GMI-1687 / GlycoMimetics, Apollomics - LARVOL DELTA

Blockade of Selectins and Integrins in Gene-Edited Pig Lungs Perfused with Human Blood (WTC 2025) - "Pigs received DDAVP to deplete vWF...In six cases, 9GE+GHRKO left lungs (one with HLA-E) were transplanted into baboons, while right lungs were perfused with rPSGL1.Fc, GMI1687, IB4, αGPIb-treated treated human blood; three of these pigs received liposomal clodronate (LC) to deplete resident tissue macrophages... Selectin and integrin blockade is associated with delayed neutrophil and platelet sequestration and reduced hemolysis and cytokine levels by GE lungs. Pulmonary macrophage depletion with LC may enhance protection and further extend lung xenograft survival."

Hematological Disorders • CXCL8 • HLA-E • IL6

Neutrophils are primed for enhanced inflammasome activation in skin microvasculature during adhesion via E-selectin (SID 2025) - "GMI-1687 is a small molecule antagonist that blocks E-selectin recognition of sLex on L-selectin... Psoriatic neutrophils in circulation are primed for enhanced inflammatory response by elevated b2-integrin binding affinity and calprotectin levels that increase with stimulation via TNFa. Here we report that rolling on inflamed endothelium via E-selectin/L-selectin can trigger inflammasome activation that is enhanced in the presence of calprotectin and TNFα, which may exacerbate the pathogenesis of psoriasis."

Dermatology • Immunology • Inflammation • Psoriasis • S100A8 • TNFA

Selectin and Integrin Blockade in Multi-Gene-Edited Pig Lungs Perfused with Human Blood (ISHLT 2025) - "Pigs received DDAVP to deplete vWF...Treated lung perfusate received P and E selectin and integrin antagonists (rPSGL1.Fc, GMI1687, IB4), and porcine sialoadhesin blocker (mAb1F1) (9GE, n=8; GalKO+/-CD55, n=4)...One donor was pretreated with clodronate liposomes (CL)...With CL-treatment, the right lung exhibited lower platelet loss and sustained MCP-1 reductions for up to 4hrs (Fig.1 e, f) relative to other 9GE lungs, while the transplanted left lung showed less parenchymal damage and lower IL-6 and IL-8 levels, compared to the lungs with fewer GEs.Conclusion Reduction in neutrophil and platelet sequestration, hemolysis, and cytokine levels demonstrate protective effects associated with multi-GE lungs treated with selectin and integrin blockade. Pulmonary macrophage depletion with CL could enhance protection and further extend lung xenograft survival."

Hematological Disorders • CD55 • CXCL8 • IL6

GlycoMimetics Announces Strategic Review and Corporate Restructuring Plan (Businesswire) - "After meeting with the U.S. Food and Drug Administration (FDA), it has been determined that the regulatory path forward for uproleselan in relapsed and refractory (R/R) Acute Myeloid Leukemia (AML) would require an additional clinical trial; The Company will conduct a strategic review of the 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 is advancing discussions with the National Cancer Institute (NCI) and Alliance for Clinical Trials in Oncology for the ongoing Phase 2/3 study of uproleselan in newly diagnosed AML patients...The Company will evaluate strategic alternatives and no timetable has been set for the conclusion of the strategic review or the consummation of any such strategic transaction."

Commercial • FDA event • Trial status • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

GMI-1687-101, A PHASE 1A FIRST IN HUMAN TRIAL OF SECOND-GENERATION E-SELECTIN ANTAGONIST GMI-1687 (EHA 2024) - "Pan-selectin inhibitor rivipanselshortened IV opioid duration and length of stay in hospitalized SCD patients treated early in VOE, comparedwith placebo (Dampier, et al. Single ascending SC doses of second-generation E-selectin antagonist GMI-1687 (3. 3 to 80 mg) are safe andwell tolerated in healthy subjects. Pharmacokinetics results support testing of fixed-dose SC GMI-1687 in SCDpatients."

P1 data • Addiction (Opioid and Alcohol) • Genetic Disorders • Hematological Disorders • Infectious Disease • Pain • Sickle Cell Disease

Do Selectins, Porcine Sialoadhesin, and CD11b/CD18 Integrin Mediate Platelet and Leukocyte Sequestration during Pig Lung Perfusion with Human Blood? (ATC 2024) - "This study aims to determine whether a combination of P- and E-selectin inhibition along with 1F1 and augmented CD11b/CD18 integrin inhibition using mAb107, an anti CD11b/CD18 mAb which is specific for the activated configuration of CD11b, can prevent these phenomena and improve lung function in an ex vivo lung perfusion model.* Twenty Lungs from GalKO background pigs with or without β4Gal and Neu5Gc knockouts and containing human transgenes CD46, CD55, TBM, EPCR, CD47, HO-1 (n=16) perfused with fresh heparinized human blood; all pigs were pre-treated with DDAVP to deplete endothelial vWF. Blood perfusate was pretreated with thromboxane synthase inhibitor 1-BIA and 2 histamine receptor blockers (n=8), the "treated" lungs received additional rPSGL1.Fc, E-selectin antagonist GMI 1687, Galectin 3 and 1F1 mAb, with (n=4) or without (n=8) mAb107; αGPIb Fab was added in some experiments... Erythrocyte fragmentation during ex vivo xenoperfusion was mildly attenuated..."

Preclinical • Respiratory Diseases • CD46 • CD55 • ICAM1 • ITGAM • ITGB2 • PROCR • VCAM1

Glycomimetic drugs targeting E-selectin for inflammatory disease and as a major cause of progression and chemoresistance in cancer (ACS-Sp 2024) - "Rivipansel inhibits selectins by mimicking sialyl Lex and the tri-sulfated domain of PSGL-1...GMI-1687 binds E-selectin with a K D of 2.3 nM, is bioavailable through a subcutaneous route, and has recently entered Phase 1 clinical studies...As of August 2023, the reported median survival in this placebo-control blinded study with Uproleselan is over 30 months. Here, data are presented to demonstrate that E-selectin plays a major role in chemoresistance among many cancers and is susceptible to treatment with a potent glycomimetic drug."

Acute Myelogenous Leukemia • Genetic Disorders • Hematological Disorders • Oncology • Pain • Sickle Cell Disease • SELP

GlycoMimetics Announces First Cohort Dosed in Human Phase 1a Study of GMI-1687 (GlycoMimetics Press Release) - "GlycoMimetics...announced dosing of the first cohort of healthy volunteers in a Phase 1a study of GMI-1687 to evaluate safety, tolerability, and pharmacokinetics....GMI-1687, a highly potent E-selectin antagonist, is being developed as a potential point-of-care treatment for inflammatory diseases with initial focus on sickle cell disease (SCD). Single ascending dose study is expected to randomize approximately 40 healthy volunteers on GMI-1687 vs placebo with endpoints for safety, tolerability, and pharmacokinetics. Initial results expected by end Q1 2024."

P1 data • Trial status • Sickle Cell Disease

GlycoMimetics, inc (GLYC) Q2 2021 Earnings Call Transcript (The Motley Fool) - "In the sickle cell setting, based on input from the FDA with respect to rivipansel as well as feedback from KOLs we've previously reported to you, we are focusing on the development of GMI-1687. We have initiated IND-enabling activities with treatment of acute vaso-occlusive crisis as a potential lead indication. This work continues toward a goal of initiation of Phase I in the first half of 2022."

New P1 trial • Preclinical • Hematological Disorders • Sickle Cell Disease

GlycoMimetics Reports Highlights and Financial Results for Second Quarter 2021 (Businesswire) - "The Company continued to advance GMI-1687 towards filing of an investigational new drug application (IND), anticipated in the first half of 2022."

IND • Hematological Disorders • Sickle Cell Disease

[VIRTUAL] Glycomimetic drugs: From rational design to clinical trials (ACS-Sp 2021) - P3 | "GMI-1070 (rivipansel) was designed to inhibit E, P, and L-selectins by incorporating a mimic of sialyl Lex together with that of the tri-sulfated domain of PSGL-1...In animal models of VOC, GMI-1687 blocked occlusion and normalized blood flow at 0.04 mg/kg BID...Based on positive phase 2 data, the FDA granted uproleselan “Breakthrough Therapy Designation”...Animal models of bone metastasis treated with GMI-1359 and chemotherapy show reduction of tumor volume and significant improvement in survival. GMI-1359 is now being studied in breast cancer patients at Duke University."

Clinical • Breast Cancer • Genetic Disorders • Hematological Disorders • Oncology • Pain • Sickle Cell Disease • Solid Tumor • CXCR4

[VIRTUAL] Restoration of Normal Blood Flow in Mouse Models of Sickle Cell Vaso-Occlusion Following Intravenous or Subcutaneous Administration of a Highly Potent E-Selectin Specific Inhibitor (ASH 2020) - "These data demonstrate that the administration of the potent and E-selectin specific compound GMI-1687 was effective in restoring blood flow in two mouse models of SCD, and support the development of GMI-1687 formulated for SC use and self-administration with the potential for early intervention of VOC."

Preclinical • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

GlycoMimetics Program Data to be Highlighted Via Three Oral Presentations and Two Posters at 62nd American Society of Hematology Annual Meeting and Exposition (Businesswire) - "Of particular note are primary and key secondary endpoint data from additional analysis of the Phase 3 RESET study evaluating the efficacy of rivipansel in VOC. These findings point to the potential benefits, clinical improvements and improved outcomes associated with early treatment with GlycoMimetics’ wholly-owned product candidate, which include shorter hospital stays for patients and reduced need for IV opioids to treat pain. A second presentation includes data from two different preclinical models of VOC using GlycoMimetics’ highly potent and specific E-selectin antagonist, GMI-1687. This presentation will highlight the product candidate’s potential for intravenous and subcutaneous administration to treat VOC by inhibiting occlusions and restoring blood flow."

P3 data • Preclinical • Sickle Cell Disease

GlycoMimetics and Apollomics announce exclusive collaboration and license agreement to develop and commercialize uproleselan and GMI-1687 in Greater China (GlycoMimetics Press Release) - "GlycoMimetics, Inc...and Apollomics, In...announced...an exclusive collaboration and license agreement for the development and commercialization of uproleselan and GMI-1687 in Mainland China, Hong Kong, Macau and Taiwan, also known as Greater China....'The work done by GlycoMimetics will allow Apollomics to leverage emerging data in AML and other hematologic malignancies in which uproleselan and GMI-1687 might be effective and beneficial for patients in Greater China.'"

Licensing / partnership