Roche Holding Ltd · SIX:RO
Roche — Investor Day (March 2024)
53 slides from Roche's investor day presentation, Mar 11, 2024
Slide 1: Roche Neurology Update Virtual IR Event
Roche Neurology Update Virtual IR Event March 11th 2024
Slide 2: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 3: Agenda
Agenda Welcome 15:00 – 15:05 CET Bruno Eschli, Head of Investor Relations Late stage pipeline Neurology 15:05 – 15:15 CET Paulo Fontoura, SVP and Global Head of Neuroscience, Immunology, Ophthalmology, Cardiometabolic, Infectious and Rare Diseases Clinical Development Elevidys in Duchenne Muscular D
Slide 4: Roche is #1 in Neurology
Roche is #1 in Neurology Neurology portfolio accounting already for 1/5 of Pharma sales FY 2023 sales Ocrevus: • Market leader in US/EU5 with 24% global patient share (YoY CER growth) 6.4 CHF bn • Further growth expected with SC approval in US / EU (expected 2024) +13% • HD Ocrevus (Ph3 data expecte
Slide 5: Late-stage pipeline updates scheduled for 2024/25
Late-stage pipeline updates scheduled for 2024/25 Upcoming IR events: “Diagnostics Day” on May 22nd and “ASCO Oncology Update” (date tbc) Pharmaceuticals Diagnostics NME Indication Newsflow Timing Product Description Launch tiragolumab NSCLC Final Ph III data H2 2024 Total solution for clinical mass
Slide 6: Building blocks for mid- to long-term growth
Building blocks for mid- to long-term growth Neuroscience portfolio with significant mid- and long-term opportunities Oncology solid tumors Hematology CT-388 / Neurology anti-TL1A ASO Factor B zilebesiran CT-996 / CT-868 Ophthalmology Immunology anti-latent tobemstomig SPK-8011 trontinemab myostatin
Slide 7: Neurology late stage pipeline
Neurology late stage pipeline Paulo Fontoura SVP and Global Head of Neuroscience, Immunology, Ophthalmology, Cardiometabolic, Infectious and Rare Diseases Clinical Development
Slide 8: Neurology pipeline
Neurology pipeline Industry leading portfolio differentiated on targets and platform technologies Ph I (5 NMEs) Ph II (6 NMEs, 1AI) Ph III (1 NME, 5AI) Launched (4) Brainshuttle™ CD20 prasinezumab Enspryng Ocrevus RG6035 RG7935 RG6168 RG1594 Multiple Sclerosis Parkinson’s gMG RD Multiple Sclerosis M
Slide 9: Neurology near term key catalysts
Neurology near term key catalysts Focus Areas Molecule Indication Ph I Ph II Ph III Status Ocrevus SC RMS & PPMS OCARINA II EU approval: mid-2024; US approval: Sept RMS GAVOTTE Data expected 2025 Ocrevus HD Multiple Sclerosis PPMS MUSETTE Data expected 2025 (MS) Data expected 2025 FENhance 1 RMS Fen
Slide 10: Neurology diagnostics: Integrated solutions along patient journey
Neurology diagnostics: Integrated solutions along patient journey Biomarker tests drive access to disease modifying therapies and support disease management Screening and triage Diagnosis Treatment Disease monitoring Alzheimer’s Elecsys® Amyloid Plasma Panel Elecsys® CSF AD assay Anti-amyloid Ab: Di
Slide 11: Ocrevus: SC Q6M dosing approval expected 2024
Ocrevus: SC Q6M dosing approval expected 2024 EU approval expected mid-year; FDA PDUFA Sept 2024 Ocrevus SC to deliver significantly reduced time & treatment burden Ocrevus HD to further improve control of disability progression SC market expansion opportunities Convenient Q6M dosing frequency CDP b
Slide 12: Fenebrutinib: Highly selective, non-covalent, brain-penetrant BTKi
Fenebrutinib: Highly selective, non-covalent, brain-penetrant BTKi Ph III (FENhance 1&2) in RMS and (FENtrepid) in PPMS data expected 2025 BTKi competitive landscape1 Ph II (FENopta) results in RMS2 Fenebrutinib Tolebrutinib Evobrutinib Remibrutinib Total new T1 Gd+ lesions* CSF concentration Non-co
Slide 13: Enspryng in neurological disorders gMG, AIE, and MOG-AD
Enspryng in neurological disorders gMG, AIE, and MOG-AD First-in-class IL-6R inhibitor and best-in-disease potential in gMG IL-6 has a key role in multiple upstream mechanism which drive Preclinical/case study data support autoantibody-mediated neurological diseases use of anti-IL6R mAb in gMG Gener
Slide 14: GYM329 (anti-latent myostatin mAb) in SMA and FSHD
GYM329 (anti-latent myostatin mAb) in SMA and FSHD Best-in-disease potential to improve muscle strength in neuromuscular diseases Neurology development GYM329 (anti-latent myostatin mAb) program Efficient inhibition of latent Increase in muscle mass and strength in mouse models1 myostatin but not GF
Slide 15: Elevidys in Duchenne Muscular Dystrophy (EMBARK) – MDA data presentation
Elevidys in Duchenne Muscular Dystrophy (EMBARK) – MDA data presentation Alex Murphy Senior Clinical Director
Slide 16: Duchenne muscular dystrophy: Unmet need remains critical
Duchenne muscular dystrophy: Unmet need remains critical DMD is progressive, irreversible, and 100% fatal 0–4 years1-4 5–7 years1,5,6 8–11 years5,6,8 Early teens2,5,6,8 Teens5,6,8 20s and 30s5,6,8 Motor delays Impaired ability to rise Impaired ability to walk, Loss of ambulation Unable to perform De
Slide 17: NSAA: A unidimensional functional scale
NSAA: A unidimensional functional scale NSAA may not capture changes in specific functional abilities in certain populations, particularly over 52 weeks NSAA assess 17 items that measure various functional abilities on a scale of 0, 1, and 2 17 assessments for ambulatory DMD patients Example - Rise
Slide 18: Timed function tests (TFT) are more responsive to disease change
Timed function tests (TFT) are more responsive to disease change Novel digital endpoint (SV95C) enables objective precise measurement of disease progression in the real world TFTs are lost in a predictable Time to rise (TTR) is strongly predictive Stride velocity 95th centile and sequential manner1-
Slide 19: Safety and efficacy of delandistrogene moxeparvovec versus placebo in DMD (EMBARK)
Safety and efficacy of delandistrogene moxeparvovec versus placebo in Duchenne muscular dystrophy (EMBARK): Pivotal Phase 3 primary results Jerry R. Mendell,*,1,2,† Francesco Muntoni,3 Craig M. McDonald,4 Eugenio M. Mercuri,5 Emma Ciafaloni,6 Hirofumi Komaki,7 Carmen Leon-Astudillo,8 Andrés Nascimen
Slide 20: Background
Background • Delandistrogene moxeparvovec is a rAAV vector-based gene therapy, designed to compensate for the absence of functional dystrophin in DMD by delivering a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered protein that retains key functional domains of the wil
Slide 21: Study design and endpoints
Study design and endpoints8 Stratification based on age at randomization (≥4 to <6 or ≥6 to <8 years) and Primary endpoint NSAA total score at screening (≤22 vs >22) • Change from baseline to Week 52 in NSAA total score PART 1: 52 weeks PART 2: 52 weeks Up to 5 years Key secondary functional endpoin
Slide 22: Patient demographics (Part 1)
Patient demographics (Part 1) Demographics were balanced between delandistrogene moxeparvovec and placebo groups Delandistrogene moxeparvovec Placebo All Characteristic (n=63) (n=62) (N=125) Age, mean (SD), years 5.98 (1.06) 6.08 (1.05) 6.03 (1.05) 4–5 years, n (%) 30 (47.6) 29 (46.8) 59 (47.2) 6–7
Slide 23: Safety overview
Safety overview Delandistrogene Placebo moxeparvovec (n=62) (n=63) Patients with any TEAE, n (%) 62 (98.4) 57 (91.9) TEAEs, n 664 502 Patients with any TR-TEAE, n (%) 48 (76.2) 17 (27.4) TR-TEAEs, n 235 43 Patients with any TR-SAE, n (%) 7 (11.1) 0 TR-SAEs, n 10 0 Patients with an AE leading to stud
Slide 24: Change from baseline in NSAA
Primary endpoint: Change from baseline to Week 52 in NSAA total score Between-group difference LSM (SE): 0.65 (0.55) points (95% CI −0.45 to 1.74) P=0.2441 Change from baseline in NSAA 3.50 3.00 total score, points, 2.50 2.57 LSM (95% CI)* 2.00 1.92 1.50 1.00 0.50 0.00 0 12 24 36 52 Time (weeks) Del
Slide 25: Functional endpoints at Week 52 in the overall population
Functional endpoints at Week 52 in the overall population Delandistrogene Placebo Favors delandistrogene LSM difference (95% CI) P-value* moxeparvovec moxeparvovec Primary NSAA 63 61 0.65 (−0.45 to 1.74) 0.2441 Key TTR 63 61 −0.64 (−1.06 to −0.23) 0.0025 secondary 10MWR 63 61 −0.42 (−0.71 to −0.13)
Slide 26: Change from baseline in TTR
Key secondary functional endpoint: Change from baseline to Week 52 in TTR Between-group difference LSM (SE): –0.64 (0.21) seconds (95% CI –1.06 to –0.23) P=0.0025* 0.75 Change from baseline in TTR, 0.50 seconds, LSM (95% CI) • Negative values indicate an improvement 0.37 0.25 in the time taken to ac
Slide 27: Post hoc analyses on TTR
Post hoc analyses on TTR • All patients had a TTR <5 seconds at screening • With delandistrogene moxeparvovec treatment, fewer patients progressed to a TTR of >5 seconds compared with placebo Patients with TTR >5 seconds at Week 52 Delandistrogene Reduction in odds • A TTR of >5 seconds is a thresho
Slide 28: Change from baseline in 10MWR
Key secondary functional endpoint: Change from baseline to Week 52 in 10MWR Between-group difference LSM (SE): –0.42 (0.15) seconds (95% CI –0.71 to –0.13) P=0.0048* 0.50 10MWR, seconds, LSM (95% CI) Change from baseline in 0.25 • Negative values indicate an improvement in the time taken to achieve
Slide 29: Conclusions at Week 52
Conclusions at Week 52 Safety findings demonstrate the manageable benefit–risk profile of delandistrogene moxeparvovec with no new safety signals identified and no deaths, study discontinuations, or clinically relevant complement-mediated AEs Delandistrogene moxeparvovec did not reach statistical si
Slide 30: Elevidys in Duchenne muscular dystrophy
Elevidys in Duchenne muscular dystrophy First and only gene therapy approved for the treatment of ambulatory DMD pts 4-5 yrs Comprehensive development program Trial Patient population N Development stage Status 101 Ambulatory, 4-7 yrs. 4 102 Ambulatory, 4-7 yrs. 41 103 Ambulatory, 3-18 years 58 (END
Slide 31: Neurology early stage pipeline
Neurology early stage pipeline Azad Bonni SVP and Global Head of Neuroscience & Rare Diseases, Roche Pharma Research & Early Development
Slide 32: Neurology pipeline
Neurology pipeline Industry leading portfolio differentiated on targets and platform technologies Ph I (5 NMEs) Ph II (6 NMEs, 1AI) Ph III (1 NME, 5AI) Launched (4) Brainshuttle™ CD20 prasinezumab Enspryng Ocrevus RG6035 RG7935 RG6168 RG1594 Multiple Sclerosis Parkinson’s gMG RD Multiple Sclerosis M
Slide 33: Rapid dose-dependent amyloid plaque depletion with trontinemab
RAPID DOSE-DEPENDENT AMYLOID PLAQUE DEPLETION WITH TRONTINEMAB, A NOVEL BRAINSHUTTLETM ANTIBODY IN DEVELOPMENT FOR THE TREATMENT OF ALZHEIMER’S DISEASE Luka Kulic1, Fabien Alcaraz1, Angeliki Thanasopoulou1, Annamarie Vogt1, Carsten Hofmann2, Maddalena Marchesi3, Jakub Wojtowicz3, Gregory Klein1, Rut
Slide 34: Trontinemab - a novel Brainshuttle antibody targeting Aβ
Trontinemab - a novel BrainshuttleTM antibody targeting Aβ Active transport across the BBB significantly increases brain penetration and target engagement Trontinemab BBB Brain resident Microglia Anti-Aβ binder IgG1 Fc domain Transferrin Receptor 1 BrainshuttleTM (TfR1) module Aggregated Aβ Transfer
Slide 35: Brainshuttle technology enables higher brain exposure and broader CNS biodistribution
BrainshuttleTM technology enables a higher brain exposure and broader CNS biodistribution of therapeutic antibodies Standard IgG1 BrainshuttleTM IgG1 CNS, central nervous system; IV, intravenous. 1 Whole-brain imaging highlights the distribution of classical IgG vs. BrainshuttleTM IgG targeting a ne
Slide 36: Brainshuttle AD is a Phase Ib/IIa dose escalation study
BrainshuttleTM AD is a Phase Ib/IIa dose escalation study Staggered, parallel-group, adaptive study design with 4 initial sequential cohorts Screening Double-blind treatment period Follow-up Continuous 28 weeks (7 IV doses) 28 weeks Dose escalation: Cohort 4: 3.6 mg/kg or Pbo IV Q4W Cohort Expansion
Slide 37: Baseline characteristics are consistent across cohorts
Baseline characteristics are consistent across cohorts Interim analysis1 included data from 15 participants in cohort 4 (3.6 mg/kg) at BL2 Cohort 1 Cohort 2 Cohort 3 Cohort 41 Baseline demographic and disease 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg/kg or Pbo 3.6 mg/kg or Pbo characteristics (n = 14
Slide 38: Dose-dependent amyloid lowering with trontinemab (cohorts 1 to 3)
Dose-dependent amyloid lowering with trontinemab (cohorts 1 to 3) Mean amyloid PET change from baseline1 Placebo n = 12 n=5 n=9 0.2 mg/kg n = 11 - n = 10 0.6 mg/kg n = 11 - n = 10 1.8 mg/kg n = 13 n = 11 n=8 Snapshot date: 23 October 2023. 1 Mean values ±SE (standard errors) of available PET results
Slide 39: Further acceleration of amyloid plaque reduction at 3.6 mg/kg
Further acceleration of amyloid plaque reduction at 3.6 mg/kg Mean amyloid PET change from baseline1 Placebo n = 12 n=5 n=9 0.2 mg/kg n = 11 - n = 10 0.6 mg/kg n = 11 - n = 10 1.8 mg/kg n = 13 n = 11 n=8 3.6 mg/kg n = 12 n=8 - Snapshot date: 23 October 2023. 1 Mean values ±SE (standard errors) of av
Slide 40: Majority of participants at 3.6 mg/kg amyloid negative at 12 weeks
Majority of participants at 3.6 mg/kg amyloid negative at 12 weeks 5 out of 8 participants below the amyloid positivity threshold at interim analysis1 Mean amyloid value in CL at visit (% amyloid negative (<24.1 CL)) Visit 0.2 0.6 1.8 3.6 Pbo mg/kg mg/kg mg/kg mg/kg 98 CL 91 CL 88 CL 100 CL 119 CL B
Slide 41: Blinded safety profile
Blinded safety profile1 Number of participants with safety events or study discontinuations due to AE 12-week interim analysis Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total number of participants, (%) 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg/kg or Pbo 3.6 mg/kg or Pbo (n = 14) (n = 14) (n = 16) (n = 15)
Slide 42: Relevant AEs and MRI findings: IRR, anemia and ARIA
Relevant AEs and MRI findings: IRR, anemia and ARIA1 Lower IRR incidence with premedication; one mild anemia; no ARIA-E / ARIA-H in cohort 4 to date 12-week interim analysis Cohort 1 Cohort 2 Cohort 3 Cohort 4 Total number of participants with at least one 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg/kg
Slide 43: Summary
Summary Trontinemab is a novel BrainshuttleTM Aβ antibody that crosses the blood brain barrier via active TfR1 mediated transcytosis at the capillary level. In people with AD, trontinemab demonstrated rapid and robust amyloid plaque reduction at relatively low doses (1.8 and 3.6 mg/kg), compared wit
Slide 44: Trontinemab in Alzheimer's disease
Trontinemab in Alzheimer’s disease Best-in-class potential: fast and highly efficient plaque removal Trontinemab clears amyloid more rapidly than conventional mAbs 120 GRADUATE I GRADUATE II 100 Amyloid PET (centiloids) Lecanemab CLARITY AD 80 Donanemab TRAILBLAZER-ALZ-2 60 Trontinemab 3.6 mg/kg q4w
Slide 45: PASADENA long-term open-label extension in early-stage Parkinson's disease
PASADENA long-term open-label extension continue to show reduced motor and functional progression in prasinezumab-treated individuals with early-stage Parkinson’s disease compared to a real-world data arm Gennaro Pagano, M.D., Ph.D.,1,2 Annabelle Monnet, M.Sc.,3 Adriana Reyes, M.Sc.,3 Tanya Simuni,
Slide 46: Prasinezumab is a humanised IgG1 monoclonal antibody binding aggregated α-synuclein
Prasinezumab is a humanised IgG1 monoclonal antibody that selectively binds aggregated α-synuclein Proposed mode of action of prasinezumab for the treatment of Parkinson’s disease1–13 Parkinson’s disease Prasinezumab’s mode of action Aggregated Prasinezumab Proposed effects: extracellular selectivel
Slide 47: Contextualising the PD progression rate in PASADENA OLE vs PPMI
Contextualising the PD progression rate in the PASADENA open- label extension (OLE) vs PPMI cohort after a 4-year follow-up Objective: To compare progression on MDS-UPDRS in the PASADENA1,2 prasinezumab population with a propensity score-balanced cohort from the PPMI dataset PASADENA First year All
Slide 48: Baseline characteristics are balanced after weighting with propensity scores
Baseline characteristics are balanced after weighting with propensity scores Before propensity score After propensity score weighting weighting Baseline demographic and disease PASADENA PPMI PPMI characteristics N=271 N=303 SMD N=269.88 SMD Age (years) (mean (SD)) 59.98 (9.0) 62.11 (8.53) 0.243 61.2
Slide 49: Disease progression: MDS-UPDRS Part III
Prasinezumab-treated individuals progress less than PPMI on MDS-UPDRS Part III OFF (motor examination) Relative progression (80% CI) @ 4yrs Adjusted mean change from baseline 12 10 Disease progression -51% -5.73 [-7.33 to -4.14] 8 6 -65% -7.26 [-8.59 to -5.93] 4 2 Delayed-start 0 Early-start 0 1 2 3
Slide 50: Disease progression: MDS-UPDRS Part II
Prasinezumab-treated individuals progress less than PPMI on MDS-UPDRS Part II (motor experiences of daily living) Relative progression (80% CI) @ 4yrs Adjusted mean change from baseline 4 Disease progression -48% -2.2 [-2.96 to -1.45] -40% -1.82 [-2.44 to -1.2] 2 Delayed-start 0 Early-start 0 1 2 3
Slide 51: Summary
Summary The comparison of PASADENA and PPMI data suggests potential benefit in slowing motor progression in favour of prasinezumab on multiple endpoints Slowing of progression on MDS-UPDRS Part III (clinician-rated motor examination) OFF and ON symptomatic medication state, consistent with previou
Slide 52: Prasinezumab in Parkinson's disease
Prasinezumab in Parkinson’s disease Ph IIb (PADOVA) data expected 2H 2024 Ph IIb (PADOVA) trial design Primary endpoint: Time to confirmed motor progression event defined as ≥5 points on MDS-UPDRS Part III in OFF medication state at 18 months • PADOVA was designed to follow up on a signal of slowing
Slide 53: Doing now what patients need next
Doing now what patients need next