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

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual ?-cell Function (clinicaltrials.gov) - P2 | N=289 | Terminated | Sponsor: Domp Farmaceutici S.p.A | N=141 ➔ 289

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

CXCL-mediated oxidative DNA damage promotes Th2 cytokine responses. (PubMed, Int J Radiat Biol) - "The role of CXCL-CXCR1/2 signaling was examined using the allosteric CXCR1/2 inhibitor ladarixin...Exposure to 5-OH-Cyt, Fapy-Ade, 8-oxo-Gua, and 5-OH-Ura significantly increased IL-4, IL-5, and IL-13 secretion, while Fapy-Gua did not affect cytokine production. These findings suggest that 5-OH-Cyt acts as a damage-associated molecular pattern that both drives Th2 immune responses and exacerbates lung DNA damage through a CXCL-mediated positive feedback loop, highlighting CXCR1/2 inhibition as a potential therapeutic strategy to mitigate double-strand DNA damage and allergic lung inflammation."

Journal • Inflammation • Pneumonia • CD4 • CXCL1 • CXCR1 • IL13 • IL4 • IL5

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

ATGLDX1-2025: A phase 2b, single-center, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of oral Ladarixin in association with a single low dose of Antithymocyte Globulin in patients with new-onset autoimmune type 1 diabetes. (clinicaltrialsregister.eu) - P1/2 | N=46 | Sponsor: Ospedale San Raffaele S.r.l.

New P1/2 trial • Diabetes • Immunology • Metabolic Disorders • Type 1 Diabetes Mellitus

Identification of key genes in the pathogenesis of hepatic ischemia-reperfusion injury based on bioinformatics and experimental verification. (PubMed, Sci Rep) - "Notably, ladarixin, a non-competitive antagonist of CXCR1/2, exhibited a protective effect against HIRI, suggesting that Cxcl1 may serve as a promising therapeutic target. However, further comprehensive research is necessary to gain deeper insights into the exact mechanisms by which these genes function."

Journal • Cardiovascular • Reperfusion Injury • ADH4 • AKR1C1 • CXCL1 • CXCR1 • MIRLET7B • SOCS1

LDX-HV-101: A single and multiple ascending dose study of topical ladarixin ophthalmic solution in healthy volunteers (clinicaltrialsregister.eu) - P1 | N=16 | Recruiting | Sponsor: Dompe' Farmaceutici S.p.A. | Not yet recruiting ➔ Recruiting

Enrollment open • Ocular Inflammation • Ophthalmology

LDX-HV-101: A single and multiple ascending dose study of topical ladarixin ophthalmic solution in healthy volunteers (clinicaltrialsregister.eu) - P1 | N=16 | Not yet recruiting | Sponsor: Dompe' Farmaceutici S.p.A.

New P1 trial • Ocular Inflammation • Ophthalmology

Ladarixin With Sotorasib in Advanced NSCLC (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: NYU Langone Health | Trial completion date: Aug 2026 ➔ Aug 2027 | Trial primary completion date: Aug 2025 ➔ Aug 2027

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

A Study of Oral Ladarixin in Recent Onset Type 1 Diabetes and a Low Residual β-cell Function (clinicaltrials.gov) - P2 | N=141 | Terminated | Sponsor: Dompé Farmaceutici S.p.A | Trial completion date: Apr 2026 ➔ Oct 2025 | Active, not recruiting ➔ Terminated; The study was stopped due to futility as per protocol

Trial completion date • Trial termination • Diabetes • 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 (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