JNJ-61803534 / J&J, Phenex Pharma - LARVOL DELTA

Identification of JNJ-61803534, a RORγt Inverse Agonist for the Treatment of Psoriasis. (PubMed, J Med Chem) - "Herein, we describe the discovery and development of potent and selective thiazole bisamide RORγt inverse agonists that avoid autoinduction in the rat. This effort culminated in the discovery of JNJ-61803534, which advanced into phase 1 clinical trials."

Journal • Dermatology • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • IL17A • IL23A

Carbon-14 Labeling Synthesis of RORγt Inhibitor JNJ-61803534. (PubMed, J Labelled Comp Radiopharm) - "The synthesis featured a highly efficient conversion of nitrile [14C]-12 to ester [14C]-17 under mild conditions via an imidate intermediate, overcoming the unsuccessful direct hydrolysis of nitrile 12 under either acidic or basic conditions. Since carbon-14 labeling via [14C]-nitrile installation and subsequent conversion to [14C]-carboxylic acid derivatives is a common labeling strategy, an efficient conversion of a nitrile to an ester under mild conditions could be of use for the future C14 labeling syntheses."

Journal

Preclinical and clinical characterization of the RORγt inhibitor JNJ-61803534. (PubMed, Sci Rep) - "JNJ-61803534 significantly inhibited disease score in the imiquimod-induced mouse skin inflammation model, and dose-dependently inhibited the expression of RORγt-regulated genes, including IL-17A, IL-17F, IL-22 and IL-23R. The compound was well tolerated in single ascending doses (SAD) up to 200 mg, and exhibited dose-dependent increases in exposure upon oral dosing, with a plasma half-life of 164 to 170 h. In addition, dose-dependent inhibition of ex vivo stimulated IL-17A production in whole blood was observed, demonstrating in vivo target engagement. In conclusion, JNJ-61803534 is a potent and selective RORγt inhibitor that exhibited acceptable preclinical safety and efficacy, as well as an acceptable safety profile in a healthy volunteer SAD study, with clear evidence of a pharmacodynamic effect in humans."

Journal • Preclinical • Dermatitis • Dermatology • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis • Rheumatology • Seronegative Spondyloarthropathies • CD4 • IFNG • IL17A • IL22

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-61803534 and to Evaluate the Effect of JNJ-61803534 on the Pharmacokinetics of Midazolam in Healthy Participants (clinicaltrials.gov) - P1; N=124; Recruiting; Sponsor: Janssen Research & Development, LLC; Trial primary completion date: Dec 2017 ➔ Sep 2018

Trial primary completion date • Biosimilar