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

The tumor microenvironment in leukemia: molecular pathways of immune evasion. (PubMed, Front Immunol) - "We further discuss implications for immunotherapy, noting that agents like magrolimab (anti-CD47) combined with azacitidine have demonstrated objective response rates (ORR) exceeding 80% in early-phase AML trials, though challenges such as on-target anemia persist. By integrating current evidence from preclinical metabolic profiling to Phase 3 clinical data on E-selectin inhibition (uproleselan)-we clarify the immune landscape of leukemia and outline avenues for innovative treatments. Ultimately, this Review underscores the need for multifaceted immunotherapeutic approaches that account for the complex interactions within the TME."

Biomarker • Journal • Review • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Uproleselan, Azacitidine, and Venetoclax for the Treatment of Treatment Naive Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=16 | Terminated | Sponsor: Brian Jonas | Active, not recruiting ➔ Terminated; Sponsor decision

Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

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 • Hematological Malignancies • Leukemia • Mucositis • Oncology • Stomatitis

A randomized study of conventional chemotherapy +/- uproleselan in older adults with Acute Myeloid Leukemia eceiving intensive induction chemotherapy (Alliance A041701) (ASH 2025) - P2/3 | "Induction chemotherapy consisted of 7+3 (cytarabine + daunorubicin) +/- uproleselan with a secondinduction cycle with 5+2 +/- uproleselan administered for residual AML. Although the addition of uproleselan to intensive chemotherapy was associated with ahigher rate of MRDneg CR/CRi in older adults with AML, uproleselan failed to improve EFS or OS and didnot overcome the adverse outcomes associated with higher E-selectin expression on AML blasts. Themedian OS of 20-24 months with an overall 3-year OS of almost 40% for patients treated on this studyexceeds previous CALGB / US Cooperative Group studies (median OS ~12 months, 3-year OS ~20%) andcontinues to support a role for intensive chemotherapy in the management of older adults with AML.Furthermore, this study suggests a potential benefit for uproleselan in patients harboring ASXL1mutations, which may warrant further investigation.ClinicalTrials.gov Identifier: NCT03701308"

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • ASXL1 • SELL • TP53

A Phase II Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate E-Selectin Inhibition with Uproleselan to Reduce GI Toxicity During Autologous Hematopoietic Cell Transplantation for Multiple Myeloma. (PubMed, Transplant Cell Ther) - No abstract available

Clinical • Journal • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

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

APAL2020SC Pediatric Acute Leukemia (PedAL) Screening Trial – Developing New Therapies for Relapsed Leukemias (ASH 2023) - P1/2 | "APAL2020D/ITCC101 is a randomized phase III study comparing fludarabine-cytarabine (FLA) to FLA-venetoclax. APAL2020E/PEPN2113 is a phase 1 study of the E-selectin inhibitor uproleselan in combination with FLA... APAL2020SC will accrue patients with relapsed acute leukemias and treatment-related AML for 5 years. This protocol will promote clinical trial development by engaging industry partners and providing a single entry point to therapeutic studies with biological rationale. APAL2020SC and the EuPAL Foundation registry will generate a large, comprehensive and longitudinal dataset that will inform future trials."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • KMT2A

Uproleselan Added to Cladribine Plus Low Dose Cytarabine (LDAC) in Patients with Treated Secondary Acute Myeloid Leukemia (TS-AML) (ASH 2023) - P1/2 | "Uproleselan combined with Cladribine + LDAC was well-tolerated with minimal therapy-related AEs – allowing a safe approach to marrow blast reduction and disease control in preparation for a potential allogeneic SCT. We are currently determining the relationship of plasmatic e-selectin concentration and response to treatment."

Clinical • Acute Myelogenous Leukemia • Cardiovascular • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Septic Shock • Thrombosis • RUNX1 • SRSF2 • TET2 • TP53

Patient Recorded Outcomes from a Randomized, Controlled Phase 2 Trial of E-Selectin Inhibition with Uproleselan Vs Placebo to Reduce GI Toxicity during Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation for Multiple Myeloma (ASH 2023) - "Upro+SoC resulted in a clinically significant improvement in GI-toxicity related symptoms as assessed via PRO-CTCAE in patients with MM undergoing melphalan-conditioned AHCT, when compared to placebo+SoC. These improvements in patient reported outcomes are further supported by data from the primary and additional secondary endpoints of the study. Taken together, these results suggest prophylactic E-selectin inhibition may represent a promising strategy to mitigate chemotherapy-associated GI-toxicity."

Clinical • P2 data • Dental Disorders • Gastroenterology • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

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=264 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | N=670 ➔ 264 | Trial completion date: Dec 2025 ➔ Oct 2026

Enrollment change • Trial completion date • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology

Study to Evaluate PK and Safety With Uproleselan Combined With Chemotherapy to Treat Chinese R/R AML Patients (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Apollomics Inc. | Recruiting ➔ Completed | Trial completion date: Feb 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2022 ➔ Jun 2024

Trial completion • Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

Study to Evaluate the Efficacy of Uproleselan in Combination With Chemotherapy in Chinese Patients With R/R AML (clinicaltrials.gov) - P3 | N=140 | Terminated | Sponsor: Apollomics Inc. | Trial completion date: Feb 2024 ➔ Aug 2024 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ Aug 2024; In light of the strategic realignment of the company's development focus, it has been determined to discontinue the further development of Uproleselan Injection.

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • IDH1

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

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

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