Undisclosed TYK2 inhibitor / Atomwise - LARVOL DELTA

A Novel, Oral, Allosteric Inhibitor of Tyrosine Kinase 2 (TYK2) Demonstrates In Vitro Potency, Selectivity, and In Vivo Efficacy in Mouse Models of Psoriasis (ACR Convergence 2024) - "Although there are allosteric TYK2 inhibitors in development, efficacy matching that of the anti-IL-23 biologics has not yet been achieved, and there remains a need for a more efficacious oral agent...An acute model of psoriasis, based on imiquimod (IMQ)-induced skin inflammation, was used to evaluate efficacy of ATMW-DC (Doses 3 and 4) via histological and clinical assessments and disease-relevant cytokine/chemokine levels in the skin...In both studies, deucravacitinib was used as a positive control (at a dose targeting clinically relevant exposures). ATMW-DC exhibited potency (TYK2-JH2 IC50= 12pM) and selectivity for TYK2-JH2 (≥350-fold over JAK1, 2 or 3) in biochemical binding assays... ATMW-DC is a novel, oral, potent and selective allosteric inhibitor of TYK2. The in vitro profile and in vivo efficacy of ATMW-DC (in both the IL-23 PD and IMQ mouse models) support its further development for the treatment of autoimmune and autoinflammatory diseases driven by..."

Preclinical • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • CCL3 • IL12A • IL17A • IL23A • IL6 • JAK1 • TYK2

A NOVEL, ORAL, ALLOSTERIC INHIBITOR OF TYK2 DEMONSTRATES IN VITRO POTENCY, SELECTIVITY, AND IN VIVO EFFICACY IN MOUSE MODELS OF PSORIASIS (EULAR 2024) - "Although there are allosteric TYK2 inhibitors in development for various autoimmune/autoinflammatory diseases, efficacy matching that of the anti-IL-23 monoclonal antibodies has not yet been achieved, and there remains a need for a more efficacious oral agent...An acute model of psoriasis, based on imiquimod (IMQ)-induced skin inflammation, was used to evaluate efficacy of ATMW-DC (Doses 3 and 4) as compared to deucravacitinib via histological and clinical assessments and disease-relevant cytokine/chemokine levels in the skin (relative to naïve and vehicle-treated animals)... ATMW-DC is a novel, oral, allosteric inhibitor of TYK2, with potency and selectivity in biochemical and cellular assays. The in vitro profile and in vivo efficacy of ATMW-DC in both the IL-23 PD and IMQ mouse models also support its further development for the treatment of autoimmune and autoinflammatory diseases driven by TYK2-mediated signaling pathways."

Preclinical • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • CCL3 • IL12A • IL17A • IL23A • IL6 • JAK1 • JAK3 • TYK2