1. CR-1 EXPRESS Results Sibel Tekin, MD Clinical Program Leader Neuroscience Clinical Development and Medical Affairs Novartis Pharmaceuticals Corporation

2. CR-2 Overview  Patient disposition and baseline characteristics  Efficacy results for the double-blind core study  Safety findings for the core and extension studies

3. CR-3 177 (83.9%) completed 96 (78.0%) completed 211 to Exe-Exelon123 to Plc-Exelon Patient Disposition Core and Extension Studies Extension study 334 out of 410 entered O-L study CSR Core T 7-1; Extension 263 (72.7%) completed 147 (82.1%) completed 99 (27.3%) discontinued 32 (17.9%) discontinued 362 Exelon179 placebo Core study 541 randomized to core study 650 screened

4. CR-4 Reasons for Discontinuation Core Study Exelon N = 362 n (%) Placebo N = 179 n (%) Total discontinued99 (27.3)32 (17.9) Adverse event62 (17.1)14 (7.8) Withdrew consent21 (5.8)2 (1.1) Protocol violations5 (1.4)2 (1.1) Lost to follow-up4 (1.1)1 (0.6) Death4 (1.1)7 (3.9) Unsatisfactory therapeutic results2 (0.6)4 (2.2) Abnormal test procedure result1 (0.3)0 Administrative problems02 (1.1) SCE T3-5.

5. CR-5 Baseline Characteristics Core Study Exelon N = 362 Placebo N = 179 Age, yr Mean ± SD72.8 ± 6.772.4 ± 6.4 Gender, n (%) Male234 (64.6)117 (65.4) Female128 (35.4) 62 (34.6) Race, n (%) Caucasian360 (99.4)179 (100) Other 2 (0.6)0 CSR Core Table 7-4, PTT7.4-1

6. CR-6 Timing of Imaging (MRI or CT Scans) Core Study—All Randomized Patients N = 541 n (%) Between screening and baseline visits179 (33.1) ≤ 6 months prior to screening278 (51.4) > 6 months to ≤ 1 year prior to screening15 (2.8) > 1 year prior to screening 6 (1.1) After baseline visit18 (3.3) Missing report, unable to retrieve, charts off site (Confirmed imaging was performed)20 (3.7) Total response received to date (5/16/06)516 (95.4) No response received to date25 (4.6) Source data verification is ongoing. 40-6

7. CR-7 Baseline Characteristics Core Study Mean ± SD Exelon N = 362 Placebo N = 179 Time since idiopathic PD was first diagnosed by physician, years 8.7 ± 5.79.4 ± 5.9 Hoehn & Yahr staging, mean ± SD2.8 ± 0.92.8 ± 0.8 UPDRS part III (‘on’ state), mean ± SD32.9 ± 14.232.5 ± 13.0 MMSE score at baseline19.4 ± 3.819.2 ± 4.1 Time between diagnosis of PD and first symptom of dementia, years 6.6 ± 5.27.2 ± 5.2 CSR Core T 7-5, PTT7.4-2

8. CR-8 Baseline Cognitive and Functional Assessment of EXPRESS Study Population Core Study—ITT-RDO Population ExelonPlacebo NMean ± SDN Cognition: ADAS-cog—total 32923.8 ± 10.216124.3 ± 10.5 Executive function: D-KEFS letter fluency † 33514.1 ± 9.516615.1 ± 9.9 Functional activity: ADCS-ADL 33341.6 ± 18.616541.2 ± 17.7 15-12 DV † Total correct responses/min. CSR 2311 PTTs 9.1-1, 9.2-1, 9.2-7, 9.2-30, 9.2-34, 9.2-9, 9.2-13

9. CR-9 Baseline Neuropsychiatric Symptoms Core Study—ITT+RDO Population NPI-10 sub-item Exelon N = 335 % Placebo N = 166 % Apathy/Indifference53.954.2 Depression/Dysphoria53.962.1 Anxiety47.350.6 Hallucinations41.047.0 Agitation/Aggression32.331.3 Irritability/Lability30.228.9 Delusions24.324.7 Aberrant motor behavior21.921.1 Disinhibition10.215.7 Euphoria/Elation3.34.2 Post-text table 9.2-24

10. CR-10 Dopaminergic Agents Before Start of Study Drug Core Study Dopaminergic agents Exelon N = 362 Placebo N = 179 Total, n (%)362 (100)178 (99.4) Adamantane derivatives38 (10.5)17 (9.5) Dopa and dopa derivatives † 347 (95.9)169 (94.4) Dopamine agonists165 (45.6)83 (46.4) Monoamine oxidase B inhibitors19 (5.2)11 (6.1) Other dopaminergic agents70 (19.3)55 (30.7) Dopa and dopa derivatives dose (mg/day), mean ± SD663.4 ± 368.0705.7 ± 349.9 CSR Core T 8-3, PTT8.2-2, 8.2-4 † Includes Levodopa, Levodopa with benserazide, and Carbidopa

11. CR-11 Efficacy Double-Blind Core Study

12. CR-12 Primary Outcomes  Two primary outcome measures – Cognition: ADAS-cog – Global dementia assessment: ADCS-CGIC  Primary endpoint – Wk 24 – ITT+RDO population

13. CR-13 † Least squares means ± SE (adjusted for baseline and country). P-value based on ANCOVA using treatment and country as factors and baseline ADAS-cog as a covariate. ADAS-cog Least Squares (LS) Mean Change from Baseline Core Study—ITT+RDO Analysis 15-14 DV Improvement p = 0.002 p < 0.001 16

14. CR-14 ADCS-CGIC—Categorical Analysis at Wk 24 Core Study—ITT+RDO Analysis CSR 2311 T 9-3, PTT9.1-8, 9.1-9, 9.1-10 p = 0.007 † † p-value based on van Elteren test blocking for country.

15. CR-15 ADAS-cog—Change from Baseline at Wk 24 Core Study ExelonPlacebo LS means difference nMean ± SDn 95% CI p value ITT+RDO Baseline32923.8 ± 10.216124.3 ± 10.5 Change at Wk 243292.1 ± 8.2161–0.7 ± 7.52.881.44, 4.31< 0.001 ITT-LOCF Baseline28724.0 ± 10.315424.5 ± 10.6 Change at Wk 242872.5 ± 8.4154–0.8 ± 7.53.542.05, 5.04< 0.001 OC Baseline25623.7 ± 10.413923.4 ± 9.8 Change at Wk 242562.9 ± 8.3139–1.0 ± 7.63.802.22, 5.37< 0.001 CSR Core T 9-1 Results were also statistically significant at Wk 16 in favor of Exelon

16. CR-16 ADCS-CGIC—Categorical Analysis at Wk 24 Core Study ITT+RDOITT-LOCFOC Exelon N = 329 Placebo N = 165 Exelon N = 289 Placebo N = 158 Exelon N = 252 Placebo N = 145 Mean ± SD at Wk 243.8±1.44.3 ± 1.53.7 ± 1.44.3 ± 1.53.7 ± 1.44.2 ± 1.5 Treatment difference0.50.60.5 Change, % Markedly improved (1) 4 2 5 2 6 2 Moderately improved (2)161216121812 Minimally improved (3)211523162315 Unchanged (4)262825282529 Minimally worse (5)21192019 Moderately worse (6)1116 917 8 Markedly worse (7) 2 7 2 6 2 6 p value 0.007< 0.001 Source: [Report 2311-Table 9-3 ] Results were also statistically significant at Wk 16 in favor of Exelon.

17. CR-17 Secondary Outcomes  Functioning – Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)  Behavior – Neuropsychiatric Inventory (NPI-10 and NPI-D for caregiver distress)  Attention – Cognitive Drug Research (CDR) computerized attention battery  Executive function – Delis-Kaplan Executive Function System (D-KEFS), letter fluency test

18. CR-18 ADCS-ADL—LS Mean Change from Baseline at Wk 24 Core Study—ITT+RDO Analysis p = 0.023 Deterioration 15-16 DV CSR 2311 T9-5 PTT 9.2-4 1624 Time, wk

19. CR-19 NPI-10—LS Mean Change from Baseline at Wk 24 Core Study—ITT+RDO Analysis 15-17 DV CSR 2311 T9-6PTT 9.2-22, STDERR_ANCOVA from Jay Hsu p = 0.015 Improvement 1624 Time, wk

20. CR-20 CDR Power of Attention—LS Mean Change from Baseline at Wk 24 Core Study—ITT+RDO Analysis Power of attention score = Simple reaction time + digit vigilance + choice reaction time. p = 0.009 15-18 DV CSR 2311 T9-7 PTT9.2-10 Improvement 1624 Time, wk

21. CR-21 Improvement D-KEFS Letter Fluency—Mean Change from Baseline at Wk 24 Core Study—ITT+RDO Analysis P-value based on van Elteren test blocking for country. p < 0.001 15-21 DV CSR 2311 T9-8 PTT 9.2-30 Exelon (N= 335) Placebo (N = 166)

22. CR-22 Additional Analyses Core Study Age, Gender, and Baseline Characteristics

23. CR-23 Patients, n ExelonPlacebo Age < 65 yr 4617 Age ≥ 65 yr 283144 Male 213104 Female 11657 Moderate dementia* 8744 Mild dementia** 237115 Visual hallucination 10760 No visual hallucination 220101 Tremor 228105 No tremor 10156 ADAS-cog—Treatment Difference (95% CI) at Wk 24 by Baseline Subgroups Core Study—ITT+RDO Population Favor ExelonFavor placebo –50510 *Mild dementia: MMSE 18 - 24 **Moderate dementia: MMSE 10 - 17

24. CR-24 p = 0.002 p = 0.015 4.3 † 2.1 † WithWithout ExelonPlacebo n = 10760220101 Patients With and Without Visual Hallucinations at Baseline—ADAS-cog at Wk 24 Core Study—ITT+RDO Population 4-11 † Least squares means adjusted for baseline and country. Visual hallucinations Improvement PTT 9.1-1c 2311 PTT 9.1-4c

25. CR-25 Patients With and Without Visual Hallucinations at Baseline—NPI-10 at Wk 24 Core Study—ITT+RDO Population 4-11 Visual hallucinations Improvement PTT 9.1-1c 2311 PTT 9.1-4c With 4.2 † ExelonPlacebo n = 11064223102 0.4 † Without p = 0.013 p = 0.713 † Least squares means adjusted for baseline and country.

26. CR-26 Antipsychotic Use Core Study Core study Patients with visual hallucinations at baseline Antipsychotic use Exelon N = 362 n (%) Placebo N = 179 n (%) Exelon N = 118 n (%) Placebo N = 70 n (%) At baseline102 (28.2)48 (26.8)52 (44.1)26 (37.1) Increased dose 9 (2.5)7 (3.9)4 (3.4)5 (7.1) Decreased dose 5 (1.4)3 (1.7)1 (0.8)2 (2.9) Newly introduced28 (7.7)20 (11.2)14 (11.9)14 (20.0) 9-25 DV Final appeal dossier Nov 30 2005 Table 2-14 Discontinuation of use of antipsychotic medication is included in decreased dose group.

27. CR-27 Efficacy Summary  Both primary outcome measures assessing cognition and overall dementia – Statistically significant results in favor of Exelon Across analysis populations At both Wk 16 and 24  Secondary outcome measures assessing activities of daily living, executive function, attention, and behavior – Statistically significant at Wk 24

28. CR-28 Safety Double-Blind Core and Open-Label Extension Studies

29. CR-29 Last Dose of Study Medication Core Study—Safety Population Dose at endpoint, mg/day Exelon N = 362 n (%) Placebo N = 179 n (%) < 3 2 (0.6)0 3 - < 6 83 (22.9) 16 (8.9) 6 - < 9 76 (21.0) 18 (10.1) 9 - 12201 (55.5) 145 (81.0) PHAT 2-105

30. CR-30 Percentage of Patients With Adverse Events (AEs) ≥ 5% in Any Group Core and Extension Studies Core Exelon N = 362 n (%) Placebo N = 179 n (%) Total patients with AE(s)303 (83.7)127 (70.9) AE preferred term Nausea105 (29.0)20 (11.2) Vomiting60 (16.6)3 (1.7) Tremor37 (10.2)7 (3.9) Diarrhea26 (7.2)8 (4.5) Anorexia22 (6.1)5 (2.8) Fall21 (5.8)11 (6.1) Dizziness21 (5.8)2 (1.1) Hypotension19 (5.2)14 (7.8) Hallucination17 (4.7)17 (9.5) Constipation17 (4.7)12 (6.7) Confusional state13 (3.6)10 (5.6) Orthostatic hypotension6 (1.7)9 (5.0) CSC T 4-2, Core PTT10.1-4; Extension PTT 10.1-4 Extension Exe-Exelon N = 211 n (%) Plc-Exelon N = 123 n (%) 159 (75.4)93 (75.6) 29 (13.7)33 (26.8) 17 (8.1)20 (16.3) 8 (3.8)15 (12.2) 4 (1.9)4 (3.3) 6 (2.8)6 (4.9) 7 (3.3)9 (7.3) 5 (2.4)3 (2.4) 8 (3.8)5 (4.1) 9 (4.3)7 (5.7) 4 (1.9)2 (1.6) 10 (4.7)7 (5.7) 5 (2.4)4 (3.3)

31. CR-31 Percentage of Patients With Serious Adverse Events (SAEs) ≥ 1% in Any Group Core and Extension Studies CSC T 4-10 Core Preferred term Exelon N = 362 n (%) Placebo N = 179 n (%) Deaths4 (1.1)7 (3.9) Total patients with SAE(s)47 (13.0)26 (14.5) Vomiting1 (0.3)0 Dehydration5 (1.4)2 (1.1) Confusional state2 (0.6)2 (1.1) Somnolence00 Syncope02 (1.1) Pneumonia3 (0.8)1 (0.6) Urinary tract infection1 (0.3)1 (0.6) Asthenia00 Extension Exe-Exelon N = 211 n (%) Plc-Exelon N = 123 n (%) 5 (2.4)2 (1.7) 37 (17.5)20 (16.3) 1 (0.5)2 (1.6) 3 (1.4)0 0 02 (1.6) 1 (0.5)1 (0.8) 2 (0.9)5 (4.1) 2 (0.9)2 (1.6) 0

32. CR-32 Most Frequent Discontinuations Due to AEs (≥ 1% in Any Group) Core and Extension Studies Core Exelon N = 362 n (%) Placebo N = 179 n (%) Total patients with AE(s)303 (83.7)127 (70.9) All AE discontinuations66 (18.2)20 (11.2) Nausea13 (3.6)1 (0.6) Vomiting7 (1.9)1 (0.6) Tremor6 (1.7)0 Diarrhea4 (1.1)2 (1.1) Hallucination4 (1.1)2 (1.1) Anorexia1 (0.3)2 (1.1) CSC T 4-11, PTT10-2-1 (Core), 10.2-1 (Extension) Extension Exe-Exelon N = 211 n (%) Plc-Exelon N = 123 n (%) 159 (75.4)93 (75.6) 21 (10.0)17 (13.8) 1 (0.5)5 (4.1) 03 (2.4) 1 (0.5)2 (1.6) 00 1 (0.5)2 (1.6) 01 (0.8) 3 Exelon-treated and 2 placebo-treated patients in the core study and 2 patients in the Plc-Exelon group had multiple above-mentioned AEs leading to discontinuation.

33. CR-33 AEs Potentially Associated With Nonmotor Symptoms of PD Core and Extension Studies Core Exelon N = 362 n (%) Placebo N = 179 n (%) Cardiac AEs16 (4.4)12 (6.7) Bradycardia5 (1.4)1 (0.6) Vascular AEs30 (8.3)31 (17.3) Hypotension19 (5.2)14 (7.8) Orthostatic hypotension 6 (1.7)9 (5.0) Psychiatric AEs86 (23.8)41 (22.9) Hallucinations17 (4.7)17 (9.5) Other Constipation17 (4.7)12 (6.7) Syncope2 (0.6)6 (3.4) CSR 2311 T10-1, PTT10-1.1; 2311e1 T10-1, PTT 10.1-1 Extension Exe-Exelon N = 211 n (%) Plc-Exelon N = 123 n (%) 10 (4.7)2 (1.6) 2 (0.9)0 19 (9.0)16 (13.0) 8 (3.8)5 (4.1) 5 (2.4)4 (3.3) 51 (24.2)23 (18.7) 9 (4.3)7 (5.7) 4 (1.9)2 (1.6) 4 (1.9)3 (2.4)

34. CR-34 Predefined Group of Motor Symptom AEs— ‘Potentially Associated With PD’  Akinesia  Balance disorder  Bradykinesia  Drooling  Dysarthria  Dyskinesia  Dsytonia  Fall  Freezing phenomenon  Gait abnormality  Hypertonia  Hypokinesia  Motor dysfunction  Movement disorder  Muscle rigidity  Musculoskeletal stiffness  On and off phenomenon  Parkinson’s disease worsening  Parkinsonism worsening  Rigors  Salivary hypersecretion  Tremor

35. CR-35 Cardinal Extrapyramidal Motor Symptom AEs Core and Extension Studies Core Exelon N = 362 n (%) Placebo N = 179 n (%) Any predefined AE(s) ‘potentially associated with PD’ 99 (27.3)28 (15.6) Tremor37 (10.2)7 (3.9) Bradykinesia9 (2.5)3 (1.7) Rigidity1 (0.3)0 SCS T8-2, PTT10.2-3, 10.1-1 (Core), PTT10.2-3, (Extension) PTT10.2-3 (SCS); Post hoc 2-26 (Extension PTL App. 7.1 1-18) 3-23DV Extension Exe-Exelon N = 211 n (%) Plc-Exelon N = 123 n (%) 28 (13.3)32 (26.0) 8 (3.8)15 (12.2) 1 (0.5)0 01 (0.8) Editor: keep apostrophe around ‘potentially...

36. CR-36 Consequences of AEs of Tremor and ‘Potentially Associated With PD’ Core Study Tremor All AEs ‘Potentially Associated with PD’ Exelon N = 362 n (%) Placebo N = 179 n (%) Exelon N = 362 n (%) Placebo N = 179 n (%) Total events, n40713242 No. of patients with events 37 (10.2)7 (3.9)99 (27.3)28 (15.6) Severity † Mild18 (5.0)5 (2.8)45 (12.4)17 (9.5) Moderate18 (5.0)2 (1.1)46 (12.7)8 (4.5) Severe1 (0.3)08 (2.2)3 (1.7) Serious AEs003 (0.8)1 (0.6) Resulted in DC6 (1.7)017 (4.7)2 (1.1) Con. meds. added ‡ 4 (10.8)019 (19.2)4 (14.3) Resolved ‡ 19 (51.4)3 (42.9)58 (58.6)17 (60.7) † For patients with more than 1 event, the most severe event was used. ‡ Percentages based on number of patients with events. 99-9 DV Final appeal dossier Nov 30 2005 T 2-7

37. CR-37 UPDRS Part III Change From Baseline at Wk 24 (Core) and Wk 48 (Extension) UPDRS part III scoreMean ± SD Core study Exelon N = 263 Placebo N = 146 Change from baseline † –0.3 ± 9.5–0.4 ± 8.5 Extension study Exe-Exelon N = 171 Plc-Exelon N = 96 Change from baseline † 1.1 ± 9.71.7 ± 12.1 9-13 DV Final appeal dossier Nov 30 2005 T 2-9 †Calculated only for patients who had Wk 24 and Wk 48 evaluations from baseline at Wk 0. Negative change from baseline indicates improvement.

38. CR-38 Safety Conclusion Core and Extension Studies  Most frequent AEs in Exelon group were nausea, vomiting, and tremor – Majority were mild to moderate events with infrequent discontinuation  SAEs and deaths were consistent with events expected in the elderly population – Fewer events in the Exelon group  No increased cardiovascular or psychiatric events in the Exelon group

39. CR-39 Safety Conclusion Core and Extension Studies  Tremor was slightly higher in the Exelon group and was the main driver of AEs ‘potentially associated with PD’ – Majority were mild to moderate events with infrequent discontinuation – Underlying PD did not worsen based on UPDRS part III total scores  Long-term (1 yr) treatment in PDD was not associated with any new safety concerns