Early Studies of 2 Possible Multiple Myeloma Treatments to Be Presented at AACR

Inês Martins, PhD avatar

by Inês Martins, PhD |

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AACR presentation

GlycoMimetics will present preclinical research at the American Association for Cancer Research (AACR) Annual Meeting 2017, demonstrating the potential of two drug candidates, GMI-1271 and GMI-1359, to treat multiple myeloma.

The oral presentation (abstract #5005) will take place Tuesday, April 4, between 3:00 p.m. and 5:00 p.m. ET. The study is titled “Inhibition of E-Selectin or E-selectin together with CXCR4 re-sensitizes multiple myeloma to treatment.”

GMI-1271, an antagonist of E-selectin (an adhesion molecule expressed on endothelial cells that line blood and lymphatic vessels), is currently being evaluated in an ongoing Phase 1/2 trial (NCT02306291) as a potential treatment for acute myeloid leukemia.

By blocking E-selectin, GMI-1271 also may protect healthy blood-producing cells and reduce the toxic side effects of chemotherapy, such as low white blood cell counts, that make some patients more prone to infections.

GMI-1359, a dual antagonist of E-selectin and CXCR4,  is now in a Phase 1 clinical trial (NCT02931214) in healthy adult subjects.

Combining E-Selectin and CXCR4 targeting in a single molecule may provide next-generation, first-in-class opportunities following on the success of the anti-CXCR4 Mozobil (plerixaflor) and other CXCR4 antagonists, particularly for treating certain blood cancers and cancers involving metastasis to bone.

Both candidates showed anti-cancer activity in preclinical models of multiple myeloma. Preclinical data to be presented at the conference demonstrates that:

  • GMI-1271 and GMI-1359 reduce myeloma cell adhesion to stromal cells, and inhibit chemotaxis of myeloma cells toward culture media containing factors from stromal cells. Stromal cells are cells from the bone marrow that support the survival and growth of myeloma cells.
  • GMI-1271 and GMI-1359 reduce stroma-induced drug resistance of myeloma cells to Kyprolis (carfilzomib) and Revlimid (lenalidomide). In a preclinical model of myeloma, combining GMI-1271 with Revlimid effectively delayed tumor growth.
  • GMI-1271 and GMI-1359 both prolonged survival of myeloma mice models when combined with Kyprolis, compared to Kyprolis treatment alone.

“Our results show a strong effect on cancer cells in combination with chemotherapy and importantly, are supportive of our ongoing Phase 1 clinical studies in multiple myeloma of GMI-1271 as well as our study of GMI-1359 in multiple cancers,” John Magnani, PhD, GlycoMimetics’ senior vice president and chief scientific officer, said in a press release. “These results complement data from other preclinical studies and continue to build the rationale for our on-going clinical programs with both compounds.”

The AACR meeting runs April 1–5 at the Walter E. Washington Convention Center in Washington, D.C.