DeepCure, a therapeutics company using AI to discover novel drugs for inflammation and immune diseases, today announced it will present data showing its selective BRD4 (BD2) inhibitor DC-9476 is superior to anti-TNF-α treatment in the collagen antibody-induced arthritis (CAIA) rheumatoid arthritis (RA) mouse model at the 11th International Conference on Autoimmunity: Mechanisms and Novel Treatments in Crete, Greece.

Activated macrophages play a central role in the onset and progression of RA. They can produce proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), which are responsible for joint damage and symptoms.

DC-9476 was evaluated in a series of preclinical studies to investigate its potential as a treatment for RA. 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, DC-9476 showed no signs of toxicity in both models. The combination of DC-9476 and etanercept resulted in significantly greater improvement compared to either treatment alone.

Details of the presentation:

Poster Title: Novel, Selective BRD4 (BD2) Inhibitor DC-9476 Demonstrates a Potent Anti-inflammatory Mechanism

Date: October 19, 10:25 am (local time)

Presenter: Dr. Michal Segal-Salto, Senior Director - Biology, DeepCure

“This is the first time we are presenting in vivo data in animal models of RA for DC-9476, which demonstrates its potential as a novel oral monotherapy or combination therapy for patients,” said Kfir Schreiber, CEO & Co-Founder of DeepCure. “In addition, this selective BRD4 (BD2) inhibitor reduced key inflammatory cytokines that could be used as biomarkers of target engagement in future clinical trials.”

About DeepCure

DeepCure is a therapeutics company focused on advancing novel drugs with the potential to transform the treatment of inflammation and autoimmune diseases. The company was founded by researchers at MIT to accelerate breakthrough therapies using artificial intelligence (AI) and AI-enabling technologies for small molecule discovery. The company is based in Boston, MA, and its engineers, chemists, and biologists collaborate to find solutions to hard problems that will have an enormous impact on patient health. For more information, visit www.deepcure.ai.

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