The HERCULES study is the first to show a reduction in disability accumulation in non-relapsing secondary progressive MS. How significant is this result for patients with nrSPMS, and what does it mean for the future of treatment in this challenging population?

Tolebrutinib is a brain-penetrant BTK inhibitor, modulating both B lymphocytes and microglia. Could you explain how this mechanism targets smoldering neuroinflammation, and why it might be particularly effective in reducing disability progression in nrSPMS?

"Patients with nrSPMS have long been underserved, with no approved therapies specifically targeting their condition. What are the biggest challenges in treating nrSPMS, and how might tolebrutinib help overcome these barriers?

Preliminary safety data in the HERCULES study, including liver toxicity, were consistent with previous studies of tolebrutinib. How would you assess the safety profile of tolebrutinib for long-term use in MS patients, particularly in the context of progressive disease?

BTK inhibitors are emerging as potential therapies in neuroinflammatory conditions. How does tolebrutinib differentiate itself from other BTK inhibitors in development, and what makes it uniquely suited for nrSPMS?

While the GEMINI 1 and 2 studies in relapsing MS did not meet the primary endpoint of reducing annualized relapse rates, there was a delay in 6-month confirmed disability worsening. How do these secondary findings support the overall efficacy of tolebrutinib in progressive MS forms?

Disability accumulation in nrSPMS significantly impacts patients' physical and cognitive abilities. What potential improvements in quality of life do you foresee for patients treated with tolebrutinib, based on the HERCULES study results?"

With the HERCULES results forming the basis for future regulatory discussions, what are the next steps for tolebrutinib's approval process? How do you see it fitting into the broader MS treatment paradigm, especially in progressive forms of the disease?