Roche (ROG) investor relations material

Overview of Fenebrutinib clinical development and differentiation

• Fenebrutinib is a highly selective, non-covalent, CNS-penetrant BTK inhibitor designed to address both relapsing and progressive MS biology, with unique non-covalent binding and high selectivity for BTK, and strong CNS penetration that may improve long-term safety.

• Demonstrated positive phase III results in both relapsing (RMS) and primary progressive MS (PPMS), making it the first and only BTKi with such outcomes and showing potential as a first and best-in-class oral therapy for both indications.

• The molecule acts on B cells and macrophages in the periphery and microglia in the CNS, aiming to reduce both relapsing and progressive disease biology, leading to decreased disability accumulation.

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

• Four positive trials in MS, including phase II and III studies, support a robust efficacy and safety profile, with regulatory filing planned mid-year or mid-2026.

Efficacy results from FENhance 1 and 2 (RMS)

• Fenebrutinib significantly reduced annualized relapse rates by 51% and 58% versus teriflunomide in FENhance 1 and 2, respectively (p<0.001 and p<0.00001).

• MRI endpoints showed a 70–83% reduction in T1 gadolinium-enhancing lesions and a 76–83% reduction in new/enlarging T2 lesions compared to teriflunomide.

• Pooled analysis of composite confirmed disability progression (cCDP) favored Fenebrutinib, with the strongest effect seen in the 9-Hole Peg Test and pooled HR 0.84 (0.71–0.99).

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

• Safety profiles were generally comparable, though there was an imbalance in fatalities (7 on Fenebrutinib vs. 1 on teriflunomide), with no clustering of causes.

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.