Roche Holding Ltd · SIX:RO
Roche — ACTRIMS 2026 Virtual Neurology IR Event
45 slides from Roche's conference presentation, Feb 9, 2026
Slide 1: Slide 1
Slide 2: ACTRIMS 2026 Virtual Neurology IR Event
ACTRIMS 2026 Virtual Neurology IR Event February 9th 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: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations MS franchise/pipeline update Hideki Garren, SVP, Global Head of Product Development Neurology Ph III (FENtrepid) fenebrutinib vs. Ocrevus in PPMS Amit Bar-Or, MD, FRCPC, Director, Center for Neuroinflammation and Experimental Therapeutics and C
Slide 6: Roche is a leader in MS: Ocrevus firmly established as global SoC
Neurology Roche is a leader in MS: Ocrevus firmly established as global SoC Total Ocrevus franchise (IV/SC) expected to peak at CHF 9bn (at CER) in 2029 Ocrevus is #1 in MS new-to-brand share Continuing to improve patient experience Number of patients treated globally (thousands) At year end >17,500
Slide 7: Neurology
Neurology Hideki Garren SVP, Global Head of Product Development Neurology
Slide 8: Neurology pipeline
Neurology Neurology pipeline First positive Ph III results for fenebrutinib in RMS (FENhance 2) and PPMS (FENtrepid), and Enspryng in MO-GAD Phase I Phase II Phase III Registration BrainShuttle CD20 Ocrevus SC OBI Enspryng Elevidys1 RG6035 RG1594 Multiple Sclerosis RG6168 MOG-AD RG6356 DMD2 Multiple
Slide 9: Roche MS portfolio
Neurology Roche MS portfolio Positioned to address both relapsing and progressive biologies with high efficacy treatments Global MS market1 MS is progressive from onset, resulting in lifelong disability 100% 90% RMS PMS Subtype 31% 80% 40% 50% Q3 Patient Share 70% 62% CIS RRMS Active SPMS naSPMS PPM
Slide 10: Multiple Sclerosis strategy
Neurology Multiple Sclerosis strategy Reduce the impact of MS by delivering a diverse portfolio of transformational therapies that revolutionize care Cure MS Ambition Our Vision STOP, REVERSE, and PREVENT Multiple Sclerosis Our Priorities Deliver our late-stage & in- Accelerate and Lead in transform
Slide 11: 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 2) and PPMS (FENtrepid) Designed to control relapsing and progressive biology Fenebrutinib development program fenebrutinib BTKi Ph I Ph II Ph III B cell
Slide 12: 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 13: Fenebrutinib has an optimized PK profile to reach its targets
Neurology Fenebrutinib has an optimized PK profile to reach its targets Fenebrutinib is the only BTKi that achieves near-maximal inhibition of B-cells and microglia in the CNS Optimized PK profile1 CNS Penetration2 Free plasma concentration of BTKis CSF: Concentration relative to microglia TNF-α IC9
Slide 14: Ph II (FENopta) data underscores confidence in fenebrutinib in RMS
Neurology Ph II (FENopta) data underscores confidence in fenebrutinib in RMS Participants treated with fenebrutinib had low clinical disease activity through week 96 ARR was low in participants receiving fenebrutinib New T1 Gd+ lesions reduced to near zero DBTP (12 weeks) OLE No. of new T1 Gd+ Lesio
Slide 15: Multiple Sclerosis: Early development pipeline
Neurology Multiple Sclerosis: Early development pipeline Diverse portfolio of modalities build on Roche’s leadership in MS RG6035: P-CD19CD20-ALLO1 CAR-T: RG6182: BrainShuttle CD20 Allogeneic CAR-T MAGLi Blood BBB Brain tissue Transferrin receptor 1 CD20 binder ▪ Transposon-based CAR insertion Brain
Slide 16: Ph III (FENtrepid) fenebrutinib vs. Ocrevus in PPMS
Ph III (FENtrepid) fenebrutinib vs. Ocrevus in PPMS Amit Bar-Or, MD, FRCPC Director, Center for Neuroinflammation and Experimental Therapeutics and Chief, Multiple Sclerosis Division, Department of Neurology Perelman Center for Advanced Medicine (PCAM), University of Pennsylvania
Slide 17: Efficacy and Safety of Fenebrutinib vs Ocrelizumab in PPMS: FENtrepid Primary Results
Late Breaking Research and Clinical Trials Saturday, February 7, 2026 https://link.roche.com/bzaym7 Efficacy and Safety of Fenebrutinib vs Ocrelizumab in Primary Progressive Multiple Sclerosis: Primary Results of the Phase III FENtrepid Study Amit Bar-Or,1 Jiwon Oh,2 Gavin Giovannoni,3 Maria Pia Sor
Slide 18: Disclosures
Disclosures • A. Bar-Or has received fees for consulting and/or advisory board participation from: AstraZeneca, Biogen, Bristol Myers Squibb, Cabaletta, Capstan, EMD Serono, F. Hoffmann-La Roche Ltd/Genentech, Inc., Gilead, GlaxoSmithKline, Immunic, Moderna, Neuron23, Novartis, Oculis, Sanofi, Sudo
Slide 19: Fenebrutinib Is a Unique, CNS-Penetrant, Noncovalent, Reversible BTKi
Background Fenebrutinib Is a Unique, CNS-Penetrant, Noncovalent, Reversible 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 uni
Slide 20: FENtrepid Is a Phase III, Multicenter, Randomized Clinical Trial
Study Design FENtrepid Is a Phase III, Multicenter, Randomized Clinical Trial Inclusion criteria Double-blind, double-dummy, parallel-group design Fenebrutinib 200 mg oral BID Age 18-65 years + ocrelizumab-matching placebo Open-label period R EDSS 3.0-6.5 1:1a Fenebrutinib at screening Ocrelizumab 6
Slide 21: FENtrepid Evaluated Noninferiority of Fenebrutinib vs Ocrelizumab
Primary Endpoint FENtrepid Evaluated the Noninferiority of Fenebrutinib in Reducing the Risk of cCDP12 vs Ocrelizumab Primary endpointa Noninferiority vs ocrelizumab CDP-EDSS Active comparator: ≥1.0-point increase with baseline EDSS ≤5.5 Ocrelizumab ≥0.5-point increase with baseline EDSS >5.5 The on
Slide 22: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 23: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 24: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 25: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 26: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 27: Baseline Characteristics Were Well Matched Between Treatment Arms
Baseline Demographics and Disease Characteristics Baseline Characteristics Were Well Matched Between Treatment Arms Fenebrutinib Ocrelizumab All Participants (n=493) (n=492) (N=985) Age, mean (SD), years 49.0 (10.3) 48.9 (10.2) 48.9 (10.2) Female, % 50.1 49.0 49.5 Time since symptom onset, mean (SD)
Slide 28: Noninferiority of Fenebrutinib Was Achieved in cCDP12
Primary Endpoint Noninferiority of Fenebrutinib Was Achieved in cCDP12 100 Fenebrutinib (n=493) 90 Ocrelizumab (n=492) 66.1% Participants with an event, % 80 70 Separation 60 at W24 58.8% 50 40 12% risk reduction 30 20 HR (95% CI), 0.88 (0.75-1.03) 10 Synthesis test statistic, −3.02a 0 BL 12 24 36 4
Slide 29: The Strongest Treatment Effect Was Observed on 9HPT
Primary Endpoint The Strongest Treatment Effect Was Observed on 9HPT Proportion with event, n (%) Fenebrutinib Ocrelizumab Risk reduction Contribution to HR (95% CI) (n=493) (n=492) with fenebrutinib cCDP12 cCDP12 290 (58.8) 325 (66.1) 0.88 (0.75-1.03) 12% 100% CDP12-EDSS 146 (29.6) 174 (35.4) 0.84
Slide 30: The Strongest Treatment Effect Was Observed on 9HPT
Primary Endpoint The Strongest Treatment Effect Was Observed on 9HPT Proportion with event, n (%) Fenebrutinib Ocrelizumab Risk reduction Contribution to HR (95% CI) (n=493) (n=492) with fenebrutinib cCDP12 cCDP12 290 (58.8) 325 (66.1) 0.88 (0.75-1.03) 12% 100% CDP12-EDSS 146 (29.6) 174 (35.4) 0.84
Slide 31: The Strongest Treatment Effect Was Observed on 9HPT
Primary Endpoint The Strongest Treatment Effect Was Observed on 9HPT Proportion with event, n (%) Fenebrutinib Ocrelizumab Risk reduction Contribution to HR (95% CI) (n=493) (n=492) with fenebrutinib cCDP12 cCDP12 290 (58.8) 325 (66.1) 0.88 (0.75-1.03) 12% 100% CDP12-EDSS 146 (29.6) 174 (35.4) 0.84
Slide 32: The Strongest Treatment Effect Was Observed on 9HPT
Primary Endpoint The Strongest Treatment Effect Was Observed on 9HPT Proportion with event, n (%) Fenebrutinib Ocrelizumab Risk reduction Contribution to HR (95% CI) (n=493) (n=492) with fenebrutinib cCDP12 cCDP12 290 (58.8) 325 (66.1) 0.88 (0.75-1.03) 12% 100% CDP12-EDSS 146 (29.6) 174 (35.4) 0.84
Slide 33: The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups
Predefined Subgroup Analysis The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups FEN OCR Hazard ratio (95% CI) Overall N=493 N=492 0.88 (0.75-1.03) ≤55 n=337 n=345 0.86 (0.71-1.04) Age, years >55 n=156 n=147 0.90 (0.67-1.21) Female n=247 n=241 0.91 (0.72-1.15) Sex Male n=246 n=2
Slide 34: The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups
Predefined Subgroup Analysis The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups FEN OCR Hazard ratio (95% CI) Overall N=493 N=492 0.88 (0.75-1.03) ≤55 n=337 n=345 0.86 (0.71-1.04) Age, years >55 n=156 n=147 0.90 (0.67-1.21) Female n=247 n=241 0.91 (0.72-1.15) Sex Male n=246 n=2
Slide 35: The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups
Predefined Subgroup Analysis The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups FEN OCR Hazard ratio (95% CI) Overall N=493 N=492 0.88 (0.75-1.03) ≤55 n=337 n=345 0.86 (0.71-1.04) Age, years >55 n=156 n=147 0.90 (0.67-1.21) Female n=247 n=241 0.91 (0.72-1.15) Sex Male n=246 n=2
Slide 36: The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups
Predefined Subgroup Analysis The Treatment Effect on cCDP12 Was Generally Consistent Across Subgroups FEN OCR Hazard ratio (95% CI) Overall N=493 N=492 0.88 (0.75-1.03) ≤55 n=337 n=345 0.86 (0.71-1.04) Age, years >55 n=156 n=147 0.90 (0.67-1.21) Female n=247 n=241 0.91 (0.72-1.15) Sex Male n=246 n=2
Slide 37: Rates of AEs and Serious AEs Were Similar Between Treatment Arms
Safety Rates of AEs and Serious AEs Were Similar Between Treatment Arms Fenebrutinib Ocrelizumab (n=491) (n=492) No. of participants with ≥1 event, n (%) Any AE 473 (96.3) 461 (93.7) Serious AE 94 (19.1) 93 (18.9) Fatal AE 7 (1.4) 1 (0.2) AE leading to withdrawal from treatmenta 69 (14.1) 25 (5.1) •
Slide 38: Overview of Reported Fatalities
Safety Overview of Reported Fatalities Age, years/ Baseline Onset, Fatal event Arm Confounding factors or risk factors Sex EDSS study day COVID-19 FEN Not vaccinated against COVID-19 37/F 3.5 51 Diabetic ketoacidosis FEN Insulin pump failure 39/M 5.0 803 Myocardial infarction FEN No other identified
Slide 39: Transient and Reversible Asymptomatic Hepatic Transaminase Elevations
Safety Transient and Reversible Asymptomatic Hepatic Transaminase Elevations Were Observed More Commonly in the Fenebrutinib Arm Fenebrutinib Ocrelizumab Maximum ALT elevation, n (%) (n=489a) (n=490a) >3× ULN 65 (13.3) 14 (2.9) >3-5× ULN 28 (5.7) 5 (1.0) >5-10× ULN 23 (4.7) 6 (1.2) >10-20× ULN 11 (2
Slide 40: Rates of Known BTKi–Related Adverse Events Were Mostly Comparable
Safety Rates of Known BTKi–Related Adverse Events Were Mostly Comparable Between Treatment Arms Fenebrutinib Ocrelizumab No. of participants with ≥1 AE, n (%) (n=491) (n=492) Infections and infestations 329 (67.0) 349 (70.9) Serious infections and infestations 30 (6.1) 45 (9.1) Hemorrhage 50 (10.2)
Slide 41: Conclusions
Conclusions • Fenebrutinib achieved noninferiority to ocrelizumab in reducing disability progression (cCDP12), with numerically favorable outcomes by Week 24 and across subgroups, including those without baseline T1 Gd+ lesions – The strongest treatment effect was observed on 9HPT • Rates of AEs and
Slide 42: 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 43: Efficacy and Safety of Fenebrutinib vs Ocrelizumab in PPMS: FENtrepid Primary Results
Late Breaking Research and Clinical Trials Saturday, February 7, 2026 https://link.roche.com/bzaym7 Efficacy and Safety of Fenebrutinib vs Ocrelizumab in Primary Progressive Multiple Sclerosis: Primary Results of the Phase III FENtrepid Study Amit Bar-Or,1 Jiwon Oh,2 Gavin Giovannoni,3 Maria Pia Sor
Slide 44: Q&A
Q&A
Slide 45: Doing now what patients need next
Doing now what patients need next