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Questions from the Committee Victor Raczkowski, MD, MS Vice President, US Regulatory Affairs Solvay Questions from the Committee Victor Raczkowski, MD, MS Vice President, US Regulatory Affairs Solvay Pharmaceuticals 1

BACKUP SLIDES BACKUP SLIDES

Serious Adverse Events: Time of Onset Females Day 0 -1 Day 2 -7 8 Serious Adverse Events: Time of Onset Females Day 0 -1 Day 2 -7 8 -28 day Tedi Plac Deaths 1 (0. 2%) 0 2 (0. 4%) 1 (0. 4%) Hypotension 2 (0. 5%) 1 (0. 4%) 0 0 0 0 2 (0. 5%) 1 (0. 4%) 1 (0. 2%) 0 Ventricular Tachycardia 2 (0. 5%) 0 0 0 Thrombo-embolic Events 1 (0. 2%) 0 3 (0. 7%) 3 (1. 3%) 2 (0. 5%) 0 Td. P 1 (0. 2%) 0 0 0 Bradycardia 1 (0. 2%) 1 (0. 4%) 1 1 (0. 4%) 0 0 Myocardial Infarction 3

Serious Adverse Events: Time of Onset Males 0 -1 Day 2 -7 Days 8 Serious Adverse Events: Time of Onset Males 0 -1 Day 2 -7 Days 8 -28 Days Tedi Plac Deaths 0 0 2 (0. 4%) 1 (0. 4%) Hypotension 0 0 0 1 (0. 4%) 0 0 Myocardial Infarction 0 0 3 (0. 6%) 1 (0. 4%) 1 (0. 2%) 0 Ventricular Tachycardia 4 ( 0. 8%) 0 0 3 (1. 2%) 1 (0. 2%) 0 Thromboembolic Events 0 0 3 (0. 6%) 0 1 (0. 2%) 0 Td. P 0 0 0 Bradycardia 0 0 2 (0. 4%) 0 1 (0. 2%) 0 4

Serious Adverse Events: Time of Onset Females Day 0 -1 Day 2 -7 8 Serious Adverse Events: Time of Onset Females Day 0 -1 Day 2 -7 8 -28 day Tedi Plac Deaths 1 (0. 2%) 0 2 (0. 5%) 1 (0. 4%) Hypotension 2 (0. 5%) 1 (0. 4%) 0 1 (0. 4%) Myocardial Infarction 0 0 2 (0. 5%) 1 (0. 4%) 1 (0. 2%) 0 Pulmonary Oedema 0 0 1 (0. 2%) 0 Thrombo-embolic Events 1 (0. 2%) 0 3 (0. 7%) 2 (0. 5%) 0 Td. P 1 (0. 2%) 0 0 0 Bradycardia 1 (0. 2%) 1 (0. 4%) 0 0 5

Serious Adverse Events: Time of Onset Males 0 -1 Day 2 -7 Days 8 Serious Adverse Events: Time of Onset Males 0 -1 Day 2 -7 Days 8 -28 Days Tedi Plac Deaths 0 0 1 (0. 2%) 2 (0. 5%) Hypotension 0 0 0 1 (0. 4%) 0 0 Myocardial Infarction 0 0 3 (0. 6%) 1 (0. 4%) 1 (0. 2%) 0 Pulmonary Oedema 0 0 1 (0. 2%) 0 0 0 Thromboembolic Events 0 0 3 (0. 6%) 0 1 (0. 4%) 0 Bradycardia 0 0 2 (0. 5%) 0 0 0 6

Medical History: Females Tedisamil (N = 476) n (%) Placebo N = 211 n Medical History: Females Tedisamil (N = 476) n (%) Placebo N = 211 n (%) Coronary Artery Disorder NEC 74 ( 19. 3%) 50 ( 22. 0%) Heart Failure NEC 73 ( 19. 1%) 37 ( 16. 3%) Myocardial Infarction 19 ( 5. 0%) 12 ( 5. 3%) Acute Myocardial Infarction 3 ( 0. 8%) 4 ( 1. 8%) Mitral Valvular Disorders 22 ( 5. 7%) 17 ( 7. 5%) Central Nervous System Haemorrhages and Cerebrovascular Accidents Vascular Hypotensive Disorders 18 ( 4. 7%) 13 ( 5. 7%) 2 ( 0. 5%) 1 ( 0. 4%) 7

Medical History: Males Tedisamil (N = 476) n (%) Placebo N = 211 n Medical History: Males Tedisamil (N = 476) n (%) Placebo N = 211 n (%) Coronary Artery Disorder NEC 116 ( 24. 4%) 53 ( 25. 1%) Cardiac Valve Disorders NEC 1 ( 0. 2%) 1 ( 0. 5%) Heart Failure NEC 91 ( 19. 1%) 39 ( 18. 5%) Myocardial Infarction 43 ( 9. 0%) 20 ( 9. 5%) Age Indeterminate Myocardial Infarction 3 ( 0. 6%) 1 ( 0. 5%) Acute Myocardial Infarction 5 ( 1. 1%) 4 ( 1. 9%) Mitral Valvular Disorders 19 ( 4. 0%) 11 ( 5. 2%) Central Nervous System Haemorrhages and Cerebrovascular Accidents Vascular Hypotensive Disorders 14 ( 2. 9%) 8 ( 3. 8%) 0 2 ( 0. 9%) 8

QTc. B Change from Baseline (SD) in Normal Subjects and Subjects with Moderate Renal QTc. B Change from Baseline (SD) in Normal Subjects and Subjects with Moderate Renal Impairment QTc prolongation (mean change from baseline) Combined Tedisamil Placebo Cr. Cl <60 ml/min ≥ 60 ml/min N=161 QTc Bazett Baseline 30 min 2. 5 hrs 4 hrs 8 hrs 12 hrs 24 hrs N=738 N=90 N=359 428. 6 ± 38. 8 29. 9 ± 40. 0 7. 0 ± 31. 4 -1. 7 ± 35. 4 -0. 9 ± 34. 1 3. 0 ± 26. 4 -2. 2 ± 31. 5 426. 2 ± 33. 7 31. 6 ± 37. 1 9. 0 ± 28. 8 3. 3 ± 31. 1 2. 5 ± 30. 3 3. 8 ± 27. 3 -3. 6 ± 29. 4 433. 8 ± 32. 7 -0. 2 ± 22. 7 2. 9 ± 26. 2 -0. 5 ± 32. 6 -2. 5 ± 28. 8 -3. 3 ± 20. 5 -2. 7 ± 27. 9 428. 9 ± 34. 5 -1. 2 ± 24. 7 -1. 1 ± 25. 5 -5. 9 ± 29. 0 -7. 2 ± 32. 9 -1. 9 ± 25. 7 -7. 6 ± 30. 4 9

Integrated Safety Database: TEAEs Converters vs Non-converters: Females Subjects who Converted to NSR 0. Integrated Safety Database: TEAEs Converters vs Non-converters: Females Subjects who Converted to NSR 0. 48 mg/kg 27 (61. 4%) Subjects who did not convert to NSR 0. 48 mg/kg 119 (65. 7%) - 3 ( 1. 7%) 20 (45. 5%) 71 (39. 2%) - 8 ( 4. 4%) Eye disorders 1 ( 2. 3%) 1 ( 0. 6%) Gastrointestinal disorders 5 (11. 4%) 8 ( 4. 4%) Gen. disorders & admin. site conditions 9 (20. 5%) 17 ( 9. 4%) Infection and infestations 3 ( 6. 8%) 10 ( 5. 5%) Injury, poisoning and procedural complications 1 ( 2. 3%) 2 ( 1. 1%) Investigations 2 ( 4. 5%) 18 ( 9. 9%) System organ class Preferred term Subjects with at least 1 TEAE Blood and lymphatic system disorders Cardiac disorders Endocrine disorders 10

FDA Analysis – Sensitivity Analysis – ITT as in file: Conversion Within 2. 5 FDA Analysis – Sensitivity Analysis – ITT as in file: Conversion Within 2. 5 hrs 3. 112 AFib males FDA Analysis mg/kg Sensitivity Analysis Placebocorrected P-value Dossier Placebocorrected P-value 0. 32 17 0. 014 17. 2 0. 014 17. 6 0. 0096 0. 48 45 <0. 001 45. 4 <0. 0001 47. 3 <0. 0001 0. 64 56 <0. 001 57. 9 <0. 0001 61. 8 <0. 0001 11

Randomized but not Treated Reasons: AFib/AFl ITT Sample Randomized but not treated Total N=1169 Randomized but not Treated Reasons: AFib/AFl ITT Sample Randomized but not treated Total N=1169 n (%) 42 (3. 6) Tedisamil N=775 n (%) 27 (3. 5) Placebo N=394 n (%) 15 (3. 8) Conversions 28 (2. 4) 15 (1. 9) 13 (3. 3) Non-conversions QTc too high AE Other safety exclusion criteria Withdrew consent Unknown 14 3 2 3 12 2 (1. 2) (0. 3) 0. 2) (0. 3) 3 (0. 3) (1. 5) (0. 3) 3 (0. 4) 2 1 0 1 (0. 5) (0. 3) (0. 0) (0. 3) 0 (0. 0) 12

Definition of Sensitivity Analysis All randomized AFib subjects are included in the analysis Subjects Definition of Sensitivity Analysis All randomized AFib subjects are included in the analysis Subjects who converted to NSR within 2. 5 hours are counted as successes regardless of whether they also received electrical cardioversion or not Subjects who converted to NSR before the initiation of the study drug infusion are counted as successes 13

Listing of Subjects with DC Cardioversion within 2. 5 hrs after start of infusion Listing of Subjects with DC Cardioversion within 2. 5 hrs after start of infusion Subj. ID Study Treatment Gender 25825 3. 112 0. 64 mg/kg M 41021 3. 114 0. 32 mg/kg M 41420 3. 114 0. 48 mg/kg M 86405* 3. 118 Placebo F 23405 3. 112 0. 48 mg/kg F Females in 3. 112 not part of primary efficacy analysis 25414 3. 112 0. 64 mg/kg F Females in 3. 112 not part of primary efficacy analysis 90136* 2. 107 0. 32 mg/kg F 2. 107 was not part of primary efficacy *DC cardioversion was unsuccessful 14

Reasons for Exclusions from AFib/AFl ITT sample BB page 35 tedisamil All randomized -3. Reasons for Exclusions from AFib/AFl ITT sample BB page 35 tedisamil All randomized -3. 112/. 114/116/117/118; -30 -min; AFib/AFl Excluded: - not treated - Conversion before infusion (treated) - No post-baseline Holter/ECG AFib/AFl ITT sample Excluded from analysis: - DC cardioversion within 2, 5 hrs placebo Total 775 394 1169 27 (3. 5%) 15 (3. 8%) 42 (3. 6%) 3 (0. 4%) 0 3 (0. 3%) 1 (0. 1%) 0 1 (0. 1%) 744 379 1123 5 1 6 15

Exclusions from AFib/AFl ITT Sample Summary all exclusions of randomized subjects from ITT analyses Exclusions from AFib/AFl ITT Sample Summary all exclusions of randomized subjects from ITT analyses were pre-specified all exclusions were done without knowledge of treatment assignment 4 categories number of exclusions were balanced between treatment groups, or very low no bias expected sensitivity analyses were performed – including DC cardioversions as failures (dossier) – including all randomized (additional analysis) no impact on efficacy findings 16

Number of Randomized Subjects per Country Argentina Bulgaria Canada Czech Republic Germany Greece Hungary Number of Randomized Subjects per Country Argentina Bulgaria Canada Czech Republic Germany Greece Hungary India Israel Italy Lithuania Poland Romania Russian Federation Serbia and Montenegro Slovakia South Africa Sweden Ukraine United Kingdom United States 2. 102 2. 107 3. 111 Study Number 3. 112 3. 113 3. 114 10 3. 116 9 3. 117 3. 118 60 27 5 59 2 2 15 25 4 23 1 42 5 32 20 4 2 16 6 13 76 24 8 97 1 17 34 6 70 16 58 23 60 2 40 77 2 1 35 30 21 2 89 26 94 1 16 137 2 9 13 Total per Country 19 60 27 53 81 2 42 5 52 4 15 243 40 184 40 95 8 2 333 4 160 17

Number of Randomized Subjects by Country Argentina Bulgaria Canada Czech Republic Germany Greece Hungary Number of Randomized Subjects by Country Argentina Bulgaria Canada Czech Republic Germany Greece Hungary India Israel Italy Lithuania 19 60 27 53 81 2 42 5 52 4 15 Poland Romania Russian Federation Serbia and Montenegro Slovakia South Africa Sweden Ukraine United Kingdom USA 243 40 184 40 95 8 2 333 4 160 18

Pharmacokinetics in Obese Subjects Cmax Dose Gender/BMI N 0. 32 mg/kg Female ≤ 28 Pharmacokinetics in Obese Subjects Cmax Dose Gender/BMI N 0. 32 mg/kg Female ≤ 28 kg/m 2 92 AUC (ng*h/m. L ng/ml ) 984 3237 0. 32 mg/kg Female > 28 kg/m 2 109 1014 3175 0. 48 mg/kg Male ≤ 28 kg/m 2 92 1227 3593 0. 48 mg/kg Male > 28 kg/m 2 77 1428 4052 19

Effect of Bodyweight Tedisamil is a non-lipophilic drug Distribution over total body water only Effect of Bodyweight Tedisamil is a non-lipophilic drug Distribution over total body water only basis for mg/kg dosing on BW For subjects BMI> 28 kg/m 2: – limit the dose to prevent high Cmax – dosing based on BW associated with a fixed BMI of 28 kg/m 2 Meta-analysis: LBM: major effect on Volume of ditribution: supports for mg/kg dosing on BW 20

Tedisamil CL Decreases up to 42% in Patients with Moderate Renal Impairment, with no Tedisamil CL Decreases up to 42% in Patients with Moderate Renal Impairment, with no Substantial Effect on Cmax following a Single Dose Short Infusion Tedisamil (ng/m. L) Tedisamil 0. 32 mg/kg Time (hrs) 21

Reasons for Stopping the Infusion Prematurely Study 3. 118 0. 32 mg/kg N Placebo Reasons for Stopping the Infusion Prematurely Study 3. 118 0. 32 mg/kg N Placebo N Safety sample (= treated) 77 75 Infusion prematurely stopped 1 0 1 – Reason - Adverse events 22

Reasons for Stopping the Infusion Prematurely Study 3. 116 0. 24 mg/kg N 0. Reasons for Stopping the Infusion Prematurely Study 3. 116 0. 24 mg/kg N 0. 32 mg/kg N Placebo N 120 118 2 3 2 Systolic BP < 90 mm. Hg – – 1 QRS duration increase > 30% 1 3 1 Conversion into NSR 1 – – Safety sample (= treated) Infusion prematurely stopped Reason 23

Reasons for Stopping the Infusion Prematurely Study 3. 117 0. 48 mg/kg N Placebo Reasons for Stopping the Infusion Prematurely Study 3. 117 0. 48 mg/kg N Placebo N Safety sample (= treated) 59 58 Infusion prematurely stopped 1 1 - Patient converted to sinus rhythm 1 – - QRS duration increase > 30% – 1 Reason 24

Reasons for Stopping the Infusion Prematurely Study 3. 114 – 30 -Minute Infusion 0. Reasons for Stopping the Infusion Prematurely Study 3. 114 – 30 -Minute Infusion 0. 16 mg/kg N 0. 32 mg/kg N 0. 48 mg/kg N Placebo N Safety sample (= treated) 58 59 54 57 Infusion prematurely stopped 0 3 2 0 - QT interval > 550 ms and/or > 20 % increase from baseline, measured after conversion – – 1 – - Conversion to sinus rhythm – 1 – – - Conversion to sinus rhythm, bradycardia – – 1 – - Due to administrator reason protocol violation – 1 – – – Onset of ventricular tachycardia – 1 – – Reason 25

Reasons for Stopping the Infusion Prematurely Study 3. 112 – Females 0. 32 mg/kg Reasons for Stopping the Infusion Prematurely Study 3. 112 – Females 0. 32 mg/kg N Safety sample (= treated) Infusion prematurely stopped Reason Systolic BP < 90 mm. Hg Threatening change in rhythm or AV conduction 0. 48 mg/kg N 0. 64 mg/kg N Placebo N 6 1 11 1 10 1 9 0 – 1 1 – 0 – 26

Reasons for Stopping the Infusion Prematurely Study 3. 112 – Males Safety sample (= Reasons for Stopping the Infusion Prematurely Study 3. 112 – Males Safety sample (= treated) Infusion prematurely stopped Reason - Threatening change in rhythm or AV conduction - QT interval > 550 ms and/or > 20 % increase from baseline, measured after conversion - Systolic BP < 90 mm. Hg, QT interval > 550 ms and/or > 20 % increase from baseline, measured after conversion 0. 32 mg/kg N 65 1 0. 48 mg/kg N 59 3 0. 64 mg/kg N 50 4 Placebo N 62 0 – 1 1 – 1 2 2 – – – 1 – 27

Primary Efficacy Parameter Study S 219. 3. 118 3 h-45 d Dose (mg/kg) n Primary Efficacy Parameter Study S 219. 3. 118 3 h-45 d Dose (mg/kg) n %-conversion 0. 32 67 12 (17. 9%)** ≤ 48 h >48 h n %-conversion 19 8 (42. 1%) n %-conversion 16 4 (8. 3%) placebo 67 48 52 3 (4. 5%) 2 (12. 5%) 1 (2. 0%) ** P < 0. 01 28

Primary Efficacy Parameter Study S 219. 3. 117 3 h-45 d Dose (mg/kg) n Primary Efficacy Parameter Study S 219. 3. 117 3 h-45 d Dose (mg/kg) n %-conversion 0. 48 48 14 (29. 2%)** ≤ 48 h >48 h n %-conversion 23 13 (56. 5%) n %-conversion 25 1 (4. 0%) placebo 48 32 16 3 (6. 3%) 3 (9. 4%) 0 ** P < 0. 01 29

Primary Efficacy Parameter Study S 219. 3. 116 3 h-45 d Dose (mg/kg) n Primary Efficacy Parameter Study S 219. 3. 116 3 h-45 d Dose (mg/kg) n %-conversion 0. 24 106 10 (9. 4%) 0. 32 107 23 (21. 5%)*** placebo 105 3 (2. 9%) ≤ 48 h >48 h n %-conversion 32 13 (35. 1%) n %-conversion 74 2 (2. 7%) 37 8 (25. 0%) 70 10 (14. 3%) 32 1 (3. 1%) 73 2 (2. 7%) *** P < 0. 001 30

Primary Efficacy Parameter Study S 219. 3. 114 3 h-45 d Dose (mg/kg) n Primary Efficacy Parameter Study S 219. 3. 114 3 h-45 d Dose (mg/kg) n %-conversion 0. 16 50 12 (24. 0) ≤ 48 h >48 h n %-conversion 26 11 (42. 3%) n %-conversion 24 1 (4. 2%) 0. 32 51 15 (29. 4)* 18 11 (61. 1%) 33 4 (12. 1%) 0. 48 45 14 (31. 1)* 20 10 (50. 0%) 24 4 (16. 7%) 5 (9. 8) 19 5 (26. 3%) 32 0 placebo 51 * P < 0. 05 31

Primary Efficacy Parameter Study S 219. 3. 112 3 h-45 d Dose (mg/kg) n Primary Efficacy Parameter Study S 219. 3. 112 3 h-45 d Dose (mg/kg) n %-conversion 0. 32 56 13 (23. 2%)** ≤ 48 h >48 h n %-conversion 26 9 (34. 6%) n %-conversion 30 4 (13. 3%) 0. 48 51 27 (52. 9%)*** 28 18 (64. 3%) 23 9 (39. 1%) 0. 64 44 29 (65. 9%)*** 27 19 (70. 4%) 17 10 (62. 5%) 28 3 (10. 7%) 25 0 placebo 53 3 (5. 7%) ** P < 0. 01 *** P < 0. 001 32

Concomitant Medications of Special Interest: Females ITT sample Agents Acting on RAS Antithrombotic Agents Concomitant Medications of Special Interest: Females ITT sample Agents Acting on RAS Antithrombotic Agents β-blocking Agents Calcium Channel Blockers Cardiac Therapy Diuretics Drugs used in Diabetes Lipid Lowering Agents Subjects, n (%) 0. 32 mg/kg Tedisamil N = 222 N = 383 156 (70. 3) 271 (70. 8) 211 (95. 0) 361 (94. 3) 178 (80. 2) 297 (77. 5) 53 (23. 9) 105 (27. 4) 157 (70. 7) 266 (69. 5) 98 (44. 1) 172 (44. 9) 28 (12. 6) 55 (14. 4) 52 (23. 4) 81 (21. 1) Placebo N = 227 165 (72. 7) 217 (95. 6) 181 (79. 7) 69 (30. 4) 162 (71. 4) 122 (53. 7) 39 (17. 2) 51 (22. 5) 33

Concomitant Medication Taken by ≥ 5% of Subjects (1) – ITT Sample ATC Second Concomitant Medication Taken by ≥ 5% of Subjects (1) – ITT Sample ATC Second Level Subgroup Agents acting on the Renin-Angiotensin System All other Therapeutic Products Analgesics Anesthetics Antibacterials for Systemic Use Antihistamines for Systemic Use Antihypertensives Anti-inflammatory and Anti-rheumatic Products Anti-thrombotic Agents Beta-Blocking Agents Blood Substitutes and Perfusion Solutions Calcium Channel Blockers Cardiac Therapy Combined Tedisamil N = 859 n (%) 546 (63. 6) 43 (5. 0) 120 (14. 0) 224 (26. 1) 61 (7. 1) < 5% 815 (94. 9) 637 (74. 2) 97 (11. 3) 197 (22. 9) 574 (66. 8) Placebo N = 438 n (%) 280 (63. 9) < 5% 52 (11. 9) 133 (30. 4) 37 (8. 4) < 5% 28 (6. 4) < 5% 412 (94. 1) 333 (76. 0) 68 (15. 5) 117 (26. 7) 312 (71. 2) 34

Baseline Characteristics History of AFib/AFl Males Females Tedisamil Placebo N = 476 N = Baseline Characteristics History of AFib/AFl Males Females Tedisamil Placebo N = 476 N = 211 N = 383 N = 227 Subjects with first episode, n (%) 237 (49. 8) 95 (45. 0) 175 (45. 7) 106 (46. 7) Subjects with recurrent episode, n (%) 239 (50. 2) 116 (55. 0) 208 (54. 3) 121 (53. 3) 190 (79. 5) 95 (81. 9) 178 (85. 6) 99 (81. 8) Atrial Flutter 19 (7. 9) 13 (11. 2) 10 (4. 8) 6 (5. 0) Both 30 (12. 6) 8 (6. 9) 20 (9. 6) 15 (12. 4) 5. 0 ± 5. 8 4. 5 ± 5. 4 3. 3 ± 3. 5 3. 3 ± 3. 4 Atrial Fibrillation Mean duration of AFib/AFl in yrs ± SD 35

Baseline Characteristics Predominant Rhythm Subjects, n (%) Males 0. 48 mg/kg Females Combined Placebo Baseline Characteristics Predominant Rhythm Subjects, n (%) Males 0. 48 mg/kg Females Combined Placebo Tedisamil 0. 32 mg/kg Combined Placebo Tedisamil AFib 174 (84. 1) 449 (85. 0) 191 (82. 7) 199 (88. 4) 351 (87. 1) 217 (90. 8) AFl 33 (15. 9) 79 (15. 0) 40 (17. 3) 26 (11. 6) 52 (12. 9) 22 (9. 2) 36

Baseline Characteristics History of AFib/AFl Males Females Tedisamil Placebo N = 476 N = Baseline Characteristics History of AFib/AFl Males Females Tedisamil Placebo N = 476 N = 211 N = 383 N = 227 Subjects with first episode, n (%) 237 (49. 8) 95 (45. 0) 175 (45. 7) 106 (46. 7) Subjects with recurrent episode, n (%) 239 (50. 2) 116 (55. 0) 208 (54. 3) 121 (53. 3) 5. 0 ± 5. 8 4. 5 ± 5. 4 3. 3 ± 3. 5 3. 3 ± 3. 4 Mean Duration of AFib/AFl in yrs ± SD* * for those with a recurrent episode 37

Primary Efficacy Parameter Conversion to NSR within 2. 5 hrs – By History of Primary Efficacy Parameter Conversion to NSR within 2. 5 hrs – By History of AFIB/AFL Male Female Dose, mg/kg 0. 16 First Recurrent episode n Converting, % 34 6 (17. 6) 24 6 (25. 0) First Recurrent episode n Converting, % 0 0 - 0. 24 0 - 63 7 (11. 1) 55 5 (9. 1) 0. 32 53 9 (17. 0) 69 19 (27. 5) 90 15 (16. 7) 112 22 (19. 6) 0. 48 99 29 (29. 3) 72 30 (41. 7) 2 1 (50. 0) 8 1 (12. 5) 0. 64 24 17 (70. 8) 25 15 (60. 0) 3 1 (33. 3) 8 2 (33. 3) 6 (7. 2) 94 5 (5. 3) 94 3 (3. 2) 107 6 (5. 6) Placebo 83 38

Primary Efficacy Parameter Conversion to NSR Within 2. 5 hrs – By Predominant Rhythm Primary Efficacy Parameter Conversion to NSR Within 2. 5 hrs – By Predominant Rhythm Male Female Dose, mg/kg 0. 16 AFib AFl n Converting, % 50 12 (24. 0) 8 0 AFib AFl n Converting, % 0 0 0. 24 0 - 106 10 (9. 4) 12 2 (16. 7) 0. 32 107 28 (26. 2) 15 0 179 36 (20. 1) 23 1 (4. 3) 0. 48 144 55 (38. 2) 27 4 (14. 8) 8 2 (25. 0) 2 0 0. 64 43 29 (67. 4) 6 3 (50. 0) 2 2 (33. 3) 3 1 (33. 3) Placebo 152 11 (7. 2) 25 0 180 6 (3. 3) 21 3 (14. 3) 39

Hemodynamics K. 219. 5005 Table 6: Effects of Tedisamil on Pulmonary and Cardiac Pressure Hemodynamics K. 219. 5005 Table 6: Effects of Tedisamil on Pulmonary and Cardiac Pressure Indices – differences post-drug and pre-drug Dosage group (mg/kg) 0. 1 Rest Max workload PAP (mm. Hg) -2. 1 -0. 6 PCWP (mm. Hg) -1. 4 -0. 9 PAEDP (mm. Hg) -2. 5 -3. 1 PRA PRV (mm. Hg) -0. 3 0. 0 0. 2 Rest Max workload -1. 6 +1. 0 -0. 9 -1. 4 -1. 3 +0. 5 -0. 3 -0. 4 0. 3 Rest Max workload +1. 8 +2. 6 +2. 3* +4. 8 +1. 6 +4. 3 +0. 9 0. 4 Rest Max workload +3. 3* -1. 8 +2. 8 -0. 1 +2. 6* -1. 0 +1. 5 Mean values * p<0. 05 ** p<0. 01 40

Hemodynamics K. 219. 5005 Study K. 219. 5005 Single, intravenous, rising dose, open study Hemodynamics K. 219. 5005 Study K. 219. 5005 Single, intravenous, rising dose, open study of tedisamil dihydrochloride (KC 8857) investigating hemodynamics in patients with documented ischemic heart disease. 41

Hemodynamics S 219. 3. 109 Secondary Parameter: Pulmonary Capillary Wedge Pressure (PCWP) at Rest Hemodynamics S 219. 3. 109 Secondary Parameter: Pulmonary Capillary Wedge Pressure (PCWP) at Rest Per-protocol patient sample (N = 56) Tedisamil Placebo p-value for Visit (N = 24) (N = 32) difference RAP Baseline 7. 4 ± 3. 7 7. 3 ± 3. 7 (mm. Hg) Visit 9 (Wk 12) 5. 2 ± 3. 4 5. 0 ± 5. 5 Change from baseline -2. 4 ± 3. 5 -2. 9 ± 4. 8 0. 784 ESRVP (mm. Hg) EDRVP (mm. Hg) Baseline Visit 9 (Wk 12) Change from baseline 39. 7 ± 12. 1 38. 4 ± 14. 2 -1. 3 ± 10. 3 42. 7 ± 15. 8 41. 2 ± 19. 2 -1. 1 ± 12. 3 0. 999 Baseline Visit 9 (Wk 12) Change from baseline 3. 6 ± 2. 5 3. 0 ± 2. 7 -0. 8 ± 2. 6 3. 7 ± 2. 6 3. 0 ± 4. 0 -0. 6 ± 3. 9 0. 849 RAP = right atrial pressure; ESRVP = endsystolic right ventricular pressure; EDRVP = enddiastolic right ventricular pressure. 42

Hemodynamics S 219. 3. 109 Primary Parameter: Pulmonary Capillary Wedge Pressure (PCWP) at Rest Hemodynamics S 219. 3. 109 Primary Parameter: Pulmonary Capillary Wedge Pressure (PCWP) at Rest Per-protocol patient sample (N = 56) Tedisamil PCWP at rest (N = 24) (mm. Hg) mean ± SD Baseline 18. 1 ± 5. 4 Visit 9 (wk 12) 16. 0 ± 6. 2 Visit 9 - baseline -2. 0 ± 5. 6 Placebo (N = 32) p-value for mean ± SD equivalence 19. 4 ± 6. 2 16. 2 ± 8. 8 -3. 2 ± 7. 5 0. 070 43

Hemodynamics S 219. 3. 109 Study S 219. 3. 109 Double-blind randomized study comparing Hemodynamics S 219. 3. 109 Study S 219. 3. 109 Double-blind randomized study comparing the hemodynamic effects of oral tedisamil and placebo in patients with symptomatic congestive heart failure 44

In Normal Sinus Rhythm at 24 hrs NSR at 24 hrs – no DC In Normal Sinus Rhythm at 24 hrs NSR at 24 hrs – no DC – DC NSR at 24 hrs Males 0. 48 mg/kg Tedisamil Placebo 88/172 84/177 (51%) (47%) 61/133 36/122 (46%) (30%) 27/39 (69%) 48/55 (87%) Females 0. 32 mg/kg Tedisamil 80/202 (40%) Placebo 69/202 (34%) 45

Conversion to NSR – Male AFib/AFl Duration tedisamil 0. 48 mg/kg 3 – 48 Conversion to NSR – Male AFib/AFl Duration tedisamil 0. 48 mg/kg 3 – 48 hrs 52. 4% 48 hrs – 7 days 8 – 45 days 28. 6% 13. 1% Placebo 12. 4% 0 0 Change 40. 0% 28. 6% 13. 1% 46

Conversion to NSR – Female AFib/AFl Duration tedisamil 0. 32 mg/kg Placebo Change 3 Conversion to NSR – Female AFib/AFl Duration tedisamil 0. 32 mg/kg Placebo Change 3 – 48 hrs 32. 4% 48 hrs – 7 days 8 – 45 days 16. 3 8. 0% 10. 0% 0% 3. 3% 22. 4% 16. 3% 4. 7% 47