Date: 2017-05-02
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Leukemia
Company: GlycoMimetics (USA - Md)
Product: GMI-1271, GMI-1359
Action mechanism: E-selectin antagonist. GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with acute myeloid leukemia cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. Preclinical research points to the drug's potential role in moving cancerous cells out of the protective environment of the bone marrow where they hide and escape the effects of chemotherapy. GMI-1359 targets both E-selectin and CXCR4, which aid in cancer cell resistance to chemotherapy. The compound is in preclinical evaluation. GMI-1359 is a potent dual antagonist of both E-selectin and CXCR4, demonstrating anti-tumor activity in preclinical models of pancreatic cancer, FLT-3+ acute myeloid leukemia (AML), and prostate cancer.
Disease: breast cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest news: • On May 2, 2017, GlycoMimetics announced the publication of results from a preclinical study that showed its drug candidate GMI-1271, an E-selectin antagonist, was able to restore sensitivity to bortezomib (the frontline standard of care for patients with multiple myeloma) in animal models of disease. The study, entitled "E-selectin Ligands Recognised by HECA452 Induce Drug Resistance in Myeloma, which is Overcome by the E-selectin Antagonist, GMI-1271," was published in an online preview of Leukemia on April 25, 2017. E-selectin ligands are recognized by an antibody known as HECA452. In this manuscript, researchers described that E-selectin ligands expressed on myeloma cell surfaces and recognized by HECA452 induced a more aggressive form of multiple myeloma, which is insensitive to bortezomib. Through use of GMI-1271, sensitivity to the proteasome inhibitor therapy, bortezomib, was able to be restored in this highly resistant myeloma model. • On May 25, 2016, GlycoMimetics announced that the peer-reviewed journal, Science Translational Medicine, has published preclinical research in its May 25 issue pointing to a potential clinical application for GMI-1271 in the treatment of breast cancer. The published study details research in an in vivo model that showed GMI-1271, a novel E-selectin antagonist, inhibits breast cancer metastasis. The study provides important new detail on how metastasis from breast cancer can lead to relapse, even if the primary cancer is in remission. The research highlights a possible new application of GMI-1271, currently in a Phase 1/2 clinical trial in AML, as a potential treatment for solid tumors. Data from the study also suggest a possible therapeutic avenue to test GMI-1359, a GlycoMimetics drug candidate that targets both E-selectin and CXCR4, for use as a potential treatment for certain cancers. The researchers found that breast cancer cells accumulate in regions of the protective bone marrow, an environment rich in E-selectin and SDF-1 (which binds to CXCR4, another molecule associated with cancer cell adhesion and proliferation). GMI-1271, by inhibiting E-selectin, blocks trafficking of breast cancer cells into bone marrow regions where metastasis can become dormant and protected from chemotherapy treatment. At the same time, researchers found that inhibition of CXCR4 as well as of E-selectin could mobilize and excise dormant metastasis from these protective niches and block their reentry, thereby potentially eliminating a common site for metastases and source of relapsed disease. These effects indicate a potential role in treatment of breast cancer not only for GMI-1271, but also for GMI-1359, which inhibits the actions of both E-selectin and CXCR4. GlycoMimetics plans to file an investigational new drug (IND) application with the FDA in the third quarter of this year for its combined E-selectin-CXCR4 antagonist GMI-1359, initially for treatment of hematologic malignancies.
