American Thoracic Society - Sanofi Investor Call

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#1sanofi#2sanofi American Thoracic Society Sanofi Investor Call Washington, D.C. May 22, 2023#3sanofi 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 pandemics or other global crises may 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. 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, 2022. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. 3 Investor Relations#4sanofi 01 Agenda American Thoracic Society - Sanofi Investor Call Leadership in immunology Dietmar Berger, MD, PhD 05 Global Head of R&D ad interim 02 Lead with Dupixent® in Type 2 06 Elizabeth Laws, PhD Global Program Head, DupixentⓇ 03 Dupixent® BOREAS data in COPD Surya Bhatt, MD, MSPH Associate Professor of Medicine, University of Alabama at Birmingham 04 Q&A (Part 1) Klaus F. Rabe, MD, PhD, FERS Professor of Medicine, LungenClinic Großhansdorf, Germany Expand and disrupt beyond Type 2 Naimish Patel, MD Therapeutic Area Head, Immunology & Inflammation Unlock sustainable growth in Immunology Bill Sibold, Executive Vice President, Specialty Care 07 Q&A (Part 2) 4 ATS Investor Call#5sanofi Leadership in immunology Dietmar Berger MD PhD Global Head of R&D ad interim#6Key Respiratory development milestones since March 2022 sanofi Immunology Event March 2022 Amlitelimab Initiated Phase 2b study in Asthma Anti-IL-13/TSLP Nanobody® VHH Demonstrated Proof of Mechanism in Phase 1 study in Asthma DupixentⓇ Positive Phase 3 results with dupilumab in COPD (BOREAS study) Itepekimab Granted a Fast Track Designation status by FDA for COPD indication in January 2023 Dupixent® is jointly developed and co-commercialized with Regeneron. Itepekimab is being developed in collaboration with Regeneron. 6 ATS Investor Call Itepekimab Positive interim analysis in COPD (AERIFY 1 & 2 studies) sanofi ATS 2023 Today#7Strong immunology pipeline with 12 novel molecules to build and expand in leading franchise AD Dermatology CSU Psoriasis Respiratory Asthma Orals rilzabrutinib (BTKI) IRAK4 degrader rilzabrutinib (BTKI) Oral TNF inhibitor rilzabrutinib (BTKI) Injectables DupixentⓇ amlitelimab (anti-OX40L) DupixentⓇ DupixentⓇ amlitelimab (anti-OX40L) Anti-IL-13/TSLP NanobodyⓇ VHH DupixentⓇ itepekimab (anti-IL-33) DupixentⓇ DupixentⓇ COPD EoE EG Gastroenterology UC eclitasertib (RIPK1i) non-beta IL-2 (SynthorinⓇ compound) Autoimmune Lupus eclitasertib (RIPK1i) frexalimab (anti-CD40L) Anti-CD38 mAb Next Generation. DupixentⓇ sanofi Dupixent® is jointly developed and co-commercialized with Regeneron. Itepekimab is being developed in collaboration with Regeneron. DupixentⓇ is under investigation in CSU, COPD, EG and UC and not yet approved by any regulatory agency to treat these indications. All other agents described above are in clinical development and the safety/efficacy has not been established nor reviewed by any regulatory agency. 7 ATS Investor Call#8sanofi Ambition to transform the practice of medicine in Respiratory 8 ATS Investor Call DUPIXENT (dupilumab) Lead Key Type 2 inflammatory diseases itepekimab amlitelimab rilzabrutinib SAR'765 Expand Breakthrough medicines beyond Type 2 Disrupt Transformative technologies#9sanofi Lead with DupixentⓇ in Type 2 Elizabeth Laws, PhD Global Program Head, Dupixent#10Tackling Type 2 inflammatory disease. Type 2 inflammatory pathway Targets Allergens and parasites Key immune cells Key cytokines Th2 ILC2 Mast cell B-cell Basophil Eosinophil IL-4 IL-5 IL-13 Dysregulated type 2 immunity leads to chronic systemic diseases manifesting in different organ systems Gandhi NA, et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016; 15(1): 35-50. McCormick J, et al. Insights into the Implications of Coexisting Type 2 Inflammatory Diseases. J Inflamm Res. 2021; 4: 4259-4266 10 ATS Investor Call sanofi Leadership strategy > Lead with science Focus on highest unmet need with first-in-class and best-in-class opportunities Anchor on strategic pillars > Be bold and execute with relentless speed#11sanofi Lead with Dupixent® in Type 2 Positive pivotal data across 12 indications in Dermatology, Respiratory, and Gastroenterology EN 57 AD 18y+ PN 18y+ Asthma EoE 12+ 12y+ AD CSU 12-18y 12y+ Asthma 6-11y EoE 1-11y CRSWNP 18+ COPD 18y+ AD 6-11y AD 6m - 5y Studies in 7 additional indications ongoing: BP, CPUO, UC, EG, Peds (Asthma, PN, CSU) Dupixent® is under investigation and not yet approved by any regulatory agency to treat these indications First-in-Class biologics Efficacy & safety data across multiple Type 2 indications 60+ clinical trials with 10,000+ patients Safety data up to 5 years 1st FDA approval March 2017 > Approved in children as young as 6 months > More than 600,000 patients on therapy globally 11 ATS Investor Call#12sanofi - COPD Following the science with decisive actions Direct-to-Phase 3 program Investment de-risked with interim analysis IL4/IL13 plays a mechanistic role in pathologic processes in Type 2 COPD DUPIXENT (dupilumab) Patient population optimized based on IL-5 learnings Prior data support Type 2 COPD guided by eosinophils Targeting differential efficacy for FiC/BIC • High unmet need with no approved biologics 3rd leading cause of death WW, COPD carries a severe burden and leads to progressive loss of lung function • Typically treated with inhaled bronchodilators and steroids -"one size fits all" therapies with small treatment effects Potential to be first- and best-in-class Opportunity to reinforce respiratory market leadership Dupixent® is under investigation in COPD and not yet approved by any regulatory agency to treat this indication. 12 ATS Investor Call#13DupixentⓇ: Best-in-class execution in COPD sanofi 2014 2015-2016-2017-2018-2019-2020-2021 2022 2023 2024 2025 DUPIXENT (dupilumab) Mepolizumab METREX/METREO 18/20%1 BOREAS 30%¹ Triple therapy, >=300 cells/μL (screening), NO asthma history MATINEE Triple therapy, >=300/hist. >= 150 cells/μL (screening), asthma history Benralizumab GALATHEA/TERRANOVA 17/7%¹ RESOLUTE NOTUS Double/triple therapy, >=220 cells/μL (HEOS baseline), asthma history 1. Reduction in annualized rate in exacerbation vs. placebo DupixentⓇ is under investigation in COPD and not yet approved by any regulatory agency to treat this indication. HEOS: High peripheral blood eosinophils (cutoff in cells/μL noted) 13 ATS Investor Call Pivotal program resulting in outstanding performance 园 BOREAS recruited as many as 500 patients during COVID pandemic Highly significant and clinically meaningful improvement in exacerbations, lung function, quality of life, and symptoms (2) NOTUS recruitment completed and on track for readout in 2024#14DICINE NEW EN GNY The NEW ENGLAND JOURNAL of MEDICINE ORIGINAL ARTICLE Dupilumab for COPD with Type 2 Inflammation Indicated by Eosinophil Counts S.P. Bhatt, K.F. Rabe, N.A. Hanania, C.F. Vogelmeier, J. Cole, M. Bafadhel, S.A. Christenson, A. Papi, D. Singh, E. Laws, L.P. Mannent, N. Patel, H.W. Staudinger, G.D. Yancopoulos, E.R. Mortensen, B. Akinlade, J. Maloney, X. Lu, D. Bauer, A. Bansal, L.B. Robinson, and R.M. Abdulai, for the BOREAS Investigators* 14 14#15Background 50% of patients continue to have persistent symptoms and exacerbations despite optimization of existing therapy COPD exacerbations are associated with: ○ Increased risk of subsequent exacerbations o Lung function decline o High morbidity and increased risk of all-cause mortality A subgroup of COPD patients have an unmet need for therapies that further reduce exacerbations and improve lung function ATS 2023 15 15#16Pharmacological Treatment for COPD DYSPNEA LABA or LAMA LABA + LAMA EXACERBATIONS LABA or LAMA if blood eos <300 if blood eos ≥300 LABA + LAMA • Consider switching inhaler device or molecules • Implement or escalate non- pharmacological treatment(s) • Investigate and treat other causes of dyspnea if blood eos <100 if blood eos ≥100 L LABA + LAMA + ICS Roflumilast ATS 2023 FEV₁ <50% & chronic bronchitis Azithromycin Preferentially in former smokers Global Strategy for Diagnosis, Management and Prevention of COPD 2023 Report 16#17Microbes COPD Endotypes: "Type 2 High" Eosinophil Predominant T2 Viruses Smoke/pollutants Neutrophil Predominant T1 & T17 Smoke/pollutants Viruses Airway epithelium Microbes Mast cell Goblet cell Goblet cell Dendritic cell IL-4 IL-33 TSLP Macrophage IL25 TSLP тно Dendritic cell THO IL-13 IL-5 IL-5 IL-13 Tc1 IL-1, IL-8, TNF-α IL-25 IL-23 ILC3 B cells Mast cell TH2 IL-13 ILC2 Eosinophils IL-13 Neutrophils TH1/T17 Present in 20 to 40% of COPD ATS 2023 Airway smooth muscle Majority of COPD 17 12#18COPD with Type 2 Inflammation is Associated with More Frequent COPD Exacerbations: The COPDGene Study Eosinophil <n ≥n IRR 95% CI cut-off 100 cells/μL 223 1330 1.16 0.90-1.52 200 cells/uL 814 739 1.24 1.04-1.48 300 cells/uL 1187 366 1.32 1.08–1.61 340 cells/μL 1350 203 1.50 1.18-1.91 400 cells/μL 1398 155 1.60 1.24-2.08 2% 408 1145 1.22 0.99-1.50 3% 859 694 1.18 0.99-1.40 4% 1166 387 1.35 1.11-1.63 5% 1334 219 1.63 1.30-2.05 A blood eosinophil cut-off of 300 cells/µL identified a subgroup of ~20% of the study population who were at risk of frequent exacerbations ATS 2023 1.00 2.00 Incidence Rate Ratio 4.00 Yun JH, et al. J Allergy Clin Immunol. 2018;141:2037-2047 18#19Dupilumab Mechanism of Action Viruses Bacteria Smoke/pollutants Airway epithelium Type 2 inflammatory cytokines IL-5 IL-4 IL-13 Goblet cell hyperplasia Dupilumab blocks the shared receptor component for IL-4 and IL-13 Eosinophil activation TH2 cell differentiation Mast cell degranulation Type 2 inflammation (20 to 40% of COPD) Airflow obstruction ATS 2023 Exacerbation Lung function decline Airway remodeling & lung parenchyma destruction Le Floc'h A, et al. Allergy. 2020 19#20BOREAS Clinical Trial Design (NCT03930732) A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Dupilumab Administered Every 2 Weeks in Patients with Moderate or Severe COPD with Type 2 Inflammation Week-4 Week 52 Week 64 Follow-up Baseline Screening Randomization N=939 Treatment Period Dupilumab SC 300 mg q2w N=468 203 Placebo SC q2w N=471 ATS 2023 20 20#21Key inclusion criteria • Aged ≥40 to ≤80 years • BOREAS Eligibility Criteria Physician diagnosis of moderate-to-severe COPD • • • History of high exacerbation risk: ≥2 moderate or ≥1 severe exacerbation(s) within the year prior to screening Background triple inhaler therapy (ICS+LAMA+LABA) for at least 3 months prior to randomization with a stable dose for ≥1 month prior to screening; dual therapy (LABA + LAMA) allowed if ICS contraindicated Self-reported signs and/or symptoms of chronic bronchitis for 3 months in the year prior to screening Blood eosinophil count ≥300 cells/μL at the screening visit Current or former smokers with ≥10 pack years smoking history (current smokers capped at 30%) Key exclusion criteria • • COPD diagnosis for <12 months • Current diagnosis or prior history of asthma Significant pulmonary disease other than COPD ATS 2023 21 24#22Primary, Secondary, and Other Endpoints Baseline Primary endpoint Secondary and other endpoints Annualized rate of moderate-to-severe exacerbations from baseline to Week 52 Change from baseline to Week 12 and 52 in lung function Change from baseline to Week 52 in SGRQ % of patients with SGRQ improvement ≥4 points at Week 52 Change from baseline to Week 52 in E-RS:COPD total score ATS 2023 Week 52 22 22#23Age, mean (SD) — years Baseline Demographics and Disease Characteristics Characteristic Dupilumab (N = 468) All (N = 939) 65.1 (8.1) Placebo (N = 471) 65.2 (8.1) 65.0 (8.0) Male, no. (%) 322 (68.4) 298 (63.7) 620 (66.0) - Race White, no. (%) 397 (84.3) 393 (84.0) 790 (84.1) Ethnicity - Hispanic or Latino, no. (%) 129 (27.4) 132 (28.2) 261 (27.8) Smoking status Former smoker, no. (%) 323 (68.6) 334 (71.4) 657 (70.0) Current smoker, no. (%) 148 (31.4) 134 (28.6) 282 (30.0) Pack-years, mean (SD) 41.4 (24.4) 39.6 (22.3) 40.5 (23.4) BMI, mean (SD) - kg/m² 27.6 (5.7) 27.5 (5.4) 27.6 (5.6) Background medication Triple therapy (ICS+LAMA+LABA), no. (%) 461 (97.9) 455 (97.2) 916 (97.6) Inhaled corticosteroid, high dose, no. (%) 126 (26.8) 131 (28.0) 257 (27.4) ATS 2023 23#24Baseline Demographics and Disease Characteristics Placebo Dupilumab Characteristic (N = 471) (N = 468) All (N = 939) Type 2 inflammation biomarkers Blood eosinophil count at randomization - 408 (331) 394 (261) 401 (298) cells/μL, mean (SD) Post-BD FeNo level, ppb, mean (SD) 23.5 (22.0) 25.2 (22.8) 24.3 (22.4) FENO level ≥20 ppb, no. (%) 188 (42.5) 195 (45.0) 383 (43.8) FENO level <20 ppb, no. (%) 254 (57.5) 238 (55.0) 492 (56.2) Moderate-severe COPD exacerbations in 1-year 2.3 (1.0) 2.2 (1.1) 2.3 (1.0) prior, mean (SD) Lung function Post-BD FEV₁ (L), mean (SD) 1.41 (0.47) 1.39 (0.47) 1.40 (0.47) Post-BD FEV1% predicted mean (SD) 50.6 (13.0) 50.6 (13.3) 50.6 (13.1) Post-BD FEV1/FVC, mean (SD) 0.5 (0.1) 0.5 (0.1) 0.5 (0.1) SGRQ total score, mean (SD) 48.4 (17.8) 48.4 (17.0) E-RS: COPD total score, mean (SD) 13.0 (6.9) 12.9 (7.2) 48.4 (17.4) 12.9 (7.1) ATS 2023 24 24#25Annualized rate of moderate or severe COPD exacerbations ± 95% CI Primary Outcome: Annualized Rate of Exacerbations 1.2 1.0- T Hå 1.10 P<0.001 -30% 0.8 0.6 0.4- 0.2- T 0.78 Cumulative mean number of events ± 95% CI 1.07 0.9- Placebo Dupilumab 0.8 0.7- 0.6- 0.5- 0.4- 0.3- 0.2- 0.1- 0.0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Week 0 Placebo N=471 Dupilumab N=468 No. at Risk Placebo ATS 2023 471 470 466 461 457 457 456 451 451 449 445 442 441 437 Dupilumab 468 467 465 464 462 460 458 457 456 454 451 450 448 437 25#26LS mean change from baseline (L) ± 95% CI 0.32- 0.28- 0.24- 0.20- 0.16- 0.12- Change in Lung Function Over Time Pre-BD FEV1 LS mean difference (95% CI) Week 12: 83ml (42-125ml); p<0.001 Week 52: 83ml (38-128ml); p<0.001 0.08- 0.04- 0.00 -0.04- -0.08 I I II 024 Placebo Dupilumab 52 42 T T 8 12 24 36 44 Week LS mean change from baseline (L) ± 95% CI Post-BD FEV₁ 0.32- 0.28- Placebo Dupilumab 0.24- 0.20- 0.16- 0.12- 0.08- 0.04- 0.00- -0.04- -0.08- 024 8 12 24 Week 36 9. No. of participants with observed change from baseline Placebo 471 455 459 Dupilumab 467 457 454 439 446 439 435 449 443 ATS 2023 415 404 420 471456458 439 431 410 417 415 410 426 468457 454 448 436 434 417 417 423 26 52 52#27LS mean change (L) ± 95% CI Change in Pre-BD FVC and Pre-BD FEF 25-75% Over Time Pre-BD FVC Pre-BD FEF 25-75% 0.20- 0.18- 0.32- Placebo 0.28- Dupilumab 0.24- 0.20- 0.16- 0.12- 0.08- 0.04- 0.00 -0.04- -0.08 LS mean change (L/sec) ± 95% CI 0.16 0.14- 0.12- 0.10 0.08 0.06 0.04 0.02 T T 0 24 8 12 24 36 44 52 Week No. of participants with observed change from baseline Placebo 471455459439439 Dupilumab 467457454446449 ATS 2023 435 443 024 8 12 24 36 36 Week Placebo Dupilumab 44 52 415 404 420 471455459439 439 435 417 404 420 415 410 426 467457454446 449 443 415 410 426 24 27#28Patient-Reported Outcomes: St. George's Respiratory Questionnaire SGRQ Total Score LS mean change ± 95% CI 0 -2 + T T -8 -10 -12 Placebo Dupilumab -14 T T 0 4 12 24 36 52 Week 461 439 Dupilumab 461 444 No. of participants with observed change from baseline Placebo 407 434 430 436 ATS 2023 Week 52 LS mean difference (95% CI) -3.4 (-5.5 to -1.3) P=0.002 414 400 407 415 Lower score indicates a better quality of life 28#29E-RS: COPD Total Score LS mean change ± 95% CI 0.2 -0.2 -0.6- Patient-Reported Outcomes: Symptoms (E-RS: COPD) Placebo Dupilumab -1.0- -1.4- -1.8 -2.2- -2.6- -3.0- -3.4 TT 01234 8 12 24 Week 36 44 467 454 448 443 Dupilumab 461 446 435 439 No. of participants with observed change from baseline Placebo 424 428 ATS 2023 52 42 414 404 379 412 403 380 Week 52 LS mean difference (95% CI) -1.1 (-1.8 to -0.4) P=0.001 Lower score indicates less severe respiratory symptoms 29#30Treatment-Emergent Adverse Events in the Safety Population* Placebo (N = 470) Dupilumab (N = 469) Participants with any TEAE, no. (%) 357 (76.0) 363 (77.4) Participants with any treatment-emergent SAE, no. (%) 73 (15.5) 64 (13.6) Participants with any TEAE leading to death, no. (%) 8 (1.7) 7 (1.5) Participants with any TEAE leading to permanent study intervention discontinuation, no. (%) 16 (3.4) 14 (3.0) * The safety population consisted of all patients who received at least one dose or part of a dose of the investigational medicinal product, analyzed according to the treatment received. One patient assigned to the placebo group inadvertently received dupilumab so was included in the dupilumab safety population. ATS 2023 30#31Treatment-Emergent Adverse Events in the Safety Population* Placebo Dupilumab (N = 470) (N = 469) Most common TEAEs (≥ 5%), no. (%) 45 (9.6) 44 (9.4) Nasopharyngitis 32 (6.8) 38 (8.1) Headache Upper respiratory tract infection 46 (9.8) 37 (7.9) Chronic obstructive pulmonary disease1 28 (6.0) 27 (5.8) 17 (3.6) 25 (5.3) Diarrhea 16 (3.4) 24 (5.1) Back pain 27 (5.7) 19 (4.1) COVID-19 Hypertension 28 (6.0) 17 (3.6) * The safety population consisted of all patients who received at least one dose or part of a dose of the investigational medicinal product, analyzed according to the treatment received. One patient assigned to the placebo group inadvertently received dupilumab so was included in the dupilumab safety population. 1. All COPD-related hospitalizations are initially reported as SAEs (investigator reported) ATS 2023 31#32• • Conclusions Dupilumab reduced the annualized rate of moderate-to-severe exacerbations by 30% compared to placebo Dupilumab improved patient reported lung function and patient reported outcomes: o 83 mL improvement in FEV₁ ○ Significant improvement in quality of life ○ Significant improvement in severity of symptoms Safety results were consistent with the known safety profile of dupilumab ATS 2023 32#33Q&A session (Part 1)#34sanofi Expand and disrupt beyond Type 2 Naimish Patel MD Global Head of Development, Immunology & Inflammation#35sanofi Potential to lead in COPD with two biologics targeting uncontrolled COPD in patients who failed standard of care Patient population G71 - 2035e Non-Type 2 Type 2 DupixentⓇ and itepekimab have two distinct mechanisms of action addressing different COPD populations with limited overlap 2023 2024 2025 Former smokers (70%) Current smokers (30%) itepekimab² ~1,139K patients DupixentⓇ3 and itepekimab² ~640K patients Boreas DUPIXENT (dupilumab) First-in- disease itepekimab DupixentⓇ3 only ~270K patients First-in-class anti-IL-33 Notus Aerify 1 Aerify 2 U.S. expected submission EU expected submission 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. Patient populations exclude never smokers. 35 ATS Investor Call#36sanofi Itepekimab: potent IL-33 blocker with sub-nanomolar affinity 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 ILC2 Itepekimab is under investigation and not yet approved by any regulatory agency. Clinical significance of the mechanism of action has not been established. 36 ATS Investor Call Potential to be best-in-class and first-in-class IL-33 biologic • • Binds to human IL-33 with high affinity (K-42PM) Amongst the longest half-life of anti-IL-33 class Amongst the best bioavailability of anti-IL-33 class • No immunogenicity signals#37sanofi Itepekimab: First IL-33 in COPD with unprecedented exacerbation reduction in former smokers with and without Type 2 inflammation Former smokers into 20 weeks post-treatment period¹ 42.4% RRR P=0.0081 45.2% RRR P=0.0488 43.2% RRR P=0.0023 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 Treatment Period Post-treatment (20 weeks) Combined Placebo Itepekimab > >40% reduction in exacerbations in former smokers • Effect present in both high and low eosinophil population Sustained efficacy 20 weeks post treatment Only member of IL-33/ST2 class with clinical data in COPD • Itepekimab was well tolerated in ph2a study 1. Rabe et al. Lancet Respir Med. 2021 Itepekimab is under investigation and not yet approved by any regulatory agency. 37 ATS Investor Call#38Itepekimab: Positive Aerify interim analysis AERIFY-1 Itepekimab Q2W SC Population 40-85 yrs Mod-to-severe COPD w/smoking history of >10 pack-years N=930 Population 40-85 yrs Mod-to-severe COPD w/smoking history of ≥10 pack-years N=1,170 Randomization Itepekimab Q4W SC Placebo SC Follow-up Former Smokers PBO + MFNS 3-5-Week Week 0 Screening Period Week 52 Primary Endpoint Week 72 End of Follow-up Randomization 3-5-Week Screening Period Itepekimab is under investigation and not yet approved by any regulatory agency. 38 ATS Investor Call AERIFY-2 Itepekimab Q2W SC Itepekimab Q4W SC Placebo SC Itepekimab Q2W SC Follow-up Former Smokers Current Smokers Placebo SC PBO MFNS Week 0 Week 52 Primary Endpoint Week 72 End of Follow-up sanofi FDA Fast Track Designation for COPD in former smokers in January 2023 Phase 3 data from AERIFY 1 & AERIFY 2 expected in 2025#39Potential to address remaining unmet need asthma with disruptive first-in-class assets. sanofi Amlitelimab OX40L Rilzabrutinib BTKi SAR'765 IL13xTSLP • Antibody Non-depleting anti-OX40L addresses both T2 and non-T2 inflammation to meet patient need for broader high efficacy Long-term disease control / potential disease modification, infrequent dosing • Small molecule Oral therapy being targeting type 2 and non-T2 pathways Potential to establish pre-biologic space and expand treatment of moderate asthma patients Phase 2b asthma readouts in 2024 • NanobodyⓇ VHH molecule Bispecific NanobodyⓇ VHH against both TSLP and IL-13 Potential for breakthrough efficacy Long-term disease control/potential disease modification Phase 1b asthma data Amlitelimab, rilzabrutinib and SAR'765 are under investigation and not yet approved by any regulatory agency. 39 ATS Investor Call#40sanofi SAR 765: IL-13/TSLP bispecific shows potential to break efficacy ceilings in type 2 Inflammation and beyond Type 2 inflammation1-3 . Mainly driven by IL-4, IL-5 and IL-13 Drives IgE synthesis, eosinophil recruitment, and FeNO production, indicating nitrosative/oxidative stress NO❤ 2022 2023 SAR'765 vs. PLACEBO Phase 1b • Phase 1b-Proof of mechanism in Asthma Mild/moderate asthma with elevated FeNO Respiratory epithelium TSLP -TARC ¡NOS* Dendritic cell Th2 cell IL-5 IL-4, IL-13 Eosinophil *INOS activation may also be driven by non type 2 inflammation e.g. in sepsis • Single dose (400 mg vs placebo) SC • N=36 (2:1) Bispecific NanobodyⓇ VHH against both TSLP and IL-13 Potential to benefit from combined approach - anti-TSLP therapy is effective in reducing exacerbations in asthma with type 2 and non-type 2 inflammation4-7; - anti-IL-13 therapy has mixed effects on exacerbations, but improves lung function and reduces fractional exhaled nitric oxide8-12 1. Ziegler, S, et al. Nat Immunol. 2006;7:709-14; 2. Ricciardolo FL, et al. Allergol Immunopathol (Madr). 2015;43:609-16; 3. Munakata M. Allergol Int. 2012;61:365-72, 4. Gavreau GM, et al NEJM. 2014;370:2102-10; 5. Corren JC, et al. NEJM. 2017;377:936; 6. Menzies-Gow A, et al. NEJM. 2021;384:1800-09; 7. Weschler M, et al. Lancet Respir Med. 2022;10:650-60; 8. Corren JC, et al. NEJM. 2011;365:1088-98; 9. Austin CD, et al. Clin Exp Allergy. 2020;50:1342-51; 10. Hanania NA, et al. Thorax. 2015;70:748-56; 11. Panettieri RA, et al. Lancet Respir Med. 2018;6:511-25; 12. Russell RJ, et al. Lancet Respir Med. 2018;6:499-510 40 ATS Investor Call#41sanofi Significant reduction in FeNO observed with SAR'765 suggests the potential for a highly competitive target product profile Mean (±SEM) change from baseline over time 30 Placebo (n=12) SAR443765 (400mg) 18,8 (n=24) -0,8 10 0 Nitric oside (ppb) -10 -30 -50 Baseline Results of SAR'765 on FeNO suggest a synergistic effect compared to TSLP or IL13 alone¹-8 0 0,8 -10 Phase 1b¹ PATHWAY² NAVIGATOR³ SOURCE4 MILLY5 LUTE & VERSE6 STRATOS7 MESOS8 -20 -31,9 -35,2 -30 -39,1 -40 Anti-TSLP trials Day 8 Anti-IL-13 trials Day 15 Day 29 -50 Highly elevated FeNO at baseline, consistent with active, Type 2 airway inflammation SAR443765 -40.9 ppb Confirmed pharmacodynamic effect, with FeNO as clinically relevant biomarker for type 2 airway inflammation (90% CI: -55.4 to -26.4)* FeNO, fractional exhaled nitric oxide. The clinical significance of FeNO is under investigation *Not head-to-head comparisons; patient populations and baseline characteristics may differ between studies. Estimates of FeNO change from baseline versus plaecbo derived from published data. +Difference vs placebo estimate from a mixed-effects model over time taking into account baseline FeNO and sex as co-variates. 1. Gavreau GM, et al NEJM. 2014;370:2102-10; 2. Corren JC, et al. NEJM. 2017;377:936; 3. Menzies-Gow A, et al. NEJM. 2021;384:1800-09; 4. Weschler M, et al. Lancet Respir Med. 2022;10:650-60; 5. Corren JC, et al. NEJM. 2011;365:1088-98; 6. Hanania NA, et al. Thorax. 2015;70:748-56; 7. Panettieri RA, et al. Lancet Respir Med. 2018;6:511-25; 8. Russell RJ, et al. Lancet Respir Med. 2018;6:499-510. 41 ATS Investor Call#42sanofi Lung function improvement corroborates SAR'765 mode of action Pre-BD FEV1 change from baseline (L) 0,4 Placebo ■SAR443765 400 mg 0,26 0,3 0,198 0,2 0,1 0 -0,1 -0,014 0,113 0,147 0,07 Potential to suppress airway inflammation and preserve airway function in asthma Rapid, numerical improvement in FEV1 after single dose of SAR'765 • Maximal improvement in pre-BD FEV1 at Day 8 largely maintained throughout the 4-week observation period -0,2 Baseline Day 8 Day 15 Placebo, n SAR443765, n 12 24 12 23 12 24 Day 29 12 24 FEV1 measured in triplicate. If the difference between the 2 largest FEV1 values was ≥0.150 L, the triplicate set was excluded. Maximal FEV1 value from the triplicate used for analysis. PD, pharmacodynamic; FEV1, forced expiratory volume in 1 second; BD, bronchodilator SEM, standard error of the mean. 42 ATS Investor Call#43Potential breakthrough medicines beyond Type 2 COPD Itepekimab • • Potent IL-33 blocker with best-in-class and first-in-class potential Unprecedented exacerbation reduction in former smokers shown in phase 2, positive interim analysis covering AERIFY 1 & 2 FDA Fast Track Designation status, pivotal data in 2025 Amlitelimab, rilzabrutinib and SAR'765 are under investigation and not yet approved by any regulatory agency. 43 ATS Investor Call Asthma SAR'765 • • . Leveraging two proven pathways Exciting results of SAR'765 on FeNO suggest a synergistic effect Potential to suppress airway inflammation preserve lung function, and disease modify . Phase 2b starting H2 2023 Amlitelimab & rilzabrutinib • Phase 2 readouts in 2024 sanofi#44sanofi Unlock sustainable growth in Immunology Bill Sibold EVP, Global Head of Specialty Care#45sanofi Dupixent® is the leader in specialty Respiratory 300 250 200 150 Leading with Pulmonologist Weekly NBRX¹ 100 www 50 DUPIXENT (dupilumab) NUCALA FASENRA TEZSPIRE XOLAIR 0 6/1/2022 7/1/2022 8/1/2022 9/1/2022 10/1/2022 11/1/2022 12/1/2022 1/1/2023 2/1/2023 3/1/2023 4/1/2023 5/1/2023 Outstanding performance #1 Asthma NBRX share (25%) March 20232 #1 total Asthma patients share 41% and new patient share 39% in Japan³ Ambition to be Best-in- disease Type 2 Asthma profile approved 6Y+ in U.S. & EU and 12Y+ in Japan 1. IQVIA SMART - Patients Insights Edition - weekly NBRX, data through 4/28/2023. 2. IQVIA National Source of Business monthly data with data through 3/31/2023. 3. Japan IQVIA, JMDC Database, Japan local ATU W17 Jan '23. 4. Type 2 phenotype: Eos ≥150 or FeNo > 20 ppb, and/or OCS dependence. Leading Immunology Brand in US NBRX. 45 ATS Investor Call#46sanofi Innovative portfolio to address significant remaining need in fast growing asthma market Global asthma advanced therapy market $11.5B +-65% $7.0B 2022 2028 Portfolio with potential to address remaining unmet needs in asthma Efficacy across subtypes SAR'765 Amlitelimab Long-term disease control / disease modification SAR'765 Amlitelimab Establish new efficacy level SAR'765 Safe, effective oral Rilzabrutinib 8 Sales Estimate source: Evaluate Pharma Q2 2023; removed 50% of Xolair sales to account for Chronic Spontaneous Urticaria. Branded advanced therapies only. 46 ATS Investor Call LI#47Opportunity to bring breakthroughs to large number of in-need COPD patients Eligible patients in G7 countries Large biologics eligible patient population in G7 COPD patients 1.7m countries Asthma patients 1.9m Biologics penetration in COPD >35% Significant growth of At peak biologics penetration in COPD expected No biologics Today Source: Sanofi Internal Analysis Dupixent and itepekimab are under investigation in COPD and not yet approved by any regulatory agency to treat this indication 47 ATS Investor Call sanofi Potential first-in-market with DupixentⓇ • Impressive data in high need, lethal disease Addressing ~35% of severe patients at launch Near-term expansion with itepekimab • Expanding patient opportunity by >2X Two complementary, potential best-in-class agents • Reaching 80+% of the severe population Maximized with proven ability to execute#48sanofi Multiple blockbuster opportunities to expand Sanofi's leadership in specialty respiratory Leadership today DUPIXENT (dupilumab) Injection 300mg #1 in Specialty Respiratory driven by Dupixent leadership across: Asthma (launched) CRSWNP (launched) COPD (positive Ph3 data) Developing blockbuster opportunities itepekimab amlitelimab rilzabrutinib SAR'765 Promising data in hand for itepekimab and SAR'765 poised to deliver towards goal of launching 3-5 new products with €2-5B peak potential in second half of decade First asthma readouts in 2024 on amlitelimab, rilzabrutinib to confirm unique profiles and potential to expand beyond lead indications DupixentⓇ is under investigation in COPD and not yet approved by any regulatory agency to treat this indication Itepekimab, amlitelimab, rilzabrutinib and SAR'765 are under investigation and not yet approved by any regulatory agency 48 ATS Investor Call#49Q&A session (Part 2)

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