Roche Holding Ltd · SIX:RO
Roche — Investor Day (October 2023)
56 slides from Roche's investor day presentation, Oct 30, 2023
Slide 1: Roche Neuroscience Update
Roche Neuroscience Update Virtual IR event 30th October 2023
Slide 2: 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 3: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 4: Agenda
Agenda Welcome 17:00 – 17:05 CET Bruno Eschli, Head of Investor Relations Neuroscience strategy update 17:05 – 17:20 CET Paulo Fontoura, SVP and Global Head of Neuroscience, Immunology, Ophthalmology, Infectious and Rare Diseases Clinical Development Multiple sclerosis (MS) - ECTRIMS data review 17:
Slide 5: Building blocks for future growth through 2030
Building blocks for future growth through 2030 Anti-TL1a mAb with significant upside added through Telavant acquisition Oncology / Hematology Neuroscience Ophthalmology Emerging assets from early pipeline and BD† Immunology CVM Telavant anti-IL6 mAb ASO Factor B zilebesiran acquisition anti-latent S
Slide 6: Building blocks for future growth through 2030
Building blocks for future growth through 2030 Today’s focus is on Ocrevus SC & fenebrutinib in MS and trontinemab & GSM in AD Oncology / Hematology Neuroscience Ophthalmology 4 Emerging assets early pipeline: GSM Immunology CVM anti-IL6 mAb ASO Factor B zilebesiran 3 anti-latent SPK-8011 tobemstomi
Slide 7: Consensus outlook 2022-26
Consensus outlook 2022-26* Growth driven by our young on-market portfolio; potential pipeline upside Biosimilar gap (22-26) Consensus sales growth (22-26) Potential upside3 Post-HY 2023 consensus survey Ronapreve 1.7 bn Vabysmo 4.3 bn Tecentriq 1.7 bn Additional upside by late-stage Lucentis 1.0 bn
Slide 8: Neuroscience strategy update
Neuroscience strategy update Paulo Fontoura SVP and Global Head of Neuroscience, Immunology, Ophthalmology, Infectious and Rare Diseases Clinical Development
Slide 9: Neuroscience pipeline
Neuroscience pipeline Industry leading portfolio differentiated on targets and platform technologies Ph I (5 NMEs) Ph II (9 NMEs, 1AI) Ph III (1 NME, 5AI) Launched (4) rugonersen prasinezumab Enspryng Ocrevus RG6091 RG7935 RG6168 RG1594 Angelman syndrome RD Parkinson’s gMG RD Multiple Sclerosis Brai
Slide 10: Neuroscience portfolio value
Neuroscience portfolio value Increasing contribution to Roche’s overall sales performance Growing Neuroscience portfolio Key pipeline assets with upside potential YTD Sep 2023 Ocrevus CHF 44.1bn* SC, high dose Enspryng gMG, MOGAD, AIE, TED Ocrevus: Elevidys 4,767 CHFm YTD* DMD fenebrutinib RMS, PPMS
Slide 11: Roche in Neuroscience
Roche in Neuroscience Preserving what makes people who they are Selected strategic focus areas Multiple Sclerosis (MS) Alzheimer’s disease (AD) Neuromuscular disease Multiple Stop, reverse andSclerosis prevent MS & Create a future of strength and independence for the Halt and prevent Alzheimer’s dis
Slide 12: Advancing the understanding & treatment options for MS
Advancing the understanding & treatment options for MS Build on Ocrevus’ leadership to further slow or stop disease progression Roche’s ambition in MS Clinical development program in MS actual approvals expected data readout 2017-18 2023 2024 2025 2026 and beyond Develop Advance transformational und
Slide 13: Ocrevus: Positive Ph III (OCARINA II) results for Q6M SC dosing
Ocrevus: Positive Ph III (OCARINA II) results for Q6M SC dosing1 Further improving treatment experience and expanding usage Ocrevus SC to deliver significantly reduced time & treatment burden Ocrevus SC market expansion SC administration time markedly Comfortable Q6M dosing frequency reduced vs IV A
Slide 14: Ongoing Ocrevus studies to further solidify leadership in MS
Ongoing Ocrevus studies to further solidify leadership in MS Investigating additional administration options and expanding patient populations Ocrevus SC Ocrevus 10-year data ● Non-inferiority of Ocrevus SC vs IV data from Ph Ib/III (OCARINA I / II) ● Long-term data from Ph III (OPERA/ORATORIO) pres
Slide 15: Fenebrutinib in RMS and PPMS
Fenebrutinib in RMS and PPMS Brain-penetrant, non-covalent BTKi with potential for best-in-class efficacy and safety BTKi competitive landscape1 Ph III program overview Fenebrutinib Tolebrutinib Evobrutinib Remibrutinib Non-covalent Covalent Covalent Covalent Reversible Irreversible Irreversible Irr
Slide 16: Continuing to invest in Alzheimer's disease to tackle high unmet need
Continuing to invest in Alzheimer’s disease to tackle high unmet need Leveraging key learnings to develop next generation therapies Roche’s ambition in AD Growing portfolio encompassing Pharma and Diagnostics Clinical development program Diagnostics portfolio Maximize the NME MOA Ph I Ph II Ph III T
Slide 17: Trontinemab in Alzheimer's disease
Trontinemab in Alzheimer’s disease First dose finding data for BrainshuttleTM anti-Aβ presented at CTAD Trontinemab Trontinemab is differentiated from conventional anti-Aβ mAbs and (BrainshuttleTM anti-Aβ Ab) other brain delivery technologies Blood BBB Brain tissue Homogeneous brain Inverted TfR1 bi
Slide 18: Gamma-secretase modulator (GSM) in Alzheimer's disease
Gamma-secretase modulator (GSM) in Alzheimer’s disease Targeting amyloid precursor protein processing to prevent Aβ-aggregation Gamma-secretase modulator (RG6289) Compelling therapeutic approach γ β β γ Golde et al. 2012, modified • γ-secretase cleaves the amyloid precursor protein (APP) to release
Slide 19: Roche's expanding portfolio in neuromuscular diseases (NMD)
Roche’s expanding portfolio in neuromuscular diseases (NMD) Creating a future of strength and independence for patients with NMDs Roche’s ambition in NMD Growing portfolio utilizing a diverse range of modalities NME MOA Indication Ph I Ph II Ph III Status SMN2 splicing Approved in >100 countries Sus
Slide 20: Multiple sclerosis (MS) - ECTRIMS data review
Multiple sclerosis (MS) - ECTRIMS data review Stephen L. Hauser Director, UCSF Weill Institute of Neurosciences Professor, Dept of Neurology, University of California, San Francisco
Slide 21: Disclosures
Disclosures Stephen L. Hauser serves on the Board of Directors for Neurona and on scientific advisory boards for Alector, Annexon and Accure and has received travel reimbursement and writing assistance from F. Hoffmann-La Roche Ltd and Novartis for CD20-related meetings and presentations. For the Ro
Slide 22: MS development is focused on addressing remaining unmet needs
MS development is focused on addressing remaining unmet needs MS unmet need Progressing or Underserved MS patient Access to IV uncontrolled MS groups capacity Up to 50% of MS experience Limited data in minority MS Limited access to infusion breakthrough disease and have populations such as paediatri
Slide 23: ECTRIMS 2023
ECTRIMS 2023 Ocrevus data overview Fenebrutinib data overview
Slide 24: Ocrevus SC shows comparable efficacy and safety to IV
Ocrevus SC shows comparable efficacy and safety to IV Twice-yearly 10 min injections for improved dosing convenience and compliance PK and B cell depletion with Ocrevus SC vs IV at week 24 (OCARINA II trial) 2 • Baseline demographics and disease characteristics in OCARINA II were reflective of the b
Slide 25: Ocrevus SC shows comparable efficacy and safety to IV
Ocrevus SC shows comparable efficacy and safety to IV Twice-yearly 10 min injections for improved dosing convenience and compliance Clinical effects and safety of Ocrevus SC vs IV at week 24 (OCARINA II trial) 2 2 • Ocrevus SC treatment led to near-complete suppression of radiological (MRI) and clin
Slide 26: Ocrevus the only aCD20 with 10 years of clinical experience
Ocrevus the only aCD20 with 10 years of clinical experience Unprecedented long-term efficacy and safety data Effect of delay in Ocrevus initiation Time to walking aid (RMS) and on 48W-cCDW on EDSS time to wheelchair (PPMS) RMS Ph III (OPERA I/II) trial PPMS Ph III (ORATORIO) trial RMS Ph III (OPERA
Slide 27: Ocrevus potential for preferred treatment for family planning
Ocrevus potential for preferred treatment for family planning RW data support using Ocrevus in women with MS during pregnancy and postpartum RW data of Ocrevus in women with relapsing-onset MS during pregnancy and postpartum TBU once team sends data • Family planning is an integral aspect in the car
Slide 28: ECTRIMS 2023
ECTRIMS 2023 Ocrevus data overview Fenebrutinib data overview
Slide 29: Fenebrutinib: Highly selective, non-covalent, brain-penetrant BTKi
Fenebrutinib: Highly selective, non-covalent, brain-penetrant BTKi Dual MoA: B-cell and myeloid cell activation High in vitro BTK selectivity Inflammatory and neuro- degenerative processes Acute begin early in MS and may Periphery Relapsing inflammation drive progressive disease Chronic disease biol
Slide 30: Cerebrospinal Fluid and MRI Analyses of Fenebrutinib Treatment in MS
https://ter.li/p8wdfo Cerebrospinal Fluid and MRI Analyses of Fenebrutinib Treatment in Multiple Sclerosis Reveal Brain Penetration and Early Reduction of New Lesion Activity: Results From the Phase II FENopta Study Amit Bar-Or,1 Michal Dufek,2 Hrvoje Budincevic,3 Jelena Drulovic,4 Mario Habek,5 Le
Slide 31: Methods
Methods Study design: FENopta—a randomised, double-blind, placebo-controlled trial (NCT05119569) • Age, 18–55 years Fenebrutinib 200 mg BID • EDSS, 0.0–5.5 at screening • RMS diagnosis with one of the following: – ≥2 relapses within the last 2 years or R Open-label period one documented clinical rel
Slide 32: Results
Results Fenebrutinib reduced T1 Gd+ lesions, few patients had new lesions after week 4 of treatmenta Gd+=gadolinium enhancing; aResults were estimated from a negative binomial model controlling for baseline T1 Gd+ lesion status (presence or absence) and included log number of scans as an offset; bTe
Slide 33: Results
Results Fenebrutinib was detected in the CSF at clinically relevant concentrations to impact mechanisms underlying chronic progressive disease biology in MS Mean fenebrutinib CSFa 43.1 ng/mL All patients had values within the active range (above IC50), and the CSF-to-plasma ratio indicated CNS penet
Slide 34: Results
Results Safety summary Fenebrutinib Placebo (n=73) (n=36) Patients with ≥1 AE, n (%) 28 (38.4) 12 (33.3) Total no. of AEs 40 19 Patients with ≥1, n (%) AE with fatal outcome 0 0 SAE 0 0 No SAEs were reported AE leading to dose interruption 0 0 Related AE 10 (13.7) 2 (5.6) All AEs were Grade 1 or 2,
Slide 35: Conclusions
Conclusions Fenebrutinib was present in the CSF at levels sufficient to reduce activation of B cells and microglia in vitro,1 suggesting that fenebrutinib may impact mechanisms underlying chronic progressive disease biology in MS The primary endpoint was met with a 69% reduction in the total number
Slide 36: Alzheimer's disease (AD) - CTAD data review
Alzheimer’s disease (AD) - CTAD data review Luka Kulic Therapeutic Area Leader Dementias, Medical Director Neuroscience and Rare Diseases
Slide 37: Roche is committed to transforming the AD journey
Roche is committed to transforming the AD journey by developing solutions across the breadth of AD Preclinical Early AD Moderate AD (primary and secondary prevention) (MCI-AD to mild AD dementia) Approved CSF biomarkers [pTau181/Aβ 42; tTau/Aβ 42] Therapy In development Decision support tools Plasma
Slide 38: CTAD 2023
CTAD 2023 Trontinemab data overview Gamma-secretase modulator data overview
Slide 39: Trontinemab in Alzheimer's disease
Trontinemab in Alzheimer’s disease First-in-clinic Aβ BrainshuttleTM antibody enhancing brain exposure Trontinemab Substantially higher brain / CNS levels with trontinemab (BrainshuttleTM anti-Aβ Ab) Blood BBB Brain tissue Non-human primates Healthy volunteers Transferrin receptor 1 Aβ binder Aggreg
Slide 40: Trontinemab rapidly reduces amyloid plaques in participants with AD
THE ANTI-AMYLOID BETA BRAINSHUTTLETM ANTIBODY TRONTINEMAB RAPIDLY REDUCES AMYLOID PLAQUES IN PARTICIPANTS WITH ALZHEIMER’S DISEASE Luka Kulic1, Fabien Alcaraz1, Annamarie Vogt1, Carsten Hofmann4, Philip Barrington3, Maddalena Marchesi6, Jakub Wojtowicz6, Gregory Klein1, Ruth Croney7, David Agnew7, D
Slide 41: Brainshuttle AD is a Phase Ib/IIa study
BrainshuttleTM AD is a Phase Ib/IIa study assessing the safety, tolerability, PK and PD study of trontinemab in participants with AD Primary Study Population Endpoints Objective Nature, frequency, severity, and timing MCI due to AD or mild-to-moderate AD (NIA-AA criteria) Safety and of AEs, includin
Slide 42: Brainshuttle AD study design
BrainshuttleTM AD study design 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: ▪ ≥10 study ▪ Expansion o
Slide 43: Rapid amyloid depletion at 1.8 mg/kg
Rapid amyloid depletion at 1.8 mg/kg 4/11 (36% of participants) below the amyloid positivity threshold at week 12, 6/8 (75%) at week 281 Mean amyloid value in CL at visit (% amyloid negative (<24.1 CL)) Visit 0.2 0.6 1.8 Placebo mg/kg mg/kg mg/kg BL 95 (0) 91 (0) 88 (0) 100 (0) Week 12 128 (0) - - 4
Slide 44: Trontinemab clears amyloid more rapidly than conventional mAbs
Trontinemab clears amyloid more rapidly than conventional mAbs BrainshuttleTM AD study results in comparison to other anti-Aβ mAb PhIII trial results Amyloid PET positivity threshold (24 CL) Gantenerumab GRADUATE I /II: presentation at CTAD 2022, publication in preparation; Lecanemab CLARITY AD: N E
Slide 45: Blinded safety profile
Blinded safety profile1 IRRs and a transient mild anemia were more common AEs in cohort 3 Cohort 1 Cohort 2 Cohort 3 Total Participants, n (%) 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg/kg or Pbo (n = 44) (n = 14) (n = 14) (n = 16) Participants with ≥1 AE 12 (85.7%) 14 (100%) 16 (100%) 42 (95.5%) Deat
Slide 46: Low incidence of ARIA despite robust amyloid lowering
Low incidence of ARIA despite robust amyloid lowering at 1.8 mg/kg One ARIA-E and one ARIA-H case occurred in cohort 3 (at 1.8 mg/kg trontinemab or Pbo)1 Cohort 1 Cohort 2 Cohort 3 Total number of participants [events per All Participants 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg/kg or Pbo participan
Slide 47: Conclusions
Conclusions 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 mg/kg Q4W), compared wit
Slide 48: CTAD 2023
CTAD 2023 Trontinemab data overview Gamma-secretase modulator data overview
Slide 49: Gamma-secretase modulator (GSM) in Alzheimer's disease
Gamma-secretase modulator (GSM) in Alzheimer’s disease Preventing Aβ-aggregation upstream in the amyloid cascade MoA Gamma-secretase modulator RG6289 in vitro pharmacology - Aβ42 lowering and Aβ38 elevation • GSM has a complementary MoA to anti-Aβ • RG6289 is a highly potent and highly selective GSM
Slide 50: RG6289, a New γ-Secretase Modulator: Phase I Healthy Volunteer Study
RG6289, a New γ-Secretase Modulator for the Treatment of Alzheimer’s Disease: Results from a Phase I Healthy Volunteer Study S. Sturm, A. Portron, A. Vogt, A. Poirier, T. Yang, A. Mohamed Abdi, G. Kollmorgen, C. Simmons, K. Mahil., L. Lindemann, K. Baumann, T. Mueggler, T. Vardar, R. Tortelli, I. Ge
Slide 51: Entry-into-Human integrated protocol
Entry-into-Human integrated protocol Evaluation of safety, tolerability, pharmacokinetics and pharmacodynamics in healthy participants Single Ascending Dose (SAD) Food Effect ▪ Healthy Participants (18 – 45 y) ▪ Healthy Participants (18 – 45 y) ▪ Doses A1-A7 RG6289 or Placebo ▪ Two-period, two-seque
Slide 52: Favorable safety and tolerability profile in healthy participants
Favorable safety and tolerability profile in healthy participants SAD and MAD study in young and elderly participants Most Commonly Reported AEs Most Commonly Reported AEs Most Commonly Reported AEs SAD Young Participants MAD Young Participants MD Elderly Participants RG6289* Placebo RG6289* Placebo
Slide 53: RG6289 pharmacodynamic profile
RG6289 pharmacodynamic profile Dose-dependent reduction of Aβ42 in plasma after multiple oral administrations ▪The dose-dependent Aβ42 reduction in plasma confirms target engagement. Aβ42 reduction (%) at predose on Day 14 MAD - Young Placebo C1 C2 C3 Time N=8 N=6 N=9 N=9 Predose -5.1 (4.4) -40.6 (4
Slide 54: RG6289 exhibits γ-secretase modulation
RG6289 exhibits γ-secretase modulation Effect of multiple administrations of RG6289 on Aβ isoforms in CSF ▪ Following multiple oral administrations of RG6289, Mean change from baseline (%) Mean change from baseline (%) Aβ37 a dose-dependent decrease in Aβ42 and Aβ40 and a dose-dependent increase in
Slide 55: Conclusions
Conclusions RG6289 showed a favorable safety and tolerability profile across all single and multiple doses in young and elderly healthy participants in this study. RG6289 exhibited a favorable PK profile supporting daily administration. Proof of RG6289 mechanism has been demonstrated based on the ob
Slide 56: Doing now what patients need next
Doing now what patients need next