Sanofi SA · EURONEXT:SAN
Sanofi SA — Investor Day (December 2021)
48 slides from Sanofi SA's investor day presentation, Dec 1, 2021
Slide 1: Vaccines Investor Event Part 2: Leading with innovation
Vaccines Investor Event Part 2 Leading with innovation December 1st, 2021 1
Slide 2: Vaccines Investor Event | Agenda
Vaccines Investor Event | Agenda Introduction Paul Hudson Chief Executive Officer We Play to Win Thomas Triomphe Head of Vaccines GBU Winning in Influenza Bill Averbeck Head of Influenza Franchise Growing current business All infant protection Kimberly Tutwiler Head of RSV Franchise against RSV Q&A
Slide 3: Building an innovative & diversified pipeline
Building an innovative & diversified pipeline Jean-François Toussaint Head of Vaccines Research & Development
Slide 4: Building an innovative and diversified pipeline to deliver sustainable growth
Building an innovative and diversified pipeline to deliver sustainable growth Opening a new chapter at Sanofi Vaccines, R&D objectives expanding to new disease areas Rejuvenated pipeline, with 10 new development Leveraging state of the art immunology & candidates by 2025 antigen design (of which 6 m
Slide 5: Broadening our pipeline & opening new areas for growth
Broadening our pipeline & opening new areas for growth Deepen our leadership in existing franchises New Growth Areas Influenza Meningitis RSV Pneumo New frontiers • Fluzone HD • MenB • RSV toddler • PCV21 • Chlamydia pediatric • MenPenta • RSV older adults • Acne < QIV • Influenza & respiratory < <
Slide 6: Innovation addressing a large part of the population
Innovation addressing a large part of the population Pediatric Adolescents – – Children(1) Young adults(2) Adults(3) Older adults(4) 61m 1.9bn 44m 1.2bn 171m 3.7bn 55m 0.7bn Population U.S. Ex-U.S. U.S. Ex-U.S. U.S. Ex-U.S. U.S. Ex-U.S. Influenza Influenza QIV & Next-Gen Flu vaccine Meningitis MenB
Slide 7: We added mRNA to our state of the art toolbox
We added mRNA to our state of the art toolbox Established platforms mRNA & LNP platforms Subunit Monoclonal mRNA Vaccine Antibodies Vaccine • Broad range of antigen • Restricted to protein-based targets antigens • Viral & bacterial • Particularly well suited for Inactivated Lipid • Protein & polysac
Slide 8: Unlocking the potential of mRNA
Unlocking the potential of mRNA Frank DeRosa Head of Research mRNA CoE CoE: Center of Excellence
Slide 9: Sanofi mRNA Center of Excellence
Sanofi mRNA Center of Excellence A biotech environment with Sanofi’s powerhouse mRNA Center of Excellence Moving fast beyond 1st generation mRNA • Deep vaccine & antigen design expertise • Well-established development platforms • Expertise in running clinical trials • 400 dedicated employees in the
Slide 10: First clinical trial with our proprietary mRNA & LNP platform
First clinical trial with our proprietary mRNA & LNP platform Unmodified mRNA & proprietary LNP, Phase I design using COVID-19 as a reference antigen Days 0 21 36 mRNA 7.5µg Optimized unmodified mRNA encoding prefusion full-length mRNA 15µg SARS-CoV-2 spike protein Screening Proprietary LNP with mRN
Slide 11: Platform potential confirmed by positive interim results
Platform potential confirmed by positive interim results 100% seroconversion for all doses ≥ 15µg Tolerability profile in line with other unmodified mRNA COVID-19 vaccines Pseudovirus nAb to D614G 14 days post-dose 2 Grade 3 adverse events (SARS-CoV-2 seronegative participants, n=41) Open label sent
Slide 12: Progressing to clinic with influenza
Progressing to clinic with influenza Unmodified mRNA & proprietary LNPs, Phase I design for monovalent influenza vaccine Days 1 9 29 mRNA 7.5µg ; LNP #1 n=30 Optimized unmodified mRNA mRNA 7.5µg ; LNP #2 n=30 encoding for the hemagglutinin protein of the A/H3N2 strain mRNA 15µg ; LNP #1 n=30 Screeni
Slide 13: First evidence that mRNA could work for influenza
First evidence that mRNA could work for influenza, pending improved reactogenicity Immunogenicity Reactogenicity(2) Sanofi’s mRNA monovalent Flu 20.5 Sanofi’s mRNA monovalent Flu 89% LNP #1 LNP #2 LNP #1 LNP #2 12.4 9.5 40% 30% 4.5 22% 20% 3.1 3.7 2.9 10% 7% GMT ratio 7.5μg 15μg 45μg Rec. HA 7.5μg 1
Slide 14: Successfully pivoted to modified mRNA
Successfully pivoted to modified mRNA Switch to modified mRNA achieved Similar immunogenicity with modified mRNA in NHP Unmodified mRNA 1-N-MEΨ modified mRNA 5 5 • Pre-clinical data generated in multiple 4 4 animal models HAI Titer (Log10) 3 3 • GMP material produced 2 2 • On track to start clinical
Slide 15: Biomarkers show clear path to reduce reactogenicity
Biomarkers show clear path to reduce reactogenicity with modified mRNA and optimized LNPs IFN𝛼2 MCP-3 1,000 10,000 Proprietary ex-vivo MIMIC 1,000 System® assay enabling 100 evaluation of immune 100 responses 10 10 1 1 Un. Mod. Ø Un. Mod. Ø Un. Mod. Ø Un. Mod. Ø Un. Mod. Ø Un. Mod. Ø LNP #1 LNP #2…
Slide 16: Overcoming mRNA thermostability challenges
Overcoming mRNA thermostability challenges Storage at 4°C is needed for Stability of lyophilized mRNA Development of fully liquid vaccines outside pandemic drug product achieved formulation underway Proprietary lyophilized LNP Liquid stabilized prototype Shelf life at 2-8°C in the 48 registered prod
Slide 17: Breaking barriers to unlock mRNA potential
Breaking barriers to unlock mRNA potential 1st gen mRNA 2nd gen mRNA 3rd gen mRNA Immunogenicity High High High Tolerability profile in line with Tolerability profile in line with Reactogenicity Moderate to high established vaccines established vaccines Lyophilized Lyophilized Thermostability ~1 mon
Slide 18: Broadening the pipeline to address unmet needs
Jean-François Broadening the pipeline Toussaint Head of Vaccines to address unmet needs Research & Development Thomas Grenier Head of Franchises & Product Strategy 18
Slide 19: Influenza: further raising the bar
Influenza: further raising the bar Market overview Sanofi strategy to keep winning in flu 18% • Accelerated mRNA QIV Influenza development • Raising the bar further with Next-Gen Flu €6.7bn Standard dose vaccines Differentiated vaccines • Machine Learning for better strain selection 2020 • Expanding
Slide 20: First milestone achieved for Sanofi mRNA QIV
First milestone achieved for Sanofi mRNA QIV Pre-clinical data generated with unmodified mRNA Pivoted to modified for final candidate Log2 HA titers at Day 42(1) 16 H1N1 H3N2 B Victoria B Yamagata 14 12 10 8 6 4 2 • Optimized modified mRNA sequence 0 • Encoding for 4 HA proteins QIV HA mRNA QIV Reco
Slide 21: Influenza mRNA QIV development: Protection Beyond Flu
Influenza mRNA QIV development with objective to demonstrate Protection Beyond Flu Phase I/II – Targeted initiation in 2022 Phase III – Targeted Initiation in 2023 • Two age cohorts (18-64yo & 65yo+) • Quadrivalent vaccine based on WHO • Dose-selection trial selected strains • Comparison against sta
Slide 22: Later strain selection not the solution for improved efficacy
Later strain selection not the solution for improved efficacy Only 2 out of past 10 years with strain mismatch Shift in strain dynamic can occur late in season Season Predominant strain Vaccine strain to predominant Example of 2014-2015 season (H3N2 late mismatch)(3) in adults ≥ 65yo(1) circulating
Slide 23: Striving for better strain selection with Machine Learning
Striving for better strain selection with Machine Learning Antigens selected for cross-clade protection Higher seroconversion for ML-selected antigens(1) 3C.3 81 79 3C.2 66 66 62 54 43 35 36 28 Read-out SoC Other ML-2 *Line represents WHO strain ML - 1 ML - 2 ML - 3 ML - 4 antibody response after va
Slide 24: Exploring the potential of neuraminidase
Exploring the potential of neuraminidase to further build Protection Beyond Flu Fluzone SD/Fluzone HD already increase Exploring combined HA + NA multivalent vaccines anti-NA titers(1) Response in ferrets of multivalent protein and mRNA vaccines H1N1 H3N2 B Victoria B Yamagata Fluzone SD 14 NA Respo
Slide 25: Respiratory Syncytial Virus: protection across all age groups
Respiratory Syncytial Virus: protection across all age groups Market overview Best-in-class protection for all ages Nirsevimab: best-in-class mAb for All Infant Protection in first season 31% <1 year old RSV toddler: first-in-class Live €8bn 1 - 5 years old Attenuated Virus vaccine for second 2030 s
Slide 26: RSV burden does not stop after the first season
RSV burden does not stop after the first season U.S. RSV-related U.S. RSV-related hospital admissions(1) outpatient visits(2) RSV toddler vaccine target profile ~1,500k • Excellent safety profile ~39k ~905k • Efficacy against medically- attended upper and lower ~18k respiratory tract infections <1 y
Slide 27: FiC RSV toddler vaccine designed by reverse genetics
FiC RSV toddler vaccine designed by reverse genetics Epithelial cells Virus NS1 NS2 N P M SH G F M2 L NS2 Deletion of NS2 Deletion of 1313 with I1314L as stabilizer • Improved immunogenicity • Improved safety • Improved safety Ongoing Phase I/II in U.S. and Latin America (n=360 participants) – read-
Slide 28: Clinical data shows evidence of efficacy
Clinical data shows evidence of efficacy by reducing medically attended acute respiratory illnesses ∆NS2 vaccine candidate selected for further Evidence of efficacy(1) for both upper development and lower respiratory tract infections Neutralization titer Vaccine shedding by PCR % VE, N=80 11 8 100 1
Slide 29: RSV in older adults: addressing a large burden
RSV in older adults: addressing a large burden Estimated U.S. Estimated U.S. outpatient acute hospitalizations Virus infection amid 65yo+ amid 65yo+ evolution • Initiating standalone RSV mRNA vaccine to address high burden of disease in older adults RSV 1,041k(1) 105k(2) Low • Low variability of RSV
Slide 30: Best-in-class RSV antigen through innovative design
Best-in-class RSV antigen through innovative design RSV F antigen designed Improved immunogenicity Proven potency in mRNA format to focus on potent site 0 over competing antigens Site potency P = 0.0003 Competitive Elisa - Log2 IT50 Site 0 16 8 (Nirsevimab) 104 P = 0.02 Log2 RSV MN titer-1 Site 1 Ne
Slide 31: State of the art HMPV antigen candidate identified
State of the art HMPV antigen candidate identified Cutting edge antigen design Proven potency in mRNA format Sanofi proprietary mAb focused on most potent site (Site 0) Log2 HMPV MN titer-1 Log2 HMPV MN titer-1 16 16 4.5-fold 2.9-fold 12 12 8 8 HMPV F 4 4 Gen1(1) preF Gen2 preF Gen3 preF D0 D28 D56
Slide 32: Pneumococcal: more serotypes for better protection
Pneumococcal: more serotypes for better protection Large established market Strong fit with existing franchises • Synergy with pediatric and older 15% adult portfolio 6% • State of the art formulation Prevnar (PCV13) expertise with multi-valent vaccines €6.2bn Synflorix (PCV10) 2020 PPV Vx • Partner
Slide 33: Raising the bar with PCV21 candidate
Raising the bar with PCV21 candidate Serotype composition per vaccine IPD coverage in all ages by serotype (%) 1 4 5 6B 7F 9V 14 18C 19F 23F 3 6A 19A 22F 33F 8 10A 11A 12F 15B 9N 17F 20 2 27.5% 38.9% Sanofi PCV21 5.2% NVT/NT PCV21 non-PCV20 Pfizer Prevnar 20 6.7% Launch phase in the U.S. 29.3% PCV20
Slide 34: Extensive Phase II program across all age groups
Extensive Phase II program across all age groups Infant Primary Toddler Adult ≥ 50 years old n=700 n=140 n=750 • 2-4-6 months primary series & • Booster dose for toddlers having • Subjects naïve to prior PCV booster dose received 3 doses of PCV13 vaccination • 3 PCV21 formulations vs. • 3 PCV21 form
Slide 35: Meningitis: Strengthening our leadership
Meningitis: Strengthening our leadership Market overview • Established leader with Menactra in the U.S. 10% • MenQuadfi as a new standard in MenACWY, 8% with superior serotype C response to ease MenACWY market conversion to quadrivalent €2.4bn 48% MenB Other • Aiming for competitive MenB with broade
Slide 36: MenQuadfi as a new standard in MenACWY
MenQuadfi as a new standard in MenACWY MenQuadfi Menveo Nimenrix Sanofi (ACWY) GSK (ACWY) Pfizer (ACWY) Enhanced immunogenicity, with superiority against MenC in toddlers (1) Fully liquid quadrivalent U.S. ≥2 yo 2 months to 55 yo Not registered Broadest age ≥6 weeks EU ≥12 months old ≥2 yo(2) ≥6 wee
Slide 37: MenQuadfi first & only ACWY vaccine superior against serogroup C
MenQuadfi is the first & only ACWY vaccine to demonstrate superior immune response against serogroup C Enabling switch from MenC to MenACWY without compromising on serotype C Human complement SBA GMTs at D30 Rabbit complement SBA GMTs at D30 (hSBA GMTs) (rSBA GMTs) 2,143 1,624 515 32 227 315 MenQuad
Slide 38: Novel MenB vaccine aiming for increased protection
Novel MenB vaccine aiming for increased protection MenB antigen formulation Broader coverage of MenB strains(1) Non-Lipidated fHBP A+B ST-103 • Two fHBP covering all MenB strains ST-41/44 • Non-lipidated formulation allowing for better safety ST-11 1/1 1/1 3/4 1/2 1/1 4/4 1/2 4/4 2/2 ST-461 1/1 NadA
Slide 39: Pioneering science to open new growth areas
Pioneering science to open new growth areas Market overview (estimate) Delivering first-in-class vaccines • Chlamydia: tackling the most common infectious cause of female infertility >€2bn Chlamydia Acne (peak) • Acne: first immunotherapy to treat acne 39 Source: Sanofi forecasts
Slide 40: Chlamydia: a silent cause of infertility in women
Chlamydia: a silent cause of infertility in women Annual U.S. incidence in women Overwhelming burden in young women ~2m infections • 69% of estimated annual cases amid young women aged 24 years old or less ~800k non-diagnosed • Undiagnosed cases can lead to severe complications, particularly in wome
Slide 41: Chlamydia: mRNA best-suited platform
Chlamydia: mRNA best-suited platform to deliver desired immune response Optimized antigen for strong CD4 T-cells Selecting additional antigens to prevent response(1) Chlamydia entry in endocervical cells IFN-γ SFC/10(6) splenocytes Chlamydia infected cells (in red)(2) 3000 2000 1000 0 without antige
Slide 42: Acne: a stigmatizing condition
Acne: a stigmatizing condition • Significant psychological impact ~140m Mild acne worldwide cases(1) • Current SoC (oral isotretinoin) with severe side effects • Significant out-of-pocket expenses ($360-$720(2) / year in the U.S.) Moderate acne • P. acnes bacterium also associated with several ~90m
Slide 43: Immune system plays a significant role in moderate-to-severe acne
Immune system plays a significant role in moderate-to- severe acne Skin dysbiosis (acne patients) Skin homeostasis (healthy) Origimm‘s antigen induce a functional immune response against C. acnes virulent strains C. acnes phylotype Origimm's antigens Epidermis ◌ Keratinocytes ◌ Keratinocytes IA1 +++
Slide 44: Building an industry leading pipeline in Vaccines
Building an industry leading pipeline in Vaccines Future mRNA targets to be announced • Target to advance 10 clinical Next-Gen Flu vaccine SP0125 Respiratory syncytial virus (toddlers) candidates by 2025, incl. 6 First-in-class SP0202 mRNA vaccines Chlamydia mRNA Pneumococcal Lifecycle management SP
Slide 45: Opening a new chapter for Sanofi Vaccines R&D
Opening a new chapter for Sanofi Vaccines R&D 3 Chronic diseases 2 Epidemic 1 Endemic diseases 45
Slide 46: Conclusion
Conclusion Thomas Triomphe Head of Vaccines GBU
Slide 47: Our ambition in Vaccines
Our ambition in Vaccines Continued strong growth Unlocking the potential of Building an industry driven by four core franchises: mRNA in Vaccines with leading pipeline to Influenza, Meningitis, PPH & Next-Generation platform address unmet needs Boosters, RSV More than doubling Vaccine sales by 2030(
Slide 48: Q&A session | Leading with innovation
Q&A session| Leading with innovation Thomas Triomphe Jean-François Frank DeRosa Head of Vaccines GBU Toussaint Head of Research for Head of Vaccines R&D mRNA CoE Thomas Grenier Jon Heinrichs Head of Franchises & Head of R&D RSV Product Strategy Franchise