KAND567 / Kancera - LARVOL DELTA

Antidepressant-like effects of ketamine involve CX3CL1/CX3CR1 signaling-mediated synaptic plasticity in the mPFC. (PubMed, Transl Psychiatry) - "Ketamine, a non-competitive N-methyl-D-aspartate acid (NMDA) receptor antagonist, produces rapid and sustained antidepressant actions, but the underlying molecular mechanism remains unclear. Furthermore, pretreatment with AZD8797 (0.8 mg/kg, i.p., twice a week) completely blocked ketamine's antidepressant-like behavioral effects and eliminated ketamine-induced enhancement in the synaptic plasticity; intra-mPFC microinjection with AAV-CX3CR1-siRNA also prevented ketamine's behavioral effects and beneficial effects on the synaptic plasticity. These findings demonstrated that CX3CL1/CX3CR1 signaling-mediated synaptic plasticity played essential roles in ketamine's antidepressant-like effects, which opened a new door to targeting chemokines to improve depression symptoms."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry • CX3CL1 • CX3CR1

Tuina therapy alleviates neuropathic pain by modulating the CX3CL1/CX3CR1 axis to inhibit degradation of the perineuronal nets. (PubMed, Front Mol Neurosci) - "To explore Tuina's mechanism, rats were divided into Sham, Model, Tuina, CX3CR1 inhibitor (AZD8797), and Tuina + AZD8797 groups...Tuina produces robust central analgesia by suppressing the CX3CL1/CX3CR1-PI3K/AKT signaling pathway. This suppression restores microglial phagocytic homeostasis and crucially protects the glycosaminoglycan lattice of PNNs against excessive degradation, thereby alleviating neuropathic central sensitization."

Journal • Neuralgia • Pain • ACAN • CX3CL1 • CX3CR1 • FOS • LAMP1 • TREM2

Microglial CX3CR1 signaling mediates stress-induced pain behavior in mice. (PubMed, Front Immunol) - "Pharmacological validation was performed using the CX3CR1 antagonist, AZD8797 in WT mice...These findings demonstrate that microglial CX3CR1 signaling contributes to chronic stress-induced pain through neuroinflammatory mechanisms and central pain sensitization. Targeting CX3CR1 may represent a promising therapeutic strategy for chronic primary pain conditions such as fibromyalgia."

Journal • Preclinical • Fibromyalgia • Inflammation • Musculoskeletal Pain • Pain • Rheumatology • CX3CL1 • CX3CR1 • GFAP

Adolescent stress and alcohol are associated with CX3CR1-linked endocrine-cardiac signatures and anxiety-like behavior in mice. (PubMed, Front Pharmacol) - "WT mice received the CX3CR1 antagonist AZD8797 (20 mg/kg, i.p.) for behavioral validation...These findings suggest that CX3CR1 signaling contributes to the long-term coordination of behavioral stress-related responses, HPA-axis activity, circulating cardiac injury biomarkers, and cardiac inflammatory/RAAS-related transcriptional programs after adolescent stress and alcohol exposure. Because cardiac function and histopathology were not assessed, these results should be interpreted as evidence of cardiac biomarker and molecular vulnerability rather than definitive myocardial pathology."

Journal • Preclinical • Endocrine Cancer • Inflammation • Psychiatry • ACKR3 • CCL2 • CX3CL1 • CX3CR1 • CXCL12 • NFKBIA

Central fractalkine-CX3CR1 signaling mediates systemic LPS-induced inhibition of LH pulses in female rats. (PubMed, Endocrinology) - "Central administration of AZD8797, an CX3CR1 antagonist significantly restored LPS-induced decreases in the mean LH concentrations and the amplitude and baseline of LH pulses. LM and PVN fractalkine neurons might suppress ARC kisspeptin neurons-the center for gonadotropin-releasing hormone/LH pulse generation-via neighboring CX3CR1-expressing microglial cells. These findings may contribute to the development of therapeutic strategies to mitigate inflammation-associated reproductive dysfunction in both livestock and humans."

Journal • Preclinical • Inflammation • CX3CL1 • CX3CR1

CX3CR1+ synovial macrophages accumulate in the joint during experimental hemophilic arthropathy but are not required for acute synovitis. (PubMed, J Thromb Haemost) - "Despite marked CX3CR1+ macrophage recruitment during experimental HA, the CX3CL1-CX3CR1 axis is dispensable for the pathogenesis of acute hemophilic synovitis in this mouse model of severe hemophilia A."

Journal • Hematological Disorders • Hemophilia • Hemophilia A • Immunology • Inflammation • Osteoarthritis • Pain • Rare Diseases • Rheumatoid Arthritis • Rheumatology • CX3CL1 • CX3CR1

Bisphenol A potentiates ischemia-reperfusion-induced endothelial and blood-brain barrier dysfunction associated with CX3CL1-CX3CR1 signaling. (PubMed, Ecotoxicol Environ Saf) - "Pharmacological inhibition of CX3CR1 using AZD8797 (0.5 μM) partially attenuated BPA-exacerbated apoptosis, tight junction loss, and barrier hyperpermeability without significantly altering CX3CL1 expression. Collectively, these findings suggest that BPA potentiates ischemia-reperfusion-associated endothelial and barrier dysfunction, accompanied by changes in CX3CL1-CX3CR1-related signaling, and support a potential role for environmental toxicants as modifiers of ischemic neurovascular vulnerability."

IO biomarker • Journal • Cardiovascular • Ischemic stroke • Reperfusion Injury • BCL2 • CLDN5 • CX3CL1 • CX3CR1 • TJP1

Abnormal FKN-CX3CR1-NR signal triggers hippocampal synaptic dysfunction in rheumatoid arthritis-related depression. (PubMed, Int Immunopharmacol) - "In contrast, both CX3CR1 receptor blocker (AZD8797) and NR receptor blocker (MK-801) ameliorated the FKN-CX3CR1-NR signal-driven microglia activation, hippocampal synaptic dysfunction and depressive-like behaviors in RAD rats. Collectively, these findings unveiled that the microglia activation-driven hippocampal synaptic dysfunction, triggered by abnormal FKN-CX3CR1-NR signal pathway, is responsible for depressive-like behaviors in RAD rats. The current results provide promising molecular targets and strategy for the treatment of RAD."

Journal • CNS Disorders • Depression • Immunology • Inflammatory Arthritis • Major Depressive Disorder • Mood Disorders • Psychiatry • Rheumatoid Arthritis • Rheumatology • CX3CL1 • CX3CR1

Safety, tolerability, and preliminary anti-tumor activity of the CX3CR1 antagonist KAND567 in combination with carboplatin in recurrent epithelial ovarian cancer: results from the phase 1b/2a KANDOVA trial (ESGO 2026) - P1/2 | "At week 18, ORR was 20% and DCR 53%. Higher ORR were seen in tumours with high or intermediate CX3CR1 mRNA levels (ORR 50% and 25%, respectively) compared to low mRNA (ORR 0%).Conclusion KAND567 in combination with carboplatin demonstrated a favourable safety profile and signs of on-target activity, supporting further clinical development in recurrent ovarian cancer."

Clinical • Combination therapy • P1/2 data • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • CX3CR1

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