DC-9476 / DeepCure - LARVOL DELTA

Selective BET inhibition as potential hidradenitis suppurativa treatment (SID 2025) - "Here we assessed the effects of a 3rd generation BET inhibitor (DC-9476, DC) on the Hidradenitis suppurativa (HS) phenotype in vitro and ex vivo...Cytokine stimulation caused intrafollicular PBMC infiltration, which was reduced by HF treatment with 300nM DC, while PBMC treatment with 1µM DC reduced CXCL8 secretion from HFs. In summary, these in vitro and ex vivo data demonstrate the potential of DC to ameliorate early HS responses but further pre-clinical studies are needed to refine treatment strategies and identify responsive patients."

Dermatology • Hidradenitis Suppurativa • Immunology • CCL2 • CCL20 • CD4 • CD8 • CSF2 • CXCL8 • IL17A • IL1B • IL6 • MKI67 • TNFA

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