Roche Holding Ltd · SIX:RO
Roche — AAN 2026 Virtual Neurology IR Event
28 slides from Roche's conference presentation, Apr 22, 2026
Slide 1: Roche
Roche Roche
Slide 2: AAN 2026 Virtual Neurology IR Event
AAN 2026 Virtual Neurology IR Event 22 April 2026
Slide 3: Forward-looking statements
This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, str
Slide 4: Agenda
Agenda Welcome & introduction Bruno Eschli, Head of Investor Relations Fenebrutinib development overview Alexandra Goodyear, Lifecycle Leader Fenebrutinib Ph III (FENhance 1/2) fenebrutinib vs. Aubagio in RMS Jiwon Oh, MD, PhD, FRCPC, Medical Director, Barlo Multiple Sclerosis Program, Associate Pro
Slide 5: Fenebrutinib development overview
Fenebrutinib development overview Alexandra Goodyear Lifecycle Leader Fenebrutinib
Slide 6: Fenebrutinib: Potential for FIC and BIC in both RMS and PPMS
Neurology Fenebrutinib: Potential for FIC and BIC in both RMS and PPMS First and only BTKi with positive results in Ph III trials in RMS (FENhance 1/2) and PPMS (FENtrepid) Designed to control relapsing and progressive biology Fenebrutinib development program fenebrutinib BTKi Ph I Ph II Ph III B ce
Slide 7: PPMS: Positive Ph III FENtrepid results
Neurology PPMS: Positive Ph III FENtrepid results Fenebrutinib is the first oral and second-ever therapy to demonstrate efficacy in PPMS Numeric improvement vs. Ocrevus in cCDP12 Individual components of cCDP12 ▪ FENtrepid study met its primary endpoint of non-inferiority and ▪ Strongest treatment e
Slide 8: Fenebrutinib: Potential best-in-class high-efficacy oral treatment
Neurology Fenebrutinib: Potential best-in-class high-efficacy oral treatment High selectivity, non-covalent reversible, oral, CNS penetrant BTKi Fenebrutinib: differentiated by design1 Fenebrutinib is highly selective for BTK2 F Fenebrutinib E Evobrutinib T Tolebrutinib R Remibrutinib Fenebrutinib E
Slide 9: Fenebrutinib has high systemic exposure and CNS penetration
Neurology Fenebrutinib has high systemic exposure and CNS penetration Fenebrutinib achieves near-maximal inhibition of microglia in the CNS Optimized PK profile1 CNS Penetration2 Free plasma concentration of BTKis CSF: Concentration relative to microglia TNF-α IC902 ▪ Fenebrutinib has high bioavaila
Slide 10: Ph III (FENhance 1/2) fenebrutinib vs. Aubagio in RMS
Ph III (FENhance 1/2) fenebrutinib vs. Aubagio in RMS Jiwon Oh, MD, PhD, FRCPC Medical Director, Barlo Multiple Sclerosis Program, Associate Professor, Division of Neurology, St. Michael’s Hospital, University of Toronto, Staff Neurologist, St. Michael’s Hospital, Scientist, Keenan Research Centre o
Slide 11: Efficacy and Safety of Fenebrutinib vs Teriflunomide in RMS
Late-Breaking Science 2 April 21, 2026 https://go.roche.link/2pewrk Efficacy and Safety of Fenebrutinib vs Teriflunomide in Relapsing Multiple Sclerosis: Results of the FENhance 1 and 2 Studies Jiwon Oh,1 Amit Bar-Or,2 Gavin Giovannoni,3 Maria Pia Sormani,4 Martin S. Weber,5 Sharon Stoll,6 Jacquelin
Slide 12: Disclosures
Disclosures • J. Oh has received compensation for consulting/speaking from Biogen, BMS, Eli Lilly, EMD Serono, F. Hoffmann-La Roche Ltd, Novartis and Sanofi Genzyme and research funding from Biogen and F. Hoffmann-La Roche Ltd • A. Bar-Or has received fees for consulting and/or advisory board partic
Slide 13: Fenebrutinib Is a Uniquely Designed, CNS-Penetrant, Noncovalent BTKi
Background Fenebrutinib Is a Uniquely Designed, CNS-Penetrant, Noncovalent BTKi • By targeting BTK signaling that is crucial to B-cell and myeloid cell activation,1,2 BTKis have the potential to address both relapsing and progressive biologies across the MS disease continuum • Fenebrutinib is a uniq
Slide 14: FENhance 1 and 2 Study Design
Study Design FENhance 1 and 2 Are Two Largely Identical, Phase III, Multicenter, Randomized Studies Inclusion criteria Double-blind, double-dummy, parallel-group design Fenebrutinib 200 mg BID oral Age 18-55 years + teriflunomide-matching placebo Open-label period R EDSS 0.0-5.5 1:1a Fenebrutinib at
Slide 15: FENhance 1 and 2 Primary and Key Secondary Endpoints
Primary Endpoint FENhance 1 and 2 Compared the Effect of Fenebrutinib vs Teriflunomide on ARR Primary endpoint Key Secondary Endpointsd Annualized Relapse Rate (ARR) 12-week composite confirmed Protocol-defined relapse: disability progression Based on any of: New or worsening neurological symptoms,
Slide 16: Baseline Characteristics Were Well Matched
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms and Across Studies FENhance 1 FENhance 2 Fenebrutinib Teriflunomide Fenebrutinib Teriflunomide (n=374) (n=372) (n=376) (n=375) Age, mean (SD), years 36.1 (9.4) 35.8 (9.5) 36.4 (9.4) 34
Slide 17: Fenebrutinib Significantly Reduced ARR Relative to Teriflunomide
Primary Endpoint Fenebrutinib Significantly Reduced ARR Relative to Teriflunomide, Translating to an Average of One Relapse Approximately Every 16-19 Years ■ Teriflunomide ■ Fenebrutinib 51.1% 58.5% Adjusted ARR (95% CI)a relative relative reduction reduction FENhance 1 FENhance 2 Adjusted rate rati
Slide 18: Treatment Effect on ARR Across Subgroups
Predefined Subgroup Analysis The Treatment Effect on ARR Favored Fenebrutinib Across Subgroups, With a Greater Effect in Younger PwMS and Those With Baseline T1 Gd+ Lesions FEN TFM Rate ratio (95% CI)a Overall N=750 N=747 0.45 (0.34-0.59) <40 n=463 n=483 0.33 (0.23-0.46) Age, years ≥40 n=287 n=264 0
Slide 19: Fenebrutinib Reduced the Number of New Brain MRI Lesions
Secondary Endpoints Fenebrutinib Reduced the Number of New Brain MRI Lesions Compared With Teriflunomide ■ Teriflunomide ■ Teriflunomide ■ Fenebrutinib ■ Fenebrutinib No. of new lesions per Annualized no. of new 77.6% lesions (95% CI)a scan (95% CI)a 82.5% 70.7% 76.0% FENhance 1 FENhance 2 FENhance
Slide 20: cCDP12 Endpoints Demonstrated a Consistent Trend Favoring Fenebrutinib
Secondary Endpoint and Post Hoc Analysis cCDP12 Endpoints Demonstrated a Consistent Trend Favoring Fenebrutinib cCDP12a Post hoc modified cCDP12 (EDSS + 9HPT) HR (95% CI) HR (95% CI) FENhance 1 0.80 (0.63-1.02) FENhance 1 0.74 (0.53-1.03) FENhance 2 0.87 (0.69-1.11) FENhance 2 0.80 (0.57-1.12) Poole
Slide 21: The Strongest Treatment Effect Was Observed on 9HPT
Secondary Endpoint The Strongest Treatment Effect Was Observed on 9HPT Proportion with event, n (%) Fenebrutinib Teriflunomide Contribution to FENhance 1 HR (95% CI) cCDP12 (n=374) (n=372) cCDP12 125 (33.4) 143 (38.4) 0.80 (0.63-1.02) 100% CDP-EDSS 52 (13.9) 62 (16.7) 0.77 (0.53-1.12) 33% T25FWT 85
Slide 22: Safety Profiles of Both Treatments Were Comparable
Safety The Safety Profiles of Both Treatments Were Comparable Across Studies FENhance 1 FENhance 2 Fenebrutinib Teriflunomide Fenebrutinib Teriflunomide (n=374) (n=371) (n=375) (n=374) Participants with ≥1 event, n (%) Any AE 338 (90.4) 329 (88.7) 349 (93.1) 327 (87.4) Serious AE 32 (8.6) 33 (8.9) 4
Slide 23: Overview of Reported Fatalities Across Studies
Safety Overview of Reported Fatalities Across Studies Age,b Onset, Baseline Study Fatal eventa Arm Confounding factors or risk factors years/ study EDSS number Sex day Intestinal ischemia/diabetic Poorly controlled insulin-dependent Type 1 FEN 49/F 3.5 1 412 hyperosmolar coma diabetesc Aneurysm, lon
Slide 24: Transient and Reversible Hepatic Transaminase Elevations
Safety Transient and Reversible Hepatic Transaminase Elevations Were Comparable Between Arms in Both Studies FENhance 1 FENhance 2 Maximum ALT elevation, n (%) Fenebrutinib Teriflunomide Fenebrutinib Teriflunomide (n=372a) (n=368a) (n=375a) (n=372a) >3× ULN 27 (7.3) 21 (5.7) 21 (5.6) 21 (5.6) >3 to
Slide 25: Conclusions
Conclusions • Fenebrutinib achieved superiority vs teriflunomide in FENhance 1 and 2, significantly reducing relapses and disease activity on MRI, demonstrating a substantial impact on relapsing biology • A consistent trend favoring fenebrutinib was observed for measures of disability progression, s
Slide 26: Acknowledgments
Acknowledgments • We thank all the participants who volunteered for this trial and their families and site staff who provided support to the participants • We are grateful to the study site investigators and staff who facilitated the trial’s recruitment, enrollment and data collection; we thank the
Slide 27: Q&A
Q&A
Slide 28: Doing now what patients need next
Doing now what patients need next