Saccovid (efprezimod alfa) / Merck (MSD) - LARVOL DELTA

Prioritizing drug targets in systemic lupus erythematosus from a genetic perspective: a druggable genome-wide Mendelian randomization study. (PubMed, Clin Rheumatol) - "This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE. Key Points • We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects. • Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE."

Journal • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • BLK • HSPA1A • IL12A • NEU1

CD24Fc to DAMPen GVHD. (PubMed, Blood) - No abstract available

Journal • Graft versus Host Disease • Immunology

A Phase 2 Trial of CD24Fc for Prevention of Graft-vs-Host Disease. (PubMed, Blood) - P2 | "Patients who undergo human leukocyte antigen-matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often develop acute graft-vs-host disease (GVHD) despite standard calcineurin inhibitor-based prophylaxis in combination with methotrexate. The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD-free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as NCT02663622."

Clinical • Journal • P2 data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation • CD24

CD24-Fc suppression of immune related adverse events in a therapeutic cancer vaccine model of murine neuroblastoma. (PubMed, Front Immunol) - "This study illustrates that the combination of Myc suppressed whole tumor cell vaccination with checkpoint inhibitors is an effective therapy, but occult immune infiltrates are induced in several organ systems in a mouse neuroblastoma model. The systemic administration of CD24-Fc suppresses autoimmune tissue responses, but appropriate timing of administration is critical for maintaining efficacy of the therapeutic vaccine."

Adverse events • Journal • Preclinical • CNS Tumor • Immune Modulation • Immunology • Neuroblastoma • Neuroendocrine Tumor • Oncology • Solid Tumor • CD24

Targeting Danger Associated Molecular Pattern (DAMP) with CD24Fc to Reduce Acute Gvhd: Study Design on a Randomized Double Blind Placebo Controlled Phase III Clinical Trial (CATHY Study) (TCT-ASTCT-CIBMTR 2020) - P2, P3; "This study will compare CD24Fc or Placebo with standard GVHD prophylaxis of tacrolimus and methotrexate in the setting of myeloablative conditioning (MAC), matched unrelated donor (MUD) allogeneic HCT in patients with AML/ALL or MDS. Z test statistics for comparing the two arms will be compared to the critical values and results be reviewed by the independent DSMB. Acknowledgement: The Phase II study is supported by R44CA221513, R44CA246991."

Clinical • P3 data

CD24-Siglec axis is an innate immune checkpoint against metaflammation and metabolic disorder. (PubMed, Cell Metab) - P1 | "A first-in-human study of CD24Fc (NCT02650895) supports the significance of this pathway in human lipid metabolism and inflammation. These findings identify the CD24-Siglec-E axis as an innate immune checkpoint against metaflammation and metabolic disorder and suggest a promising therapeutic target for metabolic disease."

Journal • Addiction (Opioid and Alcohol) • Dyslipidemia • Genetic Disorders • Hepatology • Immune Modulation • Immunology • Inflammation • Metabolic Disorders • Non-alcoholic Steatohepatitis • Obesity • CD24

CD24Fc ameliorates immune-related adverse events while preserving anti-tumor therapeutic effect. (PubMed, Signal Transduct Target Ther) - No abstract available

Adverse events • Journal • Oncology

Precise O-Glycosylation Site Localization of CD24Fc by LC-MS Workflows. (PubMed, Anal Chem) - "The EThcD workflow directly identified glycosylation sites by tandem mass spectrometry (MS/MS) for singly, doubly, and triply O-glycosylated peptides. Together, both workflows validated each other's results and can be applied to a complex mucin-type O-glycosylation site analysis of other glycoproteins and Fc-fusion therapeutics."

Journal • CD24

CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study (clinicaltrials.gov) - P1/2 | N=3 | Terminated | Sponsor: Tianhong Li | N=78 ➔ 3 | Active, not recruiting ➔ Terminated; Terminated early by the Sponsor due to the sponsor change.

Adverse events • Enrollment change • Trial termination • Immune Modulation • Oncology • Solid Tumor • CD24

Efficacy and safety of CD24Fc in hospitalised patients with COVID-19: a randomised, double-blind, placebo-controlled, phase 3 study. (PubMed, Lancet Infect Dis) - P3 | "CD24Fc is generally well tolerated and accelerates clinical improvement of hospitalised patients with COVID-19 who are receiving oxygen support. These data suggest that targeting inflammation in response to tissue injuries might provide a therapeutic option for patients hospitalised with COVID-19."

Journal • P3 data • Allergy • Immune Modulation • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Oncology • Respiratory Diseases

CD24Fc: an emerging COVID-19 therapy. (PubMed, Lancet Infect Dis) - No abstract available

Journal • Infectious Disease • Novel Coronavirus Disease

Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology. (PubMed, J Hematol Oncol) - P3 | "Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19."

Journal • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • CD24 • CD8 • HMGB1 • NCAM1

CD24Fc ameliorates immune-related adverse events while preserving anti-tumor therapeutic effect (SITC 2021) - "We treated Ctla4h/h mice with Ipilimumab and anti-PD-1 Ab in conjunction with hIgFc or CD24Fc on day 10, 13, 16 and 19 after birth. These data suggest CD24Fc has the potential to optimize tumor microenvironment and augment antitumor immunity. Conclusions Our data demonstrate that CD24Fc treatment ameliorates irAEs in multiple organs induced by combination of anti-CTLA-4 and anti-PD-1 Abs while modestly enhancing its anti-tumor activity, potentially by reducing the intratumor regulatory T cells and reverse exhaustion of tumor-infiltrating T cells."

Adverse events • Oncology • CD24 • CD8 • HAVCR2

The impact of DAMP-mediated inflammation in severe COVID-19 and related disorders. (PubMed, Biochem Pharmacol) - "Further, we review clinical data on proposed therapeutics targeting DAMP pathways to treat SARS-CoV-2 infection and the regulation of these signaling cascades in COVID-19. We also discuss the potential impact of DAMP-mediated inflammation in other indications related to COVID-19, such as ARDS, endothelial dysfunction, hypercoagulation, and sepsis."

Journal • Review • Acute Respiratory Distress Syndrome • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • Septic Shock • CD24 • CD52

CATHY: CD24Fc for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005) (clinicaltrials.gov) - P3; N=11; Terminated; Sponsor: OncoImmune, Inc.; Active, not recruiting ➔ Terminated; Business Reasons

Clinical • Trial termination • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

CATHY: CD24Fc for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005) (clinicaltrials.gov) - P3; N=11; Active, not recruiting; Sponsor: OncoImmune, Inc.; N=180 ➔ 11

Clinical • Enrollment change • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

CD24Fc for the Treatment of Immune Related Adverse Events in Patients With Advanced Solid Tumors, TIRAEC Study (clinicaltrials.gov) - P1/2; N=78; Active, not recruiting; Sponsor: Tianhong Li; Recruiting ➔ Active, not recruiting

Enrollment closed • Immune Modulation • Oncology • Solid Tumor • CD24

CATHY: CD24Fc for the Prevention of Acute Graft Versus Host Disease (GVHD) Following Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-005) (clinicaltrials.gov) - P3; N=11; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.

New P3 trial • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

Phase II Trial of CD24Fc for the Prevention of Acute Graft-Versus-Host Disease (GVHD) Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (MK-7110-002) (clinicaltrials.gov) - P2; N=44; Completed; Sponsor: OncoImmune, Inc.; Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

CD24Fc Administration to Decrease Low-Density Lipoprotein (LDL) and Inflammation in Human Immunodeficiency Virus (HIV) Patients (CALIBER) (MK-7110-003) (clinicaltrials.gov) - P2; N=8; Terminated; Sponsor: OncoImmune, Inc.; N=64 ➔ 8; Trial completion date: Oct 2022 ➔ May 2021; Active, not recruiting ➔ Terminated; Trial primary completion date: Oct 2022 ➔ May 2021; Business Reasons

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Dyslipidemia • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • CD4 • CD8 • LEP

CATHY: CD24Fc for the Prevention of Acute GVHD Following Myeloablative HSCT (clinicaltrials.gov) - P3; N=180; Active, not recruiting; Sponsor: OncoImmune, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Feb 2024 ➔ Nov 2021; Trial primary completion date: Aug 2023 ➔ Nov 2021

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

CD24Fc With Ipilimumab and Nivolumab to Decrease irAE (CINDI) (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: OncoImmune, Inc.; N=48 ➔ 0; Not yet recruiting ➔ Withdrawn

Checkpoint inhibition • Clinical • Enrollment change • Trial withdrawal • Melanoma • Oncology • Solid Tumor

Merck Discontinues Development of SARS-CoV-2/COVID-19 Vaccine Candidates; Continues Development of Two Investigational Therapeutic Candidates (Businesswire) - P1, N=252; NCT04569786; P1/2, N=260; NCT04498247; Sponsor: Merck Sharp & Dohme Corp.; "Merck...announced that the company is discontinuing development of its SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591, and plans to focus...on advancing two therapeutic candidates, MK-4482 and MK-7110. This decision follows Merck’s review of findings from Phase 1 clinical studies for the vaccines. In these studies, both V590 and V591 were generally well tolerated, but the immune responses were inferior...MK-7110 (formerly CD24Fc)...Full results from this study are expected in the first quarter of 2021....Molnupiravir is currently being evaluated in Phase 2/3 clinical trials in both the hospital and out-patient settings....The company anticipates initial efficacy data in the first quarter of 2021, which Merck plans to share publicly if clinically meaningful."

Discontinued • P1 data • P2/3 data • P3 data • Infectious Disease • Novel Coronavirus Disease

Phase II Trial of CD24Fc for the Prevention of Acute GVHD Following Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) (clinicaltrials.gov) - P2; N=44; Active, not recruiting; Sponsor: OncoImmune, Inc.; Completed ➔ Active, not recruiting; Trial completion date: Jan 2021 ➔ May 2021

Enrollment closed • Trial completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Myeloid Leukemia • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HLA-DRB1

CD24Fc Administration to Decrease Low-Density Lipoprotein (LDL) and Inflammation in Human Immunodeficiency Virus (HIV) Patients (CALIBER) (MK-7110-003) (clinicaltrials.gov) - P2; N=64; Active, not recruiting; Sponsor: OncoImmune, Inc.; Trial completion date: Oct 2023 ➔ Oct 2022

Clinical • Trial completion date • Cardiovascular • Dyslipidemia • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Metabolic Disorders • CD4 • CD8 • LEP