DC-9476 / DeepCure - LARVOL DELTA

DC-9476, a Novel Selective BRD4(BD2) Inhibitor, Improves Arthritis Scores in Preclinical Models of Rheumatoid Arthritis by Regulating Key Inflammatory Pathways (ACR Convergence 2024) - "At the onset of arthritis, mice were treated with DC-9476 (p.o., 15, 50 or 150 mg/kg, BD), Etanercept (i.p., 10 mg/kg, QD) or Tofacitinib (p.o., 25 mg/kg, BD). We demonstrate that the selectivity for a single BET protein and bromodomain of DC-9476 resulted in favourable anti-inflammatory effects in murine RA models and reduced BET inhibitor-related toxicities. These data indicate that DC-9476 could be a novel class of BET inhibitor for treating RA and warrants the assessment of DC-9476 in ex vivo models derived from active RA patients."

Preclinical • Hematological Disorders • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • BRD2 • BRD3 • BRD4 • BRDT • IL17A • IL6 • TNFA

DeepCure to Present First Ex Vivo Rheumatoid Arthritis Patient Data for Selective BRD4 (BD2) Inhibitor DC-9476 at ACR Convergence 2024 (Businesswire) - "DeepCure...will present new in vivo data demonstrating its selective BRD4 (BD2) inhibitor DC-9476 is superior to anti-TNFα, anti-IL6 and JAK2 inhibitor (tofacitinib) therapy in the collagen induced arthritis (CIA) mouse model at ACR Convergence 2024, held November 14-19, in Washington DC....DC-9476 was evaluated in a series of preclinical studies as a potential therapy for RA. In the CIA model, DC-9476 resulted in a dose-dependent reduction in arthritis score and paw thickness without hematological or other toxicities across a ten-fold dose range. The reduction in arthritis score by DC-9476 was significantly better than an anti-TNFα antibody (etanercept), a JAK inhibitor (tofacitinib) and an anti-IL6 antibody."

Preclinical • Immunology • Rheumatoid Arthritis

DeepCure to Present In Vivo Data Showing Its Selective BRD4 (BD2) Inhibitor DC-9476 is Superior to Etanercept in Rheumatoid Arthritis (Businesswire) - "Results from an in vitro cell-based assay that stimulated the activation of human macrophage-like cells and IL-6 production demonstrated that DC-9476 decreased IL-6 production and it was more potent than tofacitinib, a currently marketed Jak-2 inhibitor for the treatment of RA. The in vivo efficacy of DC-9476 was evaluated using two mouse models. In a lipopolysaccharide (LPS)-induced inflammation model, DC-9476 reduced both serum IL-6 and TNF-α levels. In the CAIA model, which mimics macrophage-driven RA, DC-9476 treatment led to a greater than 80% reduction in the clinical disease score, outperforming etanercept, a currently approved anti-TNF-α antibody, which only achieved a 47% reduction. Importantly..."

Preclinical • Rheumatoid Arthritis

DeepCure Announces Collaboration with Leeds Institute to Evaluate DC-9476 in Rheumatoid Arthritis (Businesswire) - "DeepCure...today announced a collaboration with one of the world’s premier research centers for rheumatoid arthritis (RA), the Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM). The collaboration will investigate DC-9476, a third-generation selective BRD4 (BD2) inhibitor, as a potential treatment for over a million patients worldwide with RA who do not respond well to current standard of care."

Licensing / partnership • Rheumatoid Arthritis