On December 13, 2021 GlycoMimetics, Inc. (Nasdaq: GLYC) reported this week at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) 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 (Press release, GlycoMimetics, DEC 13, 2021, View Source [SID1234596922]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

The accepted abstracts are available online through the ASH (Free ASH Whitepaper) meeting website. Both posters are available on the Company’s website, www.glycomimetics.com under the PUBLICATIONS tab.

About GMI-1359

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.

About Uproleselan

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.