Roche (ROG) Investor update summary

Fenebrutinib development and clinical program

• Fenebrutinib is a highly selective, non-covalent, CNS-penetrant BTK inhibitor designed to address both relapsing and progressive MS biology.

• Demonstrated positive Phase III results in both relapsing (RMS) and primary progressive MS (PPMS), 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.

• 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 significantly reduced annualized relapse rate (ARR) vs teriflunomide: 51.1% and 58.5% relative reduction in FENhance 1 and 2, respectively (p<0.001 and p<0.00001).

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

• Marked reduction in new or enlarging MRI lesions: 70–83% fewer T1 Gd+ and T2 lesions compared to teriflunomide.

• Trend favoring fenebrutinib for disability progression (CCDP12), with pooled HR 0.84 (0.71–0.99) and stronger effect on 9HPT.

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.