Sanofi SA · EURONEXT:SAN
Sanofi SA — ACTRIMS Forum 2022
33 slides from Sanofi SA's conference presentation, Feb 25, 2022
Slide 1: Sanofi
sanofi
Slide 2: Tolebrutinib Investor Call
Tolebrutinib Investor Call ACTRIMS Forum 2022 February 24-26 | West Palm Beach, Florida February 25, 2022
Slide 3: Forward-looking statements
Forward-looking statements This document contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward- looking statements are statements that are not historical facts. These statements include projections and estimates and their underlyi
Slide 4: Introduction
Introduction Dietmar Berger, MD PhD Global Head of Development, CMO
Slide 5: Agenda
Agenda ACTRIMS Investor Call 01 Introduction 04 Tolebrutinib 18month data Dietmar Berger, MD PhD Anthony Traboulsee, MD Global Head of Development, CMO Professor and Research Chair of the MS Society of Canada at the University of British Columbia, Vancouver 02 Sanofi in Neurology Tom Snow, 05 Tolebr
Slide 6: Significant progress made in neurology since 2020
Significant progress made in neurology since 2020 Key achievements Acquisitions / Collaborations Initiated four Phase 3 trials of tolebrutinib across the full spectrum of MS Initiated Phase 3 study of tolebrutinib in Myasthenia Gravis Initiated Phase 2 study of SAR4413441 (anti-CD40L mAb) in relapsi
Slide 7: Sanofi in Neurology
Sanofi in Neurology Tom Snow Global Franchise Head, Neurology
Slide 8: Building on a strong foundation in MS
Building on a strong foundation in MS Multiple Sclerosis (MS) market in 2026e3 Sanofi MS portfolio Anti CD-20 Orals Injectables - Investigational brain-penetrant (Aubagio, (IFNs, Tolebrutinib BTKi, designed to treat the entire $11.8bn dimethyl glatiramer target profile disease spectrum fumarate, ace
Slide 9: Neurology represents a highly attractive opportunity
With high unmet need and rapidly advancing science, Neurology represents a highly attractive opportunity Projected to be a key driver of industry growth1 30% Cancer High burden Rapidly 2026 Total Market Share €129bn of disease advancing science I&I Neurology 10% Others* Diabetes Infections Cardiovas
Slide 10: Targeted strategic approach
Targeted strategic approach Neuroinflammation Neurodegeneration Genetic Disorders Multiple sclerosis ALS Monogenic Neurological Disorders Myasthenia gravis Synucleinopathies: Parkinson’s Neuromuscular Disorders Disease, Multiple System Atrophy CIDP Complex Neurological Disorders Tauopathies: Alzheim
Slide 11: Neurology Pipeline Overview
Neurology Pipeline Overview Erik Wallstroem, MD PhD Therapeutic Area Head, Multiple Sclerosis
Slide 12: Clinical pipeline
Clinical pipeline Neuroinflammation Compound Description Target indication Phase Planned submission Tolebrutinib BTK inhibitor Relapsing Multiple Sclerosis 3 2024 Tolebrutinib BTK inhibitor Primary Progressive Multiple Sclerosis 3 2025 Tolebrutinib BTK inhibitor Secondary Progressive Multiple Sclero
Slide 13: Potential first in class bi-specific alpha-synuclein antibody for Parkinson's Disease
Potential first in class bi-specific alpha- synuclein antibody for Parkinson’s Disease Donor neuron Acceptor neuron ABL301 is a potential first-in-class bispecific antibody that targets alpha-synuclein, with a brain penetrant shuttle Brain shuttle targeting insulin-like growth factor 1 receptor Anti
Slide 14: RIPK1-inhibitor SAR443820
RIPK1-inhibitor SAR443820 Neuron Proposed impact on inflammation P and degeneration RIPK1i RIPK1 P Left: RIPK1 inhibition abrogates RIPK1 Damaged Damaged Proinflammatory Microglia inflammatory cell death and lysosome mitochondrion TBK1 OPTN Cytokines promotes survival of neurons RIPK1i and oligodend
Slide 15: Genetic, model and human tissue rationale for RIPK1 inhibition in ALS
Genetic, model and human tissue rationale for RIPK1 inhibition in ALS Genetics of ALS are enriched in RIPK1 RIPK1 inhibition in a mouse model RIPK1 activation is prominent in ALS interactors1 of ALS (SOD1G93A model)2 patient derived tissue2 Western blot analysis of human post-mortem RIPK1 modulators
Slide 16: Phase 2 Trial of SAR443820 in ALS (n=261)
Phase 2 Trial of SAR443820 in ALS (n=261) Study design: Study type: Phase 2, multi-center, randomized, double-blind, placebo-controlled study followed by an open-label long-term extension period SAR443820 Randomization (2:1) Primary endpoint: Change in ALS progression (ALSFRS-R score) SAR443820 Plac
Slide 17: Anti-CD40L SAR441344
Anti-CD40L SAR441344 A pleiotropic approach to MS therapy CD40L, a member of the TNF family is the classical ligand for CD40; targeting the CD40-CD40L co- stimulatory pathway could affect inflammation in MS via blockade of several interrelated mechanisms1. - Suppression of T-cell co-stimulation and
Slide 18: Potential for a personalized treatment approach
Potential for a personalized treatment approach Literature Biomarker data - Indication of the possibility of a biomarker approach to segment the population 1.0 - Highest needs are in the progressive forms of MS CD40L activation data is from 216 RRMS patients taken at baseline in the Druggable geneti
Slide 19: Phase 2 trial of SAR441344 in MS (n=120)
Phase 2 trial of SAR441344 in MS (n=120) ACT16877 study design Primary endpoint: - Number of new Gd-enhancing T1- hyperintense lesions at the Week 12 as measured by brain MRI Secondary endpoint: - Number of new or enlarging T2 lesions at Week 12 - Total number of Gd-enhancing T1 hyperintense lesions
Slide 20: Tolebrutinib 18-month data
Tolebrutinib 18-month data Anthony Traboulsee, MD Professor and Research Chair of the MS Society of Canada at the University of British Columbia, Vancouver Tolebrutinib is an investigational agent that has not been reviewed by any regulatory agency worldwide.
Slide 21: Strong impact on Gd-enhancing lesions and long term data on focal lesions
Strong impact on Gd-enhancing lesions and the only BTKi demonstrating long term data on focal lesions - New Gd-enhancing lesions remain low in patients who started on or switched to tolebrutinib 60mg - T2 lesion volume change remain low for the 60/60-mg arm - Median SEL volume lowest (284 [168-504]
Slide 22: 85% of patients remained relapse-free at 18 months
85% of patients remained relapse-free at 18 months ARR (A) and Relapse Frequency (B) up to the LTS Week 72 Cut-off 1 (A) (B) 2.0 100.0 ARR at 18 months = 0.17 84.7 1.5 80.0 ARR (95% CI) 1.23 Patients % 60.0 1.0 40.0 0.5 0.17 20.0 12.1 3.2 0 0.0 0.0 Year prior Week 72 cut-off 0 1 2 ≥3 to DBP (60 mg)
Slide 23: Continued favorable tolerability and safety profile
Continued favorable tolerability and safety profile Most common TEAEs occurring in ≥5% of patients 1 94% TEAE Patients, n (%) of patients remained in the study COVID-192 20 (16) at the 18-month cut-off Headache 16 (13) Nasopharyngitis 13 (10) Upper respiratory tract infection 10 (8) Arthralgia 7 (6)
Slide 24: Conclusion
Conclusion - Nearly all patients (94%) who enrolled in the long-term extension study of tolebrutinib in patients with RMS have remained on study as of September 6, 2021 (18-month cut-off). - New Gd-enhancing lesion counts remained low for the tolebrutinib 60-mg arm and were reduced in lower dose arm
Slide 25: Tolebrutinib pharmacology
Tolebrutinib pharmacology Tim Turner, PhD Global Project Head, Tolebrutinib Tolebrutinib is an investigational agent that has not been reviewed by any regulatory agency worldwide.
Slide 26: Fast and potent BTK inhibition with tolebrutinib
Fast and potent BTK inhibition with tolebrutinib BTK Conf. IC50 Interval Hill Curve (nM) 95% tolebrutinib 0.676 0.355 1.25 Kinact/Ki = 4.37 mM-1 * s-1 Kinetic experiments revealed that tolebrutinib inhibited BTK 64x faster than evobrutinib, 1,780x fenebrutinib 6.21 9.25 0.69 k1 = 0.00245 mM-1 * s-1
Slide 27: B-cell inhibition consistent with biochemical results
B-cell inhibition consistent with biochemical results 150 150 150 Normalized CD69 Expression Normalized CD69 Expression Normalized CD69 Expression IC50 = 3.62 nM IC50 = 19.8 nM IC50 = 80.9 nM R2 = 0.744 R2 = 0.918 R2 = 0.643 100 100 100 50 50 50 0 0 0 -4 -2 0 2 -4 -2 0 2 -4 -2 0 2 Log [tolebrutinib]
Slide 28: Superior brain penetrance in non-human primates
Tolebrutinib demonstrated intrinsically superior brain penetrance in non-human primates Comparison of Kp,uu,CSF on Day 4 at 10 mg/kg 0.50 0.45 0.397 AUC, CSF Cmax, CSF 0.40 BTK inhibitor (h*ng/mL) (ng/mL) 0.35 Kp,uu,CSF 0.30 tolebrutinib 19.6 4.84 0.25 0.20 evobrutinib 10.8 3.20 0.131 0.147 0.15 0.1
Slide 29: Conclusion
Conclusion Only tolebrutinib exceeded the IC90 value in CSF - Tolebrutinib was more potent in terms of BTK inhibition than evobrutinib (50x) or fenebrutinib (9.3x). Relative potency to 2.0 inhibit B-cell activation was consistent with biochemical results. Ratio of Cmax / IC90 in NHP 1.57 tolebrutini
Slide 30: Q&A session
Q&A session Dietmar Berger, MD PhD Tom Snow Erik Wallstroem, MD PhD Global Head of Development, Global Franchise Head, Therapeutic Area Head, CMO Neurology Multiple Sclerosis Anthony Traboulsee, MD Tim Turner, PhD Professor and Research Chair of the MS Global Project Head, Society of Canada at the U
Slide 31: Appendix
sanofi Appendix
Slide 32: ALS Study Population
ALS Study Population Inclusion criteria Exclusion criteria - Age 18 - 80 years - Currently taking moderate/strong CYP3A4 inhibitors or strong CYP3A4 inducers - Diagnosis of possible, clinically probable ALS, clinically probable laboratory-supported ALS, or - History of seizures clinically definite A
Slide 33: Ph2b LTS study design
Ph2b LTS study design 2 1 3 3 3 3 (1) Gap period in the transition between last dose in the DBP and first dose in the LTS study was variable (mean ± SD, 7 ± 7.3 weeks; range, 0-21 weeks). (2) Duration of Part A of the LTS study was variable (mean ± SD, 27.4 ± 6.3 weeks; range, 15-47 weeks). (3) DBP