KAND567 / Kancera - LARVOL DELTA

Cx3cr1 signaling mediates the suppression of luteinizing hormone secretion induced by lipopolysaccharides (Neuroscience 2025) - "A CX3CR1 antagonist (AZD8797) or 50% dimethyl sulfoxide (50% DMSO, as a vehicle) was administered into the third ventricle (3V) of the OVX + low E2 rats, followed by intravenous (iv) administration of LPS or saline...Double in situ hybridization for the kisspeptin gene (Kiss1) and CX3CR1 gene (Cx3cr1) revealed that both Cx3cr1-expressing cells and Kiss1-expressing cells were present in the ARC of OVX + low E2 rats, while only a small subset of Kiss1-expressing cells co-expressed Cx3cr1. These findings suggest that the iv LPS-induced suppression of LH pulses is, at least in part, mediated by CX3CR1 signaling through an indirect effect on ARC kisspeptin neurons."

CNS Disorders • CX3CR1

A CX3CR1 (fractalkine receptor) Small Molecular Antagonist (KAND567) Suppressed the Growth Promoting Effect of Monocytes on Chronic Lymphocytic Leukemia Cells (ASH 2023) - "The CX3CR1/CX3CL1 (fractalkine receptor/ligand)) axis appears to be activated in CLLand might be of importance for the NLC-driven growth of CLL cells. This is the first report of a small molecule antagonist of CX3CR1 reducing the growth supportive effect of autologous CLL monocytes on leukemic CLL cells. Disruption of growth promotion induced by monocytes may prevent leukemic cell proliferation and survival."

Cardiovascular • Chronic Lymphocytic Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Myocardial Infarction • Novel Coronavirus Disease • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • CD14 • CX3CL1 • CX3CR1

CX3CL1/CX3CR1 involved modulation of microglial activation and eosinophilic meningoencephalitis in angiostrongyliasis. (PubMed, Food Waterborne Parasitol) - "Pharmacological inhibition of CX3CR1 using AZD8797 mitigated these effects by downregulating CX3CL1/CX3CR1 signaling and attenuating neuronal degeneration...These findings establish the CX3CL1/CX3CR1 axis as a crucial regulator of microglial activation and neuroinflammation in A. cantonensis infection. Targeting this pathway can offer a viable therapeutic strategy to mitigate inflammation of the CNS and prevent neurodegenerative consequences."

Journal • CNS Disorders • Infectious Disease • Inflammation • CX3CL1 • CX3CR1

Role of the CX3CL1/CX3CR1 axis in iron metabolism and immune regulation during acute Trypanosoma cruzi infection. (PubMed, Front Immunol) - "This study evaluated the effects of blocking CX3CR1 with the allosteric antagonist AZD8797 in a murine model of acute T. cruzi infection...Liver tissue showed reduced IL-15, IL-6, and IL-1β levels, alongside lowered plasma hepcidin and ferritin concentrations. These findings highlight CX3CL1's site-specific role in modulating inflammation and iron metabolism during acute T. cruzi infection, suggesting its potential as a therapeutic target for infection management and disease prognosis."

Journal • Heart Failure • Infectious Disease • Inflammation • CCL2 • CX3CL1 • CX3CR1 • IFNG • IL10 • IL15 • IL17A • IL1B • IL4 • IL6

Early blood-derived predictors of final infarct size in patients with anterior STEMI and primary PCI (ESC-WCC 2025) - "FRACTAL was a two-armed, double-blinded and placebo-controlled study of KAND567, a CX3CR1 receptor-blocking drug candidate... Cardiac specific troponin is the most sensitive biomarker used to exclude myocardial damage in patients with acute chest pain, and is also often used to estimate IS in patients post STEMI. However, our study results suggest that there are better parameters to estimate final IS, most importantly LDH at 24h. Whilst LDH has an inferior specificity to TnT, its 5-times longer half-life may explain its superiority when predicting IS."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • CX3CL1 • CX3CR1 • IL6

Inhibition of fractalkine signalling reduces intramyocardial haemorrhage and left ventricular thrombus in patients with acute myocardial infarction by modulating immunothrombosis (The FRACTAL trial) (ESC-WCC 2025) - "Its main goals were to evaluate KAND567's safety and tolerability when administered orally and iv, as well as to reduce the symptoms of reperfusion injury in STEMI patients receiving PPCI...Our data show the potential of fractalkine signalling inhibition in acute MI, reducing reperfusion injury as well as thrombotic complications, that are both linked to a potential novel mechanism of immunothrombosis. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase IIb/III study."

Clinical • Cardiovascular • Myocardial Infarction • Reperfusion Injury • Thrombosis • CX3CL1 • CX3CR1 • PPBP

KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination With Carboplatin Therapy, in Women With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=18 | Completed | Sponsor: Kancera AB | Active, not recruiting ➔ Completed

Platinum resistant • Trial completion • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • HRD

Kancera reports positive top-line results from the KANDOVA study (TradingView) - P1b/2a | N=18 | KANDOVA (NCT06087289) | Sponsor: Kancera AB | "Kancera AB (publ) (Kancera) today reports the top-line results from the KANDOVA study, a one-arm, open-label, multi-centre combined phase Ib/IIa study of KAND567 in combination with carboplatin in ovarian cancer...Disease progression, assessed according to RECIST 1.1 and GCIG, showed that the share of patients with partial response or stable disease was 73% at week 12 and 53% at week 18 (N=15). Exploratory analyses of tumor biopsies (N=15) showed that high levels of the fractalkine receptor CX3CR1 in the cancer cells* before the start of treatment resulted in partial response or stable disease in 75% of the evaluable study subjects according to RECIST 1.1 and GCIG, while low levels of CX3CR1 in the cancer cells resulted in 43% of the study subjects with stable disease (no partial response)."

P1/2 data • Platinum resistant • Fallopian Tube Cancer • Ovarian Cancer • Peritoneal Cancer

TREK- 1 Ameliorates Secondary Brain Injury by Regulating Inflammatory Microenvironment via CX3 CL1-CX3 CR1 Pathway After Intracerebral Hemorrhage. (PubMed, Mol Neurobiol) - "These effects may be mediated through the CX3CL1-CX3CR1 pathway, as validated by specific inhibitors AZD8797. This study identified TREK-1 as a crucial modulator in alleviating SBI by regulating the inflammatory microenvironment via the CX3CL1-CX3CR1 pathway."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • CX3CL1 • CX3CR1

Kancera reports Last Patient Last Visit in the KANDOVA study (Kancera Press Release) - "Kancera reports that the last patient has completed the last visit in the ongoing KANDOVA study. KANDOVA is a combined phase Ib/IIa study of the company’s candidate drug KAND567 in ovarian cancer. In total, 18 patients were recruited to the study and the top-line results are expected to be presented in the third quarter 2025."

P1/2 data • Trial status • Ovarian Cancer

Upregulation of Cathepsin S Expression Contributes to Neuronal Damage Following Kainic Acid-Induced Status Epilepticus. (PubMed, J Neurochem) - "An increase in chemokine CX3C motif ligand 1 (CX3CL1) immunoreactivity on microglia was observed following KA-induced SE, and CX3C motif chemokine receptor 1 (CX3CR1) antagonist AZD8797 treatment significantly attenuated SE-induced microglia activation and neuronal damage. Altogether, these results indicate a crucial role of Ctss in SE-induced neuronal damage, possibly through CXC3L1-mediated microglial activation, and provide a new perspective for preventing SE-induced neuronal damage."

Journal • CNS Disorders • Epilepsy • Vascular Neurology • CTSS • CX3CL1 • CX3CR1 • CXCL1 • CXCR1

KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination with Carboplatin Therapy, in Women with Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=18 | Active, not recruiting | Sponsor: Kancera AB | Recruiting ➔ Active, not recruiting | Phase classification: P2 ➔ P1/2 | N=30 ➔ 18 | Trial completion date: Jun 2024 ➔ Mar 2025 | Trial primary completion date: Jun 2024 ➔ Mar 2025

Combination therapy • Enrollment change • Enrollment closed • Phase classification • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • HRD

T follicular helper cell is essential for M2 macrophage polarization and pulmonary vascular remodeling in hypoxia-induced pulmonary hypertension. (PubMed, Respir Res) - "TFH/IL-21 axis amplified pulmonary vascular remodelling in HPH. This involved M2 macrophage polarization, PASMCs proliferation and pyroptosis. These data suggested that TFH/IL-21 axis may be a novel therapeutic target for the treatment of HPH."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • BCL6 • CX3CR1 • IL2 • IL21 • MMP9 • STAT5 • STAT5AWqe

Dual Targeting of CX3CR1 and PARP in Models of High-Grade Serous Ovarian Carcinoma. (PubMed, Cancers (Basel)) - "While the exact mechanisms determining the nature of the PARPis and AZD8797 interaction remain to be uncovered, our data indicate that, in a subset of models, selected PARPis strongly synergize with the inhibition of CX3CR1, suggesting a potential therapeutic opportunity."

Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CX3CL1 • CX3CR1 • PARP1

A Small Molecule Antagonist of CX3CR1 (KAND567) Inhibited the Tumor Growth-Promoting Effect of Monocytes in Chronic Lymphocytic Leukemia (CLL). (PubMed, Cancers (Basel)) - "Our data suggest that the CX3CR1/CX3CL1 axis is activated in CLL and may contribute to the NLC-driven growth-promoting effects of CLL cells. KAND567, which is in clinical trials in other disorders, should also be explored in CLL."

Journal • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CX3CL1 • CX3CR1

Periadventitial Delivery of Nanoparticle-Encapsulated AZD8797 Reduces Venous Stenosis in a Murine Arteriovenous Fistula Model (KIDNEY WEEK 2024) - "Peri-adventitial delivery of AZD8797 NPs significantly reduces VNH/VS with improved vascular remodeling. This approach shows promise as a therapeutic strategy to enhance AVF patency."

Preclinical • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • CD68 • CX3CL1 • CX3CR1 • CXCR1

Fractalkine Inhibition in Acute Myocardial Infarction leads to reduced intramyocardial haemorrhage (ESC 2024) - "This seemed to be related to the smaller distribution IMH+, as the IMH+ infarcts were much larger in both arms, whilst overall infarct size in IMH subgroup were identical. Conclusion KAND567 appears to prevent the transition from IMH- to IMH+, while it doesn’t change infarct size in the respective subgroups of IMH+ or IMH-."

Cardiovascular • Myocardial Infarction • CX3CL1 • CX3CR1

Inhibition of fractalkine signalling in patients with acute myocardial infarction - First results from the FRACTAL trial (ESC 2024) - "Our pre-clinical studies also found an improvement in infarct size, inflammation and intramyocardial haemorrhage (IMH) when rats were pre-treated with the fractalkine inhibitor KAND567...Conclusion This first in-man study demonstrates that inhibition of the fractalkine pathway in STEMI patients appears safe and well-tolerated, while demonstrating a promising potential in preventing LV thrombus and IMH. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase III study."

Clinical • Cardiovascular • Myocardial Infarction • Reperfusion Injury • Thrombosis • CX3CL1 • CX3CR1

A CX3CR1 (FRACTALKINE RECEPTOR) SMALL MOLECULE ANTAGONIST (KAND567) SUPPRESSED THE GROWTH-PROMOTING EFFECT OF NURSE-LIKE CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) (EHA 2024) - "Our data indicate that the CX3CR1/CX3CL1 axis is activated in CLL, which might be of importance for NLC-driven growth and survival of CLL cells. The CX3CR1 antagonist KAND567 inhibited NLC and NLC-mediatedgrowth-supportive effects on CLL cells in various read-out systems. The effect was specific for CLL monocytescompared to healthy monocytes."

Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Ovarian Cancer • Solid Tumor • ANXA5 • CASP3 • CASP7 • CD14 • CX3CL1 • CX3CR1

Chemokine Fractalkine and Non-Obstructive Coronary Artery Disease-Is There a Link? (PubMed, Int J Mol Sci) - "Moreover, promising preliminary results have shown that FKN/CX3CL1 receptor inhibitor (KAND567) administered in the population of patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), inhibits the adverse reaction of the immune system that causes hyperinflammation. Whereas the link between FKN/CX3CL1 and NO-CAD appears evident, further studies are necessary to unveil this complex relationship. In this review, we critically overview the current data on FKN/CX3CL1 in the context of NO-CAD and present the novel clinical implications of the unique structure and function of FKN/CX3CL1 as a compound which distinctively contributes to the pathomechanism of this condition."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Inflammation • Myocardial Infarction • CX3CL1

CX3CR1 deficiency promotes resolution of hepatic ischemia-reperfusion injury by regulating homeostatic function of liver infiltrating macrophages. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "Kupffer cells(KCs) were depleted by clodronate liposome(CL) in advance to focus on infiltrating macrophages, and repopulation kinetics were determined by FACS, IF and RNA-Seq. CX3CR1 antagonist AZD8797 was injected i.p. to interrogate potential pharmacological therapeutic strategies...We observed that deficiency or pharmacological inhibition of CX3CR1 facilitated HIRI resolution via promoted macrophages migration in CCR1/CCR5 manner, as well as enhanced MerTK-mediated efferocytosis. Our study demonstrated the critical roles of CX3CR1 in progression of HIRI and identified it as a potential therapeutic target in clinical liver transplantation."

Journal • Cardiovascular • Hepatology • Liver Failure • Reperfusion Injury • Transplantation • CX3CR1 • MERTK

CX3CL1/CX3CR1 Signaling Mediated Neuroglia Activation Is Implicated in the Retinal Degeneration: A Potential Therapeutic Target to Prevent Photoreceptor Death. (PubMed, Invest Ophthalmol Vis Sci) - "AZD8797, a CX3CR1 antagonist, was injected into the vitreous cavity of an RD model to modulate the neuroglia activation...Targeting the CX3CL1/CX3CR1 signaling may serve as an effective therapeutic strategy. Future refinements of these findings may cast light into the discovery of new medications for RD."

Journal • CNS Disorders • Inflammation • Ophthalmology • CX3CL1 • CX3CR1

CX3CR1 mediates Motor Dysfunction in Mice through 5-HTR2a. (PubMed, Behav Brain Res) - "While inhibiting the function of CX3CR1 by AZD8797 could decrease the expression of 5-Hydroxytryptamine receptor(5-HTR2a), which involved in the regulation of motor function...For the first time, we reported that neuronal CXCR1 mediates motor dysfunction. Our results suggest that modulating CXCR1 activity offers a novel therapeutic strategy for motor dysfunction."

Journal • Preclinical • CNS Disorders • CX3CR1 • CXCR1 • HTR2A

SARS-CoV-2 Causes Brain Damage: Therapeutic Intervention with AZD8797. (PubMed, Microsc Microanal) - "Histopathological analyses supported the protective effects of AZD8797 against SARS-CoV-2-induced damage. The CX3CL1-CX3CR1 signaling pathway could offer a promising target for reducing SARS-CoV-2's neurological impact, but additional research is needed to confirm these findings in combination with other therapies and assess the clinical significance."

Journal • CNS Disorders • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Vascular Neurology • CX3CL1 • CX3CR1 • MPO

KANDOVA: A Study to Evaluate the Safety of KAND567, in Combination With Carboplatin Therapy, in Women With Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Kancera AB

Combination therapy • New P2 trial • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • HRD