Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of the joints. Credit: brizmaker via Shutterstock.

Massachusetts Institute of Technology-spinout DeepCure has teamed up with the Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM) to advance its BET inhibitor for rheumatoid arthritis (RA) into the clinic. 

The candidate, dubbed DC-9476, targets the BRD4 protein, which regulates gene expression by binding to specific marks on histones. By selectively inhibiting the BD2 domain of BRD4, DC-9476 reduces the production of pro-inflammatory substances, making it a potential candidate for inflammatory conditions such as RA. 

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The two entities will conduct a study using blood samples and joint biopsies from various patient subgroups, focusing on those resistant to current treatments. They will then leverage advanced translational tools to analyse gene expression patterns and cytokine levels in patient cells and tissues.  

The current treatment landscape for RA involves blockbuster JAK inhibitors, such as AbbVie’s Rinvoq (upadacitinib), and Pfizer’s Xeljanz (tofacitinib). It also includes tumour necrosis factor (TNF) inhibitors, like Humira (adalimumab), which is marketed by AbbVie.  

While these treatments can be effective, they don’t work for everyone, and some patients don’t respond well or stop responding over time. Additionally, JAK inhibitors can have significant side effects including serious infections, malignancies, and major adverse cardiovascular events. In September 2021, the US Food and Drug Administration (FDA) said it would require safety warnings for JAK inhibitors after a study in RA patients showed an increased risk of cardiovascular events. 

DC-9476 is said to offer an alternative approach by inhibiting BET pathway that can potentially reduce inflammation more selectively and effectively, especially in patients who are resistant to current treatments. In preclinical RA models, DC-9476 showed better safety and efficacy standard of care treatments, including TNF and JAK inhibitors, according to the 19 August announcement. 

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DC-9476 was generated using Boston-based DeepCure’s artificial intelligence (AI) drug discovery platform. According to a report on GlobalData’s Pharma Intelligence Center, healthcare professionals expect AI to have the greatest impact out of all emerging technologies in the pharmaceutical industry.  

GlobalData is the parent company of Pharmaceutical Technology. 

In the announcement accompanying the deal, DeepCure’s CEO Kfir Schreiber said: “We’re excited to work with the clinicians and scientists at LIRMM and will benefit from their deep expertise in the complexities of RA and the unmet needs of patients. This collaboration allows us to evaluate the efficacy of DC-9476 in patient-derived samples and help identify RA patient subgroups that will benefit the most from this compound.”