Clinical Trials Appendices July 29, 2019 R&D Pipeline – New Molecular Entities(*)
Phase 1 Phase 2 Phase 3 Registration (Total : 19) (Total : 7) (Total : 6) (Total : 2)
SAR441344(**)(1) BIVV001(**)(5) SAR440340(**)(12) SAR422459(**)(14) avalglucosidase alfa isatuximab Anti-CD40L mAb rFVIIIFc – vWF – XTEN(6) Anti-IL33 mAb ABCA4 gene therapy Neo GAA Anti-CD38 mAb Multiple Sclerosis Hemophilia A Atopic Dermatitis Stargardt Disease Pompe Disease 3L RRMM (ICARIA) (U.S.,EU)
SAR408701 ST400(**)(7) SAR156597 SAR442168(**)(15) venglustat SAR341402 (insulin aspart) Maytansin-loaded anti-CEACAM5 Ex Vivo ZFN Gene-Edited Cell IL4/IL13 bispecific mAb BTK inhibitor Oral GCS inhibitor Rapid acting insulin mAb, Solid Tumors Therapy, Beta thalassemia Systemic Scleroderma Multiple Sclerosis ADPKD(16) Type 1/2 Diabetes (EU)
SAR439459 BIVV003(**)(7) R olipudase alfa HIV fitusiran anti-TGFb mAb Ex Vivo ZFN Gene-Edited Cell rhASM Viral vector prime & rgp120 boost RNAi targeting anti-thrombin Advanced Solid Tumors Therapy, Sickle Cell Disease AS Deficiency(13) vaccine Hemophilia A and B
O REGN5458(**)(2) SAR443060(**)(8) SAR339375 sutimlimab Anti-BCMA-CD3 bispecific mAb RIPK1 inhibitor(9) miRNA-21 Anti Complement C1s mAb Relapsing Refractory MM Amyotrophic Lateral Sclerosis Alport Syndrome Cold Agglutinin Disease
O REGN4018(**)(2) Next Gen PCV(**)(10) efpeglenatide(**)(17) Anti-MUC16-CD3 bispecific mAb Pneumococcal Conjugate Long-acting GLP-1 agonist Ovarian Cancer Vaccines Type 2 Diabetes
SAR439859 nirsevimab(**)(18) Herpes Simplex Virus Type 2 SERD Respiratory syncytial virus HSV-2 therapeutic vaccine Metastatic Breast Cancer R Registrational Study (other than Phase 3) Monoclonal Antibody Opt-in rights products for which rights have not been exercised yet SAR442720(**)(3) Respiratory syncytial virus O SHP2 inhibitor Infants 4-month and older Immuno-inflammation MS & Neuro Solid Tumors Vaccines Oncology Diabetes SAR440234 SAR441169(**)(11) Rare Diseases Cardiovascular & metabolism T cell engaging multi spe mAb RORC (ROR gamma T) antagonist, Leukemia Psoriasis Rare Blood Disorders Vaccines
SAR441000(**)(4) SAR441255 (1) Developed in collaboration with Immunext (12) Developed in collaboration with Regeneron Cytokine mRNA Trigonal GLP1R/GIPR/GCGR agonist (2) Regeneron product for which Sanofi has opt-in rights (13) Acid Sphingomyelinase Deficiency also known as Niemann Pick type B Solid tumors Obesity / Type 2 Diabetes (3) Developed in collaboration with REVOLUTION Medicines (14) Identification of out-licensing partner ongoing (4) Developed in collaboration with BioNtech (15) Developed in collaboration with Principia (5) Sanofi product for which Sobi has opt-in rights in SOBI territories SAR441236 (16) Autosomal Dominant Polycystic Kidney Disease (6) Recombinant Coagulation Factor VIII Fc – von Willebrand Factor – XTEN Fusion protein Tri-specific neutralizing mAb (17) Developed in collaboration with Hanmi (7) Developed in collaboration with Sangamo HIV (18) Developed in collaboration with AstraZeneca (8) Developed in collaboration with Denali (*) Phase of projects determined by clinicaltrials.gov disclosure timing (9) Receptor-interacting serine/threonine-protein kinase 1 (**) Partnered and/or in collaboration – Sanofi may have limited or (10) Developed in collaboration with SK shared rights on some of these products (11) Developed in collaboration with Lead Pharma 2 Additional Indications(*)
Phase 1 Phase 2 Phase 3 Registration (Total : 5) (Total : 17) (Total : 23) (Total : 4) SAR439459 + cemiplimab(**)(1) dupilumab(**)(1) isatuximab + cemiplimab(**)(1) Dupixent®(**)(1) isatuximab Dupixent®(**)(1) Anti-TGFb mAb + PD-1 inh mAb Anti-IL4Rα mAb Anti-CD38 mAb + PD-1 inh mAb dupilumab Anti-CD38 mAb dupilumab Advanced Solid Tumors Grass Immunotherapy Relapsing Refractory MM Asthma 6 - 11 years old Newly Diag. MM Te(8) (GMMG) AD 12 – 17 years old (EU)
O cemiplimab(**)(1) + REGN4018(**)(2) R sarilumab(**)(1) isatuximab + cemiplimab(**)(1) dupilumab(**)(1) isatuximab dupilumab(**)(1) PD-1 inh mAb + Anti-MUC16-CD3 bispe Anti-IL6R mAb Anti-CD38 mAb + PD-1 inh mAb Anti-IL4Rα mAb Anti-CD38 mAb Anti-IL4Rα mAb mAb - Ovarian Cancer Polyarticular Juvenile Idiopathic Arthritis Advanced Malignancies Eosinophilic Esophagitis 1-3L RRMM (IKEMA) CRSwNP(9) (EU)
SAR439859 + palbociclib(3) sarilumab(**)(1) isatuximab + cemiplimab(**)(1) Dupixent®(**)(1) Aubagio® Fluzone® QIV HD SERD + CDK4/6 inh Anti-IL6R mAb Anti-CD38 mAb + PD-1 inh mAb dupilumab teriflunomide Quadrivalent inactivated Metastatic Breast Cancer Systemic Juvenile Arthritis Lymphoma AD 6 – 11 years old RMS – Pediatric Influenza vaccine - High dose
sutimlimab SAR440340(**)(1) isatuximab + atezolizumab(6) Dupixent®(**)(1) Lemtrada® MenQuadfiTM Anti Complement C1s mAb Anti-IL33 mAb Anti-CD38 mAb + PD-L1 inh mAb dupilumab alemtuzumab Advanced generation meningococcal Immune Thrombocytopenic Purpura COPD mCRC AD 6 months - 5 years old RRMS - Pediatric ACYW conjugate vaccine 2y+ (U.S.)
SAR443060(**)(4) dupilumab(**)(1) isatuximab + atezolizumab(6) sarilumab(**)(1) Cerdelga® RIPK1 inhibitor(5) Anti-IL4Rα mAb Anti-CD38 mAb + PD-L1 inhibitor mAb Anti-IL6R mAb Eliglustat Multiple sclerosis Peanut Allergy - Pediatric Solid Tumors Giant Cell Arteritis Gaucher T1, ERT switch Pediatric
SAR440340(**)(1) venglustat sarilumab(**)(1) Praluent® (**)(1) Anti-IL33 mAb Oral GCS inhibitor Anti-IL6R mAb Alirocumab Asthma Fabry Disease Polymyalgia Rheumatica LDL-C reduction - Pediatric
R cemiplimab(**)(1) venglustat dupilumab(**)(1) MenQuadfiTM PD-1 inhibitor mAb Oral GCS inhibitor Anti-IL4Rα mAb Advanced generation meningococcal 2-L Basal Cell Carcinoma Gaucher Type 3 COPD ACYW conjugate vaccine EU 1y+, US/EU 6w+
isatuximab venglustat cemiplimab(**)(1) Pediatric pentavalent vaccine Anti-CD38 mAb Oral GCS inhibitor PD-1 inh mAb DTP-Polio-Hib 1-2L AML / ALL pediatrics Gaucher related Parkinson’s Dis. 1L NSCLC Japan
(**)(1) SP0173 cemiplimab + chemotherapy Shan 6 R Registrational study (other than Phase 3) Tdap booster US PD-1 inh mAb + chemotherapy DTP-HepB-Polio-Hib 1L NSCLC Pediatric hexavalent vaccine Immuno-inflammation O Opt-in rights products for which rights have not been exercised yet (**)(1) Oncology cemiplimab VerorabVax® (VRVg) PD-1 inhibitor mAb Purified vero rabies vaccine (1) Developed in collaboration with Regeneron (6) Studies in collaboration with Roche (atezolizumab) 2L Cervical Cancer Rare Diseases (2) Regeneron product for which Sanofi has opt-in rights (7) Transplant ineligible Rare Blood Disorders (3) Pfizer product (palbociclib) (8) Transplant eligible cemiplimab(**)(1) isatuximab (9) Chronic rhinosinusitis with nasal polyps (4) Developed in collaboration with Denali PD-1 inhibitor mAb Anti-CD38 mAb MS & Neuro (5) Receptor-interacting serine/threonine-protein kinase 1 adjuvant in CSCC 1L Newly Diag. MM Ti(7) (IMROZ) (*) Phase of projects determined by clinicaltrials.gov disclosure timing Diabetes (**) Partnered and/or in collaboration - Sanofi may have limited or shared rights on some of these products fitusiran Cardiovascular & metabolism RNAi targeting anti-thrombin Hemophilia A and B pediatric Vaccines 3 Expected Submission Timeline(1)
fitusiran avalglucosidase alfa SAR156597 nirsevimab(**)(7) RNAi anti-thrombin Neo GAA IL4/IL13 bi-specific mAb Respiratory syncytial virus mAb Hemophilia A/B Pompe Disease Systemic Scleroderma
sutimlimab olipudase alfa efpeglenatide(**)(5) venglustat SAR440340(**)(3) HIV
NMEs Anti Complement C1s mAb rhASM Long acting GLP1-R agonist Oral GCS inhibitor Anti-IL33 mAb Viral vector prime & rgp120 boost Cold Agglutinin Disease ASD(4) Type 2 Diabetes ADPKD(6) Atopic dermatitis vaccine 2019(2) 2020(2) 2021(2) 2022(2) 2023 and beyond(2)
TM Dupixent®(**)(3) Aubagio® isatuximab Dupixent®(**)(3) sarilumab(**)(3) SAR440340(**)(3) isatuximab MenQuadfi Adv. generation meningococcal dupilumab teriflunomide Anti-CD38 mAb (IMROZ) dupilumab Anti-IL6R mAb Anti-IL33 mAb Anti-CD38 mAb EU: 12m+ AD 6 - 11 years old Relapsing MS – Ped. 1L Newly Diagnosed MM Ti AD 6 months - 5 years old Giant Cell Arteritis COPD Newly Diagnosed MM Te (GMMG)
isatuximab Shan 6 cemiplimab(**)(3) Dupixent®(**)(3) sarilumab(**)(3) SAR440340(**)(3) venglustat Anti-CD38 mAb DTP-HepB-Polio-Hib PD-1 inhibitor mAb dupilumab Anti-IL6R mAb Anti-IL33 mAb Oral GCS inhibitor 1-3L RRMM (IKEMA) Polymyalgia Rheumatica (8) Pediatric hexavalent vaccine 2L Cervical Cancer Asthma 6 - 11 years old Asthma GrPD
(**)(3) cemiplimab(**)(3) cemiplimab(**)(3) venglustat sarilumab(**)(3) dupilumab venglustat
Indications PD-1 inhibitor mAb PD-1 inhibitor mAb Oral GCS inhibitor Anti-IL6R mAb Anti-IL4Rα mAb Oral GCS inhibitor 2L BCC 1L NSCLC Gaucher Type 3 Systemic Juvenile Arthritis Peanut Allergy - Pediatric Fabry Disease ® sarilumab(**)(3) Cerdelga Pediatric pentavalent eliglustat ® Anti-IL6R mAb SP0173 VerorabVax (VRVg) Tdap booster US Gaucher Type 1, switch from ERT – vaccine Purified vero rabies vaccine Polyarticular Juvenile Idiopathic DTP-Polio-Hib (Japan) Arthritis Pediatric Praluent®(**)(3) MenQuadfiTM dupilumab(**)(3) alirocumab Adv. generation meningococcal Anti-IL4Rα mAb Additional LDL-C reduction - Pediatric U.S. & EU: 6w+ Eosinophilic Esophagitis Immuno-inflammation MS & Neuro Lemtrada® dupilumab(**)(3) Oncology Diabetes alemtuzumab Anti-IL4Rα mAb COPD Rare Diseases Cardiovascular & metabolism RRMS Ped. Rare Blood Disorders Vaccines isatuximab Anti-CD38 mAb 1-2L AML / ALL ped. (1) Excluding Phase 1 (7) Developed in collaboration with AstraZeneca (2) Projects within a specified year are not arranged by submission timing (8) Gaucher related Parkinson’s Disease (3) Developed in collaboration with Regeneron (**) Partnered and/or in collaboration – Sanofi may have limited or shared rights on some of these products (4) Acid Sphingomyelinase Deficiency (5) Developed in collaboration with Hanmi (6) Autosomal Dominant Polycystic Kidney Disease 4 Pipeline Movements Since Q1 2019
Additions / Moves Removals from Sanofi pipeline
isatuximab SAR341402, insulin aspart ZynquistaTM(**)(3) (sotagliflozin) Registration Anti-CD38 mAb Rapid acting insulin Oral SGLT-1&2 inhibitor 3L RRMM (ICARIA) (U.S.,EU) Type 1/2 Diabetes (EU) Type 1 Diabetes (U.S.)
MenQuadfiTM Advanced generation meningococcal ACYW conjugate vaccine 2y+ (U.S.)
dupilumab(**)(1) cemiplimab(**)(1) sotagliflozin(**)(3) Anti-IL4Rα mAb PD-1 inhibitor mAb Oral SGLT-1&2 inhibitor Phase 3 COPD adjuvant in CSCC Type 2 Diabetes
nirsevimab(**)(2) (**)(3) VerorabVax® (VRVg) sotagliflozin Respiratory syncytial virus Oral SGLT-1&2 inhibitor Purified vero rabies vaccine Monoclonal Antibody Worsening Heart Failure in Diabetes
fitusiran RNAi targeting anti-thrombin Hemophilia A and B pediatric
Phase 2
SAR441236 SAR441255 Phase 1 Tri-specific neutralizing mAb Trigonal GLP1R/GIPR/GCGR agonist HIV Obesity / Type 2 Diabetes
(1) Developed in collaboration with Regeneron (2) Developed in collaboration with AstraZeneca 5 (3) Developed in collaboration with Lexicon (**) Partnered and/or in collaboration – Sanofi may have limited or shared rights on some of these products R&D Pipeline Summary – Total Projects(1)
Phase 1 Phase 2 Phase 3 Registration TOTAL
Immuno-inflammation 2 8 7 2 19
Oncology 11 7 7 1 26
Rare Diseases 0 4 3 0 7
Rare Blood Disorders 4 0 3 0 7 Multiple Sclerosis and 3 3 2 0 8 Neurology Diabetes 1 0 1 1 3
Cardiovascular Disease 0 0 1 0 1
Vaccines 3 2 5 2 12
TOTAL 24 24 29 6 83 Total Projects 48 35
(1) Includes 3 Phase 1 products for which Sanofi has Opt-in rights but has not yet exercised these rights 6 Expected R&D Milestones
Products Expected milestones Timing SAR439859 (SERD) Proof of concept study read-out in metastatic Breast Cancer Q3 2019 Dupixent®(**)(1) EU regulatory decision in Atopic Dermatitis in adolescent patients Q3 2019 sutimlimab Proof of concept study read-out in refractory Immune Thrombocytopenic Purpura Q4 2019 Fluzone® QIV HD U.S. regulatory decision for ≥ 65-year old age group Q4 2019 sutimlimab Pivotal trial read-out in Cold Agglutinin Disease Q4 2019 Dupixent®(**)(1) Pivotal trial read-out in Atopic Dermatitis in 6-11 years Q4 2019 SAR440340 (Anti-IL33 mAb)(**)(1) Proof of concept study read-out in Chronic Obstructive Pulmonary Disease Q4 2019 dupilumab(**)(1) EU regulatory decision in Chronic Rhinosinusitis with Nasal Polyps Q1 2020 isatuximab Pivotal trial read-out in 1-3L RRMM (IKEMA) Q1 2020 olipudase alfa Pivotal trial read-out in Acid Sphingomyelinase Deficiency Q1 2020 isatuximab U.S. regulatory decision in 3L Relapsed-Refractory Multiple Myeloma Q2 2020 isatuximab EU regulatory decision in 3L Relapsed-Refractory Multiple Myeloma Q2 2020 MenQuadfiTM U.S. regulatory decision for > 2 year old age group Q2 2020 Fluzone® QIV HD EU regulatory decision for ≥ 65-years old age group Q2 2020 avalglucosidase alfa Pivotal trial read-out in Pompe Disease Q2 2020
(1) Developed in collaboration with Regeneron (**) Partnered and/or in collaboration – Sanofi may have limited or shared rights on some of these products 7 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
8 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (1/5) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
LIBERTY Phase 2/3 2 284 • For patients coming from DRI12544, • Primary: N and % of patients • SSD: Jul. 2014 ASTHMA enrolled PDY14192, EFC13579, EFC13691 studies, experiencing any TEAE • DE: 2019 Open label extension study added to current controller medications • Secondary: Safety TRAVERSE long-term safety & tolerability • Open-label, evaluation in patients with LTS12551 asthma who participated in previous studies NCT02134028
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 ASTMA Continuation of TRAVERSE treatment period in the previous 100 patient-year dupilumab asthma clinical study TRAVERSE evaluating Dupilumab safety in Patients with Asthma (Long LTS12551 term follow-up) • Open-label, Single group assignement LPS15023 NCT03620747
9 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (2/5) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
LIBERTY Phase 3 377 • Primary: N of patients • SSD: June 2018 ASTHMA • Open-label experiencing any TEAE • DE: 2026 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
10 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (3/5) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
CHILDREN Phase 3 471 • In children 6 to <12 years of age with • Primary: Annualized rate of • SSD: Jun. 2017 ASTHMA uncontrolled persistent asthma severe exacerbation events • DE: 2021 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
11 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Asthma (4/5) 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 4 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
12 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
13 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: 2021 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
AD in 6 - 11 Phase 3 367 • Randomized, Double-blind, Placebo- • Primary: Proportion of patients • SSD: Jan. 2018 Years Old controlled Study with Investigator's Global • DE: 2019 Efficacy and safety of Assessment "0" or "1" (on a 5- R668-AD-1652 Dupilumab administered with point scale) at week 16 • Secondary: NCT03345914 Topical Corticosteroids in participants ≥6 to <12 years with Change from baseline to week Severe Atopic Dermatitis 16 in Children's Dermatology Life Quality Index, Percent change in EASI score from baseline to week 16, Incidence of serious TEAEs through week 16
14 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: Last Patient Last R668-AD-1225 Open-Label study of Dupilumab dupilumab AD trials. The study primarily special interest, % of patients Visit: 2022 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
15 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 3 160 • Chinese patients with chronic AD • Primary: Investigator’s Global • SSD: Jan. 2019 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
16 Immuno-inflammation Diabetes Dupilumab (anti-IL4Rα mAb) Oncology Cardiovascular Grass Immunotherapy Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
GRASS Phase 2 100 • Patients with history of grass pollen- • Primary: % change from • SSD: June 2018 induced seasonal allergic rhinitis baseline in Total Nasal • DE: 2019
Evaluation of dupilumab as an confirmed by SPT with Timothy grass Symptom Score (TNSS) after R668 – ALG - adjunct for Subcutaneous Grass extract and Timothy grass specific IgE, nasal allergen challenge (NAC) 16115 Immunotherapy to reduce • Randomized, double-blind, placebo- with Timothy grass extract, controlled study, • Secondary: change from NCT03558997 Provoked Allergic Rhinitis Symptoms using The Nasal • 4 arms: dupilumab + Timothy Grass baseline in TNSS AUC post Allergen Challenge (NAC) Mode SCIT; placebo dupilumab + SCIT; NAC over the 1st hour after the dupilumab + placebo SCIT; placebo challenge across the arms, dupilumab + placebo SCIT; specific immunoglobulin G4, • 16 weeks of Tx TEAEs
17 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
18 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
19 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.
20 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
assignment, placebo-controlled study, • Secondary: change in pre- EFC15804 Efficacy, Safety and Tolerability • 2 arms: dupilumab vs placebo bronchodilator FEV1, change in NCT03930732 of Dupilumab in Patients with SGRQ score, Improvement in Moderate-to-Severe Chronic SGRQ, change in post- 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.
21 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
22 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 repeated dose-finding Study; 4-week efficacy and the safety of (60 patients CSR); Adolescents in children and adolescents with Polyarticular-course Juvenile screening, 12-week core Tx, 144-week sarilumab in patients with 2023 (CSR with 3-
Idiopathic Arthritis (pcJIA) extension, 6-week post-Tx 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 repeated dose finding study, 4-week and the safety of sarilumab in (48 patients CSR), in children and adolescents with screening, 12-week coreTx, 144-week patients with sJIA, Long term 2025 (CSR with 3- Systemic Juvenile Idiopathic Arthritis (sJIA) extension, 6-week post-Tx safety of sarilumab in patients year extension) DRI13926 with sJIA NCT02991469(1)
23 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
Efficacy of sarilumab in disease at week 52 completion:2021, full EFC15068 combination with corticosteroid • Randomized, parallel assignment, • Secondary: components of completion 2022 NCT03600805 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 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
24 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: 2021
Efficacy of sarilumab in double-blind, placebo controlled, 2 at week 52 EFC15160 combination with corticosteroid groups: sarilumab + CS, placebo +CS • Secondary: components of NCT03600818 (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 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,
25 Immuno-inflammation Diabetes SAR440340 (Anti-IL33 mAb) Oncology Cardiovascular Asthma Combination with dupilumab (1/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Asthma in Phase 1 38 • Patients with mild allergic asthma for • Primary: Difference in bronchial • SSD: July 2017 combination at least 6 months, allergen challenge (BAC)-induced • DE: 2020 with dupilumab Effetcs of SAR440340 • Randomized, Placebo –controlled, changes in sputum inflammatory (completion) dupilumab, combination of Parallel Assignment markers in individuals treated with both on markers of • 5 arms: SAR440340 alone, dupilumab SAR440340, dupilumab and the R3500-AS-1633 inflammation after bronchial alone, SAR440340 + dupilumab, combination of both, or placebo allergen challenge in placebo and fluticasone propionate [Screening (pre-treatment) to week NCT03112577 patients with Allergic Asthma (active comparator, open label dosing) 4 after treatment initiation] • Secondary: TEAEs (incidence and severity), PK profile, immunogenicity, difference in the BAC-induced changes in sputum inflammatory mRNA signature in individual patients treated with fluticasonea
26 Immuno-inflammation Diabetes SAR440340 (Anti-IL33 mAb) Oncology Cardiovascular Asthma Combination with dupilumab (2/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Asthma SA and Phase 2 297 • Adults patient with a physician • Primary: LOAC (lost of asthma • SSD: Mar. 2018 combination diagnosis of asthma for at least 12 control ) events • DE: 2019 with dupilumab Efficacy, Safety and months, • Secondary: change in FEV1 Tolerability (POC) of • Randomized, Double-blind, Placebo- (forced expiratory volume 1) SAR440340 and the controlled, Parallel Group, with ACT15102 coadministration with fluticasone w/wo salmeterol dupilumab in patients with • Arm 1: SAR440340 monotherapy NCT03387852 Moderate-to-severe Asthma, • Arm 2 : dupilumab monotherapy Not Well Controlled on • Arm 3: coadministration of Inhaled Corticosteroid (ICS) SAR440340 and dupilumab Plus Long-acting β2 • Arm 4: placebo Adrenergic Agonist (LABA) • Ttmt every 2 weeks for 12 weeks Therapy • Total duration for one patient: appr. 36 weeks, including 4 weeks screening,12 weeks ttmt and 20 weeks post-ttmt
27 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
28 Immuno-inflammation Diabetes SAR440340 (Anti-IL33 mAb) Oncology Cardiovascular Atopic Dermatitis, Combination with dupilumab (1/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AD Phase 2a 280 • Patients with chronic AD present for at • Primary: Eczema Area and Severity • SSD: Nov. 2018 least 3 years Index (EASI) % of change • DE: 2020
Efficacy and Safety of • Randomized, Double-blind, Placebo- • Secondary: % of patients with EASI R3500-AD-1798 SAR440340 Monotherapy controlled, Parallel-Group, ≥ 50% improvement , % of patients NCT03736967 and in Combination with • 4 Arms: SAR440340, dupilumab, with EASI ≥ 75% improvement, % Dupilumab in patients with combination SAR440340 + dupilumab, of patients with EASI ≥ 90% moderate-to-severe Atopic placebo improvement, absolute change in Dermatitis (AD) EASI scores, Investor’s Global Assessment (IGA), Pruritus Numerical Rating Scale (NRS), SCORing Atopic Dermatitis (SCORAD), SAR440340 serum concentration and antibodies, TEAEs, SAEs, AESIs.
29 Immuno-inflammation Diabetes SAR440340 (Anti-IL33 mAb) Oncology Cardiovascular Atopic Dermatitis (2/2) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
DR in AD Phase 2b 300 • Patients with chronic AD present for at • Primary: Eczema Area and Severity • SSD: Nov. 2018 least 3 years Index (EASI) % of change • DE: 2020
Efficacy, Safety and • Randomized, Double-blind, Placebo- • Secondary: % of patients with EASI R3500-AD-1805 Pharmacokinetics of controlled, Parallel-Group, Dose- ≥ 50% improvement , % of patients NCT03738423 SAR440340 in patients with Ranging study with EASI ≥ 75% improvement, % moderate-to-severe Atopic • 5 Arms: 4 SAR440340 doses and of patients with EASI ≥ 90% Dermatitis (AD) placebo improvement, absolute change in EASI scores, Investor’s Global Assessment (IGA), Pruritus Numerical Rating Scale (NRS), SCORing Atopic Dermatitis (SCORAD), SAR440340 serum concentration and antibodies, TEAEs, SAEs, AESIs.
30 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,
31 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 activity at • Secondary: DOR, PFS, OS, • DE: 2019 Dose escalation, completed) different doses/schedules and to select Immune Response TED10893 Pharmacokinetics and efficacy dose and regimen as single agent or in combination with dexamethasone NCT01084252 study of isatuximab in patients with selected CD38+ HM 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
32 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 20 • In Patients with known diagnosis of • Primary: Pharmacokinetics • SSD: Oct. 2018 symptomatic multiple myeloma, • Secondary: Aes, ORR, DOR, • DE: 1st data: 2020; Pharmacokinetics Safety and • Open-label, Single Group assignment TTP, PFS, OS, immunogenicity Full completion 2022 TED15085 Preliminary Efficacy of • Isatuximab every week in Cycle 1 (4 weeks) followed by every 2 weeks NCT03733717 isatuximab in Chinese Patients with Relapsed and/or Refractory (Q2W) in subsequent cycles MM
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
Lenalidomide Phase 1b 57 • Patients with diagnosis of MM and • Primary: N of patients with AE • SSD: Feb. 2013 Combination (enrollment documentation of at least 2 prior • Secondary: ORR, PFS, PK, PD, • DE: 2019 Isatuximab, in Combination With completed) therapies (induction therapy, autologous Immunogenicity RRMM lenalidomide and stem cell transplant, consolidation and dexamethasone for the Tx of maintenance therapy is considered one prior therapy) TCD11863 Relapsed or Refractory MM • Open-label, Parallel assignment NCT01749969 • 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
34 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 MM • Primary: DLTs, N of patients • SSD: May 2015 Combination (enrollment based on standard criteria and currently with AE • DE: 2020 Isatuximab, in combination with completed: require Tx because MM has relapsed • Secondary: ORR, PK, 1st set of data 2019 RRMM pomalidomide and 45 patients following a response Immunogenicity, DOR, CB (included in Isatuximab dexamethasone for the Tx of in Part A; • Open-label, Single-Group assignment BLA) 47 patients • Isatuximab + pomalidomide + TCD14079 Relapsed/Refractory MM in Part B) dexamethasone NCT02283775 • Part A, doses ranging for isatuximab, (5mg/kg, 10mg/kg, 20mg/kg); Part B isatuximab (10mg/kg) from a fixed infusion volume
35 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 and • SSD: Sep. 2015 Combination (17 pts in evidence of measurable disease, having Recommended Dose (RC), • DE: 1st set of data: Isatuximab in combination with VCdl, 27 received prior Tx with an IMiD and with based on DLTs, ORR and CR; 2019; next 2020, NDMM bortezomib - based regimens in pts in VRdl at least 3 prior lines of therapy Full completion: 2022 adult patients with newly cohort A, • Open-label, Single Group assignment • Primary VRDI cohort: CR 44 pts in • Isatuximab (escalating dose) + TCD13983 diagnosed MM non eligible for transplantation or with no intent cohort B) bortezomib + cyclophosphamide + • Secondary: overall safety NCT02513186 for immediate transplantation dexamethasone: VCDI cohort (3-week profile, PK, isatuximab screening, 50-week duration for immunogenicity, ORR, PFS, AE induction and then up to disease and tumor response, infusion progression, or unacceptable AEs + duration, MRD in patients follow-up) achieving CR or 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)
36 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: ORR • DE: 2019
Safety, PK and Efficacy of completed: with evidence of disease progression • Secondary: PK, N of patients TED14154 isatuximab in patients with 26 pts in • Open-label, Single Group assignment, with AEs, DOR, CB, PFS, NCT02514668 Relapsed/Refractory MM Part A, 32 isatuximab (escalating doses) Immunogenicity pts in Part • Total duration for one patient: up to 21 B post- days screening, Tx period up to disease dara) progression or AEs , 60- day follow-up at least
37 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 symptomatic • Primary: • SSD: Sep. 2016 Phase 2 (enrollment MM, having received at least 3 prior lines Phase 1: DLTs • DE: primary (Japanese completed) of therapy OR whose disease is double Phase 2: ORR completion 2018; full Patients) Isatuximab single-agent in refractory to an IMiD and a PI • Secondary: N of patients with completion 2020 RRMM Japanese patients with • Open-label, Single Group assignment, AE, CB, OS, PFS, DOR, TTR, isatuximab monotherapy PK, PD, Immunogenicity Relapsed and Refractory MM • Total duration for one patient: up to TED14095 21-day screening, Tx period up to NCT02812706 disease progression or unacceptable AEs, post-Tx follow-up
38 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, having with AE, ORR • DE: Primary: 2019, received prior Tx with an IMiD and with • Secondary: CB, DOR, TTR, Next: 2021, Full RRMM Safety, PK and Efficacy of at least 3 prior lines of therapy PFS, OS, PK, Immunogenicity completion :2020 isatuximab in combination with • Randomized, Open-label, Parallel (isatuximab and cemiplimab) (OS secondary Assignment analysis: 2020; Final TCD14906 cemiplimab in patients with Relapsed/Refractory MM • Isatuximab + cemiplimab and safety CSR : NCT03194867 • 3 Arms: Isa +cemi regimen 1; isa + cemi 2021) 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
39 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 (enrollment pomalidomide and low-dose • Secondary: ORR, OS, TTP, • DE (1st Part)(1): RRMM Isatuximab, pomalidomide, and completed) dexamethasone, compared to PFS, DOR, safety, PK profile, 2019; full completion dexamethasone to pomalidomide and low-dose immunogenicity 2020 dexamethasone in patients with RRMM EFC14335 pomalidomide and dexamethasone in Refractory or • Randomized, Open-label, Parallel NCT02990338 Relapsed and RRMM assignment
(1) Final Data Collection date for primary outcome measure 40 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 with • Primary: PFS • SSD: Oct. 2017 (enrollment prior 1 to 3 lines and with measurable • Secondary: ORR, % of patients • DE: Primary: 2020, RRMM Isatuximab combined with completed) serum M-protein (≥ 0.5 g/dL) and/or with CR, and VGPR, OS, TTP, Next: 2021, Full carfilzomib and dexamethasone urine M-protein (≥ 200 mg/24 hours) Second PFS, DOR, TTP, PFS2, completion: 2023 EFC15246 vs. carfilzomib with • Randomized, Open-label, Parallel AE, PK, Immunogenicity (OS, CSR in 2024) dexamethasone in patients With assignment, 2-arm: (a) isatuximab NCT03275285 Relapse and/or Refractory MM +carfilzomib+dexamethasone, (b) previously treated with 1 to 3 carfilzomib+dexamethasone prior lines
41 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 for • Primary: PFS • SSD: 2017 (randomized) transplant due to age (≥ 65 years) or • Secondary: ORR, % of patients • DE: Primary: 2021, NDMM Ti Isatuximab in combination patients < 65 years with comorbidities with CR, and VGPR, % of Next: 2023, Full with bortezomib (Velcade®), impacting possibility of transplant patients with MRD (Minimal completion: 2025 EFC12522 lenalidomide (Revlimid®) and • Randomized, Open-label, Parallel Residual Disease) negative, dexamethasone vs. assignment OS, TTP, DOR, PFS on next NCT03319667 bortezomib, lenalidomide and • IVRd arm line of therapy (PFS2), AE, PK, dexamethasone in patients (Isatuximab/bortezomib/lenalidomide Immunogenicity, QOL with newly diagnosed MM not /dexamethasone) eligible for transplant • VRd arm (Bortezomib/lenalidomide /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
42 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 multiple • Primary: MRD negative after • SSD: Oct. 2018 myeloma requiring systemic therapy and induction Tx, PFS after 2nd • DE: 1st part Q4 2021
Effect of Isatuximab in eligible for high dose therapy and randomization (IIA & IIB) for MRD negativity GMMG HD7 induction therapy with autologous stem cell transplantation • Secondary: PFS, OS, CR, after induction and NCT03617731 lenalidomide - bortezomib - • Randomized, Open-label, Parallel MRD, Best response to Tx, PFS 2023 (PFS IA); full dexamethasone (RVd) and assignment after next line of therapy from completion 2025 lenalidomide maintenance Tx in • Induction: 2 arms: IA: 3 cycles RVd, IB: 3 2nd randomization, AEs, QOL, patients with newly diagnosed cycles RVd + isatuximab PK, immunogenicity myeloma • After induction therapy autologous stem cell transplantation performed, • Maintenance: 2 arms: IIA lenalidomide for 3 years; IIB: lenalidomide + isatuximab for 3years
43 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 or • SSD: Apr. 2019 • Open-label, Single-group assignment T-ALL, • DE: Interim analysis: ALL/AML Anti-tumor Activity, Safety and • 2 cohorts: AML & ALL, in combination • Secondary: AE²s, incidence and 2020; Full Pharmacokinetics of isatuximab with chemotherapy severity of infusion reactions, completion: 2022 ACT15378 in combination with isatuximab PK, minimal residual Chemotherapy in Pediatric disease, ORR, OS, Event free NCT03860844 Patients from 28 days to less survival, DR than 18 years of Age with Relapsed/Refractory B or T Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia in First or Second Relapse
44 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination cemiplimab Oncology Cardiovascular Rare Diseases Rare Blood Disorders (PD-1 inhibitor) – Advanced Malignancies 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: Primary:2021, Safety and tolerability of (mCRPC) who are naïve to anti- • Secondary: Immunogenicity Full completion: 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
45 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination cemiplimab Oncology Cardiovascular Rare Diseases Rare Blood Disorders (PD-1 inhibitor) – Lymphoma 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: 2021, 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
46 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination atezolizumab Oncology Cardiovascular Rare Diseases Rare Blood Disorders (PD-1 inhibitor) – Advanced Malignancies 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,
47 Immuno-inflammation Diabetes Isatuximab (anti-CD38 mAb) combination atezolizumab Oncology Cardiovascular Rare Diseases Rare Blood Disorders (PD-1 inhibitor) – Solid Tumors MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1b/2 160 • 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
48 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, Parallel • Primary: TEAE, Incidence of • SSD: Jan. 2015 assignment, ascending-dose abnormal laboratory findings, N • DE: 2020 A first-in-human study of repeat • Monotherapy, cemiplimab alone of participants with DLT R2810-ONC- dosing with cemiplimab, as • Dual combination: cemiplimab in • Secondary, RECIST as 1423 single therapy and in combination with hypofractionated measured by CT or MRI, combination with other Anti- radiotherapy or with cyclophosphamide Immune-Related Response NCT02383212 Cancer therapies in patients or with docetaxel with AM • Triple combination: cemiplimab with 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
49 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 PK • SSD: Sep. 2017 patients AM confirmed diagnosis of malignancy with parameters • DE: primary To investigate the safety and no alternative standard-of-care • Secondary: Immunogenicity completion 2019; PKs of cemiplimab in Japanese therapeutic option against cemiplimab, ORR, DOR full completion 2023 R2810-ONC- patients with AM • Part 2: Histologically or cytologically 1622 documented squamous or non- squamous NSCLC with stage IIIB or NCT03233139 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
50 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 & 2), • SSD: Early 2019 • Randomized, Parallel Group assignment, Anticipated recommended dose • DE: 2025 CNS tumors Phase 2 Open-label from Phase 1 to Phase 2, ND R Glioma a) Safety and • Phase1: cemiplimab monotherapy in cemiplimab PK (monotherapy Pharmacokinetics of both cohorts: Solid Tumor and CNS and in combination with cemiplimab single agent in cohorts radiation therapy), anticipated R2810-ONC- Pediatric Patients with • Phase 2: Newly Diagnosed DIPG, Newly cemiplimab RP2D when co- 1690 Relapsed Refractory Solid Diagnosed HGG, recurrent HGG: administered with radiation NCT03690869 or CNS Tumors cemiplimab in combination with radiation therapy in DIPG and HGG, anti- b) Safety and Efficacy of therapy tumor activity: OS12, PFS12, cemiplimab in combination • Secondary: anti-tumor activity with Radiotherapy in (children objective response), Pediatric Patients with immunogenicity, tolerability Newly Diagnosed Diffuse profile (DLTs & AEs) Intrinsic Pontine Glioma, Newly Diagnosed High- Grade Glioma or Recurrent High-Grade Glioma
51 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 (actual) • For Histologically confirmed diagnosis of • Primary: Correlation between • SSD: Apr. 2017 Melanoma stage III (unresectable) or stage IV changes in the tumor • DE: 2019 Exploratory Tumor Biopsy- cutaneous melanoma (non-acral microenvironment and the driven study to understand the lentiginous) with at least 1 lesion that is change in tumor volume R2810-ONC- relationship between biomarkers measurable by RECIST 1.1 criteria and following cemiplimab Tx 1606 and clinical response in accessible for biopsies • Secondary: Correlation Melanoma patients receiving between baseline tumor NCT03002376 cemiplimab characteristics and the change in tumor volume following Tx, cemiplimab serum concentrations, antibodies levels, PFS, ORR
52 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 (actual) • For Histologically confirmed • Primary: Correlation between • SSD: Jul. 2017 Head & Neck diagnosis recurrent and/or metastatic changes in the tumor • DE (1st Part) (1): Exploratory Tumor Biopsy- SCCHN (squamous cell carcinoma of the microenvironment and the 2019; full completion driven study to understand the head and neck) with no curative options change in tumor volume 2020 R2810-ONC- relationship between biomarkers with at least 1 lesion that is measurable following cemiplimab Tx 1655 and clinical response in by Response Evaluation Criteria in Solid • Secondary: Correlation Immunomodulatory Treatment- Tumors (RECIST) between baseline tumor NCT03198130 Naïve patients with Recurrent • Open-label, Single Group Assignment characteristics and the change and/or Metastatic Squamous in tumor volume following Tx, Cell Carcinoma of Head and ORR, PFS, TAES, cemiplimab Neck receiving cemiplimab serum concentration, anti- cemiplimab antibodies level
(1) Final Data Collection date for primary outcome measure 53 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Cutaneous Squamous Cell Carcinoma (CSCC) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Advanced Phase 2 266 • Non-Randomized, Open-label, Parallel • Primary: ORR (96 weeks), • SSD: May 2016 CSCC assignment Groups 1,3 and 4: RECIST • DE: Primary:2020; Cemiplimab monotherapy • Group 1: Patients with metastatic CSCC: version 1.1 will be used to Full completion 2021 for patients with metastatic to distant sites or lymph nodes determine ORR, Group 2 and 4: R2810-ONC- (nodal or distant) CSCC cemiplimab administered intravenously Clinical response criteria will be 1540 (Groups 1 and 3) or with every 2 weeks used to determine ORR unresectable locally • Group 2: Patients with unresectable • Secondary: Investigator NCT02760498 advanced CSCC locally advanced CSCC. cemiplimab Assessments of ORR, DOR, (Group 2) administered intravenously every 2 PFS, OS, CRR, cemiplimab PK weeks and antibodies levels. • Group 3: Patients with metastatic CSCC: to distant sites or lymph nodes, cemiplimab administered 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)
Expanded Expanded Access Intermediate- Provide access to cemiplimab to patients Access CSCC Tx IND/Protocol size Population with mCSCC or locally advanced CSCC, who are not candidate for surgery prior to R2810-ONC- cemiplimab being commercially available 17103 NCT03492489 54 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, injection • SSD: Apr. 2019 CSCC resectable CSCC site reactions, • DE: 2020 Study of Pre-Operative • Open-label, Single-Group assignment • Secondary: ORR, pathologic cemiplimab administered • Three dose cohorts planned followed by complete response rate, major R2810-ONC- Intralesionally, for Patients with a 3+3 dose-escalation design with cohort pathologic response rate, 1787 Recurrent Cutaneous expansion cemiplimab serum Squamous Cell Carcinoma concentration, cemiplimab NCT03889912 (CSCC) antibodies, selection of the recommended cemiplimab dose for further study based on clinical and PK observations.
55 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 pathologically • Primary: DFS (time from • SSD: June 2019 CSCC confirmed CSCC, and qualified as High randomization to the first • DE: primary: 2025, Adjuvant Cemiplimab vs Risk CSCC, documented disease full completion: 2026 Placebo after Surgery and • Randomized, placebo-controlled, recurrence) R2810-ONC- Radiation Therapy in Patients double-blind, parallel assignment, • Secondary: OS, FFLRR (from st 1788 with High risk CSCC • 2 arms: cemiplimab and placebo, randomization to the 1 locoregional recurrence LRR), NCT03969004 FFDR (from randomization to the 1st distant recurrence), cumulative occurrence of second primary CSCC, TEAEs, incidence of deaths, lab. abnormalities,
56 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Basal Cell Carcinoma (BCC) 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 version • DE: Primary: 2021, Cemiplimab in patients with • Non-Randomized, Open-label, Parallel 1.1 ORR for unresectable Full completion 2022 R2810-ONC- Advanced BCC who assignment locally advanced BCC 1620 experienced progression of • Group 1: Patients with metastatic BCC measured by Composite disease on Hedgehog Pathway • Group 2: Patients with unresectable Response Criteria NCT03132636 Inhibitor Therapy, or were locally advanced BCC • Secondary: DOR, CR, PFS, intolerant of Prior Hedgehog OS, TEAEs, PK, Pathway Inhibitor Therapy immunogenicity
57 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Non-Small Cell Lung Cancer (NSCLC) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
mNSCLC Phase 3 700 • For histologically or cytologically • Primary: PFS as assessed by a • SSD: May 2017 documented squamous or non blinded Independent review • DE: 2023
First-line Tx in patients with squamous NSCLC with stage IIIB or committee using RECIST 1.1 R2810-ONC- advanced or metastatic NSCLC stage IIIC who are not candidates for Tx • Secondary: OS, Objective 1624 whose tumors express PD-L1, with definitive chemoradiation or patients response rates, BOR, DOR with stage IV disease who received no NCT03088540 vs. Platinum Based Chemotherapy prior systemic Tx 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
58 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Non-Small Cell Lung Cancer (NSCLC) 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 documented squamous or non Part 2: OS and PFS as • DE: 2023
Combination of cemiplimab and squamous NSCLC with stage IIIB or IIIC assessed by a blinded R2810-ONC- Platinum-based Doublet disease who are not candidates for Tx independent review committee 16113 Chemotherapy in patients with with definitive concurrent chemoradiation using RECIST1.1 or stage IV disease who received no NCT03409614 Lung Cancer prior systemic Tx for recurrent or metastatic NSCLC • Part 1: Randomized, Open-label, Parallel assignment • 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
59 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Non-Small Cell Lung Cancer (NSCLC) MS, Neuro, Gene therapy Vaccines
Patien Study Description Design Endpoints Status ts mNSCLC Phase 3 5* • For histologically or cytologically • Primary: PFS as assessed by a • SSD: June 2018 documented squamous or non squamous blinded Independent review • DE: 2020
Combination of cemiplimab, NSCLC with stage IIIB or stage IV disease committee using RECIST 1.1 R2810-ONC- Platinum-based Doublet who received no prior systemic Tx for • Secondary: OS, ORR, TEAEs, 16111 Chemotherapy, and ipilimumab recurrent or metastatic NSCLC DLTs, SAEs, death, lab. • Randomized, Open-label, Parallel abnormalities, OS, QoL NCT03515629 vs pembrolizumab in Patients 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
60 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Non-Small Cell Lung Cancer (NSCLC) 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, TEAEs, • DE: 2020
squamous NSCLC with stage IIIB or IIIC SAEs, death, lab. abnormalities R2810-ONC- and not candidates for definitive 1763 Cemiplimab and Ipilimumab in chemoradiation or stage IV. Patients must have PD after receiving one prior NCT03430063 Patients with Lung Cancer 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
61 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 3 436 • Patients with recurrent or metastatic CC • Primary: OS • SSD: Oct. 2017 for which there is no curative intent • Secondary: PFS, ORR, DOR, • DE: Primary: 2020;
Cemiplimab vs. therapy of option, QOL Next 2022; Full R2810-ONC- Investigator Choice • Randomized, Open-label, Parallel completion 2023 1676 chemotherapy in Recurrent or assignment, Tx cycle 6 weeks, Planned Tx for up to 96 weeks NCT03257267 Metastatic Platinum-Refractory CC • 2 arms: cemiplimab and Investigator Choice (IC) chemotherapy
62 Immuno-inflammation Diabetes Cemiplimab (PD-1 inhibitor) Combination REGN4018 Oncology Cardiovascular Ovarian cancer (OC) Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
CC Phase 1/2 264 • Histologically or cytologically confirmed • Primary: DLTs, TEAEs, SAEs, • SSD: May 2018 diagnosis of advanced, epithelial ovarian deaths, lab abnormalities, drugs • DE: 2022
REGN4018 alone or in (except carcinosarcoma), primary serum concentrations, ORR R4018-ONC- combination with cemiplimab in peritoneal, or fallopian tube cancer with • Secondary: BOR, DOR, 1721 patients with Platinum-Resistant CA-125 ≥ 2 xULN, progression or disease control, PFS, CA-125 relapse within 6 months of the most NCT03564340 Ovarian Cancer recent Tx with Platinum-containing chemotherapy, documented progression and no standard therapy options • Non- Randomized, Open-label, Parallel assignment, • Arm 1: REGN4018 • Arm 2: REGN4018 + cemiplimab
63 Immuno-inflammation Diabetes SAR439459 (TGFß inhibitor mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Advanced Solid Tumors (AST) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AST Phase 1/1b 130 • Patients with histologically confirmed, • Primary: incidence of DLTs • SSD: Jun. 2017 advanced unresectable or metastatic (Part 1), ORR (Part 2) • DE: 2022 Monotherapy Safety, PK, PD and Anti-tumor solid tumor • Secondary: Safety profile, and activity of SAR439459 • Open-label, Parallel assignment Immunogenicity, PK, PFS (Part combination Monotherapy and in • Part 1A: SAR439459 monotherapy 2), TTP (Part 2) with combination with cemiplimab in escalating doses cemiplimab adult patients with Advanced • Part 2A: SAR439459 monotherapy with the previously recommended dose Solid Tumors • Part 1B: SAR439459 escalating dose + TCD14678 cemiplimab standard dose NCT03192345 • Part 2B: SAR439459 at previously recommended dose + cemiplimab standard dose • Escalation periods non randomized followed by expansion periods randomized
64 Immuno-inflammation Diabetes SAR408701 (maytansin loaded anti-CEACAM5 mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Advanced Solid Tumors (AST) 1/2 MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
First-in-Human Phase 1 313 • Patients with locally advanced or • Primary: MTD, Anti-tumor • SSD: Sep. 2014 metastatic solid malignant tumor response RECIST • DE: 2021 Phase 2 • Non-Randomized, Open-label, Parallel • Secondary: Overall Safety, TED13751 Safety, PK and antitumor assignment Immunogenicity, PK, duration of NCT02187848 activity of SAR408701 in • Arm 1 : SAR408701 monotherapy response, time to progression patients with AST escalating cohorts • Arm 2: SAR408701 expansion cohort in 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
65 Immuno-inflammation Diabetes SAR408701 (maytansin loaded anti-CEACAM5 mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Advanced Solid Tumors (AST) 2/2 MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Japanese Phase 1 24 • Patients with malignant solid tumor • Primary: DLTs, Phase 1 and 1B • SSD: Oct. 2017 patients (expected) • Non-Randomized, Open-label, • Secondary: Safety, • DE: 2019 Safety and PK of SAR408701 Sequential assignment Immunogenicity, PK, Plasma Monotherapy Monotherapy in Japanese • Phase 1 : SAR408701 monotherapy CEACAM5 levels, Anti-tumor patients with Advanced escalating doses/ 4 weeks response RECIST • Arm to test loading dose at first cycle TCD15054 Malignant Solid Tumors followed by MTD NCT03324113
66 Immuno-inflammation Diabetes SAR439859 (SERD) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Breast cancer MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1 156 • Primary: Parts A & C:DLTs, • SSD: Sept. 2017 • Non-Randomized, Open-label, Parallel Parts B & D: ORR • DE: 2021 Phase 2 Assignment • Secondary: Safety, ORR, DCR, TED14856 SAR439859 single agent and in • Part A: SAR439859 monotherapy dose DR, PK for both drugs, CYP450 NCT03284957 combination with palbociclib in escalation, 3A induction/inhibition, ER Postmenauposal Women with • Part C: dose escalation for the occupancy/PET imaging Estrogen Receptor Positive combination SAR439859 and Advanced Breast Cancer palbociclib, • Part B: SAR439859 dose expansion from the dose determined in part A, • Part D: combination SAR439859 and palbociclib at the doses recommended from part C • SAR439859 administered in 28-day cycle; palbociclib in 21-day cycle
Phase 1 12 • Primary: :DLTs, • SSD: Apr. 2019 • Open-label, Single-Group Assignment • Secondary: AEs, • DE: 2020
Safety, Efficacy, • SAR439859, administered orally once Pharmacokinetics of TED15954 Pharmacokinetics and daily as monotherapy in fasted or fed SAR439859, ORR, CBR,DR, NCT03816839 Pharmacodynamics Evaluation conditions non-progression rate, of SAR439859 single agent in Japanese Postmenopausal Women with Estrogen Receptor Positive Advanced Breast Cancer
67 Immuno-inflammation Diabetes SAR440234 (T-cell engaging bispecific mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Leukemia and Myelodysplastic Syndrome MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1 77 • Primary: DLTs, allergic • SSD: Nov. 2018 • Patients with confirmed diagnosis of reactions/hypersensitivity, ORR, • DE: 2021 Phase 2 AML (except acute promyelocytic DOR, event-free survival TED15138 SAR440234 single agent in leukemia) or MDS with a risk category • Secondary: AEs, PK, NCT03594955 patients with Relapsed or intermediate or higher, and not eligible Preliminary Anti-Leukemia Refractory Acute Myeloid for any Tx known to provide clinical Activity, immunogenicity Leukemia (RR AML), B-cell benefit, Acute Lymphoblastic Leukemia • Open-label, Single Group Assignment (B-ALL) or High Risk • 2 dose escalation schemes, Myelodysplasia (HR-MDS) • Cycle defined as 6 weeks of study Tx • Tx may be continued as long as it is clinically beneficial
Study on clinical hold; complete response letter sent to the FDA mid-July
68 Immuno-inflammation Diabetes SAR442720 (SHP2 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Relapsed/Refractory Solid Tumors MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1 200 • 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 considered ineligible for standard of care Safety, Tolerability, PK and NCT03634982 anticancer Tx PD profiles of SAR442720 • Open-label, Single Group Assignment single agent in patients with • 1 Arm: SAR442720, oral administration Relapsed/Refractory Solid Tumors
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
69 Immuno-inflammation Diabetes SAR441000 (Cytokine mRNA) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Advanced Solid Tumors MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1 264 • Primary: DLTs (SAR441000 • SSD: Jan. 2019 • Patients with advanced solid malignant alone and in combination), MTD • DE: 2021
tumors for which no standard alternative (SAR441000 alone and in TED15297 therapy is available, combination), TEAEs, ORR for Safety, Pharmacokinetics, NCT03871348 • Non-randomized, Open-label, Parallel expansion, Pharmacodynamics and Assignment, • Secondary: PK (SAR441000 Anti-Tumor activity of • Dose escalation Phase, 2 arms: alone and in combination), SAR441000 as Monotherapy SAR441000 (intra-tumoral injection as immunogenicity (SAR441000 and in Combination with monotherapy) and SAR441000 (intra- and cemiplimab), DCR and DoR cemiplimab in patients with tumoral injection) + cemiplimab over a (SAR441000 alone and in Advanced Solid Tumors 21-day cycle, combination), PFS, TEAEs, • Expansion cohorts in melanoma with Recommended dose for SAR441000 monotherapy and with the SAR441000 alone and in combination (SAR441000 + cemiplimab), combination for the expansion • Expansion cohorts in CSCC, HNSCC cohorts, ORR for dose with the combination. escalation.
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 3 100 • 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 • SSD: Oct. 2017 avalglucosidase alfa In Patients with AE, N of participants with • DE Primary: 2019 Infantile Onset To assess safety and efficacy of Infantile-onset PD previously treated with immunogenicity response • DE Full completion: avalglucosidase alfa (neoGAA) alglucosidase alfa Secondary: PK parameters, 2022 ACT14132 in Pediatric patients with (Myozyme®/Lumizyme®) who Change at 6 months from infantile-onset PD previously demonstrate clinical decline or sub- baseline in Gross Motor NCT03019406 treated With alglucosidase alfa optimal clinical response Function (GMF) Measure-88 (Myozyme®/Lumizyme®) • Randomized, Open-label, Ascending Test, revised GMF dose, Parallel assignment Classification System score, • Total study duration for one patient: 3 Pompe specific Pediatric years [14-day screening, 25-week Tx Evaluation of Disability period, a 120-week extension period Inventory, Functional Skills and 4-week post-Tx observation period Scale, Mobility Domain Test score and Quick Motor Function Test scores, Left 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, • SSD: Feb. 2014 avalglucosidase alfa In patients with PD including IARs & deaths, • DE: 2021 (for post Phase 3 who previously completed a Hematology, biochemistry and trial access) LTS13769 Long-term safety and PK of avalglucosidase alfa study [adult, senior] urinalysis, vital signs NCT02032524 repeated biweekly infusions of • Non-randomized, Open-label, single • Secondary: ECG, PK avalglucosidase alfa (neoGAA) group assignment parameters, anti- in patients with PD • Total study duration for one patient: 6 avalglucosidase alfa antibodies, years [until the patient withdraws, the and neutralizing antibody Investigator withdraws the patient, or the formation in anti- Sponsor terminates the study] avalglucosidase alfa positive patients, anti-alglucosidase alfa IgG antibodies, Skeletal muscle glycogen content, Qualitative and 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) (1/3) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
ASCEND Phase 2 36 • Randomized, Double-blinded, Placebo- • Primary: % change in spleen • SSD: June 2016 Phase 3 controlled, Parallel assignment volume, % change in diffusing • DE: 2019(2) Niemann-Pick • Study duration is composed of blinded capacity of the lung for carbon • DE: 2023(3) disease Efficacy, Safety, PD, and PK period and an open label extension monoxide (Dlco) type B(1) study of olipudase alfa in allowing patients that were on placebo to • Secondary: Change in patients with ASMD cross over to active treatment splenomegaly-related symptom score (except US, where it is DFI12712 part of the primary "combination NCT02004691 spleen 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) (2/3) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
ASCEND Phase 1 20 • Open-label, ascending dose, Single • Primary: Safety parameters and • SSD: June 2015 group assignment Clinically significant changes in • DE: 2020 Peds Phase 2 • Total study duration for one patient laboratory parameters, Safety, Tolerability, PK, and approximately 18 months [up to 60-day Clinically significant changes in DFI13803 efficacy evaluation of olipudase screening, 64-week Tx period, 37-day physical examinations alfa in pediatric patients <18 post Tx period except if patient enrolled • Secondary: PK parameters, NCT02292654 years of age with ASMD in a long-term extension study] Change in sphingomyelin levels and sphingomyelin metabolite levels
75 Immuno-inflammation Diabetes Olipudase Alfa (rhASM ERT) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Acid Sphingomyelinase Deficiency (ASMD) (3/3) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Long-Term Phase 2 25 • 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, and including neurologic LTS13632 alfa in patients with ASDM DFI13412 for adult patients) examinations, vital signs, NCT02004704 • Open-label, Single group assignment echocardiograms and • Total study duration for one patient: up electrocardiograms, clinical to 9 years laboratory tests, safety biomarkers, immune response assessment, liver 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.
76 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Gaucher disease (GD) Type 3 MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
LEAP Phase 2 10 • 156-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): 2021 GD Type 3 Tolerability, PK, PD, and • Part 1: Evaluate CNS biomarkers in (GL-1 and lyso GL1 ) in CSF exploratory efficacy of adult GD type 3 patients that distinguish and plasma PDY13949 venglustat in combination with GD3 from GD type 1, • Secondary: PK parameters cerezyme in adult patients with Screen adult GD3 patients who qualify (CSF and Plasma) NCT02843035 GD Type 3 for Ttmt with venglustat in Part 2, Total duration 45 days • Part 2 and 3: Safety and tolerability in GD3 patients, Total duration up to 156 weeks including : treatment of 52 weeks (Part 2) and 104 weeks (Part 3) for long term follow-up, respectively
(1) Final Data Collection date for primary outcome measure 77 Immuno-inflammation Diabetes Oncology Cardiovascular Venglustat (GCS inhibitor) Rare Diseases Rare Blood Disorders Autosomal Dominant Polycystic Kidney Disease (ADPKD) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
STAGED-PKD Phase 3 560 • 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 (1st Part)(1): 2021
Efficacy, safety, tolerability and months) magnetic resonance imaging EFC15392 PK of venglustat in patients at • Study duration per participant is 26 (MRI) and rate of change in NCT03523728 risk of rapidly progressive months (maximal) per stage, including a glomerular filtration rate (eGFR) ADPKD screening period of 15 days, run-in • Secondary: Rate of change in period of 2 weeks, a 24-month treatment eGFR, rate of change in TKV, period, and a follow-up 30 days after rate of change in urine final dose osmolaity,rate of change in nocturia, adverse events, assessment of PK, change in lens clarity
(1) Accelerated approval 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 2023 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 2a 40 • 18-60 year old males with ALPS • Primary: AEs, eGFR slope, • SSD: Nov. 2017 • Randomized, double-blind, placebo- • Secondary: PK, anti-drug • DE: 2022
control, Parallel assignment, antibodies, eGFR slope (week Safety, Efficacy, • 2 arms: SAR339375 (RG012) and 24 and 94) , absolute change in ACT 16248 / Pharmacodynamics and placebo, eGFR, Tx responders. • Duration: 48 week SC injections double- RG012-03 Pharmacokinetics of SAR339375 (RG-012) in blinded treatment period. After 48 week NCT02855268 patients with ALPS 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 2021 EFC11759 Patients With Relapsing Forms • With at least one relapse (or attack) in enlarged T2 lesions, N of T1 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 SAR422459 (ABCA4 gene therapy)* Oncology Cardiovascular Rare Diseases Rare Blood Disorders Stargardt Disease MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Stargardt’s Phase 1 41 • Patients with a diagnosis of Stargardt's • Primary: IAE, Change from • SSD: Jun. 2011 Macular Phase 2/2a Macular Degeneration, with at least one baseline in ocular safety • DE: 2019 Degeneration pathogenic mutant ABCA4 allele on assessments Safety and tolerability of each chromosome • Secondary: Delay in retinal
ascending doses of SAR422459 • Non-randomized, Single Group degeneration TDU13583 in patients with Stargardt's assignment, Open-label, ascending doses NCT01367444 Macular Degeneration
Stargardt’s Phase 1/2 46 • Long Term safety and tolerability of • Primary: IAE • SSD: Dec. 2012 Macular SAR422459 in patients with Stargardt ‘s • Secondary: Delay in retinal • DE: 2034 Degeneration Follow-up study of SAR422459 Macular Degeneration degeneration in patients With • No ttmt administered, in this LTS only Stargardt ‘s Macular follow-up after ttmt in TDU13583 LTS13588 Degeneration • Patients will be followed for 15 years after treatment SG1/002/11 NCT01736592
* Identification of out-licensing partner ongoing
84 Immuno-inflammation Diabetes SAR421869 (Myosin 7A gene therapy)* Oncology Cardiovascular Rare Diseases Rare Blood Disorders Usher 1B Syndrome MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
UshStat® Phase 1 27 • Patients with clinical and molecular • Primary: IAE • SSD: Mar. 2012 Phase 2a diagnosis of Retinitis Pigmentosa • Secondary: Delay in retinal • DE: 2021 Usher associated with Usher Syndrome type degeneration Syndrome Type Safety and tolerability of 1B. With at least one pathogenic 1B ascending doses of subretinal mutation in the MYO7A gene on each injections of UshStat® in patients chromosome • Non-randomized, Single Group TDU13600 with Retinitis Pigmentosa associated with Usher syndrome assignment, Open-label, ascending NCT01505062 Type 1B doses
UshStat® Phase 2b 18 • Long-term follow up of patients who • Primary: IAE • SSD: Sep. 2013 received UshStat® in a previous study • Secondary: Change from • DE: 2033 Usher Long-Term Safety, Tolerability (TDU13600) baseline in ocular safety Syndrome Type and Biological Activity of • Patients will be followed for 15 years assessments, Delay in retinal 1B UshStat® in Patients With Usher after treatment degeneration Syndrome Type 1B LTS13619 NCT02065011
* Project discontinued and identification of out-licensing partner ongoing
85 Immuno-inflammation Diabetes Venglustat (GCS inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders GBA-PD MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
MOVES-PD Phase 2 243 • 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 2022 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
86 Immuno-inflammation Diabetes SAR443060 (DNL747) (RIPK1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Alzheimer’s Disease MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1* 16 • Patients suffering from Alzheimer’s • Primary: AEs and SAEs, lab • SSD: Feb. 2019 Disease test abnormalities • DE: 2019
Safety, Tolerability, • Randomized, Double-blind, Placebo • Secondary: Pharmacokinetics, DNLI-D-0002 Pharmacokinetics, and Controlled, Cross-over Assignment Pharmacodynamics NCT03757325 Pharmacodynamics of • SAR443060 and placebo SAR443060(DNL747) in Subjects with Alzheimer’s disease
* Phase 1 study performed by Denali
87 Immuno-inflammation Diabetes SAR443060 (DNL747) (RIPK1 inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Amyotrophic Lateral Sclerosis (ALS) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1* 16 • Patients with a diagnosis of laboratory- • Primary: AEs and SAEs, lab • SSD: Dec. 2018 supported probable, probable or definite test abnormalities, clinically • DE: 2019
Safety, Tolerability, ALS significant neurological DNLI-D-0003 Pharmacokinetics, and • Randomized, Double-blind, Placebo abnormalities NCT03757351 Pharmacodynamics of Controlled, Cross-over Assignment • Secondary: Pharmacokinetics, SAR443060(DNL747) in • SAR443060 and placebo Pharmacodynamics Subjects with Amyotrophic Lateral Sclerosis
* Phase 1 study performed by Denali
88 Immuno-inflammation Diabetes SAR442168 (BTK inhibitor) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Multiple Sclerosis (MS) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Relapsing MS Phase 2b 120 • 18 to 55 years old Patients with a • Primary: Number of new Gd- • SSD: Apr. 2019 diagnosis of RMS, enhancing T1 hyperintense • DE: 2019
Dose finding study of • Dose-finding study, Randomized, lesions, DRI15928 SAR442168 in Patients with Double-blind, Cross-over Assignment, • Secondary: Number of new or NCT03889639 Relapsing Multiple Sclerosis • Total 8 arms: 4 arms with SAR442168 (4 enlarging T2 lesions, total doses tested) 12 weeks Tx with number of Gd-enhancing T1 SAR442168 + 4 weeks placebo; and 4 hyperintense lesions, AEs. arms with SAR442168 (same 4 doses) but 4 weeks of placebo followed by 12 weeks of SAR442168 (same 4 doses) • Duration: 24 weeks: 4-week screening period, 16-week Tx period and 4-week follow-up
89 Immuno-inflammation Diabetes Lixisenatide Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus (T2DM) Pediatrics MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 1 24 • Pediatric patients (≥ 10 and < 18 years • Primary: AEs, TEAEs, number • SSD: May 2017 old with documented T2DM insufficiently of patients with anti-lixisenatide • DE: 2020
PK and PD of lixisenatide in controlled with metformin and/or basal Ab, Pediatric Patients insulin • Secondary: lixisenatide PK TDR14311 With T2DM not adequately • Randomized, double-blind, placebo- parameters, PD ( plasma controlled with metformin and/or controlled, dose escalation (3 ascending glucose AUC-0-4,5 hours) NCT02803918 basal insulin repeated doses) • Study duration: up to 10 weeks including 6-week Tx period with dose escalation every 2 weeks
90 Immuno-inflammation Diabetes iGlarLixi (Glargine/Lixisenatide) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus (T2DM) (1/3) 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
91 Immuno-inflammation Diabetes iGlarLixi (Glargine/Lixisenatide) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus (T2DM) (3/3) 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
92 Immuno-inflammation Diabetes Efpeglenatide (Long acting GLP1-R agonist) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AMPLITUDE-M Phase 3 400 • A 56-week, multicenter, double-blind, Primary: change in HbA1c (%) • SSD: Dec. 2017 • placebo-controlled, 4 parallel arms, from Baseline to Week 30 • DE: 2020
Efficacy and Safety of randomized study to demonstrate the Secondary EFC14822 efpeglenatide in Patients with superiority of once-weekly injection of • Number of participants with NCT03353350 T2DM Inadequately Controlled efpeglenatide 2, 4, or 6 mg in HbA1c <7.0% at Week 30 with Diet and Exercise comparison to placebo in HbA1c change • Change from Baseline to from baseline to Week 30 Weeks 30 and 56 in fasting plasma glucose • Change in HbA1c (%) from Baseline to Week 56 • Change from Baseline to Weeks 30 and 56 in body weight • Number of patients with at least one hypoglycemic event during treatment period • Number of hypoglycemic events per participant-year during treament period • Number of patients with AEs
93 Immuno-inflammation Diabetes Efpeglenatide (Long acting GLP1-R agonist) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AMPLITUDE-O Phase 3 4000 • T2DM patients with Hb1Ac > 7% with • Primary: time to first Major • SSD: Apr. 2018 either established cardiovascular Adverse Cardiovascular Event • DE: 2021
Effects of efpeglenatide on disease or renal impairment 25 ≤ eGFR (MACE) EFC14828 Cardiovascular outcomes in < 60 mL/min and at least one • Secondary: time to first, NCT03496298 high cardiovascular risk T2DM cardiovascular risk factor Expanded Cardiovascular patients • Randomized, double-blind, placebo- Outcome event, Composite controlled, parallel-group (efpeglenatide Renal event, AEs 4mg, 6mg, placebo) • Estimated study duration per patient up to 36 months approximately • Study is event driven; mean follow up of 2,5 years is expected
94 Immuno-inflammation Diabetes Efpeglenatide (Long acting GLP1-R agonist) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AMPLITUDE-D Phase 3 900 • Patients with T2DM on HBA1c between • Primary: change from baseline • SSD: Oct. 2018 7-10% (inclusive) on a stable dose of at to week 56 in HbA1c, • DE: 2020
Efficacy and safety of least 1500 mg metformin or tolerated • Secondary: EFC14829 efpeglenatide vs duraglutide in maximum dose for at least 3 months - Change from baseline to NCT03684642 patients with T2DM prior to screening week 56 in FPG inadequately controlled with • Randomized, multi-center, open-label for - Change from baseline to metformin the drug (efpeglenatide and dulaglutide) week 56 in body weight and double-blind for the doses of - Number of patients with efpeglenatide, active-controlled HbA1c < 7% at week 56 • Three arms: - Number of patients with at efpeglenatide 4, or 6 mg vs dulaglutide least one hypoglycemic • Study duration: overall 56 weeks event during treatment period - Number of hypoglycemic events per participant-year during treatment period - Number of patients with Aes
95 Immuno-inflammation Diabetes Efpeglenatide (Long acting GLP1-R agonist) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AMPLITUDE-L Phase 3 400 • Patients with T2DM on HBA1c between • Primary: change from baseline • SSD: 2019 7-10% (inclusive) on basal insulin alone to week 30 in HbA1c, • DE: 2021
Efficacy and safety of or in combination with oral antidiebetic • Secondary: EFC14893 efpeglenatide vs placebo in drug(s) at a stable dose for at least 6 - Change from baseline to NCT03713684 patients with T2DM months prior to screening week 56 HBA1c inadequately controlled with • Randomized, multi-center, double-blind, - Change from baseline to basal insulin alone or in parallel-arms, parallel groups week 56 in FPG combination with oral • Four arms: - Number of patients with antidiabetic drug(s) efpeglenatide 2, 4, or 6 mg vs placebo HbA1c < 7.0% at week 30 • Study duration: overall 56 weeks - Change from baseline to week 30 and week 56 in body weight - Number of patients with at least one hypoglycemic event during treatment period - Number of hypoglycemic events per participant-year during treatment period - Number of patients with AEs
96 Immuno-inflammation Diabetes Efpeglenatide (Long acting GLP1-R agonist) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
AMPLITUDE-S Phase 3 640 • Patients with T2DM on HBA1c between • Primary: change from baseline • SSD: 2019 7-10% (inclusive) on metformin with or to week 30 in HbA1c • DE: 2021
without sulfunylurea at a stable dose for • Secondary: EFC15337 Efficacy and safety of at least 12 weeks prior to screening - Number of patients with NCT03770728 efpeglenatide vs placebo in • Randomized, multi-center, double-blind, HbA1c < 7.0% at week 30 patients with T2DM parallel-arms, parallel groups - Change from baseline to week inadequately controlled with • Four arms: 56 in FPG controlled with metformin alone • efpeglenatide 2, 4, or 6 mg, placebo - Change from baseline to week or in combination with • Study duration: 30 weeks, 30 in body weight sulfonylurea - Number of patients with at least one hypoglycemic event during treatment period - Number of hypoglycemic events per participant-year during treatment period - Number of patients with Aes
97 Immuno-inflammation Diabetes SAR341402 (Rapid Acting Insulin) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Type 1 & 2 Diabetes Mellitus MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
GEMELLI 1 Phase 3 597 • Patients with T1DM or T2DM diagnosed • Primary: Change in HbA1c (%) • SSD: Aug. 2017 for at least 12 months, who have been from baseline to Week 26 • DE: 2019
Comparison of SAR341402 to treated with a multiple daily injection • Secondary: Change in HbA1c, EFC15081 NovoLog®/NovoRapid® in adult regimen with NovoLog®/NovoRapid® OR Patients with HbA1c <7%, NCT03211858 patients with Diabetes also insulin lispro (100 U/mL) in the last 6 Change in FPG, Change in using Insulin Glargine, with a 6- months prior to screening visit AND mean 24-hour plasma glucose month safety extension period insulin glargine (100 U/mL) in the last 6 concentration, Change in PPG, months prior to screening visit OR insulin Change in 7-point SMPG, detemir (Levemir®) in the last 12 months Hypoglycemic patients, prior to screening visit Hypoglycemic events, Anti- • Randomized, Open-label, Parallel-group SAR341402/NovoLog/NovoRap • Active comparator: id antibody status, Tx-induced, NovoLog®/NovoRapid® Tx-boosted and Tx-emergent • Study duration: 54-week per patient: anti-insulin antibodies 2-week screening period, 26-week Tx period, 26-week comparative safety extension, 1-day follow-up period
98 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 3 184 • Patients with T1DM, on continuous • Primary: AUClast, AUC and • SSD: 2019 insulin Tx for at least 12 months prior to Cmax of SAR341402 and • DE: 2019
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 to 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.
99 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Heterozygous Familial Hypercholesterolemia Rare Diseases Rare Blood Disorders (HeFH) (1/2) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
ODYSSEY KIDS Phase 2 42 • Patients with diagnosis of HeFH through • Primary: % change in • SSD: Sep. 2016 genotyping or clinical criteria., 8 to 17 calculated LDL-C from baseline • DE: 2019
Efficacy and safety of years old, treated with optimal dose of to week 8 DFI14223 alirocumab in children and statin +/- other LMT(s) or non-statin • Secondary: Absolute change in NCT02890992 adolescents with heFH followed LMT(s) if statin intolerant at stable dose calculated LDL-C, % change in by an extension phase for at least 4 weeks prior to screening APO B (Apo B), % change in lipid sampling non-high density LP cholesterol • Open-Label, Sequential, Repeated (non HDL-C), % change in Dose-Finding Study (6 doses tested) Total-C, in LP, in TG, in HDL-C, • Background therapies: optimal dose of in Apo A-1, Absolute change in statin with or without other LMT or non- Apo B, in non-HDL-C, in Total statin LMT if statin intolerant at stable C, in Lp(a), in TG, in HDL-C, in dose Apo A-1, in ratio apo B/Apo A- • Study duration: approximately 16-23 1, % of participants achieving a weeks: up to 6 (+1) weeks screening calculated LDL-C level lower period, 8 weeks open-label Tx period, 6 than 130 mg/dL (3.37 mmol/L), to 8 weeks follow-up period % of participants achieving a calculated LDL-C level lower than 110 mg/dL (2.84 mmol/L)
100 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Heterozygous Familial Hypercholesterolemia Rare Diseases Rare Blood Disorders (HeFH) (2/2) 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, treated with optimal dose of from baseline to week 24 • DE: 2022 Adolescents Efficacy and safety of statin +/- other LMT(s) or non-statin • Secondary: % change in LDL- alirocumab in children and LMT(s) if statin intolerant at stable dose C, % change in APO B (Apo B), adolescents with HeFH • Randomized, double-Blind, placebo- % change in non-high density EFC14643 controlled followed by an open label LP cholesterol (non HDL-C), % treatment period (2 dose tested) change in Total-C, patients with NCT03510884 • Study duration: approximately 110 LDL-C level lower than 130 weeks (run-in period, if needed,: up to 4 mg/dL (3.37 mmol/L), patients weeks [+2 days], screening period, up to with LDL-C level lower than 110 2 weeks (+5 days), double-blind mg/dL (2.84 mmol//L), % treatment period: 24 weeks, open label change in Lp(a), in HDL-C, in treatment: 80 weeks) TG and in ApoA-1. Number of AE, maturing cognition (Cogstate battery test) and pubertal development (Tanner stage)
101 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Homozygous Familial Hypercholesterolemia Rare Diseases Rare Blood Disorders (HoFH) (1/2) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
ODYSSEY Phase 3 74 • Diagnosis of HoFH by specific genotype • Primary: % change in LDL-C • SSD: Oct. 2017 HoFH or clinical criteria (all patients on LDL ITT population from baseline to • DE: 2020 Evaluate the efficacy and safety apheresis must be diagnosed based on week 12 Regeneron of alirocumab in patients with genotype) • Secondary: % change in Apo B, HoFH • Randomized, Double-Blind, Placebo- % change in non-HDL-C, % Controlled, Parallel-Group, 2-Arm change in TC, % change in R727-CL-1628 (alirocumab Q2W, placebo) LP(a), % change in HDL-C, % NCT03156621 • Study duration: 12-week double-blind Tx change in fasting TG, % period followed by 10-week alirocumab change in Apo A-1, % change open-label Tx period in LDL-C, % change in LDL-C, ApoB B, non-HDL-C, TC, Lp(a), HDL-C, fasting TG, Apo A-1 / (m)ITT population, Absolute change in the ratio of Apo B/Apo A-1 (ITT), % of patients with ≥15% reduction in LDL-C, % of patients with ≥30% reduction in LDL-C, % of patients with ≥50% reduction in LDL-C, % of patients with ≥15% reduction, ≥30% reduction, and ≥50% reduction in LDL-C
102 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Homozygous Familial Hypercholesterolemia Rare Diseases Rare Blood Disorders (HoFH) (2/2) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
HoFH Children Phase 3 18 • Patients with diagnosis of HoFH, 8 to 17 • Primary: % change in • SSD: Sep. 2018 and years old, treated with optimal dose of calculated LDL-C from baseline • DE: 2020 Adolescents Efficacy and safety of statin +/- other LMT(s) or non-statin to week 12 alirocumab in children and LMT(s) if statin intolerant at stable dose • Secondary: % change in LDL- adolescents with HoFH • Single group assignment, open label (2 C, % change in APO B (Apo B), EFC14660 doses) % change in non-high density • Study duration: up to 62 weeks, includes LP cholesterol (non HDL-C), % NCT03510715 (if needed) a run-in period of up to 4 change in Total-C, % change in weeks, a screening period of up to 2 Lp(a), in HDL-C, in TG and in weeks, a treatment period of up to 48 ApoA-1. Absolute change in weeks, and a follow-up of 8 weeks LDL-C, number of patients with AE and pubertal development (Tanner stage)
103 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Neurocognitive Evaluation (1/2) 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).
104 Immuno-inflammation Diabetes Alirocumab (anti-PCSK-9 mAb) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Neurocognitive Evaluation (2/2) MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Long Term Phase 4 1600 • Participants randomized into the • Primary: Incidence of adverse • SSD: Sep 2018 Safety Study of neurocognitive function study (R727-CL- events (AEs) after first • DE: 2023 Praluent Evaluate the long term safety of 1532) who completed treatment and the administration of study drug PRALUENT in participants with end of study (EOS) visit with no through the last dose of study Regeneron heterozygous familial premature or permanent discontinuation drug plus 2 weeks hypercholesterolemia (heFH) or of study drug • Secondary: Changes in LDL-C non-familial • Open Label, up to 192 weeks and other lipid parameters, R727-CL-1609 hypercholesterolemia (FH) • Drug: Praluent changes in gonadal steroid NCT03694197 patients at high or very high hormones cardiovascular risk who completed the neurocognitive function study (R727-CL-1532: NCT02957682)
105 Immuno-inflammation Diabetes Fitusiran (siRNA targeting Antithrombin/AT3) Oncology Cardiovascular Rare Diseases Rare Blood Disorders Hemophilia A & B (1/6) 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 • SSD: Sep. 2015 A or B Hemophilia A • Single Group assignment, Open- treatment-emergent AEs, • DE: 2024 Hemophilia B label SAEs, and AEs leading to • Subjects are administred SC study drug discontinuation LTE14762 Long term Safety and fitusiran once every month for Secondary: Annualized bleed ALN- AT3SC- Efficacy of Fitusiran in approximately 4 years. rate, time intervals between 002 patients with moderate or bleeding episodes, Weight- severe Hemophilia A or B, adjusted consumption of FVIII, NCT02554773 who have previously FIX, or BPA, QOL assessed participated in ALN-AT3SC- by an EQ-5D questionnaire 001 and HAEM-A-QoL, Antithrombin levels, Thrombin Generation levels
106 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
107 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: 2020 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
108 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
109 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: 2024 Hemophilia B label seriousness of AEs, and • 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), Efficacy of Fitusiran in a follow-up period up to 6 months annualized spontaneous ALN-AT3SC-005 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
110 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: 2019 Hemophilia A • Single Group assignment, Open- antithrombin (AT) activity • DE: 2022 Hemophilia B label level [ Time Frame: Day 1 to An Open-label, Multinational • Study duration per participant is Day 85 ] Study of Fitusiran approximately 160 weeks, including ALN-AT3SC-005 Prophylaxis in Male Pediatric a 12-week fitusiran efficacy period • Secondary: Number of NCT03754790 Subjects Aged 1 to Less participants reported with Than 12 Years With adverse events , Hemophilia A or B pharmacokinetics (PK): Cmax, Tmax, Ctrough.
111 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.
112 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: 2020 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.
113 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
114 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: 2021 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)
115 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
116 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: 2019 • Open-Label, Single Group post-transplantation at • DE: 2022 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
117 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: Aug. 2016 HERCULES patients (18 years and older) with subjects with TTP-related • DE: 2020 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.
118 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
NCT02992418 Phase 3 688 • Randomized, multicenter, open-label • Immunogenicity and safety of • SSD: Dec. 2016 study in 688 subjects aged from 9 to 60 CYD dengue vaccine and Tdap • DE: 2020 Study of a Tetravalent Dengue years vaccine when both vaccines are Vaccine Administered administered concomitantly or Concomitantly or Sequentially sequentially With Adacel® in Healthy Subjects
119 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
NCT02628444 Phase 2a 1050 • Two-stage, multi-national, multi-center, • Immunogenicity and safety of 3- • SSD: May. 2016 observer-blind, randomized, placebo- dose primary series and • DE: 2020 Immunogenicity and Safety of 3- controlled Phase II immunogenicity and booster dose Dose and Booster Dose of safety study of tetravalent dengue Tetravalent Dengue Vaccine in vaccine Healthy Subjects 9 to 50 Years of Age
120 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Booster dose Rare Diseases Rare Blood Disorders Latin America Region MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02623725 Phase 2b 251 • Multi-center, observer-blind, randomized, • Immunogenicity and safety of a • SSD: Apr. 2016 placebo-controlled, Phase II trial booster dose • DE: 2019 Study of a Booster Dose of a Tetravalent Dengue Vaccine in Subjects Who Previously Completed the 3-dose Schedule
121 Immuno-inflammation Diabetes Rabies Vaccine Oncology Cardiovascular Verorab Rare Diseases Rare Blood Disorders Asia Pacific Region MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT01622062 Phase 3 600 • Open-label, randomized, controlled, • Immunogenicity and safety of • SSD: Jun. 2012 multi-center, multi-country trial Verorab® in a "One-week" • DE: 2019 Immunogenicity and Safety of intradermal post-exposure Verorab® in a "One-week" prophylaxis regimen Intradermal Post-exposure Prophylaxis Regimen
122 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi Rare Diseases Rare Blood Disorders Greater Europe, Latin America, Asia Pacific Regions MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT03205371 Phase 3 1183 • Open-label (immunology laboratory • Immunogenicity and safety • SSD: Nov. 2016 technicians will be blinded to group • DE: 2019 Immunogenicity and Safety of a assignment), randomized, parallel-group, Meningococcal Conjugate active-controlled, multi-center study Vaccine Given Concomitantly With Other Vaccines in Toddlers
123 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Booster Rare Diseases Rare Blood Disorders Asia Pacific Region MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02824198 Phase 2b 260 • Multi-center, observer-blind, randomized, • Immunogenicity and safety of a • SSD: Jul. 2016 placebo-controlled, Phase II non- booster dose • DE: 2019
Immunogenicity and Safety of a inferiority trial Tetravalent Dengue Vaccine Booster Injection in Subjects Who Previously Completed a 3- dose Schedule
124 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
NCT02979535 Phase 3b 480 • Randomized, open-label, multicenter • Immunogenicity and safety of a • SSD: Nov. 2016 study Tetravalent Dengue Vaccine • DE: 2019 Immunogenicity and Safety of a administered concomitantly or Tetravalent Dengue Vaccine sequentially with Cervarix® Administered Concomitantly or Sequentially With Cervarix®
125 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
NCT02993757 Phase 3b 528 • Randomized, open-label, multicenter • Immunogenicity and safety of a • SSD: Dec. 2016 study Tetravalent Dengue Vaccine • DE: 2020 Immunogenicity and Safety of a administered concomitantly or Tetravalent Dengue Vaccine sequentially with Gardasil® Administered Concomitantly or Sequentially With Gardasil®
126 Immuno-inflammation Diabetes AcP Primary Oncology Cardiovascular Africa and Middle East Regions Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02817451 Phase 4 100 • multicenter, open-label, two-arm study • immunogenicity and safety of 3- • SSD: Jul. 2016 dose primary series and • DE: 2019 DTaP-IPV-HB-PRP-T Combined booster dose Vaccine as a Primary Series and a 2nd Year of Life Booster in HIV-Exposed Infected and Uninfected
127 Immuno-inflammation Diabetes Dengue Vaccine Oncology Cardiovascular Asia Pacific Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02827162 Exploratory Phase 334 • Exploratory, single-center study • Host generic analysis and • SSD: Mar. 2016 correlate of protection • DE: 2019 Association of Host Genetics With Vaccine Efficacy and Study of Immune Correlates of Risk From a Tetravalent Dengue Vaccine
128 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
NCT02948933 Epidemiology Phase 30 000 • Observational • Incidence of selected AEs and • SSD: Dec. 2016 SAEs, occurrence and • DE: 2025 Cohort Event Monitoring for frequency of hospitalized Dengvaxia®, CYD-TDV Dengue dengue disease and SAEs Vaccine leading to hospitalization or death
129 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
NCT00855855 Phase 4 510 000 • Observational • Surveillance for Hib disease. • SSD: Feb. 2009 • DE: 2020 Surveillance Program to Determine Product Specific Rates of Invasive Hib Disease
130 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
NCT01129362 Phase 4 1 538 • Observational • Occurrence of pertussis • SSD: May 2010 disease, as determined by the • DE: 2019 Rates of Pertussis Disease Wisconsin Division of Public Among Persons Receiving Health (WDPH). Pentacel® or Other Pertussis Vaccines
131 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular Asia Pacific Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02864927 Phase 4 600 • Open, Multi-center, observational, active • Occurrence of solicited and • SSD: Jul. 2016 safety surveillance study unsolicited events • DE: 2020 Postmarketing Surveillance Study for Use of Menactra® in the Republic of Korea
132 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
NCT03147898 Phase Epidemiology 90 • Observational, multicenter trial • Immune response to booster • SSD: Apr. 2017 dose • DE: 2019 Observational Study Describing the Immune Profile Induced By Pertussis Vaccines
133 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
NCT01945424 Phase Epidemiology 500 • Observational • Pregnancy registry • SSD: Aug.2013 • DE: 2020 Sanofi Pasteur Quadrivalent Influenza Vaccine (QIV) Pregnancy Registry
134 Immuno-inflammation Diabetes Japanese Encephalitis Vaccine Oncology Cardiovascular Asia Pacific Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT02933710 Phase 4 50 • Multi-center, open, observational, active • Occurrence of solicited and • SSD: Jul. 2016 safety surveillance study. unsolicited events • DE: 2019 Postmarketing Surveillance Study for IMOJEV® in Republic of Korea
135 Immuno-inflammation Diabetes Meninge Vaccine Oncology Cardiovascular MenQuadfi - Booster Rare Diseases Rare Blood Disorders Greater Europe Region MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
NCT03476135 Phase 3 91 • Open label, multicenter study to describe • Immunogenicity and safety • SSD: Feb. 2018 immune persistence of the priming dose • DE: 2019 Immunogenicity and safety and immuno and safety of booster dose booster dose in subjects previously vaccinated as toddlers
136 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, randomized, • Immunogenicity and safety • SSD: Apr. 2018 NCT03537508 parallel groups, active controlled, • DE: 2023 Safety and Immunogenicity for multicenter Infants, with co administration with routine pediatric vaccines
137 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 for controlled, multi center alternative schedules in infants
138 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 4 240 • Interventional, open label, randomized, • Immunogenicity and safety • SSD: Sep. 2018 NCT03617523 • DE: 2019 Safety and immunogenicity Fluzone Quadrivalent, Flublock Quadrivlent and Fluzone High Dose
139 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 assignement, active controlled multi NCT03630705 Safety and immunogenicity • DE: 2023 3 dose schedule center study Quadrivalent Meningococcal conjugate vaccine
140 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 blind, • Immunogenicity and safety • SSD: Oct. 2018 NCT03691610 Randomized, parrallel assignement • DE: 2021 Safety & Immunogenicity 2-dose active controlled multi center study. Trial in Toddlers
141 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, Sequential • Dose response, immunogenicity • SSD: Oct. 2018 NCT03698279 Assignment, modified double blind, and safety • DE: 2020 Safety and immunogenicity of multi center study Flu Quadrivalent HD 3 dose schedule in Pediatric population
142 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, Parallel • Immunogenicity and safety • SSD: Sep. 2018 NCT03700242 Assignment, • DE: 2020 Immunogenicity and safety of HDCV with abbreviated pre- exposure regimens Trial
143 Immuno-inflammation Diabetes Flu Vaccine Oncology Cardiovascular Asia Pacific Region Rare Diseases Rare Blood Disorders MS, Neuro, Gene therapy Vaccines
Study Description Patients Design Endpoints Status
Phase 3 230 • Open-label, uncontrolled, mono-center • Safety Assessment. • SSD: Jan.2019 NCT03765437 study to be conducted in Vietnam. • DE: 2019 Safety of a Quadrivalent Influenza Vaccine in Subjects Aged 6 Months and Older in Vietnam
144 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: Jul.2019 NCT03890367 modified double-blind (triple masking - Assessment. • DE: 2020 Immunogenicity and Safety of Participant, Investigator, Outcomes Quadrivalent Meningococcal Assessor) conducted in Denmark, Conjugate Vaccine Compared Finland, and Germany. With Two Meningococcal Reference Vaccines in Europeans Toddlers
145 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 in Assessment. • DE: 2020 Immunogenicity and Safety of a Turkey. Quadrivalent Meningococcal Conjugate Vaccine in Potential Pilgrims Aged 56 Years and Older in Turkey
146 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: 2020 Purified Vero Rabies Vaccine blind groups + one open label group. Compared With Two Reference Rabies Vaccines in a Simulated Post-Exposure Regimen in Adults
147 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: 2021 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
148