magrolimab (ONO-7913) / Ono Pharmaceutical, Gilead - LARVOL DELTA

Phase 1b/2 Study of Magrolimab (Magro), Azacitidine (AZA) and Venetoclax (VEN) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High Risk Acute Myeloid Leukemia (AML) and Relapsed Refractory (R/R) AML: Final Clinical Data and Genomic Markers of Resistance/Relapse (ASH 2024) - "Interestingly, pts with TP53mut AML who underwent alloSCT had med EFS 12 mos and med OS NR. Potential mechanisms of resistance/relapse included erythroid differentiation, inflammatory tumor microenvironment, and CD47 upregulation."

Clinical data • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • CD47 • IFNG • TNFA • TP53

MAGROLIMAB (MAGRO) + AZACITIDINE (AZA) VS PLACEBO (PBO) + AZA IN PATIENTS (PTS) WITH UNTREATED HIGHER-RISK (HR) MYELODYSPLASTIC SYNDROMES (MDS): PHASE 3 ENHANCE STUDY FINAL ANALYSIS (EHA 2024) - P3 | "In the ENHANCE study, Magro+AZA did not meet the primary endpoint of OS and CRR and showed moresevere TEAEs overall, including a higher rate of Gr ≥3 TEAEs, in treatment-naïve pts with HR-MDS. Confounding factors, such as imbalance in pts eligible for transplant and a partial clinical hold duringenrollment, may limit data interpretation. Findings highlight challenges of developing anti-CD47 therapies andother new treatments in HR-MDS."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • TP53

Azacitidine, Venetoclax and Magrolimab in Newly Diagnosed and Relapsed Refractory Acute Myeloid Leukemia: Phase 1b/2 Study and Correlative Analysis. (PubMed, Clin Cancer Res) - "The triplet regimen was safe but did not lead to promising survival outcomes."

Journal • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD47 • IFNG • TNFA • TP53

Bifunctional Phagocytic Synapse Enhancers Remodel the Tumor Microenvironment to Overcome Immunosuppression. (PubMed, Cancer Res) - "The lead molecule, longPSE, and its half-life-extended variant fused to the albumin binding domain, ABD- longPSE, showcased superior efficacy than the macrophage enhancer magrolimab in a syngeneic tumor model of colorectal cancer and an orthotopic model of pancreatic cancer...These findings establish PSEs as bifunctional molecules that complement innate and adaptive immune modulation. The bifunctional design offers a versatile approach for next-generation immunotherapies and provides a blueprint for a plug-and-play platform of immune engagers targeting diverse cancer-associated pathways."

Biomarker • Journal • Colorectal Cancer • Immune Modulation • Immunology • Oncology • Pancreatic Cancer • Solid Tumor • NRP1 • PD-L1

Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: Phase 1b results. (ASCO 2022) - P1b, P3 | "In high-risk frontline TP53m AML pts unsuitable for intensive chemotherapy, magrolimab+AZA showed durable responses and encouraging OS in a single-arm study. A Phase 3 trial in TP53m AML (ENHANCE-2; NCT04778397) of this combination vs standard of care is ongoing."

Clinical • P1 data • Acute Myelogenous Leukemia • Anemia • Constipation • Cough • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • TP53

Nature of Clinical Response and Depth of Molecular Response in Patients with TP53 Mutant Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Treated with Magrolimab with Azacitidine (ASH 2022) - P1b | "In AML, VAF 0.10 at all timepoints. Conclusions In this phase 1b study, magrolimab demonstrated a reduction in the allele frequency of TP53 mutations as early as cycle 3 in patients with MDS or AML treated with magrolimab + azacitidine, potentially altering the course of disease in patients with TP53-mutated malignancies."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • CALR • DNMT3A • NRAS • RUNX1 • TET2 • TP53

Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. (ASCO 2022) - P1b, P3 | "Magrolimab+AZA was well tolerated with promising efficacy in pts with untreated HR-MDS including those with TP53-mut and TP53-wt disease. A Phase 3 trial of magrolimab/placebo+AZA (ENHANCE: NCT04313881) is ongoing."

Combination therapy • P1 data • Anemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • CD47 • TP53

Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML (ASH 2022) - P1/2, P3 | "The triplet combination of AZA VEN Magro appears safe with encouraging CR rates in a cohort of ND pts with 93% adverse risk ELN and 71% with adverse cytogenetic features. Responses in R/R AML were modest with prior VEN exposed pts faring poorly. Further trial enrollment and correlative analysis is underway and a phase III placebo controlled, randomized, international study to evaluate this triplet in ND AML has been initiated (ENHANCE-3, NCT05079230)."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Hepatology • Idiopathic Arthritis • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Transplantation • TP53

MAGROLIMAB VS PLACEBO IN COMBINATION WITH VENETOCLAX AND AZACITIDINE IN PREVIOUSLY UNTREATED PATIENTS WITH ACUTE MYELOID LEUKEMIA WHO ARE INELIGIBLE FOR INTENSIVE CHEMOTHERAPY: THE ENHANCE-3 STUDY (EHA 2024) - P3 | "In pts with newly diagnosed AML ineligible for intensive chemotherapy, Magro + VEN + AZA did not improveOS or CR, with a higher incidence of fatal AEs occurring in pts treated with Magro. The study was stopped earlyas the prespecified futility boundary for OS (HR, 1. 1) was crossed."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Transplantation • TP53

Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia. (PubMed, EJHaem) - P2 | "This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML. Magrolimab was safely combined with existing AML therapies with no new safety signals. This trail was registered at www.clinicaltrials.gov as NCT04778410."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study. (PubMed, J Clin Oncol) - P1b, P3 | "Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ENHANCE: NCT04313881)."

Combination therapy • Journal • P1 data • Bone Marrow Transplantation • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Thrombocytopenia • Transplantation • TP53

A phase 1b/2 study of pivekimab sunirine (PVEK, IMGN632) in combination with venetoclax/azacitidine or magrolimab for patients with CD123-positive acute myeloid leukemia (AML). (ASCO 2023) - P1b/2 | "The PVEK+Magro doublet (Regimen E) is planned to be open for enrollment mid-2023 at sites in the USA. Clinical trial information: NCT04086264."

Clinical • Combination therapy • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD123

Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study. (PubMed, Blood) - P3 | "Patients determined inappropriate for intensive therapy were randomized to receive Magro/Aza or venetoclax plus azacitidine (Ven/Aza); those appropriate for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. ENHANCE-2 did not meet its primary endpoint of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • TP53

Atezolizumab Plus Magrolimab, Niraparib, or Tocilizumab in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Randomized Umbrella Study. (PubMed, Clin Cancer Res) - P1/2 | "The evaluated regimens in MORPHEUS-UC were tolerable. However, response rates for the combinations did not meet the criteria for further development in platinum-experienced locally advanced or mUC."

IO biomarker • Journal • Metastases • P1/2 data • Tumor mutational burden • Oncology • Solid Tumor • Urothelial Cancer • PD-L1 • TMB

Tolerability and Efficacy of the Anticluster of Differentiation 47 Antibody Magrolimab Combined With Azacitidine in Patients With Previously Untreated AML: Phase Ib Results. (PubMed, J Clin Oncol) - P1b, P3 | "Magrolimab with azacitidine was relatively well tolerated with promising efficacy in patients with AML ineligible for intensive induction chemotherapy, including those with TP53 mutations, warranting further evaluation of magrolimab with azacitidine in AML. The phase III randomized ENHANCE-2 (ClinicalTrials.gov identifier: NCT04778397) and ENHANCE-3 (ClinicalTrials.gov identifier: NCT05079230) studies are recruiting frontline patients with AML."

Journal • P1 data • Acute Myelogenous Leukemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • TP53

A potent anti-CD47 antibody decoupling anti-tumor efficacy from hematotoxicity. (PubMed, Int Immunopharmacol) - "LD002 addresses key translational bottlenecks in anti-CD47 therapy by decoupling target blockade from RBCs hemagglutination, thereby largely mitigating hematotoxicity while preserving robust antitumor efficacy. These preclinical data position LD002 as a differentiated, promising CD47 inhibitor with significant translational potential."

Journal • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Oncology • Small Cell Lung Cancer • Solid Tumor • SIRPA

MORPHEUS mUC: Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC) (clinicaltrials.gov) - P1/2 | N=272 | Terminated | Sponsor: Hoffmann-La Roche | Completed ➔ Terminated; Study was closed early as the sponsor decided not to continue development of certain treatment combinations.

Trial termination • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Magrolimab Plus Azacitidine Versus Placebo Plus Azacitidine in Patients With Untreated Higher-Risk Myelodysplastic Syndromes: The Phase III ENHANCE Study. (PubMed, J Clin Oncol) - P3 | "ENHANCE did not meet the primary end points of CR rate and OS, and showed more frequent severe AEs in patients treated in the Magro/Aza arm."

Journal • P3 data • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

The Longevity-Associated LAV-BPIFB4 variant enhances platelet CD47 to restrain monocyte inflammatory response: a mechanism for healthy Aging (ISTH 2026) - "ELISA assays examined platelet suppression of LPS-induced IL-6 secretion in monocytes in co-colture, with CD47 blockade (Magrolimab) establishing causality...Most significantly, rhLAV-BPIFB4 protein extends benefits to non-carriers, offering a pharmacological strategy to democratize longevity advantages for broader populations and prevent age- related cardiovascular disease. Table or Figure Upload (1) BPIFB4 and CD47 imprint platelets with an immunoregulatory signature Table or Figure Upload (2) DOI*10.1016/j.rpth.2026.105149"

Clinical • Cardiovascular • Immune Modulation • Inflammation • CD47 • IL6

Anti-CD47 antibody magrolimab with pembrolizumab in patients with relapsed / refractory classic Hodgkin lymphoma. (PubMed, Haematologica) - "Not available."

Journal • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Testing the Combination of Two Immunotherapy Drugs (Magrolimab and Dinutuximab) in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: National Cancer Institute (NCI) | Completed ➔ Terminated; Drug supply issues

Trial termination • Neuroblastoma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=8 | Terminated | Sponsor: Ranjana Advani | Trial completion date: Oct 2027 ➔ Aug 2025 | Active, not recruiting ➔ Terminated; Discontinuation of magrolimab development

Trial completion date • Trial termination • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

DISSECTING THE REGULATORY MECHANISMS OF CD47 EXPRESSION AND ITS THERAPEUTIC TARGETING IN CENTRAL NERVOUS SYSTEM LYMPHOMA (EHA 2026) - "Consistently, pharmacological inhibition of BCR signaling (ibrutinib) or actin cytoskeleton regulation (latrunculin B) decreased CD47 protein expression across DLBCL and CNSL cell lines. Left panel: Genome-wide CRISPR–Cas9 knockout screen identified positive regulators of CD47 expression, with significant enrichment of genes involved in BCR signaling, AKT–mTOR signaling, and actin cytoskeleton regulation. Right panel: Treatment with anti-CD47 antibody magrolimab significantly prolonged survival in the CNSL PDX model."

IO biomarker • B Cell Lymphoma • Brain Cancer • CNS Lymphoma • CNS Tumor • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • AKT2 • CD47 • CD79A • SIRPA

MODELLING, DECIPHERING AND THERAPEUTIC TARGETING OF THE CD47–SIRPΑ AXIS IN THE PHAGOCYTIC NICHE OF ACUTE MYELOID LEUKEMIA (EHA 2026) - "Critically, the combination of Azacitidine and D11 showed ef/cacy comparable to, or exceeding, the Azacitidine- Magrolimab association. This study establishes a mechanistic framework to optimize allosteric targeting of myeloid checkpoints in AML. Ultimately, we aim to elucidate the molecular and cellular determinants governing the efficacy of this innovative SIRP α -targeting strategy."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • SIRPA

Optimizing timing of [89Zr]-anti-CD47 antibody delivery using focused ultrasound in vivo (SNMMI 2026) - "Magrolimab, a humanized anti-CD47 monoclonal antibody, is currently under evaluation in adult and pediatric clinical trials, including glioma (Bernstock et al., 2022)... These findings demonstrate that FUS enhances brain delivery of a radiolabeled anti-CD47 monoclonal antibody in a DIPG xenograft model, with maximal uptake observed at later FUS timepoints. Ongoing studies using murine [89Zr]Zr-CD47 antibodies in syngeneic models will further characterize tumor-specific antibody uptake and therapeutic potential."

Preclinical • Brain Cancer • CNS Disorders • Diffuse Intrinsic Pontine Glioma • Glioma • Solid Tumor