uproleselan (APL-106) / Apollomics, GlycoMimetics - LARVOL DELTA

NCI-2021-10020: Highest Dose of Uproleselan in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Mixed Phenotype Acute Leukemia Relapsed or Refractory and That Expresses E-selectin Ligand on the Cell Membrane (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=22 ➔ 8 | Trial completion date: Dec 2026 ➔ May 2026 | Trial primary completion date: Dec 2026 ➔ Mar 2025

Enrollment change • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SELL

Updated Results of a Phase I Study of Uproleselan Combined with Azacitidine and Venetoclax for the Treatment of Older or Unfit Patients with Treatment Naïve Acute Myeloid Leukemia (ASH 2024) - P1 | "No DLTs were observed, and the most common Grade 3-4 AE and SAE were hematologic. The combination shows promising preliminary efficacy, including a 64% rate of MRD-ve CR/CRi."

Clinical • P1 data • Acute Myelogenous Leukemia • Anemia • Anorexia • Constipation • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Respiratory Diseases • Septic Shock • ASXL1 • BCOR • DDX41 • DNMT3A • FLT3 • IDH2 • NPM1 • NRAS • RUNX1 • TET2 • TP53

Final Results of a Phase II Study of Uproleselan Combined with Cladribine and Low-Dose Cytarabine for Patients with Treated Secondary Acute Myeloid Leukemia (ts-AML) (ASH 2024) - P1/2 | "Patients received a median of 1 line of therapy (range, 1-5) for their AHD, including HMA (100%), venetoclax (41%), and allogeneic SCT (16%). There was no additional toxicity with the addition of uproleselan, and a trend toward better response among patients with higher E-sel ligand expression was observed. Randomized trials evaluating the role of uproleselan in patients with adverse-risk AML are ongoing."

Clinical • P2 data • Acute Myelogenous Leukemia • Cerebral Hemorrhage • Chronic Myelomonocytic Leukemia • CNS Disorders • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • ASXL1 • NRAS • RUNX1 • SRSF2 • TET2 • TP53

Apollomics Announces Top-line Results for Phase 3 Bridging Trial of Uproleselan in China in Patients with Relapsed or Refractory Acute Myeloid Leukemia (GlobeNewswire) - P3 | N=140 | NCT05054543 | Sponsor: Apollomics Inc. | "The trial did not demonstrate favorable benefit for uproleselan...A total of 140 subjects were enrolled in the Phase 3 trial and randomized 1:1 to receive either uproleselan with chemotherapy (n=69) or chemotherapy alone (n=71). The median OS in the uproleselan arm was 9.3 months (95% CI 6.1 – 16.0 months) versus 14.3 months (95% CI 6.2 – NA months) in the chemotherapy-only arm (p=0.48). Addition of uproleselan to chemotherapy was generally well tolerated, with a similar safety profile to the control arm. The incidence of serious adverse events was 43% in the uproleselan arm versus 39% in the chemotherapy-only arm...'Our regulatory and commercial strategy in China has always required a positive global Phase 3 trial, and therefore we are currently wrapping up this program.'....Apollomics is concluding the clinical trial and expects future expenses for the uproleselan program to be less than $500,000."

Discontinued • Financing • P3 data: top line • Acute Myelogenous Leukemia

Efficacy and Safety of Uproleselan Combined with Chemotherapy Vs. Chemotherapy Alone in Relapsed/Refractory Acute Myeloid Leukemia: Findings from an International Phase 3 Trial (ASH 2024) - P2/3, P3 | "Conclusions : Although this Phase 3 trial did not meet its primary OS endpoint for the ITT population, these clinical data provide compelling evidence of uproleselan efficacy in patients with primary refractory AML without additional toxicity. In primary refractory AML, a mOS of 31.2 months highlights the potential of uproleselan to significantly improve treatment outcomes in this high unmet medical need population."

Clinical • P3 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Mucositis • Oncology • Stomatitis

Uproleselan Plus Chemo Fails to Produce OS Benefit in Relapsed/Refractory AML (OncLive) - P3 | N=388 | NCT03616470 | Sponsor: GlycoMimetics Incorporated | "The median duration of response (DOR) among the uproleselan-treated primary refractory patients was not reached, compared with a median DOR of 12.7 months in the placebo group (HR, 0.26; 95% CI, 0.09-0.75)....In patients who achieved CR or CRi, uproleselan showed a higher rate of MRD negativity. Among patients achieving CR, 67.1% of those treated with uproleselan were MRD-negative vs 61.5% in the placebo group....Notably, patients who underwent transplantation experienced a marked survival benefit when treated with uproleselan. Of those who achieved CR and proceeded to allo-SCT, the median OS was not reached (NR) for the uproleselan group compared with 24.8 months for the placebo group (HR, 0.59; 95% CI 0.38-0.91)."

P3 data • Acute Myelogenous Leukemia

Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=37 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Oct 2024 | Trial primary completion date: Dec 2026 ➔ Oct 2024

Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

GlycoMimetics Announces New Uproleselan Clinical Data Will Be Presented at ASH Annual Meeting (Businesswire) - "GlycoMimetics, Inc...announced that data from multiple clinical trials studying uproleselan in patients with acute myeloid leukemia (AML) have been accepted for presentation at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Diego, California, on December 7-10, 2024."

Clinical data • Acute Myelogenous Leukemia

GlycoMimetics Announces National Cancer Institute Phase 2/3 Study of Uproleselan Did Not Meet Primary Endpoint (Businesswire) - P2/3 | N=670 | NCT03701308 | "GlycoMimetics, Inc...announced the Phase 2 analysis of the adaptive Phase 2/3 study of uproleselan being conducted by the National Cancer Institute (NCI) and the Alliance for Clinical Trials in Oncology in adults with newly diagnosed acute myeloid leukemia (AML) who are 60 years or older and fit for intensive chemotherapy. This study did not show a statistically significant improvement in event free survival (EFS) for patients receiving uproleselan in combination with 7+3 chemotherapy versus chemotherapy alone....Top-line results from NCI/Alliance trial are expected to be presented by the NCI at a future medical conference."

P2 data • Acute Myelogenous Leukemia

NCI-2021-10020: Highest Dose of Uproleselan in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Mixed Phenotype Acute Leukemia Relapsed or Refractory and That Expresses E-selectin Ligand on the Cell Membrane (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Combination therapy • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SELL

Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy (clinicaltrials.gov) - P2/3 | N=670 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Uproleselan With Pre-Transplant Conditioning in Hematopoietic Stem Cell Transplantation for AML (clinicaltrials.gov) - P1 | N=1 | Terminated | Sponsor: Malika Kapadia | Phase classification: P1/2 ➔ P1 | N=28 ➔ 1 | Trial completion date: Dec 2028 ➔ Dec 2023 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2027 ➔ Oct 2023; On 7/26/24 the Sponsor-Investigator was notified GlycoMimetics was terminating contracting for NCT05569512 following company restructuring. This notification came ahead of the study meeting criteria to progress from Phase 1 to Phase 2.

Enrollment change • Phase classification • Pre-transplantation • Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Pediatrics • Transplantation • HLA-DRB1 • RUNX1

Uproleselan, Azacitidine, and Venetoclax for the Treatment of Treatment Naive Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=16 | Active, not recruiting | Sponsor: Brian Jonas | Recruiting ➔ Active, not recruiting | N=25 ➔ 16 | Trial completion date: Jan 2025 ➔ Oct 2025 | Trial primary completion date: Jul 2024 ➔ Apr 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

NCI-2021-10020: Highest Dose of Uproleselan in Combination With Fludarabine and Cytarabine for Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Mixed Phenotype Acute Leukemia Relapsed or Refractory and That Expresses E-selectin Ligand on the Cell Membrane (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • SELL

Study to Determine the Efficacy of Uproleselan (GMI-1271) in Combination With Chemotherapy to Treat Relapsed/Refractory Acute Myeloid Leukemia (clinicaltrials.gov) - P3 | N=388 | Terminated | Sponsor: GlycoMimetics Incorporated | Trial completion date: Dec 2024 ➔ Mar 2024 | Active, not recruiting ➔ Terminated; Trial failed to meet primary endpoint.

Combination therapy • Trial completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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

GlycoMimetics Announces Comprehensive Results from Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) (Businesswire) - P3 | N=388 | NCT03616470 | Sponsor: GlycoMimetics Incorporated | "GlycoMimetics, Inc...announced comprehensive results from the company’s pivotal Phase 3 study of uproleselan in R/R AML....Primary Endpoint: mOS in the intent-to-treat (ITT) population (n=388) was 13.0 months for the uproleselan arm, compared to 12.3 months for the placebo arm (hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.69-1.15); this difference is not statistically significant. Primary Refractory: mOS for primary refractory patients in the uproleselan arm (n=62) was 31.2 months, compared to 10.1 months (HR 0.58; 95% CI 0.37-0.91) for the placebo arm (n=66). This benefit was irrespective of backbone chemotherapy."

P3 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

GlycoMimetics to Host Key Opinion Leader Event to Review Comprehensive Results from Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) on June 4, 2024 (Businesswire) - "GlycoMimetics...announced that it will host a key opinion leader event on Tuesday, June 4, 2024, at 8:30am ET to provide a comprehensive overview of data from the company’s pivotal Phase 3 study of uproleselan in relapsed/refractory (R/R) acute myeloid leukemia (AML). The event will feature the study’s principal investigator Daniel DeAngelo, M.D., Ph.D., Professor of Medicine, Harvard Medical School, and Chief of the Division of Leukemia, Dana-Farber Cancer Institute, who will discuss results from the pivotal Phase 3 study of uproleselan..."

P3 data • Acute Myelogenous Leukemia

GlycoMimetics Announces Results of Pivotal Phase 3 Study of Uproleselan in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) (Businesswire) - P3 | N=388 | NCT03616470 | Sponsor: GlycoMimetics Incorporated | "GlycoMimetics, Inc...announced topline results from its Phase 3 global pivotal study of uproleselan in 388 patients with R/R AML. In the study, 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 study."

P3 data: top line • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Combining 5-azacitidine with the E-selectin antagonist uproleselan is an effective strategy to augment responses in myelodysplasia and acute myeloid leukaemia. (PubMed, Br J Haematol) - "Finally, we present clinical evidence showing that BM myeloid cells from higher risk MDS and AML patients have the potential to bind E-selectin, and these cells are more abundant in 5-azacitidine-non-responsive patients. The collective data provide a strong rationale to evaluate 5-azacitidine in combination with the E-selectin antagonist, uproleselan, in this patient population."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • FUT7

GlycoMimetics Reports Highlights and Financial Results for Fourth Quarter and Full Year 2023 (Businesswire) - "Topline results from pivotal Phase 3 study of uproleselan in relapsed/refractory (R/R) Acute Myeloid Leukemia (AML) to be reported in Q2 2024; New Drug Application (NDA) for uproleselan to be submitted to the U.S. Food and Drug Administration (FDA) by end of 2024 if outcome of R/R AML pivotal study is positive."

NDA • P3 data: top line • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Targeting hematologic malignancies by inhibiting E-selectin: A sweet spot for AML therapy? (PubMed, Blood Rev) - "In this review we summarize E-selectin biology and the rationale for uproleselan in combination with other therapies for hematologic malignancies. We also describe uproleselan pharmacology and ongoing clinical trials."

Journal • Review • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Mucositis • Oncology • Stomatitis

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

Uproleselan, Cladribine, and Low Dose Cytarabine for the Treatment of Patients With Treated Secondary Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Apollomics Completes Enrollment in Phase 3 Bridging Study of Uproleselan in Chinese Patients with Relapsed/Refractory Acute Myeloid Leukemia (GlobeNewswire) - "Apollomics Inc...announced the completion of enrollment in its Phase 3 bridging study evaluating uproleselan (APL-106), an investigational, first-in-class E-selectin antagonist, added to a standard chemotherapy regimen for the treatment of adults with relapsed or refractory acute myeloid leukemia (relapsed/refractory AML)."

Enrollment closed • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology