DeepCure, a biotechnology company, has unveiled promising data on its selective BRD4 (BD2) inhibitor, DC-9476. Preclinical studies indicate its superiority to existing anti-TNF-α treatments in a rheumatoid arthritisarthritis (RA) mouse model.
Activated macrophages play a crucial role in RA. They release inflammatory cytokines such as TNF-α, IL-1β, and IL-6, leading to joint damage and symptoms.
In vitro assays demonstrated that DC-9476 effectively reduced IL-6 production, surpassing the potency of tofacitinib, an approved Jak-2 inhibitor for RA treatment.
Animal model studies further supported DC-9476’s efficacy. In a lipopolysaccharide-induced inflammation model, it significantly lowered serum IL-6 and TNF-α levels. In the CAIA model, which mimics macrophage-driven RA, DC-9476 exhibited remarkable potency, reducing clinical disease scores by over 80%. This outperformed etanercept, an established anti-TNF-α antibody, which achieved only a 47% reduction.
Crucially, DC-9476 exhibited no toxicity. Its combination with etanercept led to enhanced improvements compared to either treatment alone.
These findings highlight DC-9476’s potential as a novel oral monotherapy or combination therapy for RA. Reducing inflammatory cytokines also suggests potential utility as target engagement biomarkers in future clinical trials.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
