GlycoMimetics, Inc. (Nasdaq: GLYC) this week at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta presented two posters providing support for targeting both CXCR4 and E-selectin with GMI-1359, the Company’s dual antagonist of CXCR4 and E-selectin, as a novel treatment strategy for patients with AML.
“Both posters demonstrate the potential value of blocking extrinsic factors of AML drug resistance in the bone marrow microenvironment with our dual-function antagonist GMI-1359. The work done at MD Anderson specifically demonstrates that by disrupting tumor-stromal interactions within the bone marrow, as measured by increased in vivo cell motility, GMI-1359 significantly enhances/restores the antileukemic activity of venetoclax/HMA and FLT3 inhibitors. Importantly, GMI-1359 also protects the normal hematopoietic stem cells and the bone marrow compartment from detrimental toxic side effects from chemotherapy as experienced with venetoclax/HMA treatments. These data support our belief that targeting extrinsic factors of chemoresistance with GMI-1359 can increase not only the efficacy but also the safety of conventional AML therapy,” said John Magnani, PhD, GlycoMimetics’ Chief Scientific Officer.
The first poster (#1171) — presented December 11 — describes the unexpected activities of FLT-3 inhibitors such as quizartinib and sorafenib in upregulating the expression of E-selectin ligands (sialyl Lex) and CXCR4, thereby increasing adhesion to protective niches in the bone marrow microenvironment and inducing chemoresistance. Using cells from a relapsed patient treated with a FLT-3 inhibitor in a murine model, the addition of GMI-1359, a dual antagonist of E-selectin and CXCR4, to quizartinib broke chemoresistance, led to a dramatic reduction in leukemic burden and a doubling of median survival time from 79 to 158 days (p<0.0001).
The second poster (#3348), presented today contains data demonstrating that in a patient derived xenograft model, both uproleselan and GMI-1359 increased the efficacy and extended median survival time in engrafted mice treated with venetoclax/HMA from 74 days to 90 and 91 days, respectively. In these studies, the inclusion of uproleselan or GMI-1359 in combination with venetoclax/HMA further significantly decreased both the leukemic blast and leukemic stem cell burden beyond that obtained with venetoclax/HMA alone. Coincident with these studies data in the poster also demonstrate through intravital microscopy that GMI-1359 reduced adhesion and stimulated mobility of leukemic stem cells within the bone marrow microenvironment suggesting the disruption of both the E-selectin/E-selectin ligand and the CXCR4/CXCL12 axes. In addition, the poster includes evidence that uproleselan and GMI-1359 preserve the nontumor bone marrow component cells from venetoclax/HMA detrimental effects through the upregulation of survival signaling cascades, while protecting the hematopoietic stem cells and the bone marrow components from this treatment.
GMI-1359 is designed to simultaneously inhibit both E-selectin and CXCR4 — both adhesion molecules involved in tumor trafficking and metastatic spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound could improve efficacy in the treatment of cancers that involve the bone marrow such as AML and multiple myeloma or in solid tumors that metastasize to the bone, such as prostate cancer and breast cancer, as well as in osteosarcoma, a rare pediatric tumor. GMI-1359 has received Orphan Drug Designation and Rare Pediatric Disease Designation from the FDA for the treatment of osteosarcoma, a rare cancer affecting about 900 adolescents a year in the United States.
Discovered and developed by GlycoMimetics, uproleselan is an investigational, first-in-class, targeted inhibitor of E-selectin. Uproleselan (yoo’ pro le’ sel an), currently in a comprehensive Phase 3 development program in AML, has received Breakthrough Therapy Designation from the U.S. FDA and from the Chinese National Medical Products Administration for the treatment of adult AML patients with relapsed or refractory disease. Uproleselan is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment.
About GlycoMimetics, Inc.
GlycoMimetics is a clinical-stage biotechnology company discovering and developing glycobiology-based therapies for cancers, including acute myeloid leukemia (AML), and for inflammatory diseases with high unmet need. The Company’s science is based on an understanding of the role that carbohydrates play on the surface of every living cell and applying its specialized chemistry platform to discover small molecule drugs, known as glycomimetics, which alter these carbohydrate-mediated pathways in a variety of disease states, including signaling in cancer and inflammation. As a leader in this space, GlycoMimetics is leveraging this unique targeted approach to advance its pipeline of wholly owned drug candidates, with the goal of developing transformative therapies for serious diseases. GlycoMimetics is located in Rockville, Maryland in the BioHealth Capital Region. Learn more at www.glycomimetics.com.
This press release contains forward-looking statements, including those relating to the planned or potential clinical development and commercialization of the Company’s product candidates, as well as the presentation of data from preclinical studies and clinical trials, and the potential benefits and impact of the Company’s drug candidates. Actual results may differ materially from those described in these forward-looking statements. For a further description of the risks associated with these statements, as well as other risks facing GlycoMimetics, please see the risk factors described in the Company’s annual report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on March 2, 2021, and other filings GlycoMimetics makes with the SEC from time to time. Forward-looking statements speak only as of the date of this release, and GlycoMimetics undertakes no obligation to update or revise these statements, except as may be required by law