Obefazimod and Methotrexate Combination (Obefazimod + MTX)

Obefazimod (ABX464) is a first-in-class small molecule that binds to the Cap Binding Complex (CBC), specifically the 80 kDa subunit (NCBP1), to enhance the splicing of a specific long non-coding RNA, thereby increasing the production of the anti-inflammatory microRNA-124 (miR-124) [1, 4]. Methotrexate is a folate antimetabolite that primarily inhibits dihydrofolate reductase (DHFR), leading to the inhibition of DNA synthesis and the accumulation of adenosine, which exerts potent immunomodulatory effects [2]. The combination of Obefazimod and Methotrexate is primarily investigated for the treatment of moderate-to-severe rheumatoid arthritis in patients who have had an inadequate response to methotrexate monotherapy [3]. By combining the novel RNA-splicing modulation of Obefazimod with the established metabolic and anti-inflammatory effects of Methotrexate, the therapy aims to achieve a synergistic reduction in pro-inflammatory cytokines such as TNF-alpha and IL-6 [1, 4]. Clinical studies, such as the Phase 2a trial NCT03817320, have demonstrated that adding Obefazimod to a stable dose of Methotrexate can significantly improve clinical outcomes while maintaining a manageable safety profile [3].

Other names

ABX464 and MethotrexateABX464 plus MTXObefazimod + MTX

Obefazimod binds to the Cap Binding Complex to promote miR-124 expression, while Methotrexate inhibits dihydrofolate reductase to suppress inflammatory pathways.