Slide 1: Slide 1
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: CTAD 2024 Virtual IR Event
CTAD 2024 Virtual IR Event October 31, 2024
Slide 4: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Roche in Alzheimer’s Disease Azad Bonni, SVP and Global Head of Neuroscience & Rare Diseases at pRED Trontinemab data at CTAD 2024 Luka Kulic, Therapeutic Area Leader Dementias and Expert Medical Director in Neuroscience & Rare Diseases, at pRE
Slide 6: Building blocks for future growth
Building blocks for future growth Neurology well-represented in upcoming launches Business development Oncology/Hematology Emerging assets from early pipeline Neurology Immunology CT-388 / gamma-secretase Ophthalmology zilebesiran CT-996 / CT-868 NXT007 modulator CVRM vamikibart vamikibart astegolim
Slide 7: 2025: Significant key newsflow ahead
2025: Significant key newsflow ahead* Compound Indication Milestone inavolisib + palbociclib + fulvestrant 1L PIK3CA-mut HR+ BC EU approval Columvi + GemOx 2L+ DLBCL US/EU approval Lunsumio SC 3L+ FL US/EU approval Elevidys DMD EU approval Regulatory Gazyva Lupus nephritis US/EU filing; US approval
Slide 8: Upcoming Roche IR events 2024
Upcoming Roche IR events 2024 CVM/EASD Pharma Day Neurology/CTAD Digitalization Day Sep 13 Sep 30 Oct 31 Nov 25 • Key data presented at EASD: • Group & Pharma strategy • Overview of the Roche • Roche digital efforts in Pharma • CT-388 (Ph I cohort 11 & 12 in update Alzheimer's Disease pipeline early
Slide 9: Neurology
Neurology Azad Bonni SVP and Global Head of Neuroscience & Rare Diseases, Roche Pharma Research & Early Development
Slide 10: Neurology R&D focus areas
Neurology Neurology R&D focus areas Preserving what makes people who they are Multiple sclerosis Neuromuscular disorders Neurodegenerative diseases Stop, reverse and prevent MS and Create a future of strength and Slow progression of Parkinson’s and preserve quality of life independence in NMD Alzhei
Slide 11: Neurology pipeline
Neurology Neurology pipeline Industry leading portfolio differentiated on targets and platform technologies Ph I Ph II Ph III Registration Brainshuttle™ CD20 prasinezumab Enspryng Evrysdi 5mg tablets RG6035 RG7935 RG6168 RG7916 Multiple Sclerosis Parkinson’s MOG-AD RD SMA RD MAGLi trontinemab Enspry
Slide 12: GYM 329: Anti-latent myostatin mAb to promote muscle growth in SMA
Neurology GYM 329: Anti-latent myostatin mAb to promote muscle growth in SMA Ph II (MANATEE) Part 1 results expected in 2025 GYM 329 (Anti-latent myostatin mAb) Pre-clinical data in a mouse models of muscle disease2 Combination rationale GYM 329 Change in muscle mass (g) • Evrysdi treats the underly
Slide 13: Ageing population and neurological conditions
Neurology Ageing population and neurological conditions Neurological conditions, including Alzheimer’s Disease, constitute significant health and socioeconomic burden Ageing population Economic burden Health threat World population ≥65 years old Economic burden* of AD and related Predicted global ma
Slide 14: Next-generation AD therapies to address unmet needs
Neurology Next-generation AD therapies to address unmet needs Defining a new standard of care for efficacy and safety Improved amyloid • Therapeutics providing faster, deeper amyloid removal1 clearance Prevention of • Convenient and effective maintenance therapy amyloid • Alternative treatment optio
Slide 15: Roche is committed to transforming the AD journey
Neurology Roche is committed to transforming the AD journey 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 Plasma biomarkers [pTa
Slide 16: RG6289, a FIC oral γ-secretase modulator for Alzheimer's disease
Neurology RG6289, a FIC oral γ-secretase modulator for Alzheimer’s disease Targeting amyloid precursor protein processing to prevent Aβ-aggregation GSMs reduce Aβ aggregation1 GSMs alter APP processing without changing the total amount of Aβ Non-aggregating Aggregating Aβ Aβ (Aβ37, Aβ38) (Aβ42, Aβ40
Slide 17: Ph I results: RG6289 modulates γ-secretase in healthy individuals
Neurology Ph I results: RG6289 modulates γ-secretase in healthy individuals Dose-dependent effect on Aβ monomers in cerebrospinal fluid Ph I: Dose escalation results in HVs1 • Daily administrations of RG6289 Mean change from Mean change from decreased Aβ42/40 and increased baseline (%) baseline (%)
Slide 18: Ph II (GABriella) trial design: RG6289 in at risk or prodromal AD
Neurology Ph II (GABriella) trial design: RG6289 in at risk or prodromal AD individuals First patient in achieved Q2 2024; interim data expected in 2026 GABriella: A Phase IIa RCT exploring safety, tolerability & effects of RG6289 on AD biomarkers over 18 months1 Baseline Treatment period EoT Follow
Slide 19: Trontinemab in AD clears Aβ more rapidly than conventional mAbs
Neurology Trontinemab in AD clears Aβ more rapidly than conventional mAbs Brainshuttle™ technology efficiently transports anti-Aβ mAb across the blood-brain-barrier (BBB) Standard IgG1 Brainshuttle™ IgG1 • Trontinemab uses Roche’s proprietary Brainshuttle™ technology, combining an Aβ binding mAb wit
Slide 20: Trontinemab CTAD data
Trontinemab CTAD data Luka Kulic Therapeutic Area Leader Dementias and Expert Medical Director in Neuroscience & Rare Diseases, at pRED
Slide 21: Latest interim results from the Brainshuttle AD study
LATEST INTERIM RESULTS FROM THE BRAINSHUTTLETM AD STUDY, A PHASE IB/IIA STUDY OF TRONTINEMAB IN PEOPLE WITH ALZHEIMER’S DISEASE Luka Kulic1, Fabien Alcaraz1, Gregory Klein1, Carsten Hofmann2, Stella Yilmaz2, João A. Abrantes2, Denise Sickert2, Maddalena Marchesi3, Jakub Wojtowicz3, Ruth Croney4, Dav
Slide 22: Affiliations
Affiliations 1. Neuroscience and Rare Diseases, Roche Pharma Early Research and Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland 2. Pharmaceutical Sciences, Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland 3. Product Development, Safety Risk Manageme
Slide 23: Disclosures
Disclosures Luka Kulic, Fabien Alcaraz, Gregory Klein, Carsten Hofmann, João A. Abrantes, Denise Sickert, Maddalena Marchesi, Jakub Wojtowicz, Ruth Croney, David Agnew, Paul Delmar, Hanno Svoboda, and Iris Wiesel are full- time employees and own stock in F. Hoffmann-La Roche Ltd. Stella Yilmaz i
Slide 24: 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 Endothelial cell Microglia (brain capillary) Anti-Aβ binder IgG1 Fc domain Transferrin Receptor 1 (TfR1) BrainshuttleTM Aggregated Aβ
Slide 25: Brainshuttle AD study design
BrainshuttleTM AD study design Phase Ib/IIa study assessing the safety, tolerability, PK and PD of trontinemab in participants with AD ▪ Study Population: MCI due to AD or mild-to-moderate AD1 (amyloid PET +; MMSE: 18–28; CDR-GS: 0.5-2) ⮚ Study Population: MCI due to AD or mild-to-moderate AD1; amyl
Slide 26: Brainshuttle AD study design
BrainshuttleTM AD study design Phase Ib/IIa study assessing the safety, tolerability, PK and PD of trontinemab in participants with AD ▪ Study Population: MCI due to AD or mild-to-moderate AD1 (amyloid PET +; MMSE: 18–28; CDR-GS: 0.5-2) ⮚ Study Population: MCI due to AD or mild-to-moderate AD1; amyl
Slide 27: Baseline characteristics at interim analysis
Baseline characteristics at interim analysis1 Analysis included 160 participants enrolled in Part 1 and Part 2 of the BrainshuttleTM AD study Completed1 Not yet completed (interim data) 1 PART 1 PART 2 (n=60) (n=100) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 Baseline demographic and 0.2
Slide 28: Blinded safety profile
Blinded safety profile1 Number of participants with safety events or study discontinuations due to AE Completed1 Not yet completed (interim data) 1 PART 1 (n=60) PART 2 (n=100) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 Total number of participants 0.2 mg/kg or Pbo 0.6 mg/kg or Pbo 1.8 mg
Slide 29: Case of intracerebral macrohemorrhage in Part 2 of the study
Case of intracerebral macrohemorrhage in Part 2 of the study Key risk factor: probable cerebral amyloid angiopathy (CAA) with superficial siderosis at screening ▪ On study day 44, a 78-year-old woman in cohort 3 Part 2 experienced a right A MRI B MRI frontal lobar macrohemorrhage and passed away: (T
Slide 30: Reduced incidence of IRR and limited, mostly mild anemia in Part 2
Reduced incidence of IRR and limited, mostly mild anemia in Part 2 so far Successful mitigation of IRR by implementation of premedication in cohort 4 (Part 1) and in Part 2. Lower incidence of anemia in Part 2 may be explained by lower blood volume drawn in Part 2 vs. Part 1. Completed1 Not yet comp
Slide 31: Latest interim results support low ARIA incidence with trontinemab
Latest interim results support low ARIA incidence with trontinemab 3 ARIA-E cases occurred in Part 1 and Part 2 as of snapshot date on September 2, 2024 Completed1 Not yet completed (interim data) 1 PART 1 PART 2 (n=60) (n=95) Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 3 Cohort 4 Total number of par
Slide 32: Amyloid PET in Part 1 (Snapshot date: October 23, 2023)
Amyloid PET in Part 1 (Snapshot date: October 23, 2023) Rapid and robust amyloid plaque depletion: -91 CL at 3.6 mg/kg after 12 weeks of treatment1 Snapshot date: September 2, 2024. 1 Mean values ±SE (standard errors) of available PET results at the different visit time points are plotted. CL, Centi
Slide 33: Amyloid PET in Part 1 (Snapshot date: September 2, 2024)
Amyloid PET in Part 1 (Snapshot date: September 2, 2024) Rapid and robust amyloid plaque depletion: -107 CL at 3.6 mg/kg after 28 weeks of treatment1 Snapshot date: September 2, 2024. 1 Mean values ±SE (standard errors) of available PET results at the different visit time points are plotted. CL, Cen
Slide 34: Amyloid PET in Part 1: most participants amyloid negative at 28 weeks
Amyloid PET in Part 1 (Snapshot date: September 2, 2024) Most participants on 3.6 mg/kg are amyloid negative at 28 weeks1 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 BL (0%) (0%) (0%) (0%) (0%) 11
Slide 35: Preliminary fluid biomarker results (Part 1)
Preliminary fluid biomarker results (Part 1) Dose-dependent, large magnitude effects of trontinemab on key downstream biomarkers in CSF CSF total tau (week 25) CSF ptau181 (week 25) CSF Neurogranin (week 25) ↓-30% ↓-34% ↓-29% Snapshot date: September 2, 2024. CSF, cerebrospinal fluid. CSF samples we
Slide 36: Summary
Summary Trontinemab has an overall favourable safety profile with very limited ARIA-E observed. ○ Lobar macrohemorrhage in a participant with significant risk factors and probable CAA led to a protocol amendment and exclusion of participants with superficial siderosis from the study. Results from th
Slide 37: Acknowledgements
Acknowledgements We thank all the study participants and their families, the investigators, and site staff for their time and commitment to the BrainshuttleTM AD study 37
Slide 38: Trontinemab in Alzheimer's disease
Neurology Trontinemab in Alzheimer’s disease Best-in-class potential: Fast and deep plaque removal with an improved safety profile Trontinemab clears amyloid more rapidly than conventional mAbs Trontinemab crosses the BBB and removes Aβ rapidly and robustly Amyloid clearance is accompanied by de
Slide 39: Elecsys Biomarker data at CTAD 2024
Elecsys Biomarker data at CTAD 2024 Margherita Carboni Indication Lead, Neurology and Clinical Development Lead in Neurology, Endocrinology and OBGYN at Roche Diagnostics
Slide 40: Developing Diagnostic solutions for the AD care pathway
Neurology Developing Diagnostic solutions for the AD care pathway Access to disease modifying therapies through timely diagnosis and integrated patient management Screening & early diagnosis Diagnosis Treatment & monitoring pTau217 EAPP (rule in & out) PET scan Patient monitoring Digital biomarker:
Slide 41: Elecsys Amyloid Plasma Panel (EAPP)
Core Lab Elecsys Amyloid Plasma Panel (EAPP) Strong rule out performance (NPV>90%) in prospective multicenter study Interim analysis of patients from 30 sites (N=492) Assay performance Endpoint: Amyloid PET Endpoint: Elecsys AD CSF Patients in study reflective of routine clinical practice and settin
Slide 42: Elecsys pTau217
Core Lab Elecsys pTau217 Method comparison shows strong clinical performance in cognitively impaired population1 Endpoint: Amyloid PET Elecsys and Lumipulse* discrimination of amyloid pathology Elecsys pTau217 assay Lumipulse* pTau217 assay Elecsys pTau217 shows a high clinical performance and a sig
Slide 43: Roche is well positioned to drive access to our neurology innovations
Neurology Roche is well positioned to drive access to our neurology innovations Build on our commercial presence around the world #1 #1 Attractive Diagnostics business case in Neurology In vitro Diagnostics Roche Pharma Neurology Differentiation in Core Lab and beyond >47,000 >150 Integrated solutio
Slide 44: Doing now what patients need next
Doing now what patients need next