#1So sanofi Immunology Investor Event Cambridge, MA March 29, 2022#2sanofi 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 underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words "expects", "anticipates", "believes", "intends", "estimates", "plans" and similar expressions. Although Sanofi's management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward- looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi's ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that COVID-19 will have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. Any material effect of COVID-19 on any of the foregoing could also adversely impact us. This situation is changing rapidly, and additional impacts may arise of which we are not currently aware and may exacerbate other previously identified risks. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under "Risk Factors" and "Cautionary Statement Regarding Forward-Looking Statements" in Sanofi's annual report on Form 20-F for the year ended December 31, 2021. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. 2 Immunology Investor Event#3Agenda Immunology Investor Event, March 29, 2022 Introduction, Eva Schaefer-Jansen sanofi 8:00-8:05 10:20-10:30 8:05-9:00 Presentation Play to Win in Immunology, Paul Hudson Immunology Strategy, Bill Sibold Leading with DupixentⓇ, Brian Foard Expand beyond Type 2, Naimish Patel Disruptive technologies, Frank Nestle 10:30-11:00 Moving to 2 breakout sessions Breakout session 1 Dermatology Moderated by Brian Foard/Frank Nestle and Sanofi panelists 11:00-11:05 Switching rooms/Break 9:00-9:10 Break 9:10-9:50 Expert encounter 11:05-11:35 Breakout session 2 'Fireside chat' John Reed in dialogue with: - Bartolome R. Celli, MD, FCCP Respiratory Moderated by Bill Sibold/Naimish Patel and Sanofi panelists Brigham and Women's Hospital Professor of Medicine, Harvard Medical School 11:35-11:40 Break and move back to main plenary session Joseph F. Merola, MD, MMSC Brigham and Women's Hospital Associate Professor, Harvard Medical School 11:40-11:50 Concluding remarks 9:50-10:20 Q&A with Presenters Paul Hudson 3 Immunology Investor Event#4sanofi Play to Win in Immunology Paul Hudson Chief Executive Officer#5Play to Win: Our six-year plan - ahead of schedule 2020-2022 Today Kil 2023-2025+ sanofi Refocus with decisive actions - Growth through winning assets Margin expansion · Transformative launches - Agile and efficient resource deployment - Leading R&D productivity 5 Immunology Investor Event#6Our key growth drivers DupixentⓇ €13bn+ COPD not included¹ Vaccines >2x sales by the end of the decade² Pipeline >90 projects Majority in Immunology, Oncology, Neurology, and Vaccines 1. €13bn+ refers to the peak sales ambition, not including COPD 2. vs. 2018, risk-adjusted, internal estimate, excluding Covid-19 vaccine DupixentⓇ is jointly developed and co-commercialized with Regeneron 6 Immunology Investor Event sanofi#7DupixentⓇ - Strong driver of sustainable growth Sales in €bn €0.1bn 2017 DUPIXENT (dupilumab) Injection 200mg 300mg €0.8bn €2.1bn €3.5bn 2018 2019 2020 €5.2bn 2021 €13bn+ COPD not included¹ Accretive to BOI margin in 2022 Economies of scale driving profitability Manufacturing improvements continue Expansion into COPD 1. €13bn+ refers to the peak sales ambition, not including COPD. DupixentⓇ is under investigation in COPD and not yet approved by any regulatory agency to treat COPD. Immunology Investor Event 7 sanofi#8Our strategic roadmap to win in Immunology Building an Immunology Megabrand DUPIXENT>> (dupilumab) Strong internal immunology science Combined with value-creating external Business Development World-class leadership team Deep bench of talent with diverse backgrounds Advancing innovative pipeline First-in-Class/ Best-in-Class potential in new therapeutic fields 8 Immunology Investor Event sanofi Immunology Sales >4x €5.5bn €2.3bn 2019 2021 2030e sanofi#9sanofi Immunology Strategy Bill Sibold EVP, Global Head of Specialty Care#10Immunology growth driven by priority areas 2020 WW Market Sales $85bn 2026 WW Market Sales Priority $116bn $31bn $47bn $22bn $10bn $17bn 57 $19bn $20bn $34bn $33bn Dermatology Respiratory Gastroenterology Source: Evaluate Pharma consensus forecasts - advanced therapy only, excludes biosimilar sales 10 Immunology Investor Event Rheumatology sanofi Dermatology Market today: Psoriasis, AD Upside: Accelerated AD and other indications CSU, HS, PN... Respiratory Market today: ~70% Asthma, ~30% IPF Upside: COPD Gastroenterology Market today: IBD - LOES vs new entrants Upside: Eosinophilic gastro diseases Rheumatology Market today: ~80% RA - LOES vs new entrants Upside: Lupus#11sanofi Substantial growth potential for AD Adult advanced therapy penetration in years after launch (in %) Psoriasis Atopic Dermatitis I 2% 1% 8% 2022 I 5% 9% 16% AD market expected to continue to grow faster than Psoriasis given high unmet need and competitive entrants AD adult penetration progressing strongly in the U.S. at 8% in the 5th year of launch, significantly ahead of Psoriasis market development We estimate adult penetration to be over 25% while adolescent and pediatrics in the 10-16% range in 10yrs Year 1 Year 5 Year 10 Year 15 Psoriasis¹ 2 4 AD1 1 42 7 7+ 12 7+ 1. Number of advance therapies; Atopic Dermatitis: estimated, pending Ph2/3 readouts 2. Abrocitinib, upadacitinib, tralokinumab and dupilumab Source: Treated patient counts directly from DRG/Clarivate 2018 report 11 Immunology Investor Event#12No effective therapies for severe COPD patients who failed standard of care Gold Guidelines (2018)¹ Group C Group D Consider roflumilast if FEV, 50% pred. and patient has chronic bronchitis Further exacerbation(s) LAMA + LABA Further exacerbation(s) LAMA LABA+ICS Further exacerbation(s) LAMA Group A Continue, stop or try alternative class of bronchodilator Group B LAMA + LABA evaluate effect A bronchodilator Consider macrolide - (in former smokers) - LAMA + LABA + ICS Persistent symptoms/further exacerbation(s) LAMA + LABA LABA + ICS Persistent symptoms A long-acting bronchodilator (LABA or LAMA) Preferred treatment →→→→ In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted - sanofi Highly symptomatic frequent exacerbations Highest mortality Major driver of healthcare costs in COPD No effective advanced therapies to date - 3rd leading cause of death worldwide, COPD is a progressive disease that imposes a significant burden - Typically treated with inhaled steroids or bronchodilators -"one size fits all" therapies DupixentⓇ & itepekimab being studied for the potential treatment of moderate to severe COPD patients estimated to be ~2 million patients² No biologics treatment approved No new MoAs in more than 10 yrs 1. Pharmacological treatment algorithms by GOLD Grade. Gold guidelines 2018 2. G7 countries: U.S., Canada, France, Germany, Italy, Japan, UK 2. 1 severe or 2 moderate exacerbations per year 12 Immunology Investor Event#13sanofi Potential to lead in COPD with two biologics to cover >80% of GOLD D COPD patients Patient population G7¹ 2035e Non-Type 2 Type 2 Former smokers (70%) itepekimab² ~1,139K patients Current smokers (30%) DupixentⓇ3 and itepekimab² ~640K patients DupixentⓇ3 only ~270K patients Up to ~30-40% of patients with COPD have evidence of Type 2 inflammation Both medicines have potential as 1st COPD biologic reaching 80% of highest unmet need patients Pivotal data expected 2023 and 2024 1. G7 countries: U.S., France, Germany, Italy, Japan, UK, Canada 2. Itepekimab is under investigation and not yet approved by any regulatory agency. Itepekimab is being developed in collaboration with Regeneron. 3. Dupixent is not yet approved for COPD and is being studied in patients with uncontrolled COPD treated with current SoC triple therapy among GOLD D. Patient populations exclude never smokers. 4. Halpin DMG, et al. EClin Med. 2019;14:32-41; Ajithkumar CS, et al. Ind ] Basic Appl Med Res. 2018;7:223-228; Oshagbemi OA, et al. Am J Respir Crit Care Med. 2017;195:1402-1404 13 Immunology Investor Event#14Blazing the trail with DupixentⓇ in priority areas Type 2 A Dermatology Atopic dermatitis DUPIXENTⓇ (dupilumab) Respiratory Asthma COPD DUPIXENTⓇ (dupilumab) Beyond Type 2 4+ Injectables Orals ✓ Topical DupixentⓇ is under investigation in COPD, EoE and in infant population in AD, and not yet approved by any regulatory agency to treat these indications 14 Immunology Investor Event 凹 sanofi Gastroenterology EOE or UC DUPIXENT® (dupilumab)#15sanofi Playing to win with 10 novel molecules in 3 priority areas. 57 Gastroenterology Dermatology Atopic dermatitis Respiratory Asthma COPD EOE or UC Type 2 DUPIXENTⓇ (dupilumab) DUPIXENTⓇ (dupilumab) DUPIXENT® (dupilumab) amlitelimab (anti-OX40L) Injectables amlitelimab (anti-OX40L) anti-IL13/TSLP anti-TNFa/IL-23 anti-IL13/OX40L NanobodyⓇ VHH NanobodyⓇ VHH anti-IL13/OX40L NanobodyⓇ VHH itepekimab (anti-IL-33) NanobodyⓇ VHH non-beta IL-2 (Synthorin™M) Beyond Type 2 Orals rilzabrutinib (BTKI) IRAK4 degrader rilzabrutinib (BTKI) eclitasertib (RIPK1) ✓ Topical BTKi Eclitasertib is being developed in collaboration with Denali. All other listed agents are currently under clinical investigation and their safety and efficacy have not been evaluated by any regulatory authority. Except with respect to Dupixent in AD (age 6+) and Asthma, all indications listed are under investigation and not reviewed/approved by any regulatory authority 15 Immunology Investor Event#16Immunology Franchise Transforming the practice of medicine 16 Immunology Investor Event DUPIXENT (dupilumab) Lead Key Type 2 inflammatory diseases Core TAS Expand Breakthrough medicines beyond Type 2 Science driven Disrupt Transformative technologies sanofi#17sanofi DupixentⓇ Leading in Type 2 Inflammatory Diseases Brian Foard Global Head of DupixentⓇ Franchise#18DupixentⓇ - Building a megabrand sanofi Indications Clinical program² Patients treated Demographics 2019 4 Positive pivotal trials in AD, Asthma and CRSwNP COPD and EoE initiated PN, CSU, BP planned 2022 61 7 new positive pivotal trials 12 new trials achieving FPI 7 new indications initiated >400K 125K adult, adolescent adult, adolescent, pediatric >4.9 million biologic eligible patients in AD U.S. and Ex-U.S.3 >2 million biologic eligible patients in Asthma and CRSWNP U.S. and Ex-U.S.4 Geographies 20 >50 Competition No other systemic biologic for Type 2 approved No other biologic with comparable breadth and scope of data on efficacy and safety across Type 2 indications and age groups 1. AD (18+Y, 12-17Y, 6-11Y), Asthma (12+Y, 6-11Y), CRSWNP; 2. For 2022, 7 positive pivotal trials (1 AD 6m-5Y, 1 Asthma 6-11Y, EoEx2, PNx2, 1 CSU), 12 FPI (1 AD 6m-5Y, 1 EoE ped, PNX2, CSUx2, 1 CIndU, 1 BP, 1 AFRS, 1 COPD, 1 CRSSNP, 1 CPUO), 7 New indications (CRSSNP, AFRS, CPUO, CIndU, BP, PN, CSU) 3. Japan, Germany, France, Italy, Spain, United Kingdom and China; 4. Japan, Germany, France, Italy, Spain & United Kingdom. 18 Immunology Investor Event#19The Leading Immunology Brand in Specialty Dermatology U.S. monthly dermatologist NBRx' 5,000 Jan 2016 Apr-17 Launch sanofi COVID19 попривет DUPIXENT (dupilumab) HumiraⓇ CosentyxⓇ TaltzⓇ TremfyaⓇ StelaraⓇ Outstanding performance 8% AD 6Y+ biologic eligible patient penetration² In 2021, Germany and Japan advanced therapy market grew >50% in a competitive environment In competitive environment, DupixentⓇ aims to be the gold-standard and foundational first-line systemic therapy in moderate to severe AD Jan 2022 1. IQVIA NPA Patient Insights, Jan'22. 2. IQVIA Custom Monthly Patient Report, Jan 22. AD: moderate to severe atopic dermatitis. All registered trademarks are owned by their respective companies. Leading Immunology Brand in US NBRx. 19 Immunology Investor Event#20sanofi Dupixent® - New MOA in CSU with positive Ph III data in bio-naïve patients Primary endpoint Study A¹: Mean changes from baselines at week 24 Itch reduction Itch severity Placebo + SOC² 35% reduction -6.01 weekly score (ISS7) ~2X Dupixent® + SoC² 63% reduction -10.243 Itch & hives reduction Urticaria activity weekly score (UAS7) 37% reduction -12.00 1. LIBERTY CUPID clinical program, 2. Non-sedating H1-antihistamine, 3. p<0.001 65% reduction -20.533 ~2X The use of Dupixent for CSU is investigational and the safety and efficacy has not been evaluated by any Regulatory Authority. The trial demonstrated safety results similar to the known safety profile of Dupixent in its approved indications. For the 24-week treatment period, the occurrence of treatment emergent adverse events were generally similar between the DupixentⓇ and placebo groups (50% of DupixentⓇ patients and 59% of placebo patients). 20 Immunology Investor Event Chronic spontaneous urticaria (CSU) is a debilitating Type 2 inflammatory disease, defined by intense itch and hives DupixentⓇ met primary endpoints in Ph3 Study A¹ of reducing itch and urticaria activity In patients refractory to omalizumab (Study B¹), DupixentⓇ did not reach statistical significance in an interim analysis; numeric improvements observed across key endpoints Ambition to move ahead with filing#21The Leading Immunology brand in Specialty Respiratory U.S. monthly respiratory NBRx¹ 3,500 Feb 2020 COVID19 Jan 2022 sanofi DUPIXENT (dupilumab) IgE IL-5s Outstanding performance 34 - - 19% Asthma 12Y+ biologic penetration² 5% Asthma 6-11Y biologic penetration² #1 Asthma NBRX share (28%) QTD Q1'22³ #1 in Asthma new patient share in Germany (31%)4 #1 total Asthma patients share 28% and new patient share 36% in Japan5 Potential best-in-disease Type 2 Asthma profile6 approved 6Y+ in U.S. & EU and 12Y+ in JP 1. IQVIA Custom US Monthly National Source of Business (Asthma, CRSWNP indications), Jan 22. 2. IQVIA Custom Monthly Patient Report, Jan'22 3. IQVIA Custom US Weekly National Source of Business, 2/18/22 4. Germany IQVIA LRX-Database. DupixentⓇ asthma biologics market (naïve and switches) Source of Business, Observational period 01/2022. 5. Japan local ATU W13 Jan '22. 6. Type 2 phenotype: Eos ≥150 or FeNo ≥ 20 ppb, and/or OCS dependence. Leading Immunology Brand in US NBRx. 21 Immunology Investor Event କ First biologic approved in CRSWNP in the U.S., EU, JP and CA#22sanofi DupixentⓇ: Potential best-in-disease in Type 2 Asthma DupixentⓇ significantly reduced Asthma attacks and demonstrated rapid and sustained improvements in lung function across a broad population of Type 2 Asthma patients ¹ as young as 6 years ≥18 Progressively declining exacerbation rate years 6-11 Rapid and sustained improvement in lung function5 Unadjusted annualized exacerbation rate across 3 years² (n=182) years FEV1 percent predicted, LS mean A from baseline (n=350) 2.1 Historical³ 0.4 0.3 0.2 Year 1 Year 2 Year 3 >60% Type 2 patients had no exacerbations for 3 years Predicted FEV, in percent 220006 + N 14 12 * Improvement as early as week 2 sustained up to 52 weeks *** ** *** ****** *** ******** ~2X *** *** ** ** DupixentⓇ4 Placebo 0 0 2 4 6 8 10 12 16 20 24 28 32 36 40 44 48 52 Week 1. Type 2 phenotype: Eos ≥150 or FeNo ≥20 ppb, and/or OCS dependence. 2. Population treated with dupilumab 300 mg Q2W across QUEST & TRAVERSE (with 96-week data on TRAVERSE). 3. Historical refers to the mean event count of severe exacerbations in the 1 year prior to QUEST. 4. Dupixent dose: 100mg q2w (16 to ≤ 30kg)/200mg q2w (> 30kg). 5. The overall rates of adverse events were 83% for DupixentⓇ and 80% for placebo 22 Immunology Investor Event#23sanofi Pivotal results support Dupixent'sⓇ potential as the first and only biologic for Eosinophilic Esophagitis U.S. regulatory submission completed, pending FDA acceptance Proportion of patients achieving peak esophageal eosinophil count ≤ 6 eos/hpf FDA Breakthrough Therapy Designation Absolute change from baseline in DSQ score, symptoms Responders (%) 80 88 100 60 60 40 Part A P < 0.0001 *** 60% 20 5% 6% 0 Placebo dupilumab 300 mg qw Placebo Part B P < 0.0001 *** 59% dupilumab 300 mg qw Absolute change from baseline, LS mean (SE) Part A Placebo dupilumab 300 mg qw Placebo 0 -15 15212 -5 -10 -9.6 -20 -25 -30 -21.9 I *** P < 0.001 I -13.9 Part B dupilumab 300 mg qw *** P < 0.0001 -23.8 Sources: Rothenberg Met al., Journal of Allergy and Clinical Immunology, Vol 149, Issue 2, Supplement, 2022, Pg AB312, The safety results of the trials were generally consistent with the known safety profile of Dupixent in its approved indications. For the 24-week treatment period, overall rates of adverse events were 84% (67/80) for Dupixent 300 mg weekly and 71% (55/78) for placebo. Dupixent in EoE is investigational and has not been fully reviewed by regulatory authorities; Dupixent is developed and commercialized in collaboration with Regeneron 23 Immunology Investor Event#24sanofi DupixentⓇ China: 'All In' to build a Blockbuster High unmet need in AD¹ Major Milestones Achieved - in less than 2 years Atopic Dermatitis launch indication ~2-5% of adult urban population Prevalence - July 2020 - fastest BLA approval in China - December 2020 - Inclusion in NRDL - September 2021 - Approval in adolescent AD indication ~9M ~900K Treated moderate-to- severe Accessible, affordable (biologic eligible) of which ~300K 2022 estimate >30K Patients treated with DupixentⓇ to date - February 2022 - Approval in children 6Y+ Launch execution Coverage in >3,000 hospitals and >15,000 HCPs >1,000 hospitals listed - 1/3 of accessible affordable market unlocked Planned indications and launch year - AD infant- 2023 - Asthma - 2024 - COPD - 2025 1 Based on China KOL estimates and publications as well as internal analysis; this is based on total urban China population (approximately 60% of total population) 24 Immunology Day#25We are just at the beginning of our journey... DUPIXENT (dupilumab) Atopic Dermatitis Adult 18+ Asthma Adult /Adol 12+ Atopic Dermatitis Adolescent 12+ CRSWNP Adult 18+ Atopic Dermatitis Ped 6-11 ୩ Asthma Ped 6-11 sanofi Today CIndU-COLD Adult/Adol 12+ CSU Adult/Adol 12+ EoE Ped 1-11 Prurigo Nodularis Adult 18+ EoE Adult / Adol 12+ Atopic Dermatitis Infant 6 mo-5Y DEN DEN EN 57 Bullous Pemphigoid Adult 18+ AFRS Adult / Ped 6+ COPD Adult 18+ CRSSNP Adult / Adol 12+ CPUO Adult 18+ by 2025 Approved Under regulatory review / submitted Investigational indications 1. Sanofi epidemiology estimates ...opportunity to add at least 1.5 million¹ of eligible patients 25 Immunology Investor Event#26Immunology Franchise Transforming the practice of medicine 26 Immunology Investor Event DUPIXENT (dupilumab) injection 300mg Lead Key Type 2 inflammatory diseases Core TAS Expand Breakthrough medicines beyond Type 2 Science driven Disrupt Transformative technologies sanofi#27sanofi Leadership in Dermatology and Respiratory Naimish Patel MD Global Head of Development, Immunology & Inflammation#28sanofi Immunology achievements since 2021 Capital Markets Day 1st DupixentⓇ COPD Study - BOREAS - completed enrollment Feb 2022 7 Phase 1 8 Phase 2 4 Phase 3 4 Pivotal Study Positive Readouts 5 Regulatory Submissions 3 Approvals DupixentⓇ CSU AD 6m - 5y EOE adult & adolescent DupixentⓇ AD 6m 5y (U.S., EU) AD pediatric 6-11y (CN) Asthma pediatric 6-11y (EU) EoE (U.S.) DupixentⓇ AD 12-17y (CN) Asthma 6-11y (U.S.) AD 6-11y (CN) itepekimab: COPD DupixentⓇ - PN - AFRS IRAK-4 degrader TNFα inhibitor oral anti-TNFα/OX40L NanobodyⓇ VHH anti-IL13/TSLP Nanobody® VHH anti-IL13/OX40L Nanobody® VHH anti-TNFα/IL23A Nanobody® VHH non-beta IL-2 amlitelimab: AD rilzabrutinib: (AD, CSU, Asthma) Topical BTKI (SAR'727): AD eclitasertib (RIPK1): CLE anti-CD40L: SLE, SJS CRSSNP CPUO These products are currently under clinical investigation and their safety and efficacy have not been evaluated by any regulatory authority. 2021 CMD: Sanofi Capital Markets Day, February 5, 2021 28 Immunology Investor Event#29Sanofi ambition to address unmet medical needs for a broad spectrum of AD and Asthma patients Mild Moderate-Severe sanofi AD sanofi Asthma Inhalers disease control, but Topicals safe and efficacious noncompliance an issue Safe Orals for less severe AD Topical BTKI rilzabrutinib IRAK-4 degrader rilzabrutinib Others AD and Asthma Except with respect to Dupixent, all listed agents are investigational and the safety and efficacy has not been evaluated by any regulatory authority 29 Immunology Investor Event sanofi Potential for higher efficacy biologics Injectables novel MoAs DUPIXENT (dupilumab) amlitelimab (T2 and mixed) anti-IL-13/OX40L NanobodyⓇ VHH DUPIXENT (dupilumab) amlitelimab (T2 and non-T2) anti-IL-13/TSLP NanobodyⓇ VHH anti-IL-13/OX40L NanobodyⓇ VHH Marketed injectables#30sanofi Beyond Type 2: Opportunity for amlitelimab and rilzabrutinib in patients with mixed inflammatory response Upstream Initiation Activation Virus Bacteria Allergens Epithelial Injury Tissue Effects Amplification Atopic Dermatitis Precision Medicine Approach ९ 2 IL-33 TSLP IL-25 Th2 APC OX40L OX40 Teff IL-5 Eosinophil IL-4 IL-13 Th2 Th17 IL-17 Th22 IL-22 B cell xx IgE Th2 dominant DupixentⓇ amlitelimab (anti-OX40L) Neutrophil Th17/22+Th2 (mixed) DupixentⓇ amlitelimab (anti-OX40L) Source: https://www.type2inflammation.com/science-cytokines. Immunity. 2019 Apr 16;50(4):778-795 Noda et al, J Al Clin Imm 2015 Nov;136(5):1254-64. All listed agents, except Dupixent, are investigational and the safety and efficacy has not been evaluated by any regulatory authority. 30 Immunology Investor Event rilzabrutinib (BTKi)#31sanofi Amlitelimab, an anti-OX40L, rebalances inflammation without immunosuppressive cell depletion in early studies. Virus Allergens Epithelial Injury OX40L blockade with advantages to OX40 depletion OX40L OX40 Blocker Depleter TSLP, IL-33, IL-25 Limited expression at sites of inflammation ✓ APC Preserves Teff, Tmem cells ✓ amlitelimab OX40L ↑ Preserves and activates Treg × OX40 eff mem Avoids cytokine release (fever, chills) Treg The information on this slide is for purposes of illustrating Amlitelimab's differentiated MoA. No conclusions should be drawn regarding the clinical efficacy of Amlitelimab alone or in comparison to any other treatment. No head to head studies comparing the referenced MoAs have been conducted. Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. Need to be confirmed in Ph3 trials. 31 Immunology Investor Event#32Amlitelimab treatment decreases key Type 2 and non- Type 2 pathway biomarkers in AD¹ patients IL-13 IL-22 IL-17A Log10(IL-13:Fold change vs Baseline) (median ± 95%CI) 0.5- 0.0- -0.5- ns Baseline D113 D29 Placebo amlitelimab Phase 2a data ns **** *** Baseline D29 D113 Log10(IL-22:Fold change vs Baseline) (median ± 95%CI) 1.0- 0.5- 0.0- -0.5- -1.0- Baseline ns **** ns * | D29 D113 Baseline D29 D113 ns *** 0.2- ns ns 0.1- Log10(IL-17A:Fold change vs Baseline) (median ± 95%CI) 0.0- -0.1- -0.2- | Baseline D29 D113 Baseline D29 D113 ****p<0.0001; ***p<0.001; *p<0.05; Baseline vs Day 29/113 (Two-way ANOVA with Dunnett's multiple comparisons test). Amlitelimab is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority 32 Immunology Investor Event sanofi#33Amlitelimab - Priority Asset with a highly competitive target profile Ph 2 study¹: >40% with clear/almost clear skin (16 weeks Q4W) 60 *** 50 44.4 40 40 37 10 Proportion of VIGA 0/1 10 20 patients, % 20 30 30 0 amlitelimab low dose (n=27) *** 8.3 amlitelimab high dose. (n=27) Placebo (n=24) Potential first-in-class anti-OX40L Convenient subcutaneous administration starting with Phase 2b Attractive target product profile due to infrequent dosing regimen and durability of response, addressing mixed-phenotype AD populations sanofi Ph 2 study²: AMG451 (16 weeks Q2W) Proportion of VIGA 0/1 patients, % 60 50 40 30.8 30 20 20 10 10 ** 18.5 1.8 0 AMG451 300mg AMG451 600mg Placebo ~70% of IGA 0/1 patients with sustained response off drug for 24 weeks ***p<0.001 vs placebo (Cochran-Mantel-Haenszel test) 1. Abstract 2729, Weidinger S, EADV 2021 The information on this slide is for purposes of illustrating amlitelimab's differentiated target profile. No head to head studies have been conducted and therefore, no conclusions should be drawn regarding the clinical efficacy of amlitelimab alone or in comparison to any investigational or approved treatment. 33 Immunology Investor Event **p<0.001; *p<0.05 vs placebo (Cochran-Mantel-Haenszel test) 2. Abstract 2867, Guttman-Yassky E, EADV 2021#34Amlitelimab - Accelerated development program following compelling Ph 2 datal Rapid Phase 2b start following positive Phase 2a in AD in 2021 Atopic Dermatitis Asthma Other indications 34 Immunology Investor Event 2022 Phase 2b 2023 Phase 3 Ambition 2024 (subject to regulatory discussions) Phase 2b 2025 sanofi Phase 3 Phase 3 Plan to run Phase 3 in Atopic Dermatitis concurrently to Phase 2 Asthma Phase 2b starting in second half of 2022 Planned development programs for other indications to start in 2023#35Rilzabrutinib and Topical BTKi positioned to address earlier stage Atopic Dermatitis Innate Immune Mast Cell/ Eosinophil IgE-mediated FCER activation and degranulation BTK signaling BTK signaling Macrophage BTK signaling Inflammation and Tissue Damage BTK signaling IgG-mediated FcyR activation, phagocytosis, inflammatory mediators BTK signaling BTK signaling Neutrophil Activation, adhesion, recruitment, oxidative burst sanofi Adaptive Immune Autoreactive B Cell Long-Lived Plasma Cell Plasma cell differentiation and antibody production Topical BTKI (SAR444727) Phase 2 study readout in H1 2023 rilzabrutinib Phase 2 study in moderate to severe AD Readout in H1 2023 Rilzabrutinib and topical BTKI are currently under clinical investigation, and their safety and efficacy have not been evaluated by any regulatory authority 35 Immunology Investor Event Autoantibodies IgE#36Rilzabrutinib is being evaluated in multiple Phase 2 clinical trials across a range of indications sanofi Target Population Clinical Trial Design AD Inadequately controlled with topicals; adults 18 or older; moderate-severe Placebo-controlled, 2 dose levels N=120 Primary efficacy evaluated at week 16 Asthma Add-on to ICS and second controller; adults 18-70 yrs, moderate-severe Placebo-controlled, 2 dose levels N=192 Primary efficacy at week 12 CSU moderate-severe disease; inadequate response to oral anti-H1 Placebo-controlled, 3 dose levels N=152 Primary efficacy evaluated at week 12 IgG4 Adult patients with IgG4-RD 2 arms, open label N=25 Primary efficacy evaluated at week 12 Primary Endpoint Change in EASI Score Loss of Asthma Control Positioning Best-in-class in oral BTKi class 36 Immunology Investor Event First-in-class ISS7/UAS7 Best-in-class Phase 2 readouts in 2023 and 2024 IgG4-RD RI First-in-class#37sanofi Itepekimab: A potent IL-33 blocker with sub-nanomolar affinity Allergen Smoke/pollutants Pathogens (virus & bacteria) IL-33 IL-33 IL-33 IL-33 IL-33 Neutrophil NK Cell Macrophage Th1 Basophil Mast cell Eosinophil Th2 Itepekimab is under investigation and not yet approved by any regulatory agency. 37 Immunology Investor Event Binds to human IL-33 with high affinity (Kd = 42 PM) Blocks the formation of the IL-33 / ST2 (IL-33 receptor) signaling complex and attenuates the downstream inflammatory cascade including both Type 2 and Type 1 immune responses - Potential to be best and first-in-class IL-33 biologic to treat former smokers with moderate to severe Type 2 and non-Type 2 COPD - Potential for best-biologic efficacy, with unprecedented exacerbation reduction in former smokers#38Itepekimab - Clear benefit in former smokers in COPD Phase 2 demonstrated regardless of Type 2 status¹ Higher IL-33 gene expression in lungs of former smokers with COPD Itepekimab reduced exacerbations in COPD former smokers, in Type 2 and non-" n-Type 2 patients IL-33 gene expression 5. 8 Current smoker (CS) Ex-smoker (CS) Smoking Status 1. Rabe et al. Lancet Respir Med. 2021 38 Immunology Investor Event Annualized rate of exacerbations 2.5 2 1.5 0.5 1 42.5% RRR 39.5% RRR 53.1% RRR 3 0 Overall <250 Itepekimab is under investigation and not yet approved by any regulatory agency. Itepekimab was generally well tolerated. Treatment emergent adverse events occurred in 78% of itepekimab patients and 80% of placebo patients. >=250 Blood eosinophil count (cells/μl) Placebo ■Itepekimab sanofi#39sanofi Address airway inflammation to improve lung function and reduce exacerbations in COPD Potential treatment paradigm Active Smoker High Blood eos DupixentⓇ Paula 67 yr woman COPD for 10 years 3 exacerbations in last year Frequent SOB, Cough Meds: ICS/LABA/LAMA DupixentⓇ High Blood eos itepekimab Former Smoker Low Blood eos itepekimab Itepekimab is under investigation and not yet approved by any regulatory agency. DupixentⓇ is under investigation in COPD and not yet approved by any regulatory agency to treat COPD. 39 Immunology Investor Event#40Parallel studies to address both Type 2 and non-Type 2 COPD DUPIXENT (dupilumab) Injection 300mg itepekimab first-in-class anti-IL-33 sanofi Itepekimab Phase 3 and DupixentⓇ Phase 3 in COPD are targeting two distinct populations with minimal overlap 2021 2022 Boreas Notus Aerify 1 2023 2024 Ambition to lead in COPD with two complementary assets, DupixentⓇ and itepekimab, with potential to deliver first-in-class and best-biologic efficacy Itepekimab pivotal program addresses an additional 40% of COPD patients not targeted by DupixentⓇ Opportunity to lead the science of emerging COPD endotypes (e.g. former smokers/frequent exacerbators) U.S. Expected Submission: EU Expected Submission 40 Immunology Investor Event Aerify 2 LPI achieved in Feb 2022 for Boreas#41Immunology Franchise Transforming the practice of medicine 41 Immunology Investor Event DUPIXENT (dupilumab) injection scomg Lead Key Type 2 inflammatory diseases Core TAS Expand Breakthrough medicines beyond Type 2 Science driven Disrupt Transformative technologies sanofi#42sanofi Breaking into New Frontiers in Immunology Frank Nestle Global Head of Research and Chief Scientific Officer#43Disruptive technologies driving FiC/BiC medicines - ✓✓ Small Molecules rilzabrutinib eclitasertib/ Antibodies - anti-CD40L - amlitelimab RIPK1 Inhibitor - itepekimab - TNFα Inhibitor - dupilumab - anti-TNFα/IL-23 - IL-17A Blocker sanofi Nanobody® Molecules Synthetic Cytokines - anti-IL-13/TSLP anti-IL-13/OX40L - anti-TNFα/OX40L Non-beta IL-2 Degraders IRAK4 Degrader 5 Respiratory | 4 Dermatology | 4 Gastroenterology | 4 Rheumatology 43 Immunology Investor Event#44AI research factory Improving quality and productivity of immunology research portfolio Target Discovery << AI Empowered >> Drug Discovery Clinical Translation Target Identification Engine Genes Features ΑΓ 44 Immunology Investor Event Single-Cell Disease Maps Normal Disease DMTA based Molecular Design Digital Pathology Design Make Exscientia Omics Association Pathology OWKIN Reducing timelines and increasing probability of success sanofi Disease Endotyping & Patient Stratification Group 1 Group 2 Group 3#45sanofi NanobodyⓇ molecules enable multi-targeting strategy A strong early clinical pipeline delivering transformative medicines 12-15kDa Anti-HSA Aspirational Profile Break efficacy ceiling anti-IL-13/TSLP Phase I Asthma Broadening patient population anti-Target 1 anti-Target 2 Half-life extension Break efficacy ceiling anti-IL-13/OX40L Phase I AD Durable disease remission Multi-targeting strategy to break efficacy ceilings Break efficacy ceiling anti-TNFα/OX40L Phase I RA Durable disease remission Convenience of dosing Convenience of administration anti-TNFα/IL-23 Phase I UC Break efficacy ceiling Address TNFI non-response Simplified development approach Break efficacy ceiling anti-TNFα/IL-6 Preclinical RA - Favorable economics and Cost of Goods Durable disease remission 45 Immunology Investor Event#46Anti-IL-13/OX40L bispecific NanobodyⓇ molecule Potential to break efficacy ceilings in Type 2 Inflammation IL-33 TSLP IL-25 Chemokines Tissue Inflammation Tissue Remodeling OX40L IL-13 OX40 Th22 Th17 Th2 mate cells IL-22 IL-17 IL-5 IL-4 Neutrophil Eosinoph B cell IgE Gene Expression Levels in Skin sanofi Control Allergen+ Placebo Allergen+ SAR443726 Allergen+ a-IL-13 mAb Allergen+ a-OX40L mAb House Dust Mite induced skin inflammation in a model of Atopic Dermatitis demonstrates potent reversal of reactions by SAR443726 Anti-IL-13/OX40L NanobodyⓇ VHH with potent picomolar binding affinity to both IL-13 and OX40L Albumin-binding designed to extend half-life Enhanced efficacy of bispecific NanobodyⓇ VHH in several preclinical models of Type 2 biology & diseases 46 Immunology Investor Event Phase 1 in healthy subjects ongoing; Indication: AD#47sanofi SAR444336/THOR-809: Precisely engineered non-ẞ IL-2 Selectively targeting regulatory T cells to restore immune homeostasis PEG SAR444336 IL-2 IL2RBy Tcon IL2RBY IL2R QIL2Ra Treg IL2RBY Signaling IL2Ra Signaling % Tregs in blood % Suppression 16 Tregs expanded in vivo are highly suppressive 60- 40- Dose-dependent Treg expansion in vivo (preclinical model) Gr1: Vehicle Gr2: 0.0025 mpk Gr3: 0.007 mpk Gr4: 0.022 mpk Gr5: 0.067 mpk Gr6: 0.2 mpk D-7 Pre 8 24 36 72 120 168 192 240 D13 D15 D22 Hours Treg suppression →Vehicle -SAR444336 20- 0-1 Days Increased ear thickness (mm) % Tregs 0.6- 0.4- 0.2- Dose-dependent control of skin inflammation (preclinical model) T T 0.0 Vehicle 0.1 0.3 Cys A SAR444336 (mg/kg) FoxP3 demethlyation 15- 10- 5 R2 0.98 P<0.0001 -20 No 16:1 8:1 4:1 2:1 1:1 Treg T T 0 80000 0 10 20 Tconv:Treg ratio 30 40 50 % demethylated FoxP3 Unique platform leverages synthetic biology technology Engineered for: Site-specific PEGylation affords absent binding to IL-2Rẞ with preserved IL-2Ra engagement Low MHC binding to limit immunogenicity Achieves high Treg selectivity Expansion of highly suppressive Tregs with demethylated FOXP3 gene Controls skin inflammation in vivo in preclinical model 47 Immunology Investor Event Phase 1 in healthy subjects in progress#48sanofi Next-generation of oral pathway medicines soluble TNFα TNFα Inh YYY IL-17A Y IL-17A Blocker IL1/IL18/IL33/IL36 Y Y Y Y Antibody-like efficacy with oral convenience Soluble TNFα Inhibitor (SAR441566) selectively blocks TNFR1 signaling Oral IL-17A Blocker target a key pro-inflammatory pathway TNFR1 INF-R TLR4 IL-17R BCR FcR TLRS IL-XR RIPK1 RIPK1 Inh BTK Inh BTK IRAK4 IRAK4 Inh Tissue Inflammation Dermatology | Respiratory | Gastroenterology | Rheumatology 48 Immunology Investor Event Tackling nodal targets RIPK1 Inhibitor (eclitasertib) targets a master regulator of cell death and proinflammatory cytokine production BTK Inhibitor covalent reversible (rilzabrutinib) targets 2 key molecular pathways IRAK4 Degrader - blockade of kinase and scaffold function for maximal disease impact#49SAR441566: The first oral TNFα inhibitor Tackling the largest therapeutic class in immunology Antibody-like efficacy in arthritis model 60 sanofi membrane TNFa W soluble TNFα Arthritis score Antibody-like efficacy seen at 10mg/kg 69% 71% 85% *** 50 15% 40 30 20 10 0 Vehicle 1 3 10 30 Anti-TNF mAb SAR441566 mg/kg SAR441566 distorts soluble TNFα trimer conformation and disrupts TNFR1 signaling Listeria infection model Y TNFR2 TNFR1 - Tissue repair - Protection from infection - Treg expansion - Pro-inflammatory cytokines and cell death. % Survival 100 80 60 Vehicle 40 SAR TNFI 30 mg/kg ▾ Anti-TNF mAb 20 0 0 4 6 8 10 12 14 Day Post Infection SAR441566, small molecule TNFα inhibitor, offers potential for antibody-like efficacy with oral convenience Selective inhibition of TNFR1 signaling offers potential for lower infection risk and improved efficacy Unique Mechanism of Action presents a potential to differentiate from marketed TNFα biologics and JAK inhibitors Oral TNFα inhibitor treated mice do not succumb to listeria infection in contrast to anti-TNF biologic 49 Immunology Investor Event Phase 1 in healthy subjects ongoing Proof of Mechanism readout in Psoriasis early 2023#50sanofi SAR444656 (KT-474): Potent orally bioavailable IRAK4 degrader TLRs Y MyD88 IRAK4 IRAK4 kinase inhibitor Inactive IRAK4 kinase PIRF5/7 NFKB IL1/IL18/IL33/IL36 scaffold function IRAK4 protein degrader (SAR444656) Inactive kinase Disabled scaffold function PIRF5/7 TNFα/ẞ, inflammatory cytokines (IL6, TNFα) & other inflammatory mediators 50 Immunology Investor Event Change from Baseline Mean (± SE) Percent IRAK4 -40 -60 Ph1 MAD PBMC IRAK4 (Kymera) -80 -100 1 2 3 4 7 14 17 21 Day Ph1 study ongoing → Placebo 25 mg QD ✰ 50 mg QD 100 mg QD 200 mg QD LLOQ 28 Degradation of IRAK4 protein abolishes its kinase activity and scaffold function Potential for oral immunology pathway drug across multiple indications SAR444656 treatment resulted in potent IRAK4 protein degradation in blood (PBMC) and skin of healthy volunteers#51Expected advances in early Immunology Pipeline 6 Phase 1 readouts 3 Phase 1b (PoM) readouts 8 Phase 2 readouts H1 2022 - TNFα inhibitor oral H2 2022 - anti-IL-13/TSLP NanobodyⓇ VHH: Asthma 2022 - Topical BTKI: AD 2023 eclitasertib (RIPK1): CLE CD40L: SJS, SLE rilzabrutinib (BTKI): AD, CSU, Asthma rilzabrutinib (oral BTKI): IgG4 - - - H2 2022 anti-IL-13/OX40L NanobodyⓇ VHH anti-TNFα/OX40L NanobodyⓇ VHH IRAK-4 degrader oral 2023 non-beta IL-2 anti-TNFα/IL-23 NanobodyⓇ VHH 2023 TNFα inhibitor oral: Psoriasis 2024 anti-IL13/OX40L NanobodyⓇ VHH: 2024 AD These products are currently under clinical investigation and their safety and efficacy have not been evaluated by any regulatory authority. 51 Immunology Investor Event sanofi#52Roadmap for leadership in Immunology Research Focus Accelerate Leverage sanofi Key Nodal Pathways Technology Innovation Precision Immunology Our Ambition: Breaking efficacy ceilings, achieving durable response and expanding into new indications 52 Immunology Investor Event#53Agenda Immunology Investor Event, March 29, 2022 Introduction, Eva Schaefer-Jansen sanofi 8:00-8:05 10:20-10:30 8:05-9:00 Presentation Play to Win in Immunology, Paul Hudson Immunology Strategy, Bill Sibold Leading with DupixentⓇ, Brian Foard Expand beyond Type 2, Naimish Patel Disruptive technologies, Frank Nestle 10:30-11:00 Moving to 2 breakout sessions Breakout session 1 Dermatology Moderated by Brian Foard/Frank Nestle and Sanofi panelists 11:00-11:05 Switching rooms/Break 9:00-9:10 Break 9:10-9:50 Expert encounter 11:05-11:35 Breakout session 2 'Fireside chat' John Reed in dialogue with: - Bartolome R. Celli, MD, FCCP Respiratory Moderated by Bill Sibold/Naimish Patel and Sanofi panelists Brigham and Women's Hospital Professor of Medicine, Harvard Medical School 11:35-11:40 Break and move back to main plenary session Joseph F. Merola, MD, MMSC Brigham and Women's Hospital Associate Professor, Harvard Medical School 11:40-11:50 Concluding remarks 9:50-10:20 Q&A with Presenters Paul Hudson 53 Immunology Investor Event#54sanofi#55Collaborations Name DupixentⓇ itepekimab KevzaraⓇ Developed in collaboration with... Regeneron eclitasertib (RiPK1i) Denali SAR444656 (IRAK-4) Kymera 55 Immunology Investor Event sanofi#56Abbreviations (Part 1) AD AFRS AI APC BD BiC BLA BOI BP BTKi CINDU CLE CMD CN COPD CPUO CRSSNP CRSWNP CSU DMTA DSQ EASI EoE Eos/hpf EU FcyR FCεR FEV1 FiC Atopic Dermatitis Allergic Fungal Rhinosinusitis Artificial Intelligence antigen-presenting cell Business Development Best In Class biologic license application Business Operating Income Bullous Pemphigoid Bruton tyrosine kinases inhibitor Chronic Inducible Cold Urticaria Cutaneous Lupus Erythematosus capital market day China Chronic Obstructive Pulmonary Disease Chronic Pruritus of Unknown Origin Chronic Rhinosinusitis without Nasal Polyps Chronic Rhinosinusitis with Nasal Polyps Chronic Spontaneous Urticaria Design, Make, Test, Analysis Dysphagia Symptom Questionnaire Eczema Area and Severity Index Eosinophilic Esophagitis Fc (fragment crystallizable)-gamma receptors Eosinophil/high power field European Union Fc-epsilon receptors Forced Expiratory Volume First-in-class FPI HCP HS HSA IBD ICS Ig IGA IgG4-RD IgG4-RD RI IL IPF IRAK4 ISS7 JAK JP kDa LABA LAMA LOE LPI LS LS mean (SE) mAb MoA Nab NBRx NK cell NRDL first patient in HealthCare Partners Hidradenitis Suppurativa human serum albumin Inflammatory Bowel Disease Inhaled corticosteroids immunoglobulin Investigator Global Assessment IgG4-related disease IgG4-RD Responder Index interleukin Idopathic Pulmonary Fibrosis Interleukin-1 receptor-associated kinase 4 Injury Severity Score Janus kinase Japan kilodalton Long-acting beta-agonists Long-acting muscarinic antagonists Loss of Exclusivity Last Patient In Least Squares least square mean (standard error) Monoclonal Antibody Mechanism of Action Nanobody® VHH New-to-brand natural killer cell National Reimbursement Drug List 56 Immunology Investor Event sanofi#57Abbreviations (Part 2) oral anti H1 OX40L PN PoM Q2W Q4W QW RA RIPK1 RRR SJS SLE SOB SoC TAS Teff TH2, (TH17, TH22,...) Tmem TNF TNFR Treg TSLP UAS7 UC Oral H1 antihistamines OX40 ligand Prurigo Nodularis Proof of Mechanism Once every two-week dosing Once every four-week dosing Once weekly dosing Rheumatoid Arthritis Receptor-Interacting serine/threonine-Protein Kinase 1 Relative Risk Reduction Sjögren's Syndrome Systemic Lupus Erythematosus Shortness of breath. Standard of Care Therapeutic Areas Effector T cells T helper 2 cells Memory T cells tumour necrosis factor TNF receptor Regulatory T cells Thymic stromal lymphopoietin Urticaria Activity Score Ulcerative Colitis 57 Immunology Investor Event sanofi#58Building an industry-leading immunology pipeline Injectable Topical DupixentⓇ Anti-IL4/IL13 mAb Oral Priority asset ΣΟ KevzaraⓇ Anti-IL6 mAb Aubagio® LemtradaⓇ EnjaymoⓇ Anti-complement C1s mAb DupixentⓇ Anti-IL4/IL13 mAb rilzabrutinib BTK inhibitor itepekimab Anti-IL33 mAb tolebrutinib BTK inhibitor MARKETED As of March 29, 2022 58 Immunology Investor Event REGISTRATION & PHASE III 8 amlitelimab Anti-OX40L mAb rilzabrutinib BTK inhibitor SAR'727 BTK inhibitor SAR'088 Complement C1s inhibitor SAR'344 Anti-CD40L mAb eclitasertib RIPK1 inhibitor SAR'820 u RIPK1 inhibitor 03 SAR'726 Anti-IL13/OX40L NanobodyⓇ VHH SAR'765 Anti-IL13/TSLP Nanobody® VHH SAR'970 Anti-TNF/OX40L NanobodyⓇ VHH Anti-TNF/IL23 NanobodyⓇ VHH SAR'999 SAR'336 Non-beta IL2 SAR'656 IRAK4 degrader SAR'566 TNF inhibitor PHASE I & II sanofi