Preliminary Assessment of the Clinical Effects ofLecanemab Following 18 Months of Treatmentin the Open Label Extension of the Phase 2 Proofof Concept Study, BAN2401-G000-201, in
Subjects With Early Alzheimer’s Disease
Chad J Swanson, PhD 1, Shobha Dhadda, PhD1, Michael C. Irizarry, MD, MPH 1, Michio Kanekiyo,
MS1, David JianJun Li, PhD 1, June Kaplow, PhD1, Robert Gordon, PhD 2, Helena Heanue-Travers2,
Mark Hodgkinson2, and Lynn D Kramer, MD, FAAN 1
1. Eisai Inc., Woodcliff Lake, NJ, USA
2. Eisai Ltd., Hatfield, United Kingdom

Presenter Disclosure• Dr. Swanson is an employee of Eisai Inc.

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Presentation Overview
Today’s presentation will focus on the following points:• Identification of individuals that show a faster pattern of progressionthat are beyond Early Alzheimer’s disease (AD) at OLE baseline• Treatment with lecanemab appears to change the trajectory of thedisease in those subjects who are Early AD at OLE baseline• Data on clinical outcomes and biomarkers supports need forcontinuous treatment2

Lecanemab (BAN2401) Phase 2b Trial Design
A global, placebo-controlled, double-blind, parallel-group, randomized trial with open-label extension
Randomization phase†• Subject eligibility criteria for Core study included
CDR global 0.5 (MCI) and 0.5-1.0 (mild AD)

Subjects with Early
Alzheimer’s disease:
MCI due to AD or mild
Alzheimer's dementia

Lecanemab (IV infusion)
2.5 mg/kg biweekly
5 mg/kg monthly
5 mg/kg biweekly
10 mg/kg monthly
10 mg/kg biweekly

Placebo biweekly(IV infusion)

Select Key Secondary Endpoints (MMRM):
Amyloid PET at 18 months
ADCOMS at 18 months
CDR-SB and 18 months
ADAS-cog at 18 months
Fluid biomarkers at 18 months

3(OLE)

GapPeriod(no treatment)

Randomization

Primary Endpoint (Bayesian):
ADCOMS at 12 months

Extension phase
10 mg/kg
biweekly(IV infusion)(average 24 months) (up to 60 months)*
9-59 months(18 months)
N = 856

AD=Alzheimer’s disease; IV= intravenous; MCI=mild cognitive impairment; OLE=open label extension.
*Any subject who completed study treatment (Visit 42 [Week 79] of the Core Study) and fulfilled the Extension Phase eligibility criteria had the option to participate in the Extension Phase. Subjects who previously completed the Core Study (through theFollow-Up Visit, Visit 43) at any time before implementation of the Extension Phase and/or fulfilled the Extension Phase eligibility criteria were eligible to participate. Any subject who had discontinued the Core Study but fulfilled the Extension Phase
eligibility criteria were eligible to participate in the Extension Phase. All subjects not continuing into the Extension Phase had a Follow-Up Visit 3 months after the last dose of study drug in the Randomization Phase.
Eisai Inc. Data on file. 2019. †Randomization assignment was determined by Bayesian Adaptive Design methodology.

Analysis Population Core Study through OLE on
Clinical Endpoints
N=856
Randomized in Core

N=531

GAP

Completed 18 M
in CoreAverage 24M( 9 to 59 M)

N=180
Enrolled in OLE

N=100
18 M OLE
CompletersCore
10 mg/kg
Biweekly

CorePlacebo

Core
Lower Doses

Core
10 mg/kg
Monthly

Core randomized subjects

247(176, 71)

195
(162, 33)

253
(225, 28)

161
(49, 112)

Core 18m completers

161(115, 46)

137
(113, 24)

149
(131, 18)

84
(10, 74)

Core 3m follow-up completers

156(114, 42)

124
(103, 21)139(122, 17)79(9, 70)

OLE enrolled subjects

45(31, 14)37(35, 2)

60(56, 4)38(3, 35)

OLE enrolled subjects
excluding those who progressed beyond Early AD**40(27, 13)

31(29, 2)

48(46, 2)31(3, 28)

OLE 18M completers*

22(15, 7)

23(23, 0)34(32, 2)

21(1, 20)

OLE 18M completers*
excluding those who progressed beyond Early AD**20(14, 6)21(21, 0)32(30, 2)

20(1, 19)

Number of ApoE4 carriers / non-carriers are also shown with parentheses* OLE 18 M completers are subjects who have CDR-SB at Core 18M, OLE Baseline, and OLE 18M** Subjects excluded because of progression beyond early AD are defined as the subjects with global CDR score>1 at OLE baseline and would have been excluded from entry into the Core study
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N=93
18 M OLE Completers
excluding CDR>1

Individuals Beyond the Early AD Stage at OLE Baseline
Showed a Faster Pattern of Progression• Patient eligibility criteria for Core study included CDR global range of 0.5 (MCI) & 0.5-1.0 (mild AD) (purple line pooled)• Subjects excluded due to progression beyond Early AD with CDR global score of >1 at OLE baseline (red line pooled) also benefitted during Core study from treatment(comparison to placebo not shown) but their worsening accelerated during Gap period on all Clinical Endpoints and no longer m et entry criteria

Figures: Adjusted mean change in clinical endpoints by severity during Core, 3-month Follow-Up & Gap*

ADCOMS**

5CDR-SB**

ADAS-Cog**••ApoE4 carrier status, visit, OLE baseline score of CDR global score and MMSE are significant covariates of disease progressio n in OLE period
MMRM model includes global CDR group (>1 or ≤1), analysis visit, global CDR group by analysis visit interaction, randomizatio n stratification variables (ApoE4 status, clinical subgroup, concurrent AD med use), region as fixed effect andbaseline as covariate•

All treatment arms are combined in these figures; Analysis population: OLE enrolled subjects*Numbers may vary due to missing assessments at certain time points. **Low doses included.

Treatment Difference in Early AD Subjects Persists afterDiscontinuing Dosing In GAP Period• Treatment effect from Core retained dose-dependently although all groups decline in Gap period• These data are consistent with disease-modifying effectFigures: Adjusted mean change in clinical endpoints by Core treatment group during Core, 3-month Follow-Up & Gap

Change in ADCOMS

Change in CDR-SB

Change in ADAS-Cog

••
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•

Data presented on Change in Clinical endpoints (CDR-SB, ADCOMS, ADAS-Cog) from Core baseline thru OLE baseline for those who participated in OLE
MMRM model includes Core treatment group, analysis visit, Core treatment group by analysis visit interaction, randomization stratification variables (ApoE4 status, clinical subgroup, concurrent AD med use), region as fixed effect andbaseline as covariate
Analysis population: OLE enrolled subjects excluding subjects who progressed beyond Early AD

Plasma Aβ42/40 Ratio Demonstrates Relationship toTreatment and Supports the Need for Continuous Treatment• [Core] Plasma Aβ42/40 ratio increases during Core Study in lecanemab treatment arms (in a dose dependent manner) but not in placebo• [Gap] Plasma Aβ42/40 ratio decrease in all three groups during Gap period• [OLE] Plasma Aβ42/40 ratio increases in all three groups with 10 mg/kg biweekly lecanemab treatment during OLE• Aβ42/40 ratio correlates with PET SUVR and clinical outcomes during lecanemab treatment phases in Core & OLE while losing correlation in untreated Gap period
Details presented in Swanson et al. 2021 AAIC Annual Meeting. July 26-30: Denver, USA [Poster #57760]

Observed Mean Change in Aβ42/40 Ratio by Core Treatment Group during Core, Gap & OLE

r* = -0.939 (P=0.0056)

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r*=-0.042 (P=0.9730)

r*=-0.900 (P=0.0007)

Analysis population: All subjects with plasma Aβ42/40 ratio at Core baseline and at least one postbaseline visit* r is population Pearson correlation coefficient between lecanemab effect on plasma Aβ42/40 ratio and lecanemab effect on PET SUVR

OLE Treatment Response in Treatment Naïve and Previously TreatedSubjects Supports Need for Continuous Treatment While Still in theEarly AD Stage on ADCOMS••••[Core] Placebo decline is similar to ADNI and all treatment arms show slowed disease progression[OLE] Newly treated core placebo subject decline is similar to ADNI initially, and plateaus, supporting clinical results of core study[OLE] Newly treated and re-treated arms have slower rate of progression as compared to ADNI
Given lecanemab’s mechanism of action for both plaque clearance and protofibril clearance, these findings suggest clinical benefit of continuous treatment even after
plaque clearance while subjects are still in the Early AD stage

CORE

Adjusted mean change in ADCOMS by Core treatment group during Core & 3-month Follow-Up8•••OLE

Adjusted mean change in ADCOMS by Core treatment group during OLE

Analy sis population: For Core: All randomized subjects with baseline and at least one post-baseline assessment. For OLE: OLE enrolled subjects excluding subjects who progressed beyond early AD. For ADNI: All subjects approximate lecanemab study eligibility
MMRM model f or Core includes Core treatment group, analysis visit, Core treatment group by analysis visit interaction, randomization stratification variables (ApoE4 status, clinical subgroup, concurrent AD med use), region as fixed effect and baseline as covariate
MMRM model f or OLE includes Core treatment group, analysis visit, Core treatment group by analysis visit interaction and ApoE4 status as fixed effect and gap duration and baseline as covariate

Similar Results Seen for CDR-SB & ADAS-Cog
CDR-SB

CORE

OLE

ADAS-Cog

CORE

OLE

Same analysis
population andmodels as
ADCOMS in theprevious slide.

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Summary of Interim Results on Clinical Endpoints fromLecanemab Study 201 OLE 18-month Completers• Early AD inclusion criteria in Core study includes CDR global score ≤ 1 (0.5 forMCI & 0.5-1.0 for mild AD). OLE baseline identified individuals beyond the EarlyAD stage that showed a faster pattern of progression• Treatment difference in Early AD subjects persists after discontinued dosing
over the Gap period• Plasma Aβ42/40 ratio changes demonstrate relationship to treatment andsupport the need for continuous treatment with lecanemab• OLE treatment response on clinical outcomes (ADCOMS, CDR-SB, ADAS-Cog)in newly treated and previously treated subjects supports need for continuous
treatment with lecanemab while still in the Early AD stage• Some of these findings are limited by the available data and will be furtherevaluated in Clarity AD
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Acknowledgments

We thank the subjects, their families and study
partners, and the sites and staff participating in thisstudy for their significant contributions
Funding for the studies and analyses was provided by Eisai Inc. and Biogen Inc.
Editorial support, funded by Eisai Inc, was provided by Mayville MedicalCommunications

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