AZD0233 / AstraZeneca - LARVOL DELTA

AZD0233: a CX3CR1 Modulator that Regulates Immune Cells, Improves Cardiac Function, and Alleviates Myocardial Fibrosis in a Mouse Model of Dilated Cardiomyopathy (AHA 2025) - "After 4 weeks of AZD0233 treatment, a significant reduction in CD11b+ Ly6Chi inflammatory monocytes was observed in the myocardial tissue by flow cytometry (0.90±0.10% at 100 mg/kg vs 1.31±0.19% in vehicle, p<0.05, n=9). Echocardiography indicated a dose-dependent improvement of systolic function as measured by an increase in left ventricular ejection fraction (percentage units 7.1 ± 1.5 higher at 100 mg/kg than vehicle treated p<0.001, n=11). After 8 weeks of treatment, histological analyses of myocardial sections showed a dose-dependent relative reduction in CX3CR1+ leukocytes by immunohistochemistry staining (48.6±21.3% at 100 mg/kg p<0.05 vs vehicle, n=11) and a decrease in myocardial fibrosis by Picrosirius Red staining (3.6±1.7% at 100 mg/kg vs 6.1±2.6% vehicle, p<0.01, n=11)."

Immune cell • Preclinical • Cardiomyopathy • Cardiovascular • Fibrosis • Immunology • Inflammation • CX3CL1 • CX3CR1 • ITGAM • PTPRC

A Study to Investigate Safety, Tolerability, and Pharmacokinetics of Oral AZD0233 Compared With Placebo in Healthy Adult Participants. (clinicaltrials.gov) - P1 | N=88 | Suspended | Sponsor: AstraZeneca | Recruiting ➔ Suspended

Trial suspension • Cardiomyopathy • Cardiovascular

AZD0233: An oral CX3CR1 antagonist in development for the treatment of cardiovascular disease (ACS-Fall 2025) - "Cardiac CX3CR1/CX3CL1 expression is elevated in humans with heart failure and a CX3CR1 antagonist has the potential to improve cardiac function in heart failure patients via immunomodulation of the CX3CR1/CX3CL1 axis.AZD0233 belongs to a new small molecule CX3CR1 antagonist series that have improved physicochemical properties, metabolic stability, secondary pharmacology, toxicity profile and lower CYP inhibition compared to previous CX3CR1 small molecule antagonists explored.When tested in a mouse model of dilated cardiomyopathy, AZD0233 demonstrated improved cardiac function, reduced macrophages and fibrotic scar. The compound has been well tolerated in animal studies and is currently in SAD/MAD Phase I clinical studies.The hit to lead identification and the optimisation of lead to clinical candidate will be presented as well as preclinical data and our current understanding of mode of action for AZD0233."

Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • CX3CL1 • CX3CR1