ladarixin (DF-2156A) / Dompe - LARVOL DELTA

Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005). (PubMed, Diabetes Metab J) - No abstract available

Journal • Preclinical • Diabetes • Metabolic Disorders • Pain • Retinal Disorders • Type 1 Diabetes Mellitus • CXCR1

Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat (Diabetes Metab J 2025;49:990-1005). (PubMed, Diabetes Metab J) - No abstract available

Journal • Preclinical • Diabetes • Metabolic Disorders • Pain • Retinal Disorders • Type 1 Diabetes Mellitus • CXCR1

Ladarixin Potential over the Effects of IL-8 and of Serum from Patients with Abdominal Aortic Aneurysm on Human Aortic Cells. (PubMed, Cells) - "AAA-like vascular cell alterations involve multiple inflammatory factors and are modulable by inhibition of IL-8 receptors. The results underline careful dose calibration."

Journal • Cardiovascular • Inflammation • CXCL1 • CXCL8 • CXCR1 • CXCR2 • MMP9

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: Dompé Farmaceutici S.p.A | Trial primary completion date: Apr 2024 ➔ Mar 2025

Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

The dual non-competitive CXCR1/2 inhibitor ladarixin impairs neutrophil extravasation without altering intravascular adhesion. (PubMed, Haematologica) - "Taken together, the allosteric CXCR1/2 inhibitor ladarixin effectively blocks neutrophil recruitment on the level of neutrophil extravasation without affecting firm adhesion. Clinically, this mode of action has interesting therapeutic potential to prevent neutrophil extravasation in inflammatory diseases including inflammatory bowel disease, psoriasis and other neutrophil driven disorders."

Journal • Cardiovascular • Dermatology • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Oncology • Psoriasis • Reperfusion Injury • CXCR1 • CXCR2 • ELANE

The CXCL1-CXCR2 Axis as a Component of Therapy Resistance, a Source of Side Effects in Cancer Treatment, and a Therapeutic Target. (PubMed, Cancers (Basel)) - "It discusses anti-CXCL1 antibodies and CXCR2 antagonists, including AZD5069, SB225002, SCH-479833, navarixin/SCH-527123, ladarixin/DF2156A, and reparixin, as well as strategies to enhance CXCR2 expression in lymphocytes during adoptive cell therapy to improve immunotherapy outcomes. CXCR2 inhibitors are well tolerated by patients in clinical trials. However, the limited number of studies evaluating these agents in combination with standard chemotherapy precludes any definitive conclusions."

Adverse events • IO biomarker • Journal • Review • Cardiovascular • Oncology • Pain • CXCL1 • CXCL8 • CXCR2

Vibrational circular dichroism of plasmonic nanostructures embedding chiral drugs. (PubMed, Sci Rep) - "We investigate the mid-infrared chiroptical response of plasmonic nanostructures based on Al-doped ZnO and layers of an aqueous solution of Ladarixin, a chiral pharmaceutical currently under clinical trial for the treatment of type 1 diabetes...Focusing on diverse plasmonic nanoshell geometries, we find that LSPRs provide an amplification factor of VCD differential absorption cross-section ranging from [Formula: see text] to [Formula: see text] thanks to near-field intensity enhancement produced by LSPRs. Our results indicate that nanoshell LSPRs are promising for probing molecular chirality at the nanoscale."

Journal • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Immunotherapy as a treatment for type 1 diabetes mellitus in children and young adults: A comprehensive systematic review and meta-analysis. (PubMed, PLoS One) - "This meta-analysis aimed to assess the effectiveness of immunotherapy in treating T1DM by examining its effects on the patients' required dose of insulin, C-peptide, and HbA1c levels. While some studies failed to show desired results, the overall effect was an increase in C-peptide levels and a decrease in HbA1c levels. However, the study did not achieve statistical significance for insulin dosing. The main study's strength is its focus on randomized clinical trials which is considered among the highest levels of epidemiological evidence. Therefore, further research is required to minimize the gaps and to explore immunotherapy-based drugs as potential treatments for T1DM."

Clinical • Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Effects of CXCR1/2 Blockade with Ladarixin on Streptozotocin-Induced Type 1 Diabetes Mellitus and Peripheral Neuropathy and Retinopathy in Rat. (PubMed, Diabetes Metab J) - "Strikingly, even in the absence of an effect on glycemic control, late LDX mitigated STZ-induced mechanical allodynia and thermal hyperalgesia and vitreous (CXCL8, CitH3) and retinal (CXCL8, CXCR1/2, myeloperoxidase, CitH3) inflammatory/pro-angiogenic (vascular endothelial growth factor, CD34) signs of DR. These data confirm the efficacy of LDX in STZ-induced T1DM and provide evidence of a protective effect also against DPN and onset of DR which is independent of its effect on β-cell functionality preservation and glycemic control."

Journal • Preclinical • Diabetes • Diabetic Neuropathy • Diabetic Retinopathy • Metabolic Disorders • Oncology • Pain • Peripheral Neuropathic Pain • Retinal Disorders • Type 1 Diabetes Mellitus • CD34 • CXCL8 • CXCR1 • IL1B • MPO • TNFA

Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. (PubMed, J Diabetes Res) - P, P1/2, P2, P2/3, P3, P4 | "FDA-approved teplizumab for Stage 2 T1D is discussed along with other immunomodulators that have been tested in Phase 3 clinical trials or higher, including otelixizumab (another anti-CD3 monoclonal antibody), daclizumab (an anti-CD25 monoclonal antibody), ladarixin (CXCR1/2 inhibitor), and antithymocyte globulin (ATG)...Several immunomodulators involved in Phase 3 clinical studies of islet transplantation are also discussed, including alemtuzumab, basiliximab, etanercept, and reparixin, some already FDA-approved for other uses...This review provides background, mechanism of action, results of completed trials, and adverse effects as well as details regarding ongoing clinical trials for each of these immunomodulators. Trial Registration: ClinicalTrials.gov identifier: NCT03875729, NCT01030861, NCT00129259, NCT00385697, NCT01280682; NCT03929601, NCT04598893, NCT05757713, NCT00678886, NCT01123083, NCT00064714, NCT00468117, NCT04628481,..."

Journal • Review • Diabetes • Immunology • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus • CXCR1

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: Dompé Farmaceutici S.p.A | Phase classification: P3 ➔ P2 | N=327 ➔ 140 | Trial primary completion date: Mar 2025 ➔ Apr 2024

Enrollment change • Phase classification • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Modulation of MMP9 and CXCR2/CXCL1/IL-8 axis in human abdominal aortic aneurysm tissues by ladarixin. (PubMed, Cardiovasc Res) - No abstract available

Journal • Cardiovascular • CXCL1 • CXCL8 • CXCR2 • MMP9

Tumor-secreted extracellular vesicles counteract therapy response by triggering inflammatory mesenchymal stem cell development. (PubMed, Clin Cancer Res) - "Our observations establish iMSCs as major contributors to drug resistance, reveal EVs as physiological triggers of iMSC development and highlight a promising combination strategy to improve therapy response in bone cancer patients."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • IL6 • TLR3

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function (clinicaltrials.gov) - P3 | N=327 | Active, not recruiting | Sponsor: Dompé Farmaceutici S.p.A | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Ladarixin With Sotorasib in Advanced NSCLC (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: NYU Langone Health | Phase classification: P1/2 ➔ P1

Metastases • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • RET • ROS1

A Study to Assess Efficacy/Safety of Ladarixin in Type 1 Diabetes Patients With Preserved ß-cell Function at Baseline. (clinicaltrials.gov) - P2 | N=25 | Terminated | Sponsor: Dompé Farmaceutici S.p.A | Trial completion date: Apr 2024 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2023 ➔ Apr 2023; low recruitment rate

Trial completion date • Trial primary completion date • Trial termination • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

CONSERVA: Clinical Trial on Ladarixin Adjunctive Therapy to Improve Glycemic Control in Type 1 Diabetes. (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: Dompé Farmaceutici S.p.A | N=86 ➔ 2 | Recruiting ➔ Terminated; low recruitment rate

Enrollment change • Trial termination • Diabetes • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function (clinicaltrials.gov) - P3 | N=327 | Recruiting | Sponsor: Dompé Farmaceutici S.p.A | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Study to Assess Efficacy/Safety of Ladarixin in Type 1 Diabetes Patients With Preserved ß-cell Function at Baseline. (clinicaltrials.gov) - P2 | N=25 | Active, not recruiting | Sponsor: Dompé Farmaceutici S.p.A | Trial completion date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: Jun 2023 ➔ Oct 2023

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Ladarixin With Sotorasib in Advanced NSCLC - Phase II (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: NYU Langone Health | N=28 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Metastases • Trial withdrawal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • RET • ROS1

Ladarixin With Sotorasib in Advanced NSCLC (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: NYU Langone Health | Not yet recruiting ➔ Recruiting | Phase classification: P1 ➔ P1/2

Enrollment open • Metastases • Phase classification • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • RET • ROS1

The therapeutic potential of an allosteric non-competitive CXCR1/2 antagonist for diabetic nephropathy. (PubMed, Diabetes Metab Res Rev) - "Treatment with Ladarixin during RSC differentiation prevented high glucose-mediated effects on podocytes and modulated either podocyte or epithelial cell-dependent leucocyte secretion of pro-inflammatory cytokines, suggesting CXCR1/2 antagonists as possible pharmacological approaches for the treatment of diabetic nephropathy."

Journal • Diabetes • Diabetic Nephropathy • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • Type 1 Diabetes Mellitus • CXCL8 • CXCR1

Post hoc analysis of a randomized, double-blind, prospective trial evaluating a CXCR1/2 inhibitor in new-onset type 1 diabetes: endo-metabolic features at baseline identify a subgroup of responders. (PubMed, Front Endocrinol (Lausanne)) - P2 | "In a recent randomized, multicenter trial (NCT02814838) a short-term anti-inflammatory treatment with ladarixin (LDX; an inhibitor of the CXCR1/2 chemokine receptors) did not show benefit on preserving residual beta cell function in new-onset type 1 diabetes...As we found differences in endo-metabolic and immunologic parameters within this subgroup, this generates the hypothesis that the interactions between host factors and drug action can contribute to its efficacy. Further research is needed to evaluate this hypothesis."

Clinical • Journal • Retrospective data • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus • CCL2 • CXCR1

Ladarixin With Sotorasib in Advanced NSCLC - Phase I (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: NYU Langone Health | N=12 ➔ 40 | Trial completion date: Apr 2025 ➔ Jul 2026 | Initiation date: Apr 2023 ➔ Jul 2023 | Trial primary completion date: Apr 2024 ➔ Jul 2025

Enrollment change • Metastases • Trial completion date • Trial initiation date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • KRAS • RET • ROS1

Single cell RNA sequencing analysis of tumor responses to triple drug oral immunotherapy in dogs with osteosarcoma (P951) (IMMUNOLOGY 2023) - "We investigated the effects of a triple drug immunotherapeutic (orally administered losartan, ladarixin, and toceranib) that was designed to deplete immune suppressive macrophages and promote antitumor immunity. Evaluation of changes to the cellular proportions following treatment revealed a marked reduction in macrophages, which suggests the combination immunotherapy was able to alter the tumor microenvironment. Overall, this study provides unique insights into the heterogeneity within canine osteosarcoma tumors and highlights the impacts of adjuvant immunotherapy on tumor infiltrating immune cell transcriptional programs."

Late-breaking abstract • Oncology • Osteosarcoma • Sarcoma • Solid Tumor