CPL'116 / Celon Pharma - LARVOL DELTA

Dual JAK/ROCK inhibition in Rheumatoid Arthritis – results of a phase 2 study of CPL'116 (EULAR 2025) - "Background: Despite the availability of various treatments, the first line approach for rheumatoid arthritis remains unchallenged for years, and relays on disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX), often accompanied with glucocorticoids...It is worth to notice that blood parameters such as lipid profile, ALT, AST, CK, red blood cell and platelet count, hematocrit, and hemoglobin did not deteriorate significantly under the influence of CPL409116, which represents a superior outcome within the JAK inhibitor group... To the best of our knowledge, we present the first dual JAK/ROCK inhibitor as a possible therapeutic option for patients suffering from RA. In the phase II clinical trial, CPL’116 demonstrated dose-dependent response and was effective in alleviating RA symptoms, reaching the statistical significance at the highest dose (240 mg). Moreover, the studied drug was well tolerated and escaped the burden of the undesired side effects of..."

P2 data • Cardiovascular • Fibrosis • Immunology • Inflammatory Arthritis • Musculoskeletal Pain • Pain • Rheumatoid Arthritis • Rheumatology

Dual JAK and ROCK inhibition with CPL'116 in patients with rheumatoid arthritis with inadequate response to methotrexate: a randomised, double-blind, placebo-controlled, phase 2 trial. (PubMed, Lancet Rheumatol) - P2 | "The findings of this study suggest a dose-dependent response with CPL'116, with significant efficacy at the high dose of 240 mg twice daily. The drug was generally well tolerated and was not associated with lipid abnormalities or creatinine kinase increase. These findings warrant further investigation in larger studies and different clinical settings."

Journal • P2 data • Bladder Cancer • Cardiovascular • Genito-urinary Cancer • Hematological Disorders • Immunology • Inflammatory Arthritis • Leukopenia • Myocardial Infarction • Oncology • Rheumatoid Arthritis • Rheumatology • Solid Tumor • CRP

First-in-human study of CPL'116 - a dual JAK/ROCK inhibitor - in healthy subjects. (PubMed, Front Pharmacol) - P1 | "The positive results of this study indicate the possibility of developing a novel class of therapeutics that address both inflammatory and fibrotic processes. clinicaltrials.gov, identifier NCT04670757."

Journal • P1 data • CNS Disorders • Fibrosis • Hematological Disorders • Inflammation • STAT5

Development of a Formulation and In Vitro Evaluation of a Pulmonary Drug Delivery System for a Novel Janus Kinase (JAK) Inhibitor, CPL409116. (PubMed, Pharmaceutics) - "Moreover, parameters such as the mixing energy, drug load, and force control agent significantly influenced the fine particle fraction (FPF), a critical parameter for pulmonary drug delivery. This study provides insights into optimizing the formulation parameters to enhance the delivery efficiency of CPL409116 to the lungs, offering potential for improved therapeutic outcomes in cytokine-dependent pulmonary diseases."

Journal • Preclinical • Immunology • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

03JAK2021: Efficacy and Safety Study Comparing CPL409116 to Placebo in Participants with Active Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=106 | Completed | Sponsor: Celon Pharma SA | Recruiting ➔ Completed

Combination therapy • Trial completion • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Celon Pharma Announces Results of Phase II clinical trial for CPL’ 116, a JAK/ROCK dual inhibitor in the treatment of Rheumatoid Arthritis (RA) (Yahoo Finance) - P2 | N=100 | NCT05374785 | Sponsor: Celon Pharma SA | "Celon Pharma S.A...today announced the successful completion of a Phase 2 trial a JAK/ROCK dual inhibitor in the treatment of Rheumatoid Arthritis (RA). The primary endpoint results are statistically significant, the primary endpoint is met....Change in the DAS28-CRP score in week 12 compared to baseline was 1.702; 2.032; 2.361 and 1.668 for doses of 60, 120, 240 mg and placebo, respectively. Change in the DAS28-CRP score compared to placebo (LS MD) was 0.145 (p=0.67); 0.564 (p=0.10), and 0.887 (p=0.01) for doses of 60, 120 and 240 mg, respectively. Hence the primary endpoint results are statistically significant, the primary endpoint is met. The response to treatment in the 240 mg dose was fast – a statistically significant benefit over placebo with regard to the DAS28-CRP score was already observed at week 4 of treatment."

P2 data • Immunology • Rheumatoid Arthritis

Celon Pharma Announces Results of Phase II clinical trial for CPL’ 116, a JAK/ROCK dual inhibitor in the treatment of Rheumatoid Arthritis (RA) (GlobeNewswire) - P2 | N=100 | NCT05374785 | Sponsor: Celon Pharma SA | "Celon Pharma...announced the successful completion of a Phase 2 trial a JAK/ROCK dual inhibitor in the treatment of Rheumatoid Arthritis (RA). The primary endpoint results are statistically significant, the primary endpoint is met....CPL’116 improved the patients’ condition measured with DAS28-CRP in a dose-dependent manner. Change in the DAS28-CRP score in week 12 compared to baseline was 1.702; 2.032; 2.361 and 1.668 for doses of 60, 120, 240 mg and placebo, respectively. Change in the DAS28-CRP score compared to placebo (LS MD) was 0.145 (p=0.67); 0.564 (p=0.10), and 0.887 (p=0.01) for doses of 60, 120 and 240 mg, respectively....In the upcoming weeks, the Company will present results of pharmacokinetic and pharmacodynamic analyses for this trial, as well as detailed safety parameter analyses."

P2 data • Trial completion • Rheumatoid Arthritis

Efficacy and Safety Study Comparing CPL409116 to Placebo in Participants With Active Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Celon Pharma SA | Trial completion date: Aug 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2023 ➔ Feb 2024

Combination therapy • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Implementation of QbD Approach to the Development of Chromatographic Methods for the Determination of Complete Impurity Profile of Substance on the Preclinical and Clinical Step of Drug Discovery Studies. (PubMed, Int J Mol Sci) - "The purpose of this work was to demonstrate the use of the AQbD with the DOE approach to the methodical step-by-step development of a UHPLC method for the quantitative determination of the impurity profile of new CPL409116 substance (JAK/ROCK inhibitor) on the preclinical and clinical step of drug discovery studies...The optimized method is specified, linear, precise, and robust. LOQ is on the reporting threshold level of 0.05% and LOD at 0.02% for all impurities."

Journal • Preclinical

Efficacy and Safety Study Comparing CPL409116 to Placebo in Participants With Active Rheumatoid Arthritis (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Celon Pharma SA

Combination therapy • New P2 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Safety and Pharmacokinetics of JAK/ROCK Inhibitor in Healthy Volunteers (clinicaltrials.gov) - P1 | N=65 | Completed | Sponsor: Celon Pharma SA | Recruiting ➔ Completed | Trial primary completion date: May 2021 ➔ Sep 2021

Trial completion • Trial primary completion date

A novel JAK/ROCK inhibitor, CPL409116, demonstrates potent efficacy in the mouse model of systemic lupus erythematosus. (PubMed, J Pharmacol Sci) - "In this paper, we present the results of the development of CPL409116, a dual JAK and ROCK inhibitor. The studies we performed demonstrate that this molecule is an effective JAK and ROCK inhibitor which efficiently blocks disease progression in NZBWF1/J mouse models of systemic lupus erythematous."

Journal • Preclinical • Complement-mediated Rare Disorders • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • JAK3