti-metastatic therapeutic benefits. These data demonstrate that high-affinity, STn-selective humanized mAbs show promise as therapies for ovarian tumors, as well as tools for patient stratification and pharmacodynamic biomarker assessments.”

Ovarian cancer is the leading cause of death from gynecological malignancies in the United States. The current standard of care is tumor debulking followed by chemotherapy. This treatment results in approximately 70% of patients achieving an initial complete clinical response. However, many of these patients will unfortunately relapse with chemoresistant disease developing in part due to the presence of CSCs within the tumor. Ovarian CSCs have been shown to be resistant to chemo- and radiotherapy.