Sanofi Sa · EURONEXT:SAN
Sanofi Sa — Technical Presentation (April 2020)
34 slides from Sanofi Sa's technical presentation, Apr 23, 2020
Slide 1: Phase 2b BTKi ('168) Trial Results
Phase 2b BTKi (‘168) Trial Results Dose-finding Study for SAR442168 in Relapsing Multiple Sclerosis April 23, 2020
Slide 2: Forward looking statements
Forward looking statements This presentation 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 under
Slide 3: Agenda
Agenda Introduction Bill Sibold EVP, Specialty Care Therapeutic Area Head, Phase 2 results Erik Wallstroem Neurology Development Progression in MS and Therapeutic Area Head, Rita Balice-Gordon underlying mechanisms Neurologic and Rare Diseases Research Phase 3 plan & John Reed EVP, Global Head of R&
Slide 4: Introduction
Introduction Bill Sibold EVP, Specialty Care 4
Slide 5: Sanofi's long-term commitment to Multiple Sclerosis
Sanofi’s long-term commitment to Multiple Sclerosis BTKi (‘168) target profile • Only oral DMT proven to reduce • Long-term disease control in the • Aiming at best-in-class across all the risk of confirmed disability absence of continuous dosing treatment dimensions worsening in 2 phase 3 trials(1,2
Slide 6: No approved therapy addresses all treatment dimensions despite ongoing improvement in SoC
No approved therapy addresses all treatment dimensions despite ongoing improvement in SoC '90s Today Time of launch Platform Platform BTKi ('168) Natalizumab Alemtuzumab Anti-CD20 injectables orals target profile Safety ✔ ✔ ✔ Low treatment burden ✔ ✔ Treatment dimensions RR reduction vs. (unmet plat
Slide 7: BTKi ('168) aims at superior target profile through dual MoA
BTKi ('168) aims at superior target profile through dual MoA Anti-CD20 MoA & clinical outcomes BTKi ('168) MoA & target profile CNS Periphery Periphery Exposure confirmed in Blood Blood CNS phase 1 (BBB crossing) Acquired Microglia Innate immunity Acquired immunity Thought to play a key B-cell B-cel
Slide 8: Large number of diagnosed MS patients receive no DMT
Large number of diagnosed MS patients receive no DMT More than 1/3 of U.S. patients and Higher proportion of untreated patients 1/2 of EU5 patients untreated as treatment options decrease Diagnosed 697 MS patients U.S. EU5 68% 62% 503 45% Treated 54% 51% 44% 66% 29% 55% Non treated 34% Total US Tota
Slide 9: Projected strong growth for B-cell targeting therapies
Projected strong growth for B-cell targeting therapies WW MS Sales (Market estimates, US$ bn) 24.1 22.9 0.2 Others 4.2 Platform injectables 6.5 8.5 Platform orals 10.4 1.6 0.2 Natalizumab 1.9 Anti-CD20 mAbs Alemtuzumab 9.5 0.3 ~40% of MS sales by 2024 Anti-CD20 3.8 2019 2024e Delivering BTKi ('168)
Slide 10: Phase 2 results
Phase 2 results Erik Wallstroem Therapeutic Area Head, Neurology Development 10
Slide 11: Dual MoA: targeting peripheral immune cell function and CNS-intrinsic inflammation
Dual MoA: targeting peripheral immune cell function and CNS-intrinsic inflammation Periphery(1) BBB Central Nervous System(1,2) (Blood vessel or subarachoid space) (CNS) T B Activation and OPC proliferation of LESION autoreactive lymphocytes B Neurodegeneration Dying neuron Cellular debris T Oligode
Slide 12: BTKi ('168) is the only molecule of its class to demonstrate pharmacologically relevant exposure in CNS
BTKi ('168) is the only molecule of its class to demonstrate pharmacologically relevant exposure in CNS Mean concentration (ng/mL) Pharmacologically relevant exposure 100.00 in CNS demonstrated in Phase 1(1) Plasma, free fraction 10.00 • Lumbar puncture performed 2hrs Plasma post-administration 1.00
Slide 13: Phase 2b study designed to assess dose and minimize exposure to placebo
Phase 2b study designed to assess dose and minimize exposure to placebo Primary endpoint Primary endpoint SAR442168 (12 weeks) 5 mg/d (n=15) • Randomized, double-blind, placebo-controlled, cross- Placebo run-in (4 weeks) 15 mg/d (n=15) over, dose-ranging Phase 2 study N=60 • Patient characteristics
Slide 14: 85% relative reduction in Gd+ lesions at 12w on 60mg
85% relative reduction in Gd+ lesions at 12w on 60mg Primary endpoint: number of new Gd+ Secondary endpoint: number of new or lesions after 12 weeks enlarging T2 lesions after 12 weeks RR in lesions,(1) -56.2 -62.8 13.5 85.0 RR in lesions,(1) 10.2 37.1 38.5 89.3 % (95% CI): (-194.0–17.1) (-356.2–41.
Slide 15: Phase 3 dosing (60mg fed) expected to maintain consistent exposure to achieve AUC
Phase 3 dosing (60mg fed) expected to maintain consistent exposure to achieve AUC Higher AUC in fed patients Higher response at higher exposure (Phase 1 data) (Phase 2 data) Daily AUC (ng.h/mL) 120 100 80 New Gd- 60 Enhancing T1- hyperintense 40 lesions 20 0 60mg fast 60mg fed 25% 75% Percentiles: A
Slide 16: BTKi ('168) safety profile in line with placebo
BTKi ('168) safety profile in line with placebo AEs during weeks 1-4 AEs during 12 weeks '168 treatment, n (%) All All Placebo(1) 5 mg 15 mg 30 mg 60 mg 5 mg 15 mg 30 mg 60 mg Patients Patients (N=66) (N=16) (N=16) (N=16) (n=16) (N=33) (N=32) (N=33) (n=32) (N=130) (N=130) Any AE (4 weeks vs. 38 (29.
Slide 17: Sampling of Phase 2 study results in RMS
Sampling of Phase 2 study results in RMS Relative Reduction in T1 Relative Reduction in T2 Molecule Design, Duration Primary endpoint Secondary endpoint lesions vs. PBO(1) lesions vs. PBO(1) Modern phase 2 design Placebo-controlled for 4Wk, with Dose-response for Gd+ Dose-response for T2 BTKi ('168)
Slide 18: Progression in MS and underlying mechanisms
Progression in MS and underlying mechanisms Rita Balice-Gordon Therapeutic Area Head, Neurologic and Rare Diseases Research 18
Slide 19: Patients continue to accumulate significant disability with currently approved therapies
Patients continue to accumulate significant disability with currently approved therapies Patients continue to accumulate 20% of patients still progress in less than disability(1) 10 years despite current therapies(3) Average EDSS score Proportion converted to SPMS 5.5 0.5 Two natural Glatiramer acet
Slide 20: Missing link: progression in MS involves mechanisms within the CNS
Missing link: progression in MS involves mechanisms within the CNS Periphery(1) BBB Central Nervous System(1,2) (CNS) T • In the CNS, the presence of B proinflammatory factors and OPC Activation and microglial activation results in proliferation of LESION autoreactive oligodendrocyte and myelin lymp
Slide 21: Microglia play a central role in MS disease progression
Microglia play a central role in MS disease progression GWAS identified enrichment of Transcriptome signatures reveal top upregulated genes in MS genes in microglia(1) progressive MS are most highly expressed in microglia(2) Multiple sclerosis SNPs MS gene enrichment = 5e-14 0.20 - 100,000 Microglia
Slide 22: Microglia from lesions of progressive MS patients express high levels of BTK
Microglia from lesions of progressive MS patients express high levels of BTK Microglia are increased BTK+ cells are microglia and BTK protein is upregulated in lesion rim increased in lesion rim in lesions Microglia PLP BTK Healthy Myelinated control RRMS SPMS PPMS BTK Actin lesion rim Demyelinated
Slide 23: BTK inhibition normalizes proinflammatory signature in microglia
BTK inhibition normalizes proinflammatory signature in microglia BTK inhibition normalizes the signature of BTK signature of mouse microglia training set mouse microglia activated by IgG segregates SPMS patient lesions from control BTK BTK dependent dependent genes genes Control + IgG + IgG +BTKi Co
Slide 24: BTK is a key regulator for microglial homeostasis
BTK is a key regulator for microglial homeostasis Scientific evidence Microglia play a central role in MS disease ✔ progression, as well as in other neurodegenerative disorders BTK inhibition has the potential to • Reduce microglial activation ✔ Microglia from progressive MS patients exhibit • Re-es
Slide 25: Phase 3 plan
Phase 3 plan John Reed EVP, Global Head of R&D
Slide 26: Launching trials for BTKi ('168) across full MS spectrum
Launching trials for BTKi ('168) across full MS spectrum Phase 3 program Non Relapsing Long Term Study Relapsing Primary Progressive Relapsing (RMS) Secondary Progressive (RMS) (PPMS) (NR-SPMS) Comparator vs. Aubagio® vs. Placebo vs. Placebo - ~900K diagnosed(1) ~120K diagnosed(1) ~172K diagnosed(1)
Slide 27: Exploratory imaging biomarkers to generate evidence for CNS activity
Exploratory imaging biomarkers to generate evidence for CNS activity Slowly Enlarging Lesions (SELs) Phase Rim Lesions (PRLs) • Chronic lesions seen on conventional T2 • Chronic lesions seen on Susceptibility images Weighted Imaging (SWI) • Inactive center, surrounded by a rim of • Paramagnetic rim
Slide 28: Beating industry cycle times to target submission in H1'24
Beating industry cycle times to target submission in H1'24 Today RMS Submission: H1 2024e Phase 1 and 2 performed, Phase 3 studies PPMS conducted 1 year on track to be initiated Submission: H1 2025e faster than benchmarks in mid 2020 NR-SPMS Submission: H1 2025e BTKi ('168): 2.9 years(1) BTKi ('168)
Slide 29: Conclusion: BTKi ('168) targets BiC profile
Conclusion: BTKi ('168) targets BiC profile Safety Similar to placebo Low treatment Oral once-daily, no monitoring burden Relapse rate In line with anti-CD20 reduction Slowing disability Only BTKi with demonstrated CNS penetration and in RMS engagement of potential markers of disability progression
Slide 30: Q&A session
Q&A session John Reed Bill Sibold EVP, Global Head of R&D EVP, Specialty Care Rita Balice-Gordon Tom Snow Therapeutic Area Head, Neurologic Global Franchise Head, and Rare Diseases Research Neurology and Immunology Erik Wallstroem Therapeutic Area Head, Neurology Development 30
Slide 31: Phase 2b BTKi ('168) Trial Results: Appendices
Phase 2b BTKi (‘168) Trial Results Appendices April 23, 2020 GettyImages
Slide 32: MRI is a predictive biomarker for relapses in MS
MRI is a predictive biomarker for relapses in MS Impact on relapses(1) 2 • Effect of MS treatments on Glatiramer acetate 40mg vs 20 mg 1 relapses are correlated with Laquinimod effect on MRI lesions (GdE Dimethyl fumarate and T2 lesions) -4 -3 -2 -1 0 1 2 Galtiramer • Effects on MRI lesions over ace
Slide 33: Patient Baseline Characteristics
Patient Baseline Characteristics SAR442168 All Patients Placebo(1) 5 mg 15 mg 30 mg 60 mg (N=130) (N=66) (N=33) (N=32) (N=33) (n=32) Age, years 37.1 (9.5) 36.3 (9.8) 36.0 (9.8) 35.9 (9.3) 39.1 (10.2) 37.1 (8.8) Female, n (%) 91 (70) 46 (70) 25 (76) 21 (66) 21 (64) 24 (75) RRMS, n (%) 128 (99) 65 (99
Slide 34: CNS exposure and high potency allows '168 to achieve pharmacologically relevant levels in the brain
CNS exposure and high potency allows ’168 to achieve pharmacologically relevant levels in the brain Mouse cerebrospinal fluid Mouse perfused brain 1hr post dose (ng/mL) 1hr post dose (ng/g) 40 200 30 Cellular IC50(1) 150 20 10 100 5 40 4 Cellular IC50(1) Cellular IC50(1) 30 3 20 2 Cellular 1 10 IC50