Roche (ROG) Investor update summary

Fenebrutinib clinical development and differentiation

• Fenebrutinib is a highly selective, non-covalent, CNS-penetrant BTK inhibitor designed for both relapsing and progressive MS, with unique structure and strong CNS penetration.

• Demonstrated positive Phase III results in both relapsing and primary progressive MS, making it the first and only BTKi with such outcomes.

• Over 2,700 patients studied across Phases I–III for MS and other autoimmune disorders.

• Four positive trials in MS, including head-to-head non-inferiority versus ocrelizumab in PPMS, support its broad efficacy.

• Data from FENhance 1/2 (RMS) and FENtrepid (PPMS) trials will support FDA filing planned for mid-2026.

Efficacy results from FENhance 1 and 2 (RMS)

• Fenebrutinib reduced annualized relapse rates by 51.1% and 58.5% versus teriflunomide in FENhance 1 and 2, respectively (p<0.001 and p<0.00001).

• MRI endpoints showed 70–83% reduction in T1 gadolinium-enhancing and T2 lesions compared to teriflunomide.

• Disability progression trends favored Fenebrutinib, with pooled HR 0.84 (0.71–0.99) and significant benefit over teriflunomide.

• The strongest treatment effect was observed in the 9-Hole Peg Test, indicating benefit for upper limb function.

• Consistent benefit observed across subgroups, with greater effect in younger patients and those with baseline T1 Gd+ lesions.

Efficacy results from FENtrepid (PPMS)

• FENtrepid met its primary endpoint of non-inferiority to ocrelizumab and showed numeric improvement in disability progression.

• Curves for disability progression separated by week 24 and remained apart for over 120 weeks.

• Strongest effect observed on 9HPT, with a 22% risk reduction in post hoc analysis using a composite endpoint.