GlycoMimetics, Inc. (NASDAQ:GLYC) is a late clinical-stage biotechnology company focused on improving the lives of people living with cancer and inflammatory diseases by leveraging the inhibition of carbohydrate interactions that occur on the surface of cells. The company is developing a pipeline of proprietary glycomimetics, which are small molecules that mimic the structure of carbohydrates involved in important biological processes, to inhibit disease-related functions of carbohydrates.

Business Overview

GlycoMimetics' lead glycomimetic drug candidate, uproleselan, is a specific E-selectin antagonist that the company is developing to be used in combination with chemotherapy to treat patients with acute myeloid leukemia (AML), a life-threatening hematologic cancer, and potentially other hematologic cancers. In 2021, the company completed enrollment of 388 patients in a randomized, double-blind, placebo-controlled Phase 3 pivotal clinical trial to evaluate uproleselan in individuals with relapsed/refractory AML.

On May 6, 2024, GlycoMimetics reported topline results from the trial, in which uproleselan combined with chemotherapy did not achieve a statistically significant improvement in overall survival in the intent to treat population versus chemotherapy alone. Patients treated with uproleselan had a median overall survival of 13 months, compared to 12.3 months in the placebo arm. Adverse events were consistent with known side effect profiles of chemotherapy used in the trial.

The company has begun to further evaluate the data with medical, statistical, and regulatory experts and plans to submit the full results for presentation at an upcoming medical meeting. GlycoMimetics has also entered into a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) to conduct a Phase 2/3 randomized, controlled clinical trial testing the addition of uproleselan to a standard chemotherapy regimen. Enrollment of 267 patients in the Phase 2 portion was completed in December 2021, and there will be a planned interim analysis that will evaluate event-free survival and whether the pre-specified threshold for continuing to Phase 3 has been met.

In addition to uproleselan, GlycoMimetics is advancing other preclinical-stage programs, including small-molecule glycomimetic compounds that inhibit the protein galectin-3, which the company believes may have potential to be an orally administered treatment for fibrosis, cancer and cardiovascular disease. In 2022, the company selected a lead galectin drug candidate, GMI-2093, for evaluation in preclinical studies.

Financials

The company has financed its operations primarily through private placements of its securities, up-front and milestone payments under its license and collaboration agreements, and the net proceeds from public offerings of common stock, including sales of common stock under at-the-market sales facilities. GlycoMimetics has no approved drugs currently available for sale, and substantially all of its revenue to date has been revenue from up-front and milestone payments under license and collaboration agreements.

Since inception, GlycoMimetics has incurred significant operating losses. The company had an accumulated deficit of $467.2 million as of March 31, 2024 and expects to continue to incur operating losses over at least the next several years. GlycoMimetics' net losses may fluctuate significantly from quarter to quarter and year to year, depending on the timing of its clinical trials and its expenditures on other research and development activities.

For the year ended December 31, 2023, GlycoMimetics reported a net loss of $36.9 million, annual revenue of $10,000, annual operating cash flow of -$34.9 million, and annual free cash flow of -$34.9 million. For the three months ended March 31, 2024, the company reported a net loss of $10.7 million, with research and development expenses of $6.0 million and general and administrative expenses of $5.1 million.

Liquidity

To fund further operations, GlycoMimetics will need to preserve its current cash resources and raise additional capital. The company may obtain additional financing in the future through the issuance of its common stock, through other equity or debt financings, potentially including the use of its at-the-market sales facility, through collaborations or partnerships with other companies, or through the sale of rights to receive royalties on sales of uproleselan or any other drug candidates.

As of March 31, 2024, GlycoMimetics had $31.3 million in cash and cash equivalents. The company believes that its existing cash and cash equivalents will be sufficient to fund its operations through the fourth quarter of 2024 without giving effect to potential business development opportunities or financing activities. However, the company plans to reduce its operating expenses in the upcoming months in order to preserve capital, as the results of the pivotal Phase 3 clinical trial of uproleselan in R/R AML patients were not as expected.

Risks and Challenges

Given the challenges faced with the uproleselan trial results, GlycoMimetics has initiated a strategic review of its business, seeking to maximize shareholder value, including the evaluation of potential business development opportunities for uproleselan and GMI-1687 to ensure their continued advancement. The company has engaged Lucid Capital Markets to act as a strategic advisor in this process. GlycoMimetics will also implement a corporate restructuring plan, which is expected to significantly reduce future operating expenses and extend the company's cash runway into the second quarter of 2025.

Conclusion

In conclusion, GlycoMimetics is navigating a challenging period following the disappointing results of its pivotal Phase 3 trial of uproleselan in R/R AML. The company is committed to thoroughly analyzing the data, engaging with regulatory authorities, and exploring strategic alternatives to maximize the potential of its drug candidates and preserve shareholder value. While the path forward is uncertain, GlycoMimetics remains dedicated to its mission of improving the lives of people living with cancer and inflammatory diseases.