Tolebrutinib — Investigational Agent

BTK Inhibitor · Phase 2 · Sanofi

Mechanism of Action

Covalent (irreversible) BTK inhibitor with exceptional CNS penetration — its defining pharmacological characteristic. Tolebrutinib achieves CSF/plasma concentration ratios substantially higher than other BTKi (ibrutinib, acalabrutinib, zanubrutinib), enabling clinically meaningful BTK inhibition within the central nervous system. This CNS penetrance is being leveraged in neuro-oncology applications (primary CNS lymphoma, CNS involvement of systemic B-cell malignancies) where the blood-brain barrier limits other BTKi.

Investigational Indications

• Primary CNS lymphoma (PCNSL)
• Systemic B-cell malignancies with CNS involvement
• Relapsed/refractory CLL/SLL
• Multiple sclerosis (primary program — FDA Breakthrough Therapy designation for non-relapsing secondary progressive MS)

Key Trials