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Orelabrutinib

Orelabrutinib, an investigational drug, is a potentially best-in-class, highly selective central nervous system (CNS)-penetrant, oral small molecule Bruton’s Tyrosine Kinase (BTK) inhibitor being developed for progressive forms of multiple sclerosis (MS) and other autoimmune diseases. By targeting BTK, a key enzyme in the B cell receptor signaling pathway, orelabrutinib has the potential to impact compartmentalized inflammation in the CNS and disability progression independent of relapse in MS. Orelabrutinib has been shown to be generally well tolerated in RMS, and other autoimmune and hematologic indications; its high selectivity may improve safety compared to less selective BTK inhibitors.

• Highly selective BTK inhibition and high CNS penetration

  Orelabrutinib binds irreversibly to BTK with minimal off-target effects, potentially reducing safety risks commonly associated with BTK inhibitors. It is designed to efficiently cross the blood–brain barrier, achieving therapeutic levels within the CNS to directly target inflammation and neurodegeneration in diseases such as MS. Orelabrutinib’s mechanism of action targets pathogenic B cells not only in the periphery but also within the CNS. Additionally, it directly modulates macrophages and microglial cells in the CNS, addressing key pathogenic drivers of progressive MS. This CNS penetration is critical for targeting the compartmentalized neuroinflammation and neurodegeneration that underlie progressive forms of the disease.

• Clinical activity observed in Phase 2 relapsing MS (RMS) trial

  Ability to suppress inflammatory activity observed in a Phase 2 clinical trial in RMS, including significant reductions in new gadolinium‐enhanced T1 lesions at week 12 across all evaluated doses compared to placebo and showed a meaningful impact on endpoints indicative of disease progression out to week 96. The safety and tolerability profile of orelabrutinib is consistent with other BTK inhibitors in development for MS and is well characterized across multiple prior autoimmune and oncology studies.

• Optimized dosing regimen

  Once-daily oral dosing provides a convenient, flexible regimen that supports consistent BTK inhibition and enhances patient adherence for long-term treatment.