DeepCure, a therapeutics company using AI to discover novel drugs for inflammation and immune diseases, 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.
In addition, Dr. Kulveer Mankia, investigator at the Leeds Institute of Rheumatic and Musculoskeletal Medicine, will share ex vivo data demonstrating the efficacy of DC-9476 in cells from RA patients that have had an inadequate response to methotrexate (MTX-IR).
RA affects approximately 1% of the population, and almost half the patients are MTX-IR. Approximately 20% of patients are classified as difficult-to-treat (D2T RA) because they are non-responsive to methotrexate or other conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and at least two biological or targeted synthetic DMARDs with different mechanisms of action. There is an huge unmet medical need for safe and effective therapies in D2T RA patients and more advanced disease subgroups.
DC-9476 has broad activity including decreasing macrophage activation, Th17 differentiation, IgG, and pro-inflammatory cytokines such as TNFα, IL-6, IL-17A and IL-17F. DC-9476 is expected to be more effective than treatments that act on a single target in patients with autoimmune diseases that have increased activity in multiple immune pathways.
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.
In peripheral blood mononuclear cells (PBMC) from MTX-IR patients, DC-9476 caused a marked reduction in the secretion and gene expression of IL-6 and CCL2, which are clinically relevant disease biomarkers.
Details of the presentation:
Poster Title: DC-9476, a novel selective BRD4 (BD2) inhibitor targets key inflammatory arthritis pathways and is highly efficacious in the collagen induced arthritis mouse model of rheumatoid arthritis
Session: RA – Animal Models Poster
Date/Time: November 17, 2024, 10:30 AM – 12:30 PM ET
Presenter: Dr. Kulveer Mankia, Clinical Associate Professor and Honorary Consultant Rheumatologist, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital
“DC-9476 has consistently shown in vivo superiority over etanercept, and now we’ve observed in vivo superiority over tofacitinib and reduction of clinical biomarkers in samples from MTX-IR patients,” said Kfir Schreiber, CEO & Co-Founder of DeepCure. “The data presented at ACR further support the progression of DC-9476 into clinical development as a novel treatment for RA.”
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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