Clinical Trials Appendices List of abbreviations

AE Adverse Events IAR Infusion Associated Reaction QNM Every N Months APO Apolipoprotein IC Investigator’s Choice QOL Quality Of Life BOR Best Overall Response IGA Investigator’s Global Assessment RECIST Response Evaluation Criteria in Solid Tumors BW Body Weight IMID Immunomodulatory Drug SAE Serious Adverse Events CB Clinical Benefit ITT Intent To Treat SBP Systolic Blood Pressure CNS Central Nervous System LP Lipoprotein SDMT Symbol Digit Modalities Test CR Complete Response MRI Magnetic Resonance Imaging SMPG Self Monitored Plasma Glucose CRR Complete Response Rate MTD Maximum Tolerated Dose SSD Study Start Date CT Computed Tomography N Number TC Total Cholesterol CV Cardiovascular NC Nasal Congestion/obstruction TEAE Treatment Emergent Adverse Events DE Data Expected NNT Number Needed to Treat TSS Total Symptom Score DCR Disease Control Rate OS Overall Survival TG Triglycerides DLT Dose-Limiting Toxicity ORR Overall Response Rate TTP Time To Progression DOD Duration Of Disease PD Pharmacodynamics TTR Time To Response DOR Duration Of Response PI Proteasome Inhibitor TX Treatment DPP4 Dipeptidyl peptidase 4 PFS Progression-Free Survival VGPR Very Good Partial Response EASI Eczema Area and Severity Index PK Pharmacokinetic FPC Fasting Plasma Glucose PPG Postprandial Glucose HbA1c Hemoglobin A1c PRO Patient Reported Outcome IAE Incidence of Adverse Events QNW Every N Weeks

2 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (1/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Continuation of Phase 3 750 • Primary: TEAEs: % of patients • SSD: Aug. 2018 LIBERTY • Patients with asthma who completed the reporting TEAs, event rates per • DE: 2022 ASTHMA Continuation of TRAVERSE treatment period in the previous 100 patient-year TRAVERSE evaluating Dupilumab safety in dupilumab asthma clinical study Patients with Asthma (Long LTS12551 term follow-up) • Open-label, Single group assignement LPS15023 NCT03620747

LIBERTY Phase 3 354 • Primary: N of patients • SSD: June 2018 ASTHMA • Open-label experiencing any TEAE • DE: 2021 Long term safety and tolerability • 1 year of Tx • Secondary: Severe asthma EXCURSION (1 year) of dupilumab in exacerbation events, change in pediatric patients with asthma % predicted FEV1, in absolute FEV1, in FVC, FEF, dupilumab LTS14424 who participated in a previous dupilumab asthma clinical study concentrations, anti-dupilumab NCT03560466 Ab, eosinophils, Ig, IgE

3 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (2/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

CHILDREN Phase 3 408 • In children 6 to <12 years of age with • Primary: Annualized rate of • SSD: Jun. 2017 ASTHMA uncontrolled persistent asthma severe exacerbation events • DE: 2020 VOYAGE Evaluation of dupilumab in • Randomized, Double-blind, Placebo- during Tx period children (6 to <12 years) with controlled, parallel group 52 weeks Tx, • Secondary: Safety and uncontrolled asthma 12 weeks post Tx tolerability, PROs, Systemic EFC14153 exposure and incidence of anti- NCT02948959 drug antibodies, Association between dupilumab Tx and pediatric immune responses to vaccines

4 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (3/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Persistent Phase 3 486 • In adults and adolescents with a • Primary: change in pre- • SSD: Jan. 2019 Asthma - China diagnosis of asthma for ≥ 12 months bronchodilator FEV1 at week • DE: 2021 Efficacy and Safety of • Randomized, Double-blind, Placebo- 12 for patients without OCS EFC13995 dupilumab in patients with controlled, parallel group, • Secondary: change in FEV1 in Persistent Asthma • 2 arms: dupilumab and placebo, with in overall population, annualized NCT03782532 each arm patients with and without oral rate of exacerbation events, of corticosteroids (OCS) maintenance LOAC event, of severe therapy exacerbation resulting in • Study duration: 40 weeks study hospitalization, time to first including 3 to 5 weeks of screening exacerbation event, time to first period, 24 weeks Tx and 12 weeks post LOAC, change in Asthma Tx Control Questionnaire, asthma symptoms score, nocturnal awakenings, use of daily puffs of rescue medication, Asthma QoL

5 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Atopic Dermatitis (AD) (1/4) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

OLE Phase 3 765 • For patients having participated in a prior • Primary: Incidence and rate of • SSD: Oct. 2015 Pediatrics expected dupilumab study in pediatrics with AD TEAEs • DE: 2023 AD A study to assess the long-term • Open label extension study • Secondary: SAEs and TEAEs safety of dupilumab of special interest, % of patients who achieve and maintain R668-AD-Reg administered in patients 6 to <18 years of age with AD remission, EASI-75: % of 1434 patients achieving and NCT02612454 maintaining at least 75% reduction in EASI score over time, EASI-50: % of patients achieving and maintaining at least 50% reduction in EASI scores over time

6 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Atopic Dermatitis (AD) (2/4) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

LIBERTY AD Phase 2/3 280 • Part A: Open-label, single-ascending • Part A: PK • SSD: Dec. 2017 PRESCHOOL dose, sequential cohort phase 2 study • Part B: Proportion of patients • DE: 2022 Safety, Pharmacokinetics and • Part B: Randomized, double-blind, with Investigator's Global R668-AD-1539 Efficacy of Dupilumab in parallel-group, placebo-controlled phase Assessment "0" or "1" (on a 5- 3 study point scale) at week 16 NTC03346434 Patients ≥6 Months to <6 Years With Severe Atopic Dermatitis

7 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Atopic Dermatitis (AD) (3/4) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Open-Label Phase 3 2678 • Open label extension study for patients • Primary: TEAEs, • SSD: Oct. 2013 who participated in placebo-controlled • Secondary: SAEs and AEs of • DE: 2022 R668-AD-1225 Open-Label study of Dupilumab dupilumab AD trials. The study primarily special interest, % of patients NCT01949311 in patients with Atopic evaluates long term safety (adverse who achieve and maintain Dermatitis events) and immunogenicity. Efficacy remission, EASI-75: % of parameters are based on IGA, EASI) patients achieving and and the NRS. maintaining at least 75% reduction in EASI score over time, EASI-50: % of patients achieving and maintaining at least 50% reduction in EASI scores over time

8 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Atopic Dermatitis (AD) (4/4) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

AD in Chinese Phase 3 163 • Chinese patients with chronic AD • Primary: Investigator’s Global • SSD: Dec 2018 Patients present for at elast 3 years before the Assessment (IGA), • DE: 2020 Efficacy and Safety of screening visit, • Secondary:, % of patients with EFC15116 Dupilumab in Chinese Patients • Randomized, Double-Blind, Placebo- EASI-75 response, % of controlled patients with reduction of peak NCT03912259 with Moderate-to-severe Atopic Dermatitis • 2 Arms: dupilumab vs Placebo daily pruritus NRS ≥ 4, % of patients with reduction of peak daily pruritus NRS ≥ 3, change in NRS, change in EASI score, change in BSA affected by AD, Dermatology QoL and EQ-5D, change in patients oriented eczema measure (POEM), sick- leave/missed school days proportion, AEs, dupimumab immunogenicity

9 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Eosinophilic Esophagitis (EoE) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

EoE Phase 3 425 • Patients with documented diagnosis of • Primary: Proportion of patients • SSD: Nov. 2018 EoE by endoscopic biopsy, achieving peak esophageal • DE: primary Efficacy and Safety of • Randomized, double-blind, parallel intraepithelial eosinophil count completion: 2022, R668 – EE - Dupilumab in Adult and assignment, placebo-controlled study, of ≤6 eosinophils per high- full completion: 2023 1774 Adolescent patients with • Part A: dupilumab or placebo (double- power field (eos/hpf), Absolute blind) for 24 weeks, change in Dysphagia Symptom NCT03633617 Eosinophilic Esophagitis • Part B: dupilumab dose regimen 1, Questionnaire (DSQ) score dupilumab dose regimen 2 or placebo • Secondary: Absolute change in (double-blind) for 24 weeks EoE endoscopic reference • Part C: for patients eligible at the end of score (EREFS), Percent Part A and Part B, dupilumab dose change in peak esophageal regimen 1, dupilumab dose regimen 2 intraepithelial eosinophil count (double-blind) for 28 weeks (eos/hpf), Absolute change in • 12-week follow-up for all patients EoE grade score from EoE (eligible and non eligible) Histology Scoring System (EoEHSS), Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤15, Proportion of patients achieving peak esophageal intraepithelial eosinophil count of ≤1, Percent change in DSQ, QOL, Absolute change in severity and/or frequency of EoE symptoms other than dysphagia

10 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) adjunct to AR101 Oncology Cardiovascular Peanut Allergy (1/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Peanut Allergy Phase 2 156 • Child 6 to 17 years experiencing dose- • Primary: % of subjects who • SSD: Oct. 2018 limiting symptoms at or before the “pass” a double-blind, placebo- • DE: primary Efficacy and Safety of challenge dose of peanut protein on controlled food challenge completion: 2020, R668 –ALG - Dupilumab as adjunct to AR101 screening and not experiencing dose- (DBPCFC) with peanut protein full completion: 2021 16114 in Pediatric Subjects with limiting symptoms to placebo at week 28, • Randomized, double-blind, parallel • Secondary: change in NCT03682770 Peanut Allergy assignment, placebo-controlled study, cumulative tolerated dose of • 2 arms: dupilumab adjunct to AR101 vs peanut protein during DBPBFC, placebo adjunct to AR101 at week 28, % of subjects who « pass » the DBPCFC at week 52 (desensitization maintenance), safety and tolerability, change in peanut- specific IgE (sIgE), IgG4 and IgG4/sIgE ratio

11 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Peanut Allergy (2/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Peanut Allergy Phase 2 48 • Child 6 to 17 years experiencing dose- • Primary: % of patients who • SSD: May 2019 limiting symptoms at or before the “pass” DBPCFC with low-dose • DE: 2022 challenge dose of peanut protein on (cumulative) peanut protein at R668 –ALG - Efficacy and Safety of screening: double-blind placebo- week 24, 1702 Dupilumab monotherapy in controlled food challenge (DBPCFC) and • Secondary: % of patients that not experiencing dose-limiting symptoms pass a DBPCFC with low-dose, NCT03793608 Pediatric Patients with Peanut Allergy to placebo mid-dose and high-dose of • Randomized, double-blind, parallel peanut protein, change in assignment, placebo-controlled study, cumulative tolerated dose of • 2 arms: dupilumab vs placebo peanut protein during DBPBFC, , % of change in peanut-specific IgE, change in titrated SPT.

12 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Chronic Obstructive Pulmonary Disease (COPD) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

COPD Phase 3 924 • Patients with COPD diagnosis, • Primary: annual rate of acute • SSD: May 2019 • Randomized, double-blind, parallel COPD exacerbation, • DE: 2022 BOREAS assignment, placebo-controlled study, • Secondary: change in pre- Efficacy, Safety and Tolerability • 2 arms: dupilumab vs placebo bronchodilator FEV1, change in EFC15804 of Dupilumab in Patients with SGRQ score, Improvement in Moderate-to-Severe Chronic SGRQ, change in post- NCT03930732 Obstructive Pulmonary Disease bronchodilator FEV1, change in (COPD) with Type 2 forced expiratory flow (FEF), inflammation annualized rate of severe COPD exacerbations (AECOPD), time to first AECOPD, AEs, PCSA changes, dupilumab immunogenicity.

13 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Bullous Pemphigoid (BP) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

LYBERTY-BP Phase 2/3 80 • Patients with clinical features of BP, • Primary: % of patients with • SSD: H1 2020 • Randomized, double-blind, parallel sustained remission (off OCS), • DE: 2022 assignment, placebo-controlled study, • Secondary: OCS-sparing R668-BP-1902 Efficacy, Safety of Dupilumab in • 2 arms: dupilumab vs placebo (+ oral effects, effect on itch, QoL, NCT04206553 Patients with Bullous cortocosteroides – OCS – in both arms) circulating BP180 and BP230 Pemphigoid antibodies, safety and tolerability, Pharmacokinetic, immunogenicity.

14 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Chronic Spontaneous Urticaria (CSU) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

CUPID Phase 3 184 • Adults and adolescents (≥ 12 years) • Primary: itch severity score • SSD: H1 2020 Patients with diagnosis of CSU refractory (ISS7), • DE: 2021 to H1 antihistamine, • Secondary: urticaria activity EFC16461 Efficacy, of Dupilumab in adults • Randomized, double-blind, parallel score (UAS7), ISS7, hives NCT04180488 and adolescents Patients with assignment, placebo-controlled study, severity score (HSS7), CSU who remain symptomatic • Studies A & B : 2 arms: dupilumab vs angioedema activity score despite the use of H1 placebo (on top of sedating H1- (AAS7), urticaria control test antihistamine and who are antihistamine – OCS - in both arms) (UCT), QoL, Patient Global naïve to Omalizumab (study A) Assessment, % of patients receiving OCS, safety. And in adults and adolescents Patients with CSU who remain symptomatic despite the use of H1 antihistamine and who are Intolerant or Incomplete responders to Omalizumab (study B)

15 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Prurigo Nodularis (PN) (1/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

PRIME Phase 3 150 • Patients with a clinical diagnosis of PN, • Primary: improvement of worst- • SSD: January 2020 • Randomized, double-blind, parallel itch numeric rating scale (WI- • DE: 2021 assignment, placebo-controlled study, NRS) ≥ 4 at week 12, EFC16459 Efficacy and Safety of • 2 arms: dupilumab vs placebo (on top of • Secondary: % of patients with NCT04183335 Dupilumab in Patients with PN moisturezers and if applicable low to improvement in WI-NRS ≥ 4 at Inadequately Controlled on medium potent topical corticosteroids or week 24, time to onset of effect Topical Prescription Therapies topical calcineurin inhibitors, in both on pruritus, change in WI-NRS, or When these Therapies are arms) Investigator’s global not Advisable assessment on PN-Stage and PN-Assess, IGA PN-Score, QoL; safety, TEAs antidrug antibodies (ADA) against dupilumab.

16 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Prurigo Nodularis (PN) (2/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

PRIME2 Phase 3 150 • Patients with a clinical diagnosis of PN, • Primary: improvement of worst- • SSD: January 2020 • Randomized, double-blind, parallel itch numeric rating scale (WI- • DE: 2021 assignment, placebo-controlled study, NRS) ≥ 4 at week 12, EFC16460 Efficacy and Safety of • 2 arms: dupilumab vs placebo (on top of • Secondary: % of patients with NCT04202679 Dupilumab in Patients with PN moisturezers and if applicable low to improvement in WI-NRS ≥ 4 at Inadequately Controlled on medium potent topical corticosteroids or week 24, time to onset of effect Topical Prescription Therapies topical calcineurin inhibitors, in both on pruritus, change in WI-NRS, or When these Therapies are arms) Investigator’s global not Advisable assessment on PN-Stage and PN-Assess, IGA PN-Score, QoL; safety, TEAs antidrug antibodies (ADA) against dupilumab.

17 Immuno-inflammation Diabetes Sarilumab (anti-IL6 mAb) Oncology Cardiovascular Rheumatoid Arthritis (RA) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

SARIL-RA- Phase 3 2000 • In patients with RA having participated to • Primary: N of patients with AE • SSD: Jun. 2010 EXTEND previous trials • Secondary: Long term efficacy • DE: 2020 Long-term evaluation of • Multi-center, uncontrolled extension, of sarilumab in patients with RA sarilumab in RA patients open-label; up to 1 week screening, at (ACR20, DAS28, EULAR LTS11210 least 264 weeks of open label Tx and up response) to 516 weeks max., 6 weeks post-Tx NCT01146652

18 Immuno-inflammation Diabetes Sarilumab (anti-IL6 mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Juvenile Idiopathic Arthritis (JIA) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Polyarticular Phase 2b 36 in core • In children and adolescents, Aged 2 to • Primary: PK parameters (Up to • SSD: Oct. 2016 JIA part, 60 17 years, with pcJIA week 12) • DE: 2018 (36 Children & Dose-finding study of sarilumab total • Open-label, sequential, ascending, • Secondary: PD profile, The patients CSR); 2021 Adolescents in children and adolescents with repeated dose-finding Study; efficacy and the safety of (60 patients CSR); sarilumab in patients with 2023 (CSR with 3- SKYPP Polyarticular-course Juvenile Idiopathic Arthritis (pcJIA) pcJIA, Long-term safety of year extension) sarilumab in patients with pcJIA DRI13925 NCT02776735

Systemic JIA Phase 2b 24 in core • In children and adolescents, aged 1 to • Primary: PK parameters (Up to • SSD: Sep. 2018 Children & part, 17 years, with sJIA week 12) • DE: 2021 (24 Adolescents Dose-finding study of sarilumab 48 total • Open-label, sequential, ascending, • Secondary: PD profile, efficacy patients CSR); 2023 SKYPS in children and adolescents with repeated dose finding study, 4-week and the safety of sarilumab in (48 patients CSR), Systemic Juvenile Idiopathic screening, 12-week coreTx, 144-week patients with sJIA, Long term 2025 (CSR with 3- Arthritis (sJIA) extension, 6-week post-Tx safety of sarilumab in patients year extension) DRI13926 with sJIA NCT02991469

19 Immuno-inflammation Diabetes Sarilumab (anti-IL6 mAb) Oncology Cardiovascular Giant Cell Arteritis (GCA) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

GCA Phase 3 360 • Patients suffering from GCA; new onset • Primary: % of patients • SSD: Nov. 2018 active disease or refractory active achieving sustained remission • DE: primary TAPERR Efficacy of sarilumab in disease at week 52 completion:2022, full combination with corticosteroid • Randomized, parallel assignment, • Secondary: components of completion 2023 EFC15068 in patients with Giant Cell double-blind, placebo controlled, 2 doses sustained remission, cumulative Arteritis of sarilumab tested vs placebo, in corticosteroid dose, time to 1st NCT03600805 association with prednisone GCA flare, change in • Study duration per patient: glucocorticoid toxicity index, approximately 82 weeks: up to 6 weeks AEs, PK, screening, 52-week Tx period, 26-week follow-up period

20 Immuno-inflammation Diabetes Sarilumab (anti-IL6 mAb) Oncology Cardiovascular Polymyalgia Rheumatica (PMR) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

PMR Phase 3 280 • Patients suffering from PMR, • Primary: % of patients • SSD: Nov. 2018 • Randomized, parallel assignment, achieving sustained remission • DE: 2022 SAPHYR Efficacy of sarilumab in double-blind, placebo controlled, 2 at week 52 combination with corticosteroid groups: sarilumab + CS, placebo +CS • Secondary: components of EFC15160 (CS short tapering regimen) in • Study duration per patient: sustained remission, cumulative comparison to placebo (CS long approximately 62 weeks: up to 4 weeks corticosteroid dose, time to 1st NCT03600818 tapering regimen) in patients screening, 52-week Tx period, 6-week PMR flare, change in with Polymyalgia Rheumatica follow-up period glucocorticoid toxicity index, AEs, PK,

21 Immuno-inflammation Diabetes SAR440340 (Anti-IL33 mAb) Oncology Cardiovascular COPD Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

POC in COPD Phase 2 343 • Adults patients with a diagnosis of • Primary: AECOPD (Acute • SSD: Jul. 2018 moderate-to-severe COPD for at least Exacerbations in COPD) • DE: 2020 Efficacy, Safety and 1 year • Secondary: average change in pre- ACT15104 Tolerability (POC) of • Randomized, Double-blind, Placebo- bronchodilator FEV1 (forced st NCT03546907 SAR440340 in patients with controlled, on top of standards of care expiratory volume 1), time to 1 moderate-to-severe COPD • Arm 1: SAR440340 COPD exacerbations, AEs, change • Arm 2 : placebo in post-bronchodilator FEV1 • Total duration for one patient: 46 to 76 weeks including 10 days to 4 weeks of screening, 24 to 52 weeks Tx period and 20 weeks post IMP Tx period

22 Immuno-inflammation Diabetes SAR441236 (Tri-specific neutralizing mAb) Oncology Cardiovascular HIV Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

HIV Phase 1 60 • Patients with HIV infection, • Primary: Occurrence of a Grade 3 • SSD: April 2019 • Randomized, Double-blind, Parallel-Group, or higher AE (DAIDS AE grading • DE: 2021 Pharmacokinetics of Ascending dose study, table), at any time, AUC12w, TDU15867 SAR441236 in • Arm A cohort 1A: SAR441236 (1mg/kg) + change in plasma HIV-1 RNA (Arm NCT03705169 Participants with HIV ART (antiretroviral Tx) from D0, B cohorts) • Arm A cohort 1B: placebo + ART from D0, • Secondary: change in plasma HIV- • Arm A cohort 2A: SAR441236 (3mg/kg) + 1 RNA (Arm B cohorts) at different ART from D0, times, maximum reduction of • Arm A cohort 2B: placebo + ART from D0 plasma HIV-1 RNA, SAR441236 • Arm A cohort 3A: SAR441236 (10mg/kg) + Antibodies, change in CD4+T cell ART from D0, counts, SAR441236 PK. • Arm A cohort 3B: placebo + ART from D0, • Arm A cohort 4A: SAR441236 (30mg/kg) + ART from D0, • Arm A cohort 4B: placebo + ART from D0, • Arm B cohort 5: SAR441236 (1mg/kg) and ART initiated at D28, • Arm B cohort 6: SAR441236 (3mg/kg) and ART initiated at D28, • Arm B cohort 7: SAR441236 (10 mg/kg) + ART from D28, • Arm B cohort 8: SAR441236 (30 mg/kg) + ART from D28, • Arm B cohort 9: SAR441236 (0,3 mg/kg) + ART from D28,

23 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Hematological Malignancies (HM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

CD38+HM Phase1/2 351 • Phase 1: MTD • Primary: DLT, ORR • SSD: Jun. 2010 (enrollment • Phase 2: Stage 1: isatuximab • Secondary: DOR, PFS, OS, • DE: Primary Dose escalation, completed) activity at different Immune Response completion:2018; TED10893 Pharmacokinetics and doses/schedules and to select Full completion: NCT01084252 efficacy study of isatuximab dose and regimen as single agent 2020 in patients with selected or in combination with CD38+ HM dexamethasone Stage 2: activity at the selected dose/schedule from stage1, as single agent (ISA arm) and in combination with dexamethasone (ISAdex arm) • Randomized, Open-label, Parallel assignment

24 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Hematological Malignancies (HM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

CD38+HM Phase1 25 • In Patients with known diagnosis of • Primary: Pharmacokinetics • SSD: Oct. 2018 (actual) symptomatic multiple myeloma, • Secondary: Aes, ORR, • DE: Primary Pharmacokinetics Safety • Open-label, Single Group DOR, TTP, PFS, OS, completion: 2020; TED15085 and Preliminary Efficacy of assignment immunogenicity Full completion NCT03733717 isatuximab in Chinese • Isatuximab every week in Cycle 1 (4 2021 Patients with Relapsed weeks) followed by every 2 weeks and/or Refractory MM (Q2W) in subsequent cycles

25 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Lenalidomide Phase 1b 57 • Patients with diagnosis of MM and • Primary: N of patients with • SSD: Feb. 2013 Combination (enrollment documentation of at least 2 prior AE • DE: 2020 RRMM Isatuximab, in completed) therapies (induction therapy, • Secondary: ORR, PFS, PK, Combination With autologous stem cell transplant, PD, Immunogenicity lenalidomide and consolidation and maintenance TCD11863 dexamethasone for the Tx therapy is considered one prior NCT01749969 of Relapsed or Refractory therapy) MM • Open-label, Parallel assignment • Isatuximab (escalating doses) + lenalidomide + dexamethasone • Total duration for one patient: up to 21 days screening, at least 4 weeks Tx, up to 60 days follow-up

26 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Pomalidomide Phase 1b 92 • Patients previously diagnosed with • Primary: DLTs, N of patients • SSD: May 2015 Combination (enrollment MM based on standard criteria and with AE • DE: 2021 RRMM Isatuximab, in completed: currently require Tx because MM • Secondary: ORR, PK, combination with 45 patients has relapsed following a response Immunogenicity, DOR, CB pomalidomide and in Part A; 47 • Open-label, Single-Group TCD14079 dexamethasone for the Tx patients in assignment NCT02283775 of Relapsed/Refractory Part B) • Isatuximab + pomalidomide + MM dexamethasone • Part A, doses ranging for isatuximab, (5mg/kg, 10mg/kg, 20mg/kg); Part B isatuximab (10mg/kg) from a fixed infusion volume

27 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Bortezomib Phase 1 88 • Patients with a diagnosis of MM with • Primary VCDI cohort: MTD • SSD: Sep. 2015 Combination (17 pts in evidence of measurable disease, and Recommended Dose • DE: 2023 NDMM Isatuximab in VCdl, 27 pts having received prior Tx with an (RC), based on DLTs, ORR combination with in VRdl cohort IMiD and with at least 3 prior lines of and CR; bortezomib - based A, 44 pts in therapy TCD13983 regimens in adult cohort B) • Open-label, Single Group • Primary VRDI cohort: CR NCT02513186 patients with newly assignment diagnosed MM non • Isatuximab (escalating dose) + • Secondary: overall safety eligible for bortezomib + cyclophosphamide + profile, PK, isatuximab transplantation or with dexamethasone: VCDI cohort (3- immunogenicity, ORR, PFS, no intent for immediate week screening, 50-week duration AE and tumor response, transplantation for induction and then up to disease infusion duration, MRD in progression, or unacceptable AEs + patients achieving CR or follow-up) VGPR • Isatuximab + bortezomib + dexamethasone + lenalidomide: VRDI cohort to begin after VCDI completion (4-week screening, 24- week duration for induction and then up to disease progression, or unacceptable AEs, + follow-up)

28 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

RRMM Phase 1 58 • Patients with a diagnosis of MM with • Primary: Part A: DLTs, N of • SSD: Sep. 2015 (enrollment evidence of measurable disease and patients with AE; Part B: • DE: 2020 Safety, PK and Efficacy of completed) with evidence of disease ORR TED14154 isatuximab in patients with progression • Secondary: PK, N of NCT02514668 Relapsed/Refractory MM • Open-label, Single Group patients with AEs, DOR, CB, assignment, isatuximab (escalating PFS, Immunogenicity doses) • Total duration for one patient: up to 21 days screening, Tx period up to disease progression or AEs , 60- day follow-up at least

29 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Relapsed/Refractory Multiple Myeloma (RRMM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

RRMM Phase 1b 46 • Patients with a diagnosis of MM • Primary: AEs, PK • SSD: Aug. 2019 based on standard criteria and parameters, • DE: Primary: 2021; Pharmacokinetics, Safety requiring Tx because of a relapse • Secondary: bioavailability, Full completion: TCD15484 and Efficacy of isatuximab following a response, OOR, DOR, TTR, TTP, OS, 2022 NCT04045795 (SC and IV) in combination • Open-label, Randomized, CBR, PFS, patients with Pomalidomide and Sequential assignment, expectations and Dexamethasone in patients • 5 arms, each in combination with satisfaction, Immunogenicity with Relapsed/Refractory pomalidomide and dexamethasone: MM isatuximab SC (3 dose levels) and isatuximab IV (2 dose levels) • Total study duration: approximately 14 months: 21 days screening, Tx period until disease progression, unacceptable adverse reaction or other reason for discontinuation; FU: 30 days

30 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ISLANDS Phase 1 36 • Patients with a diagnosis of • Primary: • SSD: Sep. 2016 (Japanese Phase 2 (enrollment symptomatic MM, having received at Phase 1: DLTs • DE: primary Patients) completed) least 3 prior lines of therapy OR Phase 2: ORR completion 2018; Isatuximab single-agent whose disease is double refractory • Secondary: N of patients full completion RRMM in Japanese patients with to an IMiD and a PI with AE, CB, OS, PFS, 2020 Relapsed and Refractory • Open-label, Single Group DOR, TTR, PK, PD, TED14095 MM assignment, isatuximab Immunogenicity NCT02812706 monotherapy • Total duration for one patient: up to 21-day screening, Tx period up to disease progression or unacceptable AEs, post-Tx follow- up

31 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Cemiplimab Phase 1 109 • Patients with a diagnosis MM with • Primary: DLTs, N of patients • SSD: Feb. 2018 Combination Phase 2 evidence of measurable disease, with AE, ORR • DE: 2021 RRMM having received prior Tx with an • Secondary: CB, DOR, TTR, Safety, PK and Efficacy of IMiD and with at least 3 prior lines of PFS, OS, PK, isatuximab in combination therapy Immunogenicity (isatuximab TCD14906 with cemiplimab in patients • Randomized, Open-label, Parallel and cemiplimab) NCT03194867 with Relapsed/Refractory Assignment MM • Isatuximab + cemiplimab • 3 Arms: Isa +cemi regimen 1; isa + cemi regimen 2; isa alone • Total duration for one patient: up to 21-day screening, Tx period up to disease progression or unacceptable AEs, 3-month post-Tx follow-up. Cycle duration 28 days

32 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ICARIA-MM Phase 3 307 • Isatuximab in combination with • Primary: PFS • SSD: Jan. 2017 : RRMM (enrollment pomalidomide and low-dose • Secondary: ORR, OS, TTP, • DE Final Isatuximab, completed) dexamethasone, compared to PFS, DOR, safety, PK completion 2021 pomalidomide, and pomalidomide and low-dose profile, immunogenicity EFC14335 dexamethasone to dexamethasone in patients with NCT02990338 pomalidomide and RRMM dexamethasone in • Randomized, Open-label, Parallel Refractory or Relapsed assignment and RRMM

(1) Final Data Collection date for primary outcome measure 33 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

IKEMA Phase 3 302 • Patients with MM previously treated • Primary: PFS • SSD: Oct. 2017 RRMM (enrollment with prior 1 to 3 lines and with • Secondary: ORR, % of • DE: Primary: 2020, Isatuximab combined with completed) measurable serum M-protein (≥ 0.5 patients with CR, and Full completion: carfilzomib and g/dL) and/or urine M-protein (≥ 200 VGPR, OS, TTP, Second 2023 EFC15246 dexamethasone vs. mg/24 hours) PFS, DOR, TTP, PFS2, AE, NCT03275285 carfilzomib with • Randomized, Open-label, Parallel PK, Immunogenicity dexamethasone in patients assignment, 2-arm: (a) isatuximab With Relapse and/or +carfilzomib+dexamethasone, (b) Refractory MM previously carfilzomib+dexamethasone treated with 1 to 3 prior lines

34 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Ti Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

IMROZ Phase 3 483 • Newly diagnosed MM not eligible • Primary: PFS • SSD: 2017 NDMM Ti (randomized) for transplant due to age (≥ 65 • Secondary: ORR, % of • DE: Primary: 2022, Isatuximab in years) or patients < 65 years with patients with CR, and Full completion: combination with comorbidities impacting possibility VGPR, % of patients with 2025 EFC12522 bortezomib (Velcade®), of transplant MRD (Minimal Residual NCT03319667 lenalidomide (Revlimid®) • Randomized, Open-label, Parallel Disease) negative, OS, and dexamethasone vs. assignment TTP, DOR, PFS on next line bortezomib, lenalidomide • IVRd arm of therapy (PFS2), AE, PK, and dexamethasone in (Isatuximab/bortezomib/lenalidomid Immunogenicity, QOL patients with newly e /dexamethasone) diagnosed MM not • VRd arm (Bortezomib/lenalidomide eligible for transplant /dexamethasone) • Ird crossover arm (Isatuximab/lenalidomide/ dexamethasone) • Total duration for each patient: screening period up to 4 weeks, induction period of 24 weeks, continuous Tx period and crossover when applicable

35 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Multiple Myeloma (MM) Te Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

NDMM Te Phase 3 662 • Confirmed diagnosis of untreated • Primary: MRD negative after • SSD: Oct. 2018 multiple myeloma requiring systemic induction Tx, PFS after 2nd • DE: 2025 Effect of Isatuximab in therapy and eligible for high dose randomization (IIA & IIB) GMMG HD7 induction therapy with therapy and autologous stem cell • Secondary: PFS, OS, CR, NCT03617731 lenalidomide - bortezomib - transplantation MRD, Best response to Tx, dexamethasone (RVd) and • Randomized, Open-label, Parallel PFS after next line of lenalidomide maintenance assignment therapy from 2nd Tx in patients with newly • Induction: 2 arms: IA: 3 cycles RVd, randomization, AEs, QOL, diagnosed myeloma IB: 3 cycles RVd + isatuximab PK, immunogenicity • After induction therapy autologous stem cell transplantation performed, • Maintenance: 2 arms: IIA lenalidomide for 3 years; IIB: lenalidomide + isatuximab for 3 years

36 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular Pediatrics: RR ALL/AML Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Pediatrics Phase 2 96 • Primary: CR in AML, B-ALL • SSD: Apr. 2019 ALL/AML • Open-label, Single-group or T-ALL, • DE: 2022 Anti-tumor Activity, Safety assignment •Secondary: AE²s, incidence and Pharmacokinetics of • 2 cohorts: AML & ALL, in and severity of infusion ACT15378 isatuximab in combination combination with chemotherapy reactions, isatuximab PK, NCT03860844 with Chemotherapy in minimal residual disease, Pediatric Patients from 28 ORR, OS, Event free survival, days to less than 18 years of DR, Relationship between Age with clinical effects and CD38 Relapsed/Refractory B or T receptor density and Acute Lymphoblastic occupancy Leukemia or Acute Myeloid Leukemia in First or Second Relapse

37 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination cemiplimab Oncology Cardiovascular (PD-1 inhibitor) – Advanced Malignancies Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Advanced Phase 1/2 134 • In Patients with metastatic, • Primary: Safety, tolerability, • SSD: Jan. 2018 Malignancies castration-resistant prostate cancer RR • DE: Full Safety and tolerability of (mCRPC) who are naïve to anti- • Secondary: Immunogenicity completion safety : Isatuximab in combination programmed cell death-1 (PD- (isa and cemi), PK, tumor 2021 ACT15319 with cemiplimab in patients 1)/programmed cell death-ligand 1 burden change, DR, PFS, NCT03367819 with metastatic castration- (PDL-1)-containing therapy, or non- Disease Control Rate resistant prostate cancer small cell lung cancer (NSCLC) who (mCRPC) or patients with progressed on anti-PD-1/PDL-1- non-small cell lung cancer containing therapy, (NSCLC) • Randomized, Open-Label, Parallel Assignment • Isatuximab alone or in combination with cemiplimab • Total duration per patient up to 28 months including 28 days screening period, , up to 24 months ttmt period and 3 months safety FU

38 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination cemiplimab Oncology Cardiovascular (PD-1 inhibitor) – Lymphoma Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Advanced Phase 1/2 130 • In Patients with Lymphoma: • Primary: • SSD: Jan. 2019 Malignancies Cohort A1: classic Hodgkin’Lymphoma Phase 1: DLTs, recommended • DE: Primary: 2023, Safety, Preliminary Efficacy (cHL) anti-PD-1/PD-L1 inhibitor naïve, Phase 2 dose (RP2D), Full completion: and Pharmacokinetics of Cohort A2: cHL ) anti-PD-1/PD-L1 Phase 2: Cohort A1: Complete 2023 ACT15320 Isatuximab in combination inhibitor progressor Remission Rate (CRR); Cohort NCT03769181 with cemiplimab in patients Cohort B: diffuse large B-cell A2 RR with Lymphoma Lymphoma (DLBCL) • Secondary: AEs, SAEs, PK, Cohort C: peripheral T-cell Lymphoma tumor burden, disease (PTCL) control rate, DR, PFS • Non-Randomized, Open-Label, Parallel Assignment • Isatuximab in combination with cemiplimab

39 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination atezolizumab Oncology Cardiovascular (PD-1 inhibitor) – Advanced Malignancies Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Advanced Phase 1/2 350 • In Patients with a known diagnosis • Primary: DLTs, AEs, MTD, • SSD: Aug. 2018 Malignancies of either unresectable HCC, Recommended Phase 2 • DE: Primary:2021, Safety, Preliminary Efficacy platinum-refractory /recurrent dose, RR, PFS, Full completion: and Pharmacokinetics of /metastatic SCCHN, platinum- • Secondary: immunogenicity 2023 ACT15377 Isatuximab monotherapy or resistant/refractory EOC with (Isatuximab and NCT03637764 in combination with evidence of measurable disease or atezolizumab), tumor Atezolizumab in patients recurrent GBM, burden change, disease with Advanced Malignancies • Non-Randomized, Open-Label, control rate, DR, PFS, RR, Parallel Assignment, PK, • Isatuximab alone or in combination with atezolizumab,

40 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination atezolizumab Oncology Cardiovascular (PD-1 inhibitor) – Solid Tumors Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

mCRC Phase 1b/2 326 • Umbrella study, Randomized, Open- • Primary: ORR, AEs • SSD: Sep. 2018 Label, Parallel Assignment, • Secondary: PFS, OS, DOR, • DE: 2022 Efficacy and Safety, of • Isatuximab in combination with % of patients alive at Month Umbrella Trial isatuximab in combination atezolizumab, 6, DCR, immunogenicity, led by Roche with atezolizumab in patients • Patients will receive Tx until For sanofi: with Metastatic Colorectal unacceptable toxicity or loss of ACT16241 Cancer clinical benefit as confirmed by NCT03555149 disease progression or lack of continued benefit as determined by the investigator

41 Isatuximab (anti-CD38 mAb) Combination Lenalidomide Immuno-inflammation Diabetes Oncology Cardiovascular and Dexamethasone Rare Diseases Rare Blood Disorders – High-risk Smoldering Multiple Myeloma MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 300 Primary: • SSD: May 2020 • Isatuximab in combination • safety run-in: To confirm the • DE: Primary: 2027, Lenalidomide and Dexamethasone recommended dose of Full: 2033 EFC15992 A Phase 3 Randomized, Open isatuximab when combined NCT04270409 Label, Multicenter Study of with lenalidomide and Isatuximab (SAR650984) in dexamethasone in Combination With participants with high-risk Lenalidomide and smoldering multiple Dexamethasone Versus myeloma (SMM) Lenalidomide and • Randomized Phase 3: To Dexamethasone in Patients demonstrate the clinical With High-risk Smoldering benefit of isatuximab in Multiple Myeloma combination with lenalidomide and dexamethasone in the prolongation of progression- free survival when compared to lenalidomide and dexamethasone in subjects with high-risk SMM

42 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) Oncology Cardiovascular – Kidney Transplant Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1b/2 42 • screening period of up to 28 days, Primary : • SSD: May 2020 • treatment period of up to 12 weeks • Phase 1: safety and • DE: 2024 A Phase 1b/2 Study to • study duration of approximately 42 tolerability of isatuximab in Evaluate the Safety, weeks. kidney transplant TED16414 Pharmacokinetics, and • study duration including extended candidates. NCT04294459 Preliminary Efficacy of FUP per participant will be • Phase 2: efficacy of Isatuximab (SAR650984) in approximately 78 weeks isatuximab in desensitization Patients Awaiting Kidney of patients awaiting kidney Transplantation transplantation. Secondary : • Phase 2: safety profile of isatuximab in kidney transplant candidates. • pharmacokinetic (PK) profile of isatuximab in kidney transplant candidates. • immunogenicity of isatuximab. • overall efficacy of isatuximab in desensitization of patients awaiting kidney transplantation.

43 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Advanced Malignancies (AM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

AM Phase 1 398 • Non-Randomized, Open-label, • Primary: TEAE, Incidence of • SSD: Jan. 2015 Parallel assignment, ascending- abnormal laboratory • DE: 2020 A first-in-human study of dose findings, N of participants R2810-ONC- repeat dosing with • Monotherapy, cemiplimab alone with DLT 1423 cemiplimab, as single • Dual combination: cemiplimab in • Secondary, RECIST as NCT02383212 therapy and in combination combination with hypofractionated measured by CT or MRI, with other Anti-Cancer radiotherapy or with Immune-Related Response, therapies in patients with AM cyclophosphamide or with docetaxel Anti-cemiplimab antibodies, • Triple combination: cemiplimab with PFS, OS hypofractionated radiotherapy plus cyclophosphamide, or hypofractionated radiotherapy plus GM-CSF or carboplatin plus paclitaxel or carboplatin plus pemetrexed or carboplatin plus docetaxel • Quadruple combination: cemiplimab with hypofractionated radiotherapy plus GM-CSF plus cyclophosphamide

44 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Advanced Malignancies (AM) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

PK in Japanese Phase 1 81 • Part 1: Histologically or cytologically • Primary: TEAEs cemiplimab • SSD: Sep. 2017 patients AM confirmed diagnosis of malignancy PK parameters • DE: primary To investigate the safety and with no alternative standard-of-care • Secondary: Immunogenicity completion 2019; PKs of cemiplimab in therapeutic option against cemiplimab, ORR, full completion R2810-ONC- Japanese patients with AM • Part 2: Histologically or cytologically DOR 2023 1622 documented squamous or non- NCT03233139 squamous NSCLC with stage IIIB or stage IV disease who received no prior systematic ttmt for recurrent or metastatic NSCLC. In Part 2 patients must have available archival or newly obtained formalin- fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated. • Sequential assignment, Open-label, non-randomized • 3 arms: Part 1: cemiplimab; Part 2/ cohort A: cemiplimab; Part 2/ cohort B: cemiplimab + ipilimumab + platinum doublet chemotherapy

45 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Pediatrics Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

RR Solid tumors Phase 1 150 • Primary: DLTs (Phase 1 & • SSD: Early 2019 CNS tumors Phase 2 • Randomized, Parallel Group 2), Anticipated • DE: 2025 assignment, Open-label recommended dose from ND R Glioma a) Safety and • Phase1: cemiplimab monotherapy in Phase 1 to Phase 2, Pharmacokinetics of both cohorts: Solid Tumor and CNS cemiplimab PK R2810-ONC- cemiplimab single agent cohorts (monotherapy and in 1690 in Pediatric Patients • Phase 2: Newly Diagnosed DIPG, combination with radiation NCT03690869 with Relapsed Newly Diagnosed HGG, recurrent therapy), anticipated Refractory Solid or CNS HGG: cemiplimab in combination cemiplimab RP2D when co- Tumors with radiation therapy administered with radiation b) Safety and Efficacy of therapy in DIPG and HGG, cemiplimab in anti-tumor activity: OS12, combination with PFS12, Radiotherapy in • Secondary: anti-tumor Pediatric Patients with activity (children objective Newly Diagnosed response), immunogenicity, Diffuse Intrinsic Pontine tolerability profile (DLTs & Glioma, Newly AEs) Diagnosed High-Grade Glioma or Recurrent High-Grade Glioma

46 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Melanoma - Biomarkers Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Biomarkers Phase 1 47 • For Histologically confirmed • Primary: Correlation • SSD: Apr. 2017 Melanoma (actual) diagnosis of stage III (unresectable) between changes in the • DE: 2020 Exploratory Tumor Biopsy- or stage IV cutaneous melanoma tumor microenvironment and driven study to understand (non-acral lentiginous) with at least the change in tumor volume R2810-ONC- the relationship between 1 lesion that is measurable by following cemiplimab Tx 1606 biomarkers and clinical RECIST 1.1 criteria and accessible • Secondary: Correlation NCT03002376 response in Melanoma for biopsies between baseline tumor patients receiving characteristics and the cemiplimab change in tumor volume following Tx, cemiplimab serum concentrations, antibodies levels, PFS, ORR

47 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Head and Neck - Biomarkers Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Biomarkers Phase 1 33 • For Histologically confirmed • Primary: Correlation • SSD: Jul. 2017 Head & Neck (actual) diagnosis recurrent and/or between changes in the • DE (1st Part) (1): Exploratory Tumor Biopsy- metastatic SCCHN (squamous cell tumor microenvironment and 2019; full driven study to understand carcinoma of the head and neck) the change in tumor volume completion 2020 R2810-ONC- the relationship between with no curative options with at least following cemiplimab Tx 1655 biomarkers and clinical 1 lesion that is measurable by • Secondary: Correlation NCT03198130 response in Response Evaluation Criteria in between baseline tumor Immunomodulatory Solid Tumors (RECIST) characteristics and the Treatment-Naïve patients • Open-label, Single Group change in tumor volume with Recurrent and/or Assignment following Tx, ORR, PFS, Metastatic Squamous Cell TAES, cemiplimab serum Carcinoma of Head and concentration, anti- Neck receiving cemiplimab cemiplimab antibodies level

(1) Final Data Collection date for primary outcome measure 48 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Cutaneous Squamous Cell Carcinoma (CSCC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Advanced Phase 2 266 • Non-Randomized, Open-label, • Primary: ORR (96 weeks), • SSD: May 2016 CSCC Parallel assignment Groups 1,3 and 4: RECIST • DE: Primary:2020; Cemiplimab • Group 1: Patients with metastatic version 1.1 will be used to Full completion monotherapy for patients CSCC: to distant sites or lymph determine ORR, Group 2 2021 R2810-ONC- with metastatic (nodal or nodes cemiplimab administered and 4: Clinical response 1540 distant) CSCC (Groups 1 intravenously every 2 weeks criteria will be used to NCT02760498 and 3) or with • Group 2: Patients with unresectable determine ORR unresectable locally locally advanced CSCC. cemiplimab • Secondary: Investigator advanced CSCC administered intravenously every 2 Assessments of ORR, DOR, (Group 2) weeks PFS, OS, CRR, cemiplimab • Group 3: Patients with metastatic PK and antibodies levels, CSCC: to distant sites or lymph patients reported outcomes nodes, cemiplimab administered (EORTC QLQ-C30), TEAEs intravenously every 3 weeks • Group 4: Patients with advanced CSCC , metastatic (nodal or distant) or unresectable locally advanced , cemiplimab administered every 4 weeks • Group 5: Patients in advanced CSCC receiving a single SC dose of cemiplimab, followed by cemiplimab IV Q3W (pilot Group)

49 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Neoadjuvant CSCC Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Neoadjuvant Phase 1 36 • Patients with history of recurrent • Primary: DLTs, TEAs, • SSD: Apr. 2019 CSCC resectable CSCC injection site reactions, • DE: 2020 Study of Pre-Operative • Open-label, Single-Group • Secondary: ORR, pathologic cemiplimab administered assignment complete response rate, R2810-ONC- Intralesionally, for Patients • Three dose cohorts planned major pathologic response 1787 with Recurrent Cutaneous followed by a 3+3 dose-escalation rate, cemiplimab serum NCT03889912 Squamous Cell Carcinoma design with cohort expansion concentration, cemiplimab (CSCC) antibodies, selection of the recommended cemiplimab dose for further study based on clinical and PK observations.

50 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Neoadjuvant CSCC post surgery Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Neoadjuvant Phase 3 412 • Patients with resection of • Primary: DFS (time from • SSD: June 2019 CSCC pathologically confirmed CSCC, and randomization to the first • DE: Primary: Adjuvant Cemiplimab vs qualified as High Risk CSCC, documented disease 2023, Full Placebo after Surgery and • Randomized, placebo-controlled, recurrence) completion: 2026 R2810-ONC- Radiation Therapy in double-blind, parallel assignment, • Secondary: OS, FFLRR 1788 Patients with High risk • 2 arms: cemiplimab and placebo, (from randomization to the NCT03969004 CSCC 1st locoregional recurrence LRR), FFDR (from randomization to the 1st distant recurrence), cumulative occurrence of second primary CSCC, TEAEs, incidence of deaths, lab. abnormalities,

51 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Neoadjuvant CSCC Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Neoadjuvant Phase 2 76 • Patients with Stage II to IV CSCC, • Primary: pCR (pathologic • SSD: Q1 2020 CSCC • Open-label, single group assignment Complete Response), • DE: Primary: Neodjuvant Cemiplimab for (cemiplimab) • Secondary: mPR (Major 2021, Full Stage II to IV CSCC Pathologic response, pCR, completion: 2025 R2810-ONC- mPR, ORR, EFS, DFS, OS, 1901 incidence of deaths, NCT04154943 laboratory abnormalities, change in surgical plan and in post chirurgical plan.

52 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Basal Cell Carcinoma (BCC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

BCC Phase 2 137 • Patients with confirmed diagnosis of • Primary: ORR for mBCC • SSD: July 2017 invasive BCC measured by RECIST • DE: Primary: 2021, Cemiplimab in patients with • Non-Randomized, Open-label, version 1.1 ORR for Full completion R2810-ONC- Advanced BCC who Parallel assignment unresectable locally 2022 1620 experienced progression of • Group 1: Patients with metastatic advanced BCC measured NCT03132636 disease on Hedgehog BCC by Composite Response Pathway Inhibitor Therapy, • Group 2: Patients with unresectable Criteria or were intolerant of Prior locally advanced BCC • Secondary: DOR, CR, PFS, Hedgehog Pathway Inhibitor OS, TEAEs, PK, Therapy immunogenicity

53 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Non-Small Cell Lung Cancer (NSCLC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

mNSCLC Phase 3 700 • For histologically or cytologically • Primary: OS, PFS as • SSD: May 2017 documented squamous or non assessed by a blinded • DE: 2023 First-line Tx in patients with squamous NSCLC with stage IIIB or Independent review R2810-ONC- advanced or metastatic stage IIIC who are not candidates committee using RECIST 1624 NSCLC whose tumors for Tx with definitive chemoradiation 1.1 NCT03088540 express PD-L1, vs. Platinum or patients with stage IV disease • Secondary: Objective Based Chemotherapy who received no prior systemic Tx response rates, BOR, DOR for recurrent or metastatic NSCLC • Randomized, Open-label, Cross- over assignment • Active Comparator: Standard-of- care chemotherapy: paclitaxel + cisplatin OR paclitaxel + carboplatin OR gemcitabine + cisplatin or gemcitabine + carboplatin OR Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR pemetrexed + carboplatin followed by optional pemetrexed maintenance

54 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Non-Small Cell Lung Cancer (NSCLC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

mNSCLC Phase 3 Part 1: 360 • For histologically or cytologically • Primary: Part 1: ORR; • SSD: Mar. 2018 Part 2: 450 documented squamous or non Part 2: OS and PFS as • DE: 2023 Combination of squamous NSCLC with stage IIIB or assessed by a blinded R2810-ONC- cemiplimab and IIIC disease who are not candidates independent review 16113 Platinum-based Doublet for Tx with definitive concurrent committee using NCT03409614 Chemotherapy in chemoradiation or stage IV disease RECIST1.1, patients with Lung who received no prior systemic Tx • Secondary: TEAEs, DLTs, Cancer for recurrent or metastatic NSCLC SAEs, incidence of deaths, • Part 1: Randomized, Open-label, laboratory abnormalities, Parallel assignment QoL • Arm 1: Standard of care Platinum- based doublet chemotherapy • Arm 2: cemiplimab + Platinum- based doublet chemotherapy • Arm 3: cemiplimab + abbreviated chemotherapy + ipilimumab • Part 2: Randomized, Double-Blind, • Arm 1: Standard of care Platinum- based doublet chemotherapy • Arm 2: cemiplimab + standard of care Platinum-based doublet chemotherapy

55 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Non-Small Cell Lung Cancer (NSCLC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Patien Study Description Design Endpoints Status ts

mNSCLC Phase 3 5* • For histologically or cytologically • Primary: PFS as assessed • SSD: June 2018 documented squamous or non by a blinded Independent • DE: 2020 Combination of cemiplimab, squamous NSCLC with stage IIIB or review committee using R2810-ONC- Platinum-based Doublet stage IV disease who received no RECIST 1.1 16111 Chemotherapy, and prior systemic Tx for recurrent or • Secondary: OS, ORR, NCT03515629 ipilimumab vs metastatic NSCLC TEAEs, DLTs, SAEs, death, pembrolizumab in Patients • Randomized, Open-label, Parallel lab. abnormalities, OS, QoL with Lung Cancer assignment • Arm 1: pembrolizumab • Arm 2: cemiplimab + ipilimumab • Arm 3: cemiplimab + chemotherapy + ipilimumab

*: study ongoing with the patients included but recruitment stopped

56 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Non-Small Cell Lung Cancer (NSCLC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

mNSCLC Phase 2 28* • For histologically or cytologically • Primary: ORR • SSD: May 2018 documented squamous or non • Secondary: OS, PFS, • DE: 2020 squamous NSCLC with stage IIIB or TEAEs, SAEs, death, lab. R2810-ONC- IIIC and not candidates for definitive abnormalities 1763 Cemiplimab and Ipilimumab chemoradiation or stage IV. Patients NCT03430063 in Patients with Lung Cancer must have PD after receiving one prior line of chemotherapy Tx for advanced NSCLC, • Randomized, Open-label, Parallel assignment • Arm 1: cemiplimab standard dose • Arm 2: cemiplimab + ipilimumab standard doses • Arm 3: cemiplimab High dose

*: study ongoing with the patients included but recruitment stopped

57 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Cervical cancer (CC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

CC Phase 3 534 • Patients with recurrent, persistent • Primary: OS • SSD: Oct. 2017 and/or metastatic CC with • Secondary: PFS, ORR, • DE: Primary: 2020; Cemiplimab vs. therapy of squamous cell histology for which DOR, QOL Next 2021; Full R2810-ONC- Investigator Choice there is no curative intent option, completion 2023 1676 chemotherapy in Recurrent • Randomized, Open-label, Parallel NCT03257267 or Metastatic CC assignment, Tx cycle 6 weeks, Planned Tx for up to 96 weeks • 2 arms: cemiplimab and Investigator Choice (IC) chemotherapy

58 Immuno-inflammation Diabetes SAR439459 (TGFß inhibitor mAb) Oncology Cardiovascular Advanced Solid Tumors (AST) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

AST Phase 1/1b 225 • Patients with histologically • Primary: incidence of DLTs • SSD: Jun. 2017 Monotherapy confirmed, advanced unresectable (Part 1), ORR (Part 2) • DE: Primary and Safety, PK, PD and Anti- or metastatic solid tumor • Secondary: Safety profile, (melanoma): 2021; combination tumor activity of SAR439459 • Open-label, Parallel assignment Immunogenicity, PK, PFS Full completion: with Monotherapy and in • Part 1A: SAR439459 monotherapy (Part 2), TTP (Part 2) 2022 cemiplimab combination with cemiplimab escalating doses in adult patients with • Part 2A: SAR439459 monotherapy Advanced Solid Tumors with the previously recommended TCD14678 dose NCT03192345 • Part 1B: SAR439459 escalating dose + cemiplimab standard dose • Part 2B: SAR439459 at previously recommended dose + cemiplimab standard dose • Escalation periods non randomized followed by expansion periods randomized

59 Immuno-inflammation Diabetes SAR408701 (maytansin loaded anti-CEACAM5 mAb) Oncology Cardiovascular Advanced Solid Tumors (AST) 1/2 Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

First-in-Human Phase 1 337 • Patients with locally advanced or • Primary: MTD, Anti-tumor • SSD: Sep. 2014 Phase 2 metastatic solid malignant tumor response RECIST • DE: 2021 • Non-Randomized, Open-label, Parallel • Secondary: Overall Safety, TED13751 Safety, PK and antitumor assignment Immunogenicity, PK, NCT02187848 • Arm 1 : SAR408701 monotherapy activity of SAR408701 in escalating cohorts duration of response, time to patients with AST • Arm 2: SAR408701 expansion cohort in progression CRC with MTD previously defined • Arm 3: SAR408701 expansion cohort in non-squamous NSCLC high expresser patients (CEACAM5 >50% of tumor cells ≥ 2+ intensity) at MTD • Arm 4: SAR408701 expansion cohort gastric adenocarcinoma at MTD • Arm 5: SAR408701 loading dose at first cycle followed by MTD • Arm 6: SAR408701 expansion cohort in non-squamous NSCLC patients (Lung bis) with CEACAM5 >1% of tumors cells ≥ 2+ intensity, at MTD • Arm 7: SAR408701 expansion cohort SCLC at MTD • Arm 8: SAR408701 expansion cohort CRC-L at MTD • Arm 9: SAR408701 dose escalation every 3 weeks

60 Immuno-inflammation Diabetes SAR408701 (maytansin loaded anti-CEACAM5 mAb) Oncology Cardiovascular Advanced Solid Tumors (AST) 2/2 Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Japanese Phase 1 24 • Patients with advanced or • Primary: DLTs, • SSD: Oct. 2017 patients (expected) metastatic malignant solid tumor • Secondary: Safety, • DE: 2021 Monotherapy Safety and PK of • Open-label, Sequential assignment Immunogenicity, PK, SAR408701 Monotherapy • 14-day cycle Plasma CEACAM5 levels, in Japanese patients with • Amendment to test loading dose Anti-tumor response TCD15054 Advanced Malignant Solid ongoing RECIST NCT03324113 Tumors

61 Immuno-inflammation Diabetes SAR408701 (maytansin loaded anti-CEACAM5 mAb) Oncology Cardiovascular NSCLC Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status CARMEN-LC03 Phase 3 554 • Patients with histologically or • Primary: PFS, OS, • SSD: Nov. 2019 cytologically proven diagnosis of • Secondary: ORR, Quality of • DE: 2024 SAR408701 vs Docetaxel in non-squamous NSCLC, with life (disease related EFC15858 patients with Previously metastatic disease progression after symptoms, physical NCT04154956 Treated Metastatic Non- platinum-based chemotherapy and function, role function), Squamous NSCLC with immune checkpoint inhibitor, and safety, DOR. CEACAM5 positive tumors with carcinoembryonic antigen- related cell adhesion molecule (CEACAM) 5 expression, • Randomized, Open-label, Parallel assignment • 2 Arms: SAR408701 & Docetaxel

62 Immuno-inflammation Diabetes SAR439859 (SERD) Oncology Cardiovascular Breast cancer (1/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 259 • Non-Randomized, Open-label, Parallel • Primary: Parts A & C:DLTs, • SSD: Sept. 2017 Phase 2 Assignment Parts B & D: ORR; safety • DE: 2021 • Part A: SAR439859 monotherapy dose • Secondary: Safety, ORR, TED14856 SAR439859 single agent escalation, TTR, DCR, DR, PK for both NCT03284957 • Part C: dose escalation for the and in combination with combination SAR439859 and drugs, CYP450 3A palbociclib in palbociclib, induction/inhibition, ER Postmenauposal Women • Part B: SAR439859 dose expansion occupancy/PET imaging with Estrogen Receptor from the dose determined in part A, Positive Advanced Breast • Part D: combination SAR439859 and Cancer palbociclib at the doses recommended from part C • SAR439859 administered in 28-day cycle; palbociclib in 21-day cycle • Part E: midazolam drug-drug interaction sub-study to assess the effect of SERD on CYPA3 Phase 1 12 • Primary: :DLTs, • SSD: Apr. 2019 • Open-label, Single-Group • Secondary: AEs, • DE: 2020 Safety, Efficacy, Assignment Pharmacokinetics of TED15954 Pharmacokinetics and • SAR439859, administered orally SAR439859, ORR, NCT03816839 Pharmacodynamics once daily as monotherapy in fasted CBR,DR, non-progression Evaluation of SAR439859 or fed conditions rate, single agent in Japanese Postmenopausal Women with ER positive and HER2 negative Advanced Breast Cancer 63 Immuno-inflammation Diabetes SAR439859 (SERD) Oncology Cardiovascular Breast cancer (2/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 2 282 • Primary: PFS, • SSD: 2019 • In patients with histological or • Secondary: ORR, DCR, • DE: Primary: 2021, SAR439859 versus cytological diagnosis of CBR, DOR, PFS, OS, PK, full Completion: ACT16105 endocrine Monotherapy With adenocarcinoma of the breast, patient reported outcomes, 2022 NCT04059484 Estrogen Receptor-positive, • Randomized, Open-label, Parallel overall safety profile HER2-Negative Locally Assignment Advanced or metastatic • 2 Arms: SAR439859 and endocrine Breast Cancer With prior monotherapy as per physician’s Exposure to Hormonal choice Therapies

64 Immuno-inflammation Diabetes SAR439859 (SERD) Oncology Cardiovascular Breast cancer (3/3) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 2 126 • Primary: change in Ki67 (% • SSD: Jan. 2020 • In patients with histological or of positive tumor cells tested • DE: 2021 Window study of cytological diagnosis of invasive by immunochemistry) ACT16106 SAR439859 versus breast adenocarcinoma, • Secondary: Ki67≥ 50%, ER, NCT04191382 Letrozole in Newly • Randomized, Parallel Assignment, safety, laboratory Diagnosed Pre-operative single masking abnormalities, Postmenopausal patients • 3 Arms: SAR439859 ( two dose With ER positive and HER2 levels) and letrozole as active Negative Primary Breast comparator. Cancer

65 Immuno-inflammation Diabetes SAR440234 (T-cell engaging bispecific mAb) Oncology Cardiovascular Leukemia and Myelodysplastic Syndrome Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 77 • Primary: DLTs, allergic • SSD: Nov. 2018 Phase 2 • Patients with confirmed diagnosis of reactions/hypersensitivity, • DE: 2022 AML (except acute promyelocytic ORR, DOR, event-free TED15138 SAR440234 single agent in leukemia) or MDS with a risk survival NCT03594955 patients with Relapsed or category intermediate or higher, and • Secondary: AEs, PK, Refractory Acute Myeloid not eligible for any Tx known to Preliminary Anti-Leukemia Leukemia (RR AML), B-cell provide clinical benefit, Activity, immunogenicity Acute Lymphoblastic • Open-label, Single Group Leukemia (B-ALL) or High Assignment Risk Myelodysplasia (HR- • 2 dose escalation schemes, MDS) • Cycle defined as 6 weeks of study Tx • Tx may be continued as long as it is clinically beneficial

FDA clinical hold lifted in August 2019 - Sites re-initiation activities ongoing .

66 Immuno-inflammation Diabetes SAR442720 (SHP2 inhibitor) Oncology Cardiovascular Relapsed/Refractory Solid Tumors Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 240 • Primary: AEs, DLTs, • SSD: Oct. 2018 • Patients with advanced solid tumors • Secondary: PK, pERK (PD • DE: 2021 that have failed, are intolerant or are markers), ORR, DOR, RMC-4630-01 Safety, Tolerability, PK and considered ineligible for standard of NCT03634982 PD profiles of SAR442720 care anticancer Tx single agent in patients with • Open-label, Single Group Relapsed/Refractory Solid Assignment Tumors • 1 Arm: SAR442720, oral administration

Phase 1 144 • Patients with advanced solid tumors • Primary: AEs, DLTs, • SSD: July 2019 RMC-4630-02 Phase 2 that have failed, are intolerant or are • Secondary: PK, ORR, • DE: 2022 considered ineligible for standard of DOR, NCT03989115 care anticancer Tx Safety, Tolerability, PK and • Open-label, Single Group PD profiles of SAR442720 Assignment and Cobimetinib in Adult • 1 Arm: SAR442720 + Cobimetinib, participants with oral administration Relapsed/Refractory Solid Tumors With Specific Genomics Aberrations

67 Immuno-inflammation Diabetes SAR441000 (Cytokine mRNA) Oncology Cardiovascular Advanced Solid Tumors Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 264 • Primary: DLTs (SAR441000 • SSD: Jan. 2019 • Patients with advanced solid alone and in combination), • DE: 2021 malignant tumors including MTD (SAR441000 alone TED15297 Safety, Pharmacokinetics, lymphomas, for which no standard and in combination), TEAEs, NCT03871348 Pharmacodynamics and alternative therapy is available, ORR for expansion, Anti-Tumor activity of • Non-randomized, Open-label, • Secondary: PK SAR441000 as Monotherapy Parallel Assignment, (SAR441000 alone and in and in Combination with • Dose escalation Phase, 2 arms: combination), cemiplimab in patients with SAR441000 (intra-tumoral injection immunogenicity Advanced Solid Tumors as monotherapy) and SAR441000 (SAR441000 and (intra-tumoral injection) + cemiplimab), DCR and DoR cemiplimab over a 21-day cycle, (SAR441000 alone and in • Expansion cohorts in melanoma combination), PFS, TEAEs, with SAR441000 monotherapy and Recommended dose for with the combination (SAR441000 + SAR441000 alone and in cemiplimab), combination for the • Expansion cohorts in CSCC, expansion cohorts, ORR for HNSCC with the combination. dose escalation.

68 Immuno-inflammation Diabetes SAR442085 (Anti CD38 mAb Fc engineered) Oncology Cardiovascular Multiple Myeloma Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 78 • Patients previously diagnosed with • Primary: MTD, • SSD: Sept. 2019 multiple myeloma based on recommended dose for Part • DE: 2022 standard criteria, B and further testing, ORR, TED16132 Safety, Pharmacokinetics, • Non-randomized, Open-label, • Secondary: TEAEs, PK, NCT04000282 Pharmacodynamics and Sequential Assignment, Anti-drug antibody, PFS, Anti-Tumor activity of • Part A: dose escalation DR, SAR442085 in Patients with • Part B: dose expansion Relapsed or Refractory Multiple Myeloma

69 Immuno-inflammation Diabetes SAR444245 - THOR 707 Oncology Cardiovascular Solid Tumors Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 300 • open-label Primary: • SSD: June 2019 • multiple ascending dose escalation • Rate of Dose-Limiting • DE:2022 and dose expansion study Toxicities (DLTs) TCD16843 An Open-Label, Multicenter • Part 1: monotherapy • Maximum Tolerated Dose NCT04009681 Phase 1/2 Dose Escalation • Part 2: combination with a (MTD) and Expansion Study of checkpoint inhibitor • Recommended Phase 2 THOR-707 as a Single Dose Agent and in Combination With a Checkpoint Inhibitor in Adult Subjects With Advanced or Metastatic Solid Tumors

70 Immuno-inflammation Diabetes GZ402666 (avalglucosidase alfa) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Pompe disease (PD) 1/3 MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

COMET Phase 3 102 • Repeated Biweekly Infusions of • Primary: Change in percent • SSD: Oct. 2016 avalglucosidase alfa (GZ402666) and predicted forced vital capacity • DE Primary: 2020 Late Onset To compare efficacy and safety alglucosidase alfa in Tx-naïve patients (%FVC) in the upright position, • DE Full Completion: of Enzyme Replacement with late-onset PD age 3 years and older from baseline to 12 months 2024 EFC14028 therapies avalglucosidase alfa • Randomized, Double-Blind, Parallel • Secondary: Change from (neoGAA) and alglucosidase Assignment baseline to 12 months in six- NCT02782741 alfa (Myozyme®/Lumizyme®) in • Total study duration for one patient: 3 minute walk test distance Tx-naïve patients with Late- years [14-day screening, 49-week walked, maximal inspiratory / onset PD blinded Tx period, 96-week open-label expiratory pressure (% Tx and 4-week post-Tx observation predicted), hand-held period dynamometry measurement of lower extremity muscle strength in Quick Motor Function Test scores, and 12- Item Short-form health survey scores

71 Immuno-inflammation Diabetes GZ402666 (avalglucosidase alfa) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Pompe disease (PD) 2/3 MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Mini-COMET Phase 2 22 • Repeated bi-weekly infusions of • Primary: N of participants with AE, • SSD: Oct. 2017 avalglucosidase alfa In Patients with N of participants with • DE Primary: 2019 Infantile Onset To assess safety and efficacy of Infantile-onset PD previously treated immunogenicity response • DE Full completion: avalglucosidase alfa (neoGAA) with alglucosidase alfa Secondary: PK parameters, 2022 ACT14132 in Pediatric patients with (Myozyme®/Lumizyme®) who Change at 6 months from baseline infantile-onset PD previously demonstrate clinical decline or sub- in Gross Motor Function (GMF) NCT03019406 treated With alglucosidase alfa optimal clinical response Measure-88 Test, revised GMF (Myozyme®/Lumizyme®) • Randomized, Open-label, Ascending Classification System score, dose, Parallel assignment Pompe specific Pediatric • Total study duration for one patient: 3 Evaluation of Disability Inventory, years [14-day screening, 25-week Tx Functional Skills Scale, Mobility period, a 120-week extension period Domain Test score and Quick and 4-week post-Tx observation Motor Function Test scores, Left period Ventricular Mass Index, Eyelid position measurements, Creatine kinase value

72 Immuno-inflammation Diabetes GZ402666 (avalglucosidase alfa) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Pompe disease (PD) 3/3 MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

NEO-EXT Phase 2 21 • Repeated biweekly infusions of • Primary: AEs and TEAEs, including • SSD: Feb. 2014 Phase 3 avalglucosidase alfa In patients with IARs & deaths, Hematology, • DE: 2021 (for post PD who previously completed a biochemistry and urinalysis, vital trial access) LTS13769 Long-term safety and PK of avalglucosidase alfa study [adult, signs NCT02032524 repeated biweekly infusions of senior] • Secondary: ECG, PK parameters, avalglucosidase alfa (neoGAA) • Non-randomized, Open-label, single anti-avalglucosidase alfa antibodies, in patients with PD group assignment and neutralizing antibody formation • Total study duration for one patient: in anti-avalglucosidase alfa positive 6 years [until the patient withdraws, patients, anti-alglucosidase alfa IgG the Investigator withdraws the antibodies, Skeletal muscle patient, or the Sponsor terminates glycogen content, Qualitative and the study] quantitative muscle degenerative assessments MRI, Urinary Hex4, plasma analyses of circulating mRNA and micro RNA, Serum analyses of skeletal muscle RNA expression

73 Immuno-inflammation Diabetes Olipudase Alfa (rhASM ERT) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Acid Sphingomyelinase Deficiency (ASMD) (1/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ASCEND Phase 2 36 • Randomized, Double-blinded, • Primary: % change in spleen • SSD: June 2016 Placebo-controlled, Parallel volume, % change in diffusing • DE: 2019(2) Niemann-Pick Phase 3 assignment capacity of the lung for carbon • DE: 2023(3) disease Efficacy, Safety, PD, and PK • Study duration is composed of monoxide (Dlco) type B(1) study of olipudase alfa in blinded period and an open label • Secondary: Change in patients with ASMD extension allowing patients that were splenomegaly-related symptom on placebo to cross over to active score (except US, where it is part DFI12712 treatment of the primary "combination spleen NCT02004691 endpoint"), % change in liver volume, % change in platelet count, change in fatigue severity as measured by item 3 of the Brief Fatigue Inventory scale, change in pain severity as measured by item 3 of the Brief Pain Inventory scale, change in dyspnea severity as measured by the functional assessment of chronic illness therapy dyspnea tool

(1) Non-neurological manifestations of ASMD (2) Primary analysis period (3) Completion of trial, end of long-term extension 74 Immuno-inflammation Diabetes Olipudase Alfa (rhASM ERT) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Acid Sphingomyelinase Deficiency (ASMD) (2/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Long-Term Phase 2 20 • For patients who have completed a • Primary: Safety parameters, • SSD: Dec. 2013 previous study with olipudase alfa complete physical examinations • DE: 2023 Long-term study of olipudase (DFI13803 for pediatric patients, including neurologic examinations, LTS13632 alfa in patients with ASDM and DFI13412 for adult patients) vital signs, echocardiograms and NCT02004704 • Open-label, Single group electrocardiograms, clinical assignment laboratory tests, safety biomarkers, • Total study duration for one patient: immune response assessment, liver up to 9 years biopsy (patients previously enrolled in DFI13412) and liver ultrasound/doppler (patients previously enrolled in DFI13803). • Secondary: Spleen and liver volumes, pulmonary imaging and function tests, hematology and lipid profiles, health outcome questionnaires. For pediatrics patients: Hand X-ray for bone age and bone maturation, linear patient growth by height Z- score.

75 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Gaucher disease (GD) Type 3 (1/3) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

LEAP Phase 2 10 • 208-week Three part, Open-label, Single • Primary: N of patients with AE, • SSD: Jan. 2017 group Assignment assessment of PD parameters • DE (1st Part)(1): 2024 GD Type 3 Tolerability, PK, PD, and • Part 1: Evaluate CNS biomarkers in adult (GL-1 and lyso GL1 ) in CSF exploratory efficacy of venglustat GD type 3 patients that distinguish GD3 and plasma PDY13949 in combination with cerezyme in from GD type 1, • Secondary: PK parameters adult patients with GD Type 3 Screen adult GD3 patients who qualify for (CSF and Plasma) NCT02843035 Ttmt with venglustat in Part 2, Total duration 45 days • Part 2 and 3: Safety and tolerability in GD3 patients, Total duration up to 208 weeks including : treatment of 52 weeks (Part 2) and 156 weeks (Part 3) for long term follow-up, respectively

(1) Final Data Collection date for primary outcome measure 76 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Autosomal Dominant Polycystic Kidney Disease (ADPKD) (2/3) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

STAGED-PKD Phase 3 640 • Randomized, double-blind, placebo- • Primary: Rate of change in total • SSD: Feb. 2019 controlled 2-stage study (18 and 24 kidney volume (TKV) based on • DE Stage 1: 2021 Efficacy, safety, tolerability and months) magnetic resonance imaging • DE Stage 2: 2023 EFC15392 PK of venglustat in patients at • Study duration per participant is 26 (MRI) (Stage 1) and rate of NCT03523728 risk of rapidly progressive months (maximal) per stage, including a change in glomerular filtration ADPKD screening period of 15 days, run-in rate (eGFR) (Stage 2) period of 2 weeks, a 24-month treatment Secondary: Rate of change in period, and a follow-up 30 days after eGFR (Stage 1) , rate of final dose change in TKV (Stage 2), PK assessment, safety/tolerability objectives

77 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders GM2 gangliosidosis (3/3) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

AMETHIST Phase 3 62 • Multicenter, Multinational, Randomized, Primary: • SSD: Q2 2020 Double-blind, Placebo-controlled Study • Change in cerebrospinal fluid • Primary DE: 2023 A Multinational, Randomized, • The total duration is up to (CSF) GM2 biomarker EFC15299 Double-blind, Placebo-controlled approximately 119 weeks, including a • Change in the 9-hole NCT04221451 Study to Assess the Efficacy, 60-day screening period, a 104-week pegboard test (9-HPT Pharmacodynamics, treatment period, and a 6-week post- • Assessment of Pharmacokinetics, and Safety of treatment safety observation period. pharmacodynamic (PD) Venglustat in Late-onset GM2 response in plasma: GL-1, GM1,GM2, GM3 biomarkers in the different subpopulations.

Secondary

• Safety/tolerability: Adverse events • Assessment of pharmacokinetic (PK) parameters in plasma: Cmax , tmax, AUC0-24h • Assessment of PK parameters in CSF: Cmax , tmax, AUC0- 24h • Change in 25-foot walk test (FWT) • Change in Friedreich's Ataxia Rating Scale (FARS) • Change in 9-hole peg test (9- HPT) 78 Immuno-inflammation Diabetes Eliglustat Oncology Cardiovascular Rare Diseases Rare Blood Disorders Gaucher’s Disease (GD) (1/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ELIKIDS Phase 3 60 • Non-randomized, open label, two cohort • Primary: PK (Cmax and AUC), • SSD: Apr. 2018 (with and without imiglucerase) adverse events • DE Primary: 2022 PK, efficacy and safety with or • Cohort 1: eliglustat monotherapy • Secondary: changes from • DE Full completion: GD Type 1/ without Imiglucerase in pediatric • Cohort 2: eligustat plus imiglucerase baseline as absolute change in 2025 Type 3 patients with GD g/dL for hemoglobin, % change Type1/Type 3 for platelets, liver volume, and spleen volume; improvement in EFC13738 pulmonary disease, improvement in bone disease, NCT03485677 thrombocytopenia, and quality of life

79 Immuno-inflammation Diabetes Eliglustat Oncology Cardiovascular Rare Diseases Rare Blood Disorders Gaucher’s Disease (GD) (2/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

EXOSKEL Phase 3 32 • Single group assignment, open label • Primary: change from baseline • SSD: Oct. 2015 in bone marrow infiltration, • DE Primary (2y Long Term skeletal response to bone mineral density (hips and primary outcome): GD Type 1 eliglustat in GD Type 1 adult lumbar spine), skeletal imaging 2019 patients who successfully GD bone disease • DE Full completion: completed Phase 2 or phase 3 manifestations (lytic lesions, 2021 EFC13781 studies osteonecrosis, fractures and NCT02536755 infarcts), clinical GD manifestations (mobility, bone pan, bone crisis), and bone biomarkers • Secondary: quality of life, measurement of GD Type 1 biomarkers and safety (i.e. incidence of adverse events, change from baseline in laboratory assessments (hematology), physical examinations)

80 Immuno-inflammation Diabetes SAR339375 (Anti-miR21 RNA) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Alport syndrome (ALPS) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

HERA Phase 2 45 • 18-60 year old males and females with • Primary: AEs; Annualized • SSD: Nov. 2017 ALPS change in eGFR from baseline (Restart in Nov. Safety, Efficacy, • Randomized, double-blind, placebo- to 48 weeks, 2019) Pharmacodynamics and control • Secondary: PK, Anti-drug • DE: Apr 2022 PoC ACT 16248 / Pharmacokinetics of • 2 arms: SAR339375 (RG012) and antibodies, Percent change in (Apr 2023 EOS) placebo, in a 2:1 ratio eGFR values from baseline to RG012-03 SAR339375 (RG-012) in patients with ALPS • Duration: 48 week SC injections double- 24 weeks and 48 weeks. NCT02855268 blinded treatment period. After 48 week treatment, subjects can receive a 48 week open-label extension period

81 Immuno-inflammation Diabetes Teriflunomide Oncology Cardiovascular Multiple Sclerosis (MS) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

TERIKIDS Phase 3 165 • Patients with RMS meeting the criteria of • Primary: Time to first clinical • SSD: Jul. 2014 MS based on McDonald criteria 2010 relapse after randomization • DE Primary: 2019 RMS Efficacy, Safety and PK of and International Pediatric MS Study • Secondary: % of relapse free • DE Full completion teriflunomide in Pediatric Group criteria for pediatric MS patients, N of new/newly for main open label EFC11759 Patients With Relapsing Forms • With at least one relapse (or attack) in enlarged T2 lesions, N of T1 period: 2021 of MS the 12 months preceding randomization Gd-enhancing T1 lesions , NCT02201108 or at least two relapses (or attack) in the Change in volume of T2 lesions 24 months preceding randomization , of T1 hypointense lesions , • Randomized, Double-Blind, Placebo- brain atrophy, % of patients free Controlled, Parallel Group , Tx 96 weeks of new or enlarged MRI T2- followed by Open-label extension (96 lesions, Change in performance weeks up to a max of 192 weeks after on SDMT and Cognitive Battery randomization), follow-up 4 weeks after Test , Safety, PK Tx discontinuation

82 Immuno-inflammation Diabetes Alemtuzumab Oncology Cardiovascular Relapsing Remitting Multiple Sclerosis (RRMS) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

LemKids Phase 3 50 • In pediatric patients from 10 to <18 years • Primary: The number of new or • SSD: Oct. 2017 of age with RRMS with disease activity enlarging T2 lesions on brain • DE: 2026 RRMS Efficacy, Safety and Tolerability on prior DMT. MRI, during continuation of of Alemtuzumab in Pediatric • Open-label, rater-blinded, single-arm, prior DMT (Period 1) compared EFC13429 Patients With Relapsing cross-over study to an equal period after the first Remitting MS (RRMS) with The study will consist of different phases: course of alemtuzumab NCT03368664 disease activity on prior disease • Prior DMT Phase (~4 months) – treatment (Period 2) modifying therapy DMT efficacy measurements on current DMT • Alemtuzumab Treatment Phase (~2 • Secondary: The proportion of years) - The MRI based primary patients with new or enlarging efficacy endpoint will be assessed over T2 lesions , Annualized relapse a 4 month period during this phase rate at Year 2, Assessment of compared to an equal period during the cognition test scores, Additional prior DMT phase secondary endpoints, including • Safety Monitoring Phase – safety PK/PD parameters and Quality monitoring for all patients treated with of Life (QoL) measures. alemtuzumab (4 years post last treatment with alemtuzumab)

83 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular GBA related Parkinson Disease Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

MOVES-PD Phase 2 245 • Patients with PD carrying a GBA • Primary: Change from baseline • SSD: Dec. 2016 mutation or other prespecified variant. in Movement Disorder Society • DE Primary: 2021 Efficacy, safety, • Randomized, Double-blind, Placebo Unified PD Rating Scale Part II • DE: Full completion: ACT14820 pharmacokinetics, and Controlled, Parallel Assignment and III score 2023 NCT02906020 pharmacodynamics of • Part 1: Increasing dose of venglustat • Secondary: Change from venglustat (GZ402671) in administered once per day. Duration: up baseline in PD Cognitive Rating patients with Parkinson's to 48 weeks outside Japan, and up to 64 Scale, Movement Disorder Disease (PD) carrying a weeks in Japan Society Unified PD Rating glucocerebrosidase gene (GBA) • Part 2: venglustat dose determined in Scale Part I, II, and III score, mutation Part 1 administered once a day Hoehn and Yahr score Duration: 5,6-week screening, 52-week Tx period, 104-week follow-up period and 6-week post Tx observation

84 Immuno-inflammation Diabetes SAR443060 (DNL747) (RIPK1 inhibitor) Oncology Cardiovascular Amyotrophic Lateral Sclerosis (ALS) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1* 15 • Patients with a diagnosis of laboratory- • Primary: AEs and SAEs, lab • SSD: Dec. 2018 supported probable, probable or definite test abnormalities, clinically • DE Primary: 2020 Safety, Tolerability, ALS significant neurological • DE full completion: DNLI-D-0003 Pharmacokinetics, and • Randomized, Double-blind, Placebo abnormalities 2021 NCT03757351 Pharmacodynamics of Controlled, Cross-over Assignment • Secondary: Pharmacokinetics, SAR443060(DNL747) in • SAR443060 and placebo Pharmacodynamics Subjects with Amyotrophic • 12 months open label extension Lateral Sclerosis

* Phase 1 study performed by Denali

85 Immuno-inflammation Diabetes SAR442168 (BTK inhibitor) Oncology Cardiovascular Multiple Sclerosis (MS) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 6 • Healthy male subjects 30 to 65 years of age. Primary: • SSD: 13 Nov 2019 Body Mass Index 18 up to 32 kg/m2, inclusive. • To determine the excretion • Completion date: Multiple Sclerosis Open-label Study of Excretion Signed informed consent. Subjects must balance and systemic Dec 2019 Balance and Pharmacokinetics agree to the use of an adequate method of exposure of radioactivity after • DE: Dec 2020 BEX16018 Following a Single Oral Dose of contraception for up to 3 months after oral administration of [14C]- SAR442168 in Healthy Male discharge from the clinical unit SAR442168. Subjects • To determine the NCT04171310 pharmacokinetics of SAR442168 and its contribution to the overall exposure of radioactivity. • To collect samples in order to determine the metabolic pathways of SAR442168 and identify the chemical structures and main excretion route of the main metabolites

86 Immuno-inflammation Diabetes SAR442168 (BTK inhibitor) Oncology Cardiovascular Multiple Sclerosis (MS) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Relapsing Multiple Phase 2 125 Part A: Double-blind period of continued Primary Objective: • SSD: sept 2019 Sclerosis treatment with SAR442168 dose assigned To determine the long-term safety • DE: 2025 Long-term Extension Safety in DRI15928 and tolerability of SAR442168 in RMS LTS16004 and Efficacy Study of participants NCT03996291 SAR442168 in Participants Secondary Objective: With Relapsing Multiple Part B: Open-label period of a single-group To evaluate efficacy of SAR442168 Sclerosis treatment with the selected Phase 3 on disease activity, assessed by SAR442168 dose. clinical and imaging methods

87 Immuno-inflammation Diabetes iGlarLixi (Glargine/Lixisenatide) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus (T2DM) (1/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Lixilan –O-AP Phase 3 940 • Patients with T2DM diagnosed for at • Primary: change in HbA1c • SSD: Feb. 2019 least 1 year, treated for at least 3 • Secondary: change in PPG, • DE: 2021 months with metformin alone or in FPG, SMPG, patients with Efficacy and Safety of iGlarLixi combination with a second oral HbA1c < 7% at week 24, EFC14943 vs Insulin Glargine and antidiabetic drug and who are not patients with HbA1c ≤ 6,5% at Lixisenatide in Patients with adequately controlled with this week 24, change in body NCT03798054 Type 2 DM Insufficiently treatment, weight, patients with HbA1c < controlled with oral Antidiabetic • Randomized, Parallel Group 7% and no body weight gain at Drugs assignment, Open label, Active- week 24, patients with HbA1c < controlled, 7% and no body weight gain • 3 arms: iGlarLixi, Lantus (insuline and no documented glargine), Lixisenatide symptomatic hypoglycemia at • Study duration per patient week 24, confirmed approximately: 31 weeks: up to 6-week hypoglycemia, AEs, anti- screening, 24-week randomized Tx and lixisenatide antibodies. 3-day post-Tx safety follow-up

88 Immuno-inflammation Diabetes iGlarLixi (Glargine/Lixisenatide) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus (T2DM) (2/2) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Lixilan-L-CN Phase 3 426 • Patients with T2DM diagnosed for at • Primary: change in HbA1c • SSD: Feb. 2019 least 1 year and treated with basal • Secondary: patients with HbA1c • DE: 2021 insulin for at least 6 months < 7% at week 30, patients with Efficacy and Safety of iGlarLixi • Randomized, Parallel Group HbA1c ≤ 6,5% at week 30, EFC14944 to Insulin Glargine With or assignment, Open label, active- PPG, SMPG profile, patients Without Metformin in Patients controlled with HbA1c < 7% and with no NCT03798080 with T2DM Insufficiently • 2 arms: iGlarLixi, Lantus body weight gain, change in controlled on Basal insulin With • Study duration per patient body weight, patients with or Without Oral Antidiabetic approximately: 33 weeks: 2-week HbA1c < 7% and with no body Drug(s) screening, 30-week randomized Tx and weight gain and no documented 3-day post-Tx safety follow-up symptomatic hypoglycemia at week 30, patients requiring rescue therapy, FPG, confirmed hypoglycemia, AEs, anti- lixisenatide antibodies

89 Immuno-inflammation Diabetes SAR341402 (Rapid Acting Insulin) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 1 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

GEMELLI X Phase 3 210 • Patients with T1DM, on continuous • Primary: AUClast, AUC and • SSD: Mar 2019 insulin Tx for at least 12 months prior to Cmax of SAR341402 and • DE: 2020 Comparison of screening, NovoLog (similarity), EFC15178 Pharmacokinetics and • Randomized, Open-label, Parallel-group • Secondary: Immunogenicity, NCT03874715 Immunogenicity of Alternating • 2 arms: experimental: alternative use of hypoglycemic event, AEs, Use of SAR341402 to SAR341402 and NovoLog 4 cylces of 4 comparison of PK parameters NovoLog® Versus Continuous weeks each, on top of lantus; Active between the two arms. Use of NovoLog® in Patients comparator: NovoLog for 16 weeks on with T1DM also using Insulin top of lantus Glargine • Study duration: 18-week + 1 day, per patient: 2-week screening period, 16- week Tx period, 1-day post-Tx follow-up period.

90 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Heterozygous Familial Hypercholesterolemia Rare Diseases Rare Blood Disorders (HeFH) MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

HeFH in Phase 3 150 • Patients with diagnosis of HeFH, 8 to 17 • Primary: % change in LDL-C • SSD: May 2018 Children and years old. Alirocumab (one of 4 doses, from baseline to week 24 • DE: 2022 Adolescents Efficacy and safety of depending on body weight and Q2W or • Secondary: % change in LDL- alirocumab in children and Q4W dose regimens) will be C, % change in APO B (Apo B), adolescents with HeFH administered subcutaneously (SC). % change in non-high density EFC14643 Patients treated with optimal dose of LP cholesterol (non HDL-C), % statin +/- other LMT(s) or non-statin change in Total-C, patients with NCT03510884 LMT(s) if statin intolerant at stable dose LDL-C level lower than 130 • Randomized, double-Blind, placebo- mg/dL (3.37 mmol/L), patients controlled followed by an open label with LDL-C level lower than 110 treatment period (2 dose tested) mg/dL (2.84 mmol//L), % • Study duration: approximately 110 change in Lp(a), in HDL-C, in weeks (run-in period, if needed,: up to 4 TG and in ApoA-1. Number of weeks [+2 days], screening period, up to AE, maturing cognition 2 weeks (+5 days), double-blind (Cogstate battery test) and treatment period: 24 weeks, open label pubertal development (Tanner treatment: 80 weeks) stage)

91 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Neurocognitive Evaluation Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Neurocognitive Phase 4 2176 • Patients with hypercholesterolemia and • Primary: Change in Cambridge • SSD: Nov 2016 Evaluation established coronary heart disease Neuropsychological Test • DE: 2020 Evaluate the effect of (CHD) or CHD risk equivalents who are Automated Battery (CANTAB) Regeneron alirocumab on Neurocognitive not adequately controlled with a cognitive domain Spatial function in patients with HeFH maximally tolerated daily dose of statin Working Memory (SWM) at a stable dose for at least 4 weeks strategy score from baseline to R727-CL-1532 and non-HeFH at high and very high cardiovascular risk prior to the screening visit week 96. NCT02957682 • Randomized, Double-Blind, Placebo- • Secondary (efficacy): % change Controlled, Parallel-Group, 2-Arm in calculated LDL-C, % change (alirocumab Q2W, placebo, 1:1) in Apo B, in non-HDL-C, in TC, • Study duration: 3 weeks screening, 96- in Lp(a), in HDL-C, in fasting weeks double-blind Tx period TG, in Apo A-1, % of patients reaching calculated LDL-C <70 mg/dL (1.81 mmol/L) and LDL- C < 50mg/dL(1.29 mmol/L).

92 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (1/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Hemophilia Phase 1/2 34 • In male patients (≥ 18 years old) • Primary: incidence of treatment- • SSD: Sep. 2015 A or B Hemophilia A • Single Group assignment, Open-label emergent AEs, SAEs, and AEs • DE: 2024 Hemophilia B • Subjects are administered SC fitusiran leading to study drug once every month for approximately 6 discontinuation LTE14762 Long term Safety and Efficacy years. Secondary: Annualized bleed rate, ALN- AT3SC-002 of Fitusiran in patients with time intervals between bleeding moderate or severe Hemophilia episodes, Weight-adjusted NCT02554773 A or B, who have previously consumption of FVIII, FIX, or BPA, participated in ALN-AT3SC-001 QOL assessed by an EQ-5D questionnaire and HAEM-A-QoL, Antithrombin levels, Thrombin Generation levels

93 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (2/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ATLAS-INH Phase 3 54 • In patients (Males ≥ 12 years old) • Primary: Annualized • SSD: Mar. 2018 Hemophilia A • Randomized in a 2:1 ratio Bleeding Rate (ABR) in the • DE: 2020 Hemophilia B - Patients randomized to the fitusiran efficacy period EFC14768 treatment arm will receive open • Secondary: ABR in the ALN- AT3SC- Efficacy and Safety of label fitusiran as an SC injection treatment period, 003 Fitusiran in patients with once monthly, for a total of 9 Annualized spontaneous NCT03417102 Hemophilia A or B, with months bleeding rate in the efficacy Inhibitory Antibodies to - Patients in on-demand arm will period, Annualized joint Factor VIII or IX, who are not receive on-demand BPA therapy bleeding rate in the efficacy receiving prophylactic per Investigator discretion to treat period, Change in HAEM-A- treatment bleeding episodes QOL score in the treatment period, ABR in the onset period

94 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (3/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ATLAS-A/B Phase 3 120 • In patients (Males ≥ 12 years old), • Primary: Annualized • SSD: Jul. 2018 Hemophilia A • Randomized in a 2:1 ratio: Bleeding Rate (ABR) in the • DE: 2021 Hemophilia B - Patients randomized to the fitusiran efficacy period EFC14769 treatment arm will receive open-label • Secondary: ABR in the ALN- AT3SC- Efficacy and Safety of fitusiran once monthly for a total of 9 treatment period, 004 Fitusiran in patients with months; Annualized spontaneous NCT03417245 Hemophilia A or B, without - Patients in the on-demand arm will bleeding rate in the efficacy Inhibitory Antibodies to receive on-demand factor concentrate period, Annualized joint Factor VIII or IX, who are not therapy per Investigator discretion to bleeding rate in the efficacy receiving prophylactic treat bleeding episodes period, Change in HAEM- treatment A-QOL score in the treatment period, ABR in the onset period

95 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (4/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ATLAS-PPX Phase 3 70 • In patients (males ≥ 12 years old), • Primary: annualized • SSD: Sept 2018 Hemophilia A • Single Group assignment, Open- bleeding rate (ABR) in the • DE: 2021 Hemophilia B label fitusiran efficacy period and EFC15110 • The study has 3 periods: the factor or BPA in ALN- AT3SC- - 6-Month factor/bypassing agent prophylaxis period 009 Switching study to describe prophylaxis period in which patients • Secondary: annualized NCT03549871 the Efficacy and safety of will continue their pre study, spontaneous bleeding rate Fitusiran prophylaxis in regularly scheduled prophylaxis and annualized joint bleed Patients with Hemophilia A regimen with factor concentrates or rate in the fitusiran efficacy or B, with or without bypassing agents period and the factor or BPA inhibitory antibodies to factor - 1-Month onset period in which in prophylaxis period, VIII (FVIII) or factor IX, and patients receive their first dose of Quality of Life (QOL) previously receiving Factor fitusiran while continuing their measured by Haem-A-QOL or Bypassing Agent factor/bypassing agent prophylaxis Questionnaire, ABR in the Prophylaxis for up to 14 days fitusiran onset period (1 - 6-Month fitusiran efficacy period in month), ABR in the fitusiran which patients receive fitusiran as a Tx period (7 months) once monthly prophylaxis

96 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (5/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 244 • In patients (≥ 12 years old), • Primary: Incidence, severity, • SSD: Jan. 2019 Hemophilia A • Single Group assignment, Open- relatedness, and • DE: 2025 Hemophilia B label seriousness of AEs, and ATLAS-OLE • Study duration: the study consists in laboratory assessments, screening period up to 30 days, a • Secondary: annualized LTE15174 Long-term Safety and 48-month open label Tx period and bleeding rate (ABR), ALN-AT3SC-005 Efficacy of Fitusiran in a follow-up period up to 6 months annualized spontaneous Patients with Hemophilia A after the last dose of fitusiran. bleeding rate and NCT03754790 or B With or Without annualized joint bleed rate Inhibitory Antibodies to in the Tx period, Quality of Factor VIII or X , who have Life (QOL) measured by previously participated in any HAEM-A-QOL of the phases 3 studies with Questionnaire fitusiran

97 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Hemophilia A & B (Pediatric) (6/6) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

ATLAS-PEDS Phase 3 12 • Male, aged 1 to <12 years, • Primary: Lowering of plasma • SSD: June 2019 Hemophilia A • Single Group assignment, Open- antithrombin (AT) activity • DE: 2024 label level [ Time Frame: Day 1 to Hemophilia B An Open-label, Multinational • Study duration per participant is Day 85 ] Study of Fitusiran approximately 160 weeks, including Prophylaxis in Male Pediatric a 12-week fitusiran efficacy period • Secondary: Number of Subjects Aged 1 to Less participants reported with Than 12 Years With adverse events , NCT03974113 Hemophilia A or B pharmacokinetics (PK): Cmax, Tmax, Ctrough)

98 Immuno-inflammation Diabetes Sutimlimab (BIVV009 - Anti Complement C1s mAb) Oncology Cardiovascular Complement Mediated Disorders Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 122 • Healthy male and female volunteers, • Primary: AEs, • SSD: 2015 • Randomized, Double-blind, Parallel • Secondary: PK, classical • DE: 2021 assignment, pathway complement BIVV009-01 Safety, Tolerability and • Part A : single ascending dose (7 system activity, complement NCT02502903 Activity of BIVV009 in BIVV009 dose levels) or placebo system-related biomarkers, Healthy Volunteers and • Part B: Multiple ascending dose (2 coagulation system-related Patients with Complement- BIVV009 dose levels) or placebo, biomarkers, disease-related Mediated Disorders • Part C: Multiple dose in a single biomarkers. cohort of patients with various complement-mediated disorders, • Part E: Multiple dose in a single cohort of patients with CAD previously treated by BIVV009.

99 Immuno-inflammation Diabetes Sutimlimab (BIVV009 - Anti Complement C1s mAb) Oncology Cardiovascular Chronic Immune Thrombocytopenia (ITP) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 16 • Patients suffering from • Primary: TEAEs, premature study • SSD: Aug. 2017 chronic ITP. Open-label, terminations, Clinical Laboratory • DE: 2022 Single Group assignment Abnormalities TNT009-201/ Safety, PK and PD of • Part A: Bi-weekly IV infusion • Efficacy endpoints: Part A & B: BIVVOO9-201 BIVV009 in patients with of BIVV009 up to 21 weeks Change in platelet count; TDR16218 Chronic Immune • Part B: long-term treatment independence from additional ITP NCT03275454 Thrombocytopenia (ITP) period (for 52 weeks) for therapy; Number of patient who patients who have had achieve complete response (CR), benefit from BIVV009 during response (R); Part A; patients undergo Duration of CR and R; Time to monitored washout from increased platelet count > 30, 50, BIVV009 at end of Part A and 100 x 109/L; number of patients and enter Part B upon return with loss of CR, loss of R, of thrombocytopenia. • PK/PD endpoints: PK parameters, anti-drug antibodies, PD measures (Complement factor measures, thrombopoietin levels , immature platelet fraction, platelet autoantibody/autoantigen)

100 Immuno-inflammation Diabetes Sutimlimab (BIVV009 - Anti Complement C1s mAb) Oncology Cardiovascular Cold Agglutinin Disease (CAgD) (1/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Cardinal Phase 3 24 • Patients suffering from primary cold • Primary (Part A): response • SSD: Nov. 2017 agglutinin disease (CAD) with at rate (≥ 2g/dl increase in Hgb • DE: Part A: 2019, least one blood transfusion within 6 OR Hgb >12g/dl AND no Part B: 2021 BIVV009-03 Efficacy and Safety of months of enrollment transfusion required); NCT03347396 BIVV009 in patients with • Open-label, Single Group • Secondary (Part A): change Primary Cold Agglutinin assignment in bilirubin, change in Disease with a recent history • Part A (required for registration): FACIT-Fatigue Scale Score, of Blood Transfusion biweekly IV infusion of BIVV009 up change in LDH, number of to week 26 transfusions and blood units • Part B: long-term safety and and change in Hgb; durability of response extension • Part B: TEAEs, hemoglobin, phase for patients having completed bilirubin, FACIT-F, LDH, Part A, BIVV009 dosing for up to 1 transfusion, haptoglobin, year after Part A LPO HRU.

101 Immuno-inflammation Diabetes Sutimlimab (BIVV009 - Anti Complement C1s mAb) Oncology Cardiovascular Cold Agglutinin Disease (CAgD) (2/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Cadenza Phase 3 40 • Patients suffering from primary cold • Primary (Part A); response • SSD: Nov. 2017 agglutinin disease (CAD) with no rate (≥ 1.5g/dl increase in • DE: : Part A: 2020, blood transfusions in prior 6 months Hgb AND no transfusion Part B: 2021 BIVV009-04 Efficacy and Safety of and no more than 1 blood required); NCT03347422 BIVV009 in patients with transfusion in the prior 1 year • Secondary (Part A): change Primary Cold Agglutinin • Randomized, double-blind, placebo in Hgb, change in bilirubin, Disease without a recent controlled change in FACIT-Fatigue history of Blood Transfusion • Part A: biweekly IV infusion of Scale Score, change in BIVV009 or placebo (up to 26 LDH, incidence of weeks) symptomatic anemia • Part B: long-term safety and symptoms durability of response extension • Part B: TEAEs, hemoglobin, phase for patients having completed bilirubin, FACIT-F, LDH, Part A. Blinded cross-over loading transfusion, haptoglobin, doses to allow all participants to HRU. receive BIVV009 while maintaining Part A blinding. BIVV009 dosing for up to 1 year after Part A LPO

102 Immuno-inflammation Diabetes ST400 (gene-editing technology) Oncology Cardiovascular Beta-thalassemia Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Transfusion- Phase 1/2 6 • Patients with clinical diagnosis of • Primary: AEs and SAEs • SSD: Mar. 2018 dependent TDT with at least 8 documented • Secondary: change from • DE: Primary: Beta- Safety, Tolerability and RBC transfusion events per year baseline in Hb fractions 2020, Full thalassemia Efficacy of ST400 and confirmed diagnosis of beta- measurements and % HbF, completion: 2022 (TDT) Autologous Hematopoietic thalassemia (genetic testing) change in frequency and Stem Cell transplant for Tx • Open-Label, Single Group volume of packed red blood of Transfusion-Dependent Assignment, single dose cells (PRBC) transfusions ST-400-01 Beta-thalassemia (TDT) NCT03432364

103 Immuno-inflammation Diabetes BIVV003 (gene-editing technology) Oncology Cardiovascular Sickle Cell Disease (SCD) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

PRECIZN-1 Phase 1/2 8 • Patients suffering from severe SCD • Primary: % of patients alive • SSD: Jan. 2019 • Open-Label, Single Group post-transplantation at • DE: 2023 Safety, Tolerability and Assignment, single dose D100, at week 52, at week Efficacy of BIVV003 for 104, % of patients with 003SCD101 Autologous Hematopoietic successful engraftment, NCT03653247 Stem Cell Transplantation in AEs, SAEs, Patients With severe Sickle • Secondary: CD34+HSPC Cell Disease yield from Plerixafor stem cell mobilization, % of patients with sufficient stem cell mobilization, yield of ZFN-edited IP, time to initial neutrophil recovery, time to platelet recovery, % of patients with maintenance of absolute neutrophil count ≥ 500/mcL, % of patients with maintenance of platelets count ≥ 50 000/mcL, change from baseline in HbF, in %F, in HbS, in REC, in LDH, in haptoglobin and bilirubin, QoL

104 Immuno-inflammation Diabetes Caplacizumab - Cablivi™ Oncology Cardiovascular Acquired Thrombotic Thrombocytopenic Purpura Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Post- Phase 3 104 • Prospective follow-up for adult • Primary: proportion of • SSD: . Oct 2016 HERCULES patients (18 years and older) with subjects with TTP-related • DE: 2021 Evaluate the long-term acquired TTP who completed events, # of and time to safety and efficacy of HERCULES TTP-related events, ALX0681-C302 caplacizumab, evaluate • Single group assignment, open label mortality rate, proportion of NCT02878603 safety and efficacy of • Study duration: Initial IV loading subjects with, # of and time repeated use of dose, followed by daily SC to recurrence of disease, caplacizumab and caplacizumab injections for the proportion of subjects with characterize the long-term duration of daily PEX and 30 days reported major impact of acquired thereafter. Treatment may be thromboembolic events, # of Thrombotic extended for a maximum of 4 and time to major Thrombocytopenic Purpura weeks. thromboembolic events, (aTTP). cognitive function, quality of life assessment and immunogenicity.

105 Immuno-inflammation Diabetes BIVV020 Complement C1S inhibitor Oncology Cardiovascular Cold Agglutinin Disease Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1b 18 • Single group assignment, open label Primary : • SSD: Jul 2020 • Up to 23 weeks (screening period up to To assess the safety and • DE: 2021 A Multicenter, Phase 1b, Open 8 weeks, treatment period 15 weeks). tolerability, after a single dose of PDY16370 Label, Nonrandomized, Single intravenous (IV) BIVV020 NCT04269551 Dose Study Evaluating the Secondary : Safety, Tolerability and To assess Activity of BIVV020 in Adults • The effect of BIVV020 on With Cold Agglutinin Disease complement mediated hemolysis • The pharmacodynamics (PD) of BIVV020 relating to complement inhibition • The pharmacokinetics (PK) of BIVV020 • The immunogenicity of BIVV020

106 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Co-administration w/ Tdap booster Rare Diseases Rare Blood Disorders Asia Pacific Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 688 • Randomized, multicenter, open- • Immunogenicity and safety • SSD: Dec. 2016 NCT02992418 label study in 688 subjects aged of CYD dengue vaccine and • DE: 2020 Study of a Tetravalent from 9 to 60 years Tdap vaccine when both Dengue Vaccine vaccines are administered Administered Concomitantly concomitantly or or Sequentially With Adacel® sequentially in Healthy Subjects

107 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Different schedules Rare Diseases Rare Blood Disorders Asia Pacific, Latin America Regions MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 2a 1050 • Two-stage, multi-national, multi- • Immunogenicity and safety • SSD: May. 2016 NCT02628444 center, observer-blind, randomized, of 3-dose primary series and • DE: 2020 Immunogenicity and Safety placebo-controlled Phase II booster dose of 3-Dose and Booster Dose immunogenicity and safety study of of Tetravalent Dengue tetravalent dengue vaccine Vaccine in Healthy Subjects 9 to 50 Years of Age

108 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Co-administration w/ HPV Rare Diseases Rare Blood Disorders Latin America Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3b 480 • Randomized, open-label, • Immunogenicity and safety • SSD: Nov. 2016 NCT02979535 multicenter study of a Tetravalent Dengue • DE: 2020 Immunogenicity and Safety Vaccine administered of a Tetravalent Dengue concomitantly or Vaccine Administered sequentially with Cervarix® Concomitantly or Sequentially With Cervarix®

109 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Co-administration w/ HPV Rare Diseases Rare Blood Disorders Asia Pacific Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3b 528 • Randomized, open-label, • Immunogenicity and safety • SSD: Dec. 2016 NCT02993757 multicenter study of a Tetravalent Dengue • DE: 2020 Immunogenicity and Safety Vaccine administered of a Tetravalent Dengue concomitantly or Vaccine Administered sequentially with Gardasil® Concomitantly or Sequentially With Gardasil®

110 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Latin America, Asia Pacific Regions Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Epidemiology Phase 30 000 • Observational • Incidence of selected AEs • SSD: Dec. 2016 NCT02948933 and SAEs, occurrence and • DE: 2025 Cohort Event Monitoring for frequency of hospitalized Dengvaxia®, CYD-TDV dengue disease and SAEs Dengue Vaccine leading to hospitalization or death

111 Immuno-inflammation Diabetes AcP Primary Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 4 510 000 • Observational • Surveillance for Hib • SSD: Feb. 2009 NCT00855855 disease. • DE: 2020 Surveillance Program to Determine Product Specific Rates of Invasive Hib Disease

112 Immuno-inflammation Diabetes New Pertussis Vaccine Oncology Cardiovascular Latin America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase Epidemiology 90 • Observational, multicenter trial • Immune response to • SSD: Apr. 2017 NCT03147898 booster dose • DE: 2020 Observational Study Describing the Immune Profile Induced By Pertussis Vaccines

113 Immuno-inflammation Diabetes Flu seasonal Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase Epidemiology 500 • Observational • Pregnancy registry • SSD: Aug.2013 NCT01945424 • DE: 2020 Sanofi Pasteur Quadrivalent Influenza Vaccine (QIV) Pregnancy Registry

114 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi - Co administration Rare Diseases Rare Blood Disorders North America Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 2475 Modified double blind study, • Immunogenicity and safety • SSD: Apr. 2018 NCT03537508 randomized, parallel groups, active • DE: 2023 Safety and Immunogenicity controlled, multicenter for Infants, with co administration with routine pediatric vaccines

115 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi - Alternative schedules Rare Diseases Rare Blood Disorders Greater Europe Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 1540 • Partially modified double blind, • immunogenicity and safety • SSD: Dec. 2018 NCT03547271 randomized, parallel group, active • DE: 2023 Safety and ImmunogenIcity controlled, multi center for alternative schedules in infants

116 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi Rare Diseases Rare Blood Disorders Latin America, Asia Pacific, Greater Europe Regions MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 825 • Interventional, randomized, parallel • Immunogenicity and safety • SSD: Oct. 2018 NCT03630705 Safety and immunogenicity 3 assignement, active controlled multi • DE: 2023 dose schedule Quadrivalent center study Meningococcal conjugate vaccine

117 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi Rare Diseases Rare Blood Disorders Latin America, North America MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 940 • Interventional, modified double • Immunogenicity and safety • SSD: Oct. 2018 NCT03691610 blind, Randomized, parrallel • DE: 2022 Safety & Immunogenicity 2- assignement active controlled multi dose Trial in Toddlers center study.

118 Immuno-inflammation Diabetes Flu QIV HD Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 2b 700 • Interventional, Randomized, • Dose response, • SSD: Oct. 2018 NCT03698279 Sequential Assignment, modified immunogenicity and safety • DE: 2020 Safety and immunogenicity double blind, multi center study of Flu Quadrivalent HD 3 dose schedule in Pediatric population

119 Immuno-inflammation Diabetes Rabies Vaccine Oncology Cardiovascular Asia Pacific Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase3 570 • Interventional, Randomized, • Immunogenicity and safety • SSD: Sep. 2018 NCT03700242 Parallel Assignment, • DE: 2021 Immunogenicity and safety of HDCV with abbreviated pre-exposure regimens Trial

120 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi Men C Rare Diseases Rare Blood Disorders Greater Europe Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 675 • Randomized, parallel assignment, • Immunogenicity and Safety • SSD: Sep.2019 NCT03890367 modified double-blind (triple Assessment. • DE: 2021 Immunogenicity and Safety masking - Participant, Investigator, of Quadrivalent Outcomes Assessor) conducted in Meningococcal Conjugate Denmark, Finland, and Germany. Vaccine Compared With Two Meningococcal Reference Vaccines in Europeans Toddlers

121 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi Rare Diseases Rare Blood Disorders Africa and Middle-East Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 330 • Interventional, single group • Immunogenicity and Safety • SSD: Apr.2019 NCT03869866 assignment, open label conducted Assessment. • DE: 2021 Immunogenicity and Safety in Turkey. of a Quadrivalent Meningococcal Conjugate Vaccine in Potential Pilgrims Aged 56 Years and Older in Turkey

122 Immuno-inflammation Diabetes Rabies Vaccine Oncology Cardiovascular VRVg Rare Diseases Rare Blood Disorders Greater Europe Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 504 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Jun.2019 NCT03965962 assignment: three modified double- Assessment. • DE: 2021 Purified Vero Rabies blind groups + one open label Vaccine Compared With group. Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults

123 Immuno-inflammation Diabetes New Pertussis Vaccine Oncology Cardiovascular North American Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 90 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Jun.2019 NCT03958799 assignment, modified double-blind. Assessment. • DE: 2022 Describe the Safety Profile and Compare the Immune Response of 4 Different Formulations of an Investigational Tdap Vaccine When Compared to Licensed Tdap Vaccine in Young Adults in Canada

124 Meninge Vaccine Immuno-inflammation Diabetes Oncology Cardiovascular MenQuadfi Rare Diseases Rare Blood Disorders North American Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3b 600 • Interventional, randomized, parallel • Immunogenicity • SSD: Sep.2019 NCT04084769 assignment, open label. Assessment. • DE: 2021 Evaluate the Immune Response After a Booster Dose of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Alone or Concomitantly With a Licensed Meningococcal Serogroup B Vaccine,in Participants Who Received Primary Quadrivalent Meningococcal Conjugate Vaccine (MCV4)

125 Immuno-inflammation Diabetes Flu QIV HD Vaccine Oncology Cardiovascular Greater Europe Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 1540 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Oct.2019 NCT04024228 assignment, modified double-blind. Assessment. • DE: 2020 Assess the Immune Response and the Safety Profile of a High-Dose Quadrivalent Influenza Vaccine (QIV-HD) Compared to a Standard- Dose Quadrivalent Influenza Vaccine (QIV-SD) in Europeans Adults 60 Years of Age and Older

126 Immuno-inflammation Diabetes Flu QIV SHZ - CN Oncology Cardiovascular Asia Pacific Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 6134 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Jan.2020 NCT04210349 assignment, open-label in step 1 Assessment. • DE: 2021 Assess the Immune and modified double-blind n step 2. Response and the Safety Profile of the Shenzhen Quadrivalent Inactivated Influenza Vaccine Versus the Shenzhen Trivalent Inactivated Influenza Vaccine in Chinese Subjects From 6 Months of Age

127 Immuno-inflammation Diabetes Next Gen Flu Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 150 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Nov.2019 NCT04144179 assignment, open label. Assessment. • DE: 2021 Assess the Immune Response and the Safety Profile of Quadrivalent Recombinant Influenza Vaccine Formulations Containing Different H3 Hemagglutinin Antigens in Healthy Adult Subjects 18 to 30 Years of Age

128 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi - Booster Rare Diseases Rare Blood Disorders Africa and Middle East Regions MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 1332 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Dec.2019 NCT04143061 assignment, modified double-blind. Assessment. • DE: 2022 Assess the Immune Response and the Safety Profile of an Investigational Quadrivalent Meningococcal Conjugate Vaccine in Healthy Adults, Adolescents, and Children in India and Healthy Adolescents and Children in the Republic of South Africa

129 Immuno-inflammation Diabetes vYF Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 572 • Interventional, randomized, parallel • Immunogenicity, Tolerability, • SSD: Jan 2020 NCT04142086 assignment, observer-blind. and Safety Assessment. • DE: 2021 Assess the Immune Response , Tolerability, and the Safety Profile of a Investigational Yellow Fever Vacine (vYF) Candidate Vaccine in Adults

130 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 560 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Oct.2019 NCT04142242 assignment, open label. Assessment. • DE: 2022 Assess the Immune Response and the Safety Profile of a Single Dose of MenACYW Conjugate Vaccine at Least 3 Years Following Initial Vaccination With Either Menomune® Vaccine or MenACYW Conjugate Vaccine in Older Adults

131 Immuno-inflammation Diabetes Rabies Vaccine Oncology Cardiovascular VRVg Rare Diseases Rare Blood Disorders Asia Pacific Region MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 1010 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: Oct.2019 NCT04127786 assignment, observer blind. Assessment. • DE: 2021 Assess the Immune Response and the Safety Profile of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Pre-exposure Regimen in Both Pediatric and Adult Populations and a Single Booster Dose of Purified Vero Rabies Vaccine - Serum Free Administered at 1 Year Post Primary Series in a Subset of Adults in Thailand

132 Immuno-inflammation Diabetes Flu QIV HD Vaccine Oncology Cardiovascular Greater Europe Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 3 68000 • Interventional, randomized, parallel • Effectiveness Assessment. • SSD: Nov.2019 NCT04137887 assignment, modified double-blind. • DE: 2022 Assess the Relative Effectiveness of a High-Dose Quadrivalent Influenza Vaccine Versus a Standard- Dose Quadrivalent Influenza Vaccine in Subjects 65 Years of Age and Older

133 Immuno-inflammation Diabetes HSV Vaccine Oncology Cardiovascular North America Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 1 / 2 381 • Interventional, randomized, • Safety & Effectiveness • SSD: Feb.2020 NCT04222985 sequential assignment, quadruple Assessment. • DE: 2023 Assess the Safety and masking. Efficacy of 4 Investigational HSV 2 Vaccines in Adults With Recurrent Genital Herpes Caused by HSV 2

134 Immuno-inflammation Diabetes Adacel Quadra Vaccine Oncology Cardiovascular Africa and Middle East Regions Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines

Study Description Patients Design Endpoints Status

Phase 4 350 • Interventional, randomized, parallel • Immunogenicity and Safety • SSD: May.2020 NCT04300192 assignment, open label, prevention. Assessment. • DE: 2022 Evaluate the Immune Response After Booster Vaccination With Tdap-IPV Vaccine (Against Tetanus, Diphtheria, Pertussis and Poliomyelitis) in Children 9- 13 Years Who Received Different Pertussis Primary Vaccine Regimens in Republic of South Africa

135