atibuclimab (IC14) / Implicit Biosci - LARVOL DELTA

CD14 Blockade Modulates Macrophage-Mediated Immunological Injury in a Translational Model of Reperfused ST-Segment Elevation Myocardial Infarction. (PubMed, JACC Basic Transl Sci) - "Multiomic studies suggest CD14 blockade downregulated macrophage-specific proinflammatory and tissue-wide remodeling processes without suppression of monocyte-macrophage infiltration or repair. These findings support a clinically practicable targeted immunomodulatory strategy of CD14 blockade initiated at reperfusion to prevent chronic immunological progression toward ischemic heart failure, and provide new insights into the pleiotropic roles of CD14 in inflammation and myocardial injury."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Immunology • Inflammation • Myocardial Infarction • CD14

CD14-dependent MAP kinase signaling is required for pathogenic neutrophil extracellular trap formation in APS (ACR Convergence 2025) - "Neutrophil CD14 appears to be required for the p38 MAPK-mediated neutrophil activation and NETosis reliably triggered by anti-β2GPI in APS. This work identifies neutrophil surface CD14 and downstream p38 MAPK signaling as novel therapeutic targets with the potential to restrain not only thrombosis, but also the upstream inflammation that underlies APS."

IO biomarker • Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Thrombosis • CD14 • ITGAM • ITGB2 • NDUFA2 • TLR4

IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P1/2 | N=5 | Suspended | Sponsor: Implicit Bioscience | Active, not recruiting ➔ Suspended

Trial suspension • Cardiomyopathy • Cardiovascular

IC14 for Treatment of Acute Decompensated Heart Failure (clinicaltrials.gov) - P1/2 | N=10 | Active, not recruiting | Sponsor: Implicit Bioscience | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure

Anti-CD14 Treatment With IC14 in Hospitalized ARDS Patients (clinicaltrials.gov) - P2 | N=56 | Recruiting | Sponsor: Implicit Bioscience | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Pilot Study of IC14 (Atibuclimab), an Anti-CD14 Monoclonal Antibody, to Treat STEMI (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Implicit Bioscience | Trial completion date: Jun 2026 ➔ Sep 2026 | Trial primary completion date: Dec 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

Dose-Escalation, Safety and Pharmacokinetic Study of IC14 in Motor Neurone Disease (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Implicit Bioscience | Phase classification: P1b ➔ P1

Phase classification • Amyotrophic Lateral Sclerosis • CNS Disorders

Anti-CD14 Treatment With IC14 in Hospitalized ARDS Patients (clinicaltrials.gov) - P2 | N=56 | Not yet recruiting | Sponsor: Implicit Bioscience | Trial completion date: Aug 2026 ➔ Oct 2027 | Trial primary completion date: Jun 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Anti-CD14 treatment in patients with severe COVID-19: Clinical and biological effects in a Phase 2 randomized open-label adaptive platform clinical trial. (PubMed, CHEST Crit Care) - P2 | "Further trials are needed to determine the efficacy of IC14 treatment in acute lung injury and the value of presepsin to identify patients most likely to respond. Clinicaltrials.gov: NCT04488081."

Journal • P2 data • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CD14 • CXCL8

IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P1/2 | N=5 | Active, not recruiting | Sponsor: Implicit Bioscience | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiomyopathy • Cardiovascular

Pilot Study of IC14 (Atibuclimab), an Anti-CD14 Monoclonal Antibody, to Treat STEMI (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Implicit Bioscience | Trial completion date: Oct 2025 ➔ Jun 2026 | Trial primary completion date: Jul 2025 ➔ Dec 2025 | Not yet recruiting ➔ Recruiting

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction • CD14

IC14 (atibuclimab) in Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P1/2 | N=5 | Recruiting | Sponsor: Implicit Bioscience | Trial completion date: Aug 2025 ➔ Dec 2025 | Trial primary completion date: Feb 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Cardiomyopathy • Cardiovascular

Anti-CD14 Treatment with IC14 in Hospitalized ARDS Patients (clinicaltrials.gov) - P2 | N=56 | Not yet recruiting | Sponsor: Implicit Bioscience | Initiation date: Aug 2024 ➔ May 2025 | Trial primary completion date: Feb 2025 ➔ Jun 2026

Trial initiation date • Trial primary completion date • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

IC14 for Treatment of Acute Decompensated Heart Failure (clinicaltrials.gov) - P1/2 | N=10 | Recruiting | Sponsor: Implicit Bioscience | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

Pilot Study of IC14 (Atibuclimab), an Anti-CD14 Monoclonal Antibody, to Treat STEMI (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: Implicit Bioscience

New P1/2 trial • Cardiovascular • Myocardial Infarction • CD14

IC14 for Treatment of Acute Decompensated Heart Failure (clinicaltrials.gov) - P1/2 | N=10 | Not yet recruiting | Sponsor: Implicit Bioscience

New P1/2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

Anti-CD14 Treatment With IC14 in Hospitalized ARDS Patients (clinicaltrials.gov) - P2 | N=56 | Not yet recruiting | Sponsor: Implicit Bioscience

New P2 trial • Acute Lung Injury • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Anti-CD14 Treatment and Mortality in Severe COVID-19: A Secondary Subgroup Analysis by Baseline Plasma Presepsin Levels in the I-SPY COVID Adaptive Platform Trial (ATS 2024) - "Our findings suggest that a baseline marker of CD14-pathway activity, presepsin, might identify severely ill patients with viral pneumonia more likely to respond to therapy blocking CD14-mediated inflammation. Although these analyses were based on small sample size, additional studies should be conducted to further test the hypothesis that presepsin-guided IC14 therapy is beneficial in severe viral pneumonia."

Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CD14

IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P1/2 | N=5 | Recruiting | Sponsor: Implicit Bioscience | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiomyopathy • Cardiovascular

IC14 (Atibuclimab) in Arrhythmogenic Cardiomyopathy (clinicaltrials.gov) - P1/2 | N=5 | Not yet recruiting | Sponsor: Implicit Bioscience

New P1/2 trial • Cardiomyopathy • Cardiovascular

Report of the first seven agents in the I-SPY COVID trial: a phase 2, open label, adaptive platform randomised controlled trial. (PubMed, EClinicalMedicine) - P2 | "Using an adaptive platform design created to rapidly evaluate investigational agents, hospitalised patients with severe COVID-19 requiring ≥6 L/min oxygen were randomised to either a backbone regimen of dexamethasone and remdesivir alone (controls) or backbone plus one open-label investigational agent...The first 7 agents evaluated were cenicriviroc (CCR2/5 antagonist; n = 92), icatibant (bradykinin antagonist; n = 96), apremilast (PDE4 inhibitor; n = 67), celecoxib/famotidine (COX2/histamine blockade; n = 30), IC14 (anti-CD14; n = 67), dornase alfa (inhaled DNase; n = 39) and razuprotafib (Tie2 agonist; n = 22)...Funding for this trial has come from: the COVID R&D Consortium, Allergan, Amgen Inc., Takeda Pharmaceutical Company, Implicit Bioscience, Johnson & Johnson, Pfizer Inc., Roche/Genentech, Apotex Inc., FAST Grant from Emergent Venture George Mason University, The DoD Defense..."

Journal • P2 data • Acute Lung Injury • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CCR2 • CD14

Safety and Activity of Anti-CD14 Antibody IC14 (atibuclimab) in ALS: Experience with Expanded Access Protocol. (PubMed, Muscle Nerve) - "Administration of IC14 in ALS was safe and well-tolerated in this intermediate-size EAP. Measuring RO guided dosing frequency. Additional placebo-controlled trials are required to determine the efficacy of IC14 in ALS."

Journal • Amyotrophic Lateral Sclerosis • CNS Disorders • CD14

Safety and Activity of Anti-CD14 Antibody IC14 (Atibuclimab) in ALS: Experience with an Expanded Access Protocol (ANA 2022) - "IC14 administration to ALS patients was safe and well tolerated in this EAP, with no significant changes in laboratory tests and no drug-related SAEs. Measuring RO Program and Abstracts, American Neurological Association S201 guided dosing frequency. Preliminary data suggest IC14 enhanced T-reg activity."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • CD14

COVID-19 and Anti-CD14 Treatment Trial (clinicaltrials.gov) - P2 | N=40 | Terminated | Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) | N=300 ➔ 40 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2021 ➔ Feb 2022; Stopped to slow rate of enrollment

Enrollment change • Trial primary completion date • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Phase 1b dose-escalation, safety, and pharmacokinetic study of IC14, a monoclonal antibody against CD14, for the treatment of amyotrophic lateral sclerosis. (PubMed, Medicine (Baltimore)) - P1b | "IC14 quickly and durably saturated its target in all patients. This study demonstrated safety and tolerability in patients with amyotrophic lateral sclerosis. Even though only a single cycle of treatment was given, there were promising beneficial trends in the neurofilament light chain, a disease biomarker. The emerging understanding of the role of systemic inflammation in neurodegenerative diseases, and the potential for IC14 to serve as a safe, potent, and broad-spectrum inhibitor of immune dysregulation merits further clinical study."

Clinical • Journal • P1 data • PK/PD data • Amyotrophic Lateral Sclerosis • CNS Disorders • Immunology • Inflammation • CD14 • CSF NfL