Rockville, Maryland – (Working wireGlycoMimetics, Inc. (Nasdaq: GLYC) Today, a phase 1b trial of GMI-1359, being conducted at the Duke University Cancer Center, has shown evidence of effects on the target, immune activation. and cell mobilization in the first two phases. Patients treated with a double anti-company of E-selectin and CXCR4. Dorothy Sibkins, MD, Ph.D., research assistant professor in cancer pharmacology and biology at Duke University School of Medicine, will present clinical study findings to demonstrate the concept, as well as a separate clinical study to support positive biological findings from the Phase 1B study. The presentation will be presented at the 2021 Annual Meeting of the American Association for Cancer Research (AACR), which will take place approximately April 10-15 and May 17-21. GMI-1359 is a new small molecule drug candidate from GlycoMimetics, a dual antagonist of E-selectin and CXCR4, designed to target tumor resistance and environmental chemotherapy in cancers with bone metastases.
Preliminary study data confirmed the specific effects of the CXCR4 antagonist and E-selectin on the target. In patients who completed treatment, peripheral blood evaluations showed constant mobilization of hematopoietic stem cells and CD34 + progenitor cells at doses starting at 5 mg / kg with a decrease in soluble E-selectin plasma levels. In addition, in one individual, after administration of 7.0 mg / kg of GMI-1359, evaluation of the immune profile of peripheral blood showed a redistribution of myeloid-derived inhibitory cells (MDSC) as indicated by increased the percentages of MDSC and monocytes and their granules. In this same person, after administration of 7.0 mg / kg of GMI-1359, the incidence of inflammatory M1 macrophages increased while anti-inflammatory M2 macrophages, which are often associated with tumor progression, decreased. The clinical poster concludes that GMI-1359 showed an acceptable manifestation of safety and tolerability in the patients treated to date. No dose-limiting toxicity was observed after multiple doses up to 7 mg / kg.
Dr. Sebkins noted that, “even though our patient numbers are very small due to the effect of COVID on recruitment, we are seeing effects on the target of antagonizing both CXCR4 and E-selectin using GMI-1359, and that the drug is well tolerated at all dose levels ”. Analysis of the experimental immunological profile also indicates that the drug could have positive effects on the immune microenvironment of the tumor, reflecting the results observed in our preclinical work.
Dr. Sebkins will reveal preclinical evidence that GMI-1359 may increase immune recognition of a tumor. Data in the mouse metastatic breast cancer model label showed a decrease in immunosuppressive monocyte MDSCs at the primary tumor site and a significant increase in the CD8 / Treg ratio at both the primary tumor and metastasis sites. bone. These results on immune cell redistribution strongly indicate the induction of a more favorable antitumor environment after GMI-1359 administration.
According to Dr. Eric J. Feldman, Senior Vice President and Chief Medical Officer, GlycoMimetics, “The information shared on this AACR label provides us with important insights that we hope to identify a potential marker for the development of GMI-1359 in the clinic. indicates that this drug is a small molecule candidate that could improve responses to treatments and potentially reduce the burden of metastatic breast cancer.
In previous clinical research supported by GlycoMimetics, Dr. Sipkins’ lab showed that E-selectin and CXCR4 / SDF-1 interactions were critical for breast cancer cell (BCC) invasion and retention, respectively, in bone. Furthermore, they found that latent and diffuse BCC occupies different regions of the bone microenvironment, with predominantly latent BCC in the regions rich in SDF-1 and E-selectin. These latent cryptocytes are expected to be highly susceptible to GMI-1359 mobilization, indicating a new intervention to break the fulcrum of latent BCE micrometastases in bone.
The details of the GMI-1359 electronic submission at the AACR meeting are as follows:
qualification: Development of GMI-1359, a new agent targeting the tumor microenvironment in metastatic bone cancer
Presenter: Dorothy Sipkins, MD, Ph.D., Research Assistant Professor of Cancer Pharmacology and Biology at Duke University School of Medicine
session: Electronic display
Date and Time: Saturday, April 10, 2021 (available online until Monday, June 21)
About the GMI-1359
GMI-1359 was designed to simultaneously inhibit E-selectin and CXCR4, which are adhesion molecules involved in tumor escape and metastasis spread. Preclinical studies indicate that targeting both E-selectin and CXCR4 with a single compound can improve efficacy in treating cancers involving the bone marrow, such as AML and multiple myeloma, or in solid tumors that have spread to bone, such as prostate cancer and breast cancer, as well as osteosarcoma, a rare childhood tumor that affects about 900 adolescents annually in the United States. GMI-1359 has completed a phase 1 clinical trial in healthy volunteers, is conducting a phase 1B clinical study in breast cancer patients, and is designed to allow researchers to define a range of study doses and generate primary biomarker data. on the activity of the drug. In the first two patients evaluated, the study showed evidence of specific effects, immune activation and cell mobilization. GMI-1359 is an orphan drug designation and a rare childhood disease designation by the US Food and Drug Administration for the treatment of osteosarcoma.
About GlycoMimetics, Inc.
GlycoMimetics is a biotechnology company focused on hematology and oncology and a line of new sugar-mimicking drugs, all designed to meet unmet medical needs arising from diseases in which carbohydrate biology plays an important role. GlycoMimetics’ candidate drug, uproleselan, an anti-E-selectin, has been evaluated in phase 1/2 clinical trials as a potential treatment for AML and is being evaluated in a group of patients, including the phase 3 trial sponsored by the company in relapse. / resistance to acute myeloid leukemia. GlycoMimetics has an ongoing Phase 1B clinical trial to evaluate the proprietary candidate drug GMI-1359, a CXCR4 antagonist and E-selectin. GlycoMimetics is located in Rockville, MD, in the BioHealth Capital District. Get more information through www.glycomimetics.com.
Forward-looking statements
This press release contains forward looking statements. These forward-looking statements include those related to the clinical development of the company’s candidate product, as well as a presentation of data from preclinical studies, clinical trials, and the potential benefits and impact of the company’s candidate drugs. Actual results could differ materially from those shown in these forward-looking statements. For a further description of the risks associated with this data, as well as other risks faced by GlycoMimetics, please refer to the risk factors described in the company’s annual report on Form 10-K filed with the US Securities and Exchange Commission. (SEC) on March 2. , 2021, and other Deposits that GlycoMimetics makes periodically with the SEC. Forward-looking statements speak only as of the date of this release, and GlycoMimetics assumes no obligation to update or revise these statements, except as required by law.
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