ADI Disease International 7-10 March, 2012 Clinical and Biomarker Characteristics of Responders to ELND005 (Scyllo-inositol): Data from a Phase 2 Study in Mild to Moderate Alzheimer’s Disease R. Jones MB FRCP1; A. Porsteinsson2 MD; G. Crans3 PhD; C. Hernandez3 PhD; and S. Abushakra3 MD   1The RICE Centre, Royal United Hospital, Bath UK; 2University of Rochester Medical Center, Rochester NY; 3Elan Pharmaceuticals, S. San Francisco CA

Disclosures Dr. Jones RICE (The Research Institute for the Care of Older People), Royal United Hospital, Bath UK Serves on scientific advisory boards of major Pharmaceutical companies including Elan Pharmaceuticals. He has also received lecture fees and his Institute has received research support grants from various Pharmaceutical/Biotech companies and foundations including Elan. Dr. Porsteinsson University of Rochester Medical Center Serves on scientific advisory boards of major Pharmaceutical companies including Elan Pharmaceuticals. He also receives research support grants from various Pharmaceutical/Biotech companies and foundations including Elan.   Dr. Abushakra, Dr. Hernandez, and Dr. Crans Elan Pharmaceuticals Inc. Employees of Elan Pharmaceuticals and hold stock and stock options in Elan Pharmaceuticals.

Legal Disclaimer The referenced activities and their execution are intended to be non-promotional and scientific in nature. Any promotional activities conducted by Elan are within product label and are for FDA approved uses only.

Objectives Objectives are to evaluate: Proportion of responders to ELND005 versus placebo Compare characteristics of responders and non responders on baseline values of: Clinical outcomes CSF biomarkers Imaging: v-MRI measures 1Study AD201 Safety and efficacy results have been published (Salloway et al. Neurology. 2011 Sep 27;77(13):1253-62)

Background ELND005 (Scyllo-inositol) is being developed as a potential disease-modifying agent: In vitro it has shown amyloid anti-aggregation and synaptic protective effects1,2 In vivo it reduced amyloid burden and improved learning deficits in Tg CRND8 mice3 Main Phase 2 results4: The 2 highest dose arms (1000mg bid and 2000mg bid) were discontinued due to safety findings, efficacy analyses compared placebo and 250mg bid arms In Mild/Moderate (M/M) group: drug effects on co-primary NTB, ADCS-ADL were NS In pre-specified Mild AD group, NTB drug effect was significant in study completers (per protocol population, p= 0.007) 1Mc Laurin et al. J Biol Chem. 2000 Jun 16;275(24):18495-502; 2Townsend et al. Ann Neurol 2006 Dec27; 668-676; 3Mc Laurin et al. Nature Med, 2006 Jul;12(7):801-8; 4Salloway et al. Neurology. 2011 Sep 27;77(13):1253-62

Methods Data was from Study AD2011 in M/M AD (MMSE 16-26) 353 patients randomized to placebo or 1 of 3 ELND005 arms m-ITT: N= 341; Placebo=83, 250mg=88, 1000mg=89, 2000mg = 91 No p-value adjustments for multiplicity testing Protocol-specified analysis: Proportion of responders defined by NTB or ADCS- ADL ≥ 0 Post hoc analyses of clinical responders: Defined as NTB change from baseline (CBL) ≥ 0 at week 78; Mild defined as MMSE 22-26 Baseline parameters of responders and non-responders from pooled 3 dose groups were compared using t-tests 1Salloway et al. Neurology. 2011 Sep 27;77(13):1253-62

NTB or ADCS-ADL Responders (Overall) m-ITT PPS p=0.54 p=0.39 Mild/Moderate AD Protocol-specified; p-values not adjusted for multiplicity Elan data on file

NTB or ADCS-ADL Responders (Mild Subgroup) m-ITT PPS p=0.04 p=0.01 Mild AD Protocol-specified; p-values not adjusted for multiplicity Elan data on file

Baseline Cognitive Scores by Responder Status (m-ITT Population) ADAS-Cog p < 0.001 N = 38 N = 105 17.6 22.7 MMSE p < 0.001 N = 39 N = 109 23.3 20.6 0.30 Mean Baseline ADAS-Cog Responders Non-responders p-values not adjusted for multiplicity Elan data on file

Baseline Global/Functional Scores by Responder Status (m-ITT Population) CDR-SB ADCS-ADL p = 0.030 p = 0.001 66.9 63.2 5.1 3.8 N = 39 N = 109 N = 39 N = 109 Responders Non-responders p-values not adjusted for multiplicity Elan data on file

Baseline CSF Biomarker Levels by Responder Status (m-ITT Population) CSF Tau Levels (pg/mL) CSF p-Tau Levels (pg/mL) p = 0.001 p = 0.001 783.17 118.32 420.29 69.38 N = 8 N = 30 N = 8 N = 30 Differences in baseline Aβ42 and Aβ40 Levels between responders and non-responders were not significant Responders Non-responders p-values not adjusted for multiplicity Elan data on file

Baseline v-MRI Characteristics by Responder Status m-ITT Population Brain Volume (cc) NS Ventricular Volume (cc) NS p = 0.099 1360264 1362904 56.98 66.39 N = 39 N = 108 N = 39 N = 108 Right Hippocampus Volume (cc) Left Hippocampus Volume (cc) NS 3.09 2.97 3.14 3.06 N = 39 N = 108 N = 39 N = 108 Responders Non-responders p-values not adjusted for multiplicity Elan data on file

Changes from Baseline (CBL) in v-MRI Measures by Responder Status at wk 78 (m-ITT Population) %CBL Brain Volume p = 0.001 %CBL Ventricular Volume -2.30 -3.73 21.37 N = 29 14.66 N = 77 N = 29 N = 80 Responders Non-responders p-values not adjusted for multiplicity Elan data on file

Conclusions Clinical Responders to ELND005 are those with baseline characteristics of Mild AD based on: Clinical scores: MMSE, ADAS-Cog, ADCS-ADL, CDR-SB CSF tau and p tau levels Clinical Responders, compared to non-responders had: Significantly less brain atrophy and ventricular enlargement over 78 weeks Study limitation: Some of the analyses presented were based on post hoc analysis with small sample sizes; therefore, it is difficult to draw conclusions based solely on statistical significance. These analyses further support the notion that Mild AD may be an appropriate population for future studies with this potentially disease modifying agent.

Acknowledgements We acknowledge and thank the 58 investigators, their coordinators/staff, the patients and their caregivers/families for participation in Study AD201