leslie holsinger, phd
TRANSCRIPT
Use of Novel Biomarkers of P. gingivalis Infection and
Neuroinflammation in the GAIN Trial:
An Ongoing Phase 2/3 Clinical Trial Assessing the Activity of Atuzaginstat in
Patients with Mild to Moderate Alzheimer’s Disease
Leslie Holsinger, PhDExecutive Vice President, Research & Development
Cortexyme, Inc.
Annual Biomarkers for Alzheimer’s Disease Summit
August 25, 2021
Disclaimer
Certain information contained in this presentation and statements made orally during this presentation relate to or are based on studies, publications, surveys and
other data obtained from third-party sources and Cortexyme's own internal estimates and research. While Cortexyme believes these third-party sources to be
reliable as of the date of this presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness
of, any information obtained from third-party sources. While Cortexyme believes its internal research is reliable, such research has not been verified by any
independent source. This presentation contains information that is highly confidential and/or privileged. The information is intended only for the use of individuals or
entities to which it is addressed. If you are not the intended recipient, you are hereby notified that any reliance, disclosure, copying, distribution, or taking of any
action on the contents of this material is strictly prohibited. This presentation contains forward-looking statements. Forward-looking statements are neither historical
facts nor assurances of future performance. Instead, they are based on Cortexyme's current beliefs, expectations and assumptions regarding the future of its
business, its future plans and strategies, its clinical results and other future conditions. All statements other than statements of historical facts contained in this
presentation, including statements regarding future results of operations and financial position, business strategy, current and prospective markets or products,
clinical activities, regulatory approvals, degree of market acceptance, and plans and objectives of management for future operations, are forward-looking
statements. The words "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "estimate," "believe," "predict," "potential" or
"continue" or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking
statements contain these identifying words. The forward-looking statements in this presentation represent Cortexyme' views as of the date of this presentation.
Although Cortexyme believes the expectations reflected in such forward-looking statements are reasonable, it can give no assurance that such expectations will
prove to be correct. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Except as required by applicable law,
Cortexyme do not plan to publicly update or revise any forward-looking statements contains herein, whether as a result of any new information, future events,
changed circumstances or otherwise. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking
statements. New risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. There can be no
assurance that the opportunity will meet your investment objectives, or that you will receive a return of all or part of such investment. Investment results may vary
significantly over any given time period. The appropriateness of a particular investment or strategy will depend on an investor's individual circumstances and
objectives. We recommend that investors independently evaluate specific investments and strategies.
Cortexyme corporate overview
Topline data in
Periodontitis:
by mid-Nov
Phase 2 in
Parkinson’s
Expanding
evidence base
$153.3 MProprietary small
molecules
Topline data in
Alzheimer’s: by
mid-Nov
Coronavirus
program
4
Growing evidence of the important role of the immune
system in Alzheimer’s pathology and risk factors
Many emerging genetic risk factors for sporadic disease relate to immune system function
• Trem2, TLR4, CR1, CD33, Etc.
AD pathology is consistent with host response to a pathogen
• Chronic low grade inflammation
• Complement activation and dysregulation
• Microglial activation
• Inflammasome activation
What is
triggering
abeta42
over-
production?
Deepak Kumar, *Se Hoon Choi, *Kevin J. Washicosky, *William A.
Eimer, Stephanie Tucker, Jessica Ghofrani, Aaron Lefkowitz,
Gawain McColl, Lee E. Goldstein, Rudolph E. Tanzi, Robert D. Moir
Amyloid-β peptide protects against
microbial infection in mouse and worm
models of Alzheimer’s disease
Stephanie J. Soscia, James E. Kirby, Kevin J. Washicosky,
Stephanie M. Tucker, Martin Ingelsson, Bradley Hyman, Mark A.
Burton, Lee E. Goldstein, Scott Duong, Rudolph E. Tanzi, Robert
D. Moir
The Alzheimer’s Disease-Associated Amyloid
β-Protein Is an Antimicrobial Peptide
“Could
Alzheimer’s Stem
From Infections?
It makes sense,
experts say”
Gosztyla, M.G., Brothers, H.M., Robinson, S.R. (2018). Journal
of Alzheimer’s Disease, 64(4), 1495- 1506.
Alzheimer’s Amyloid-b is an antimicrobial
peptide: a review of the evidence
Bruce L. Kagan, Hyunbum Jang, Ricardo Capone,
Fernando Teran Arce, Srinivasan Ramachandran,
Ratnesh Lal, and Ruth Nussinov
Antimicrobial Properties of Amyloid
Peptides
Epidemiological
& twin studies
show that
periodontal
bacteria increase
the risk for
Alzheimer’s
disease
Angela R. Kamer, Elizabeth Pirraglia, Wai Tsui, Henry Rusinek, Shankar
Vallabhajosula, Lisa Mosconi, Li Yi, Pauline McHugh, Ronald G. Craig, Spencer
Periodontal disease associates with
higher brain amyloid load in normal
elderly
Pamela Sparks Stein, DMD; Mark Desrosiers, PhD; Sara Jean Donegan,
SSND, DDS; Juan F. Yepes, DDS, MD, MPH; Richard J. Kryscio, PhD
Tooth loss, dementia and
neuropathology in the Nun Study
Pamela Sparks Stein, Michelle J. Steffen, Charles Smith, Gregory Jicha,
Jeffrey L. Ebersole, Erin Abner, and Dolph Dawson III
Serum antibodies to periodontal
pathogens are a risk factor for
Alzheimer’s disease
6
Elizabeth Krall Kaye, PhD, Aileen Valencia, BS, Nivine Baba, MA, Avron Spiro,
III, PhD, Thomas Dietrich, DMD, and Raul I. Garcia, DMD
Tooth loss and Periodontal Disease
Predict Poor Cognitive Function in
Older Men
Ryan T. Demmer, Faye L. Norby, Kamakshi
Lakshminarayan, Keenan A. Walker, James S. Pankow, Aaron R.
Folsom, Thomas Mosley, Jim Beck, Pamela L. Lutsey
Periodontal Disease and Incident
Dementia: The Atherosclerosis Risk
in Communities Study (ARIC)
7
Active periodontal disease is associated with rapid decline in Alzheimer’s patientsIde M, et al (2016)
Periodontitis and Cognitive
Decline in Alzheimer’s Disease.
PLoS ONE 11(3)
Mean
ch
an
ge f
rom
base
lin
e A
DA
S-C
og
rati
ng
-2
-1
0
1
2
3
4
5
6
7
8
0 1 2 3 4 5 6 7
Months
ADAS-Cog
No or mild periodontitis(low bacterial load)
Moderate to severe Periodontitis (high bacterial load)
p< 0.005
NeurodegenerationTau fragmentation
ApoE fragmentation
Lysosomal dysfunction
Host response
P. gingivalis
infection
Brain
infiltration
Gingipain
secretionAging
Genetic risk (ApoE4,
TLR4, CR1, TREM2)
Trauma
Bacterial load
Microglia activation
Neuroinflammation
Complement induction
Inflammasome
Amyloid beta production
8
Growing body of evidence shows that bacterial brain infiltration
triggers Alzheimer’s pathology in physiological models
P. gingivalis discovered in the brain of 90-100% of
Alzheimer’s patients
P. gingivalis DNA also
confirmed through
sequencing of multiple
genes in Alzheimer’s
brain tissue and CSF
Gingipain
Immuno-
histochemistry
Source: Dominy et al 2019, Science Advances
P. gingivalis brain infiltration precedes and is
correlated with Alzheimer’s disease symptoms and pathology
Controls Alzheimer’s
Immunohistochemistry
of middle temporal gyrus
microarray
Confirmed with multiple
antibodies/antigens and
PCRArg
inin
e g
ingip
ain
load
(norm
aliz
ed t
o c
ontr
ol)
Source: Collaboration with University of Auckland/ Neurovalida study ****p<0.0001; Dominy et al 2019 Sciences Advances
**** ****
Arg
inin
e g
ingip
ain
load
(norm
aliz
ed t
o c
ontr
ol)
Tau load
(normalized to control)
Source: Adapted from Ilievski, et al.
Chronic oral application of a
periodontal pathogen results in brain
inflammation, neurodegeneration and
amyloid beta production in wild type
mice. PLOS: One 2018
Rela
tiv
e T
NF
alp
ha
gen
e e
xp
ress
ion
Neuroinflammation
2.5
2
1.5
1
0.5
0
P.
gin
giv
ali
s16S
RN
A c
op
ies
/ 5 F
FP
E
x1010
8
6
4
2
0
P. Gingivalis Infiltrates the Brain
Am
ylo
id b
eta
Pla
qu
es
/ fi
eld
0
1
2
3
4
5
6
Amyloid Beta Plaques
# p
Ta
u/
field
0
14
8642
10
12
Tau Tangle-Like Neurons
Mic
rogli
a /
fie
ld
0
14
8642
10
12
Activated Microglia
% I
nta
ct
neu
ron
s /
field
0
80
60
40
20
100
CA1
DG
Neurodegeneration
Evidence of
causation:
Oral Pg infection
of WT mice
induces AD
pathology after
22 weeks
*p< 0.05,**p<0.01, ***p<0.001, ****p<0.001
Virulence factor inhibition will block gingipain activity, reduce
bacterial load, and normalizes immune function
Microglial
Activation
Aβ-42
Production and Plaques
Tau Tangles
P. Gingivalis
Gingipain
Pyroptosis &
Necrosis
Tau and Other Protein
Fragmentation Neuronal Degradation
and Synaptic Dysfunction
NLRP1 Infla
m
ma some
Assembly & Activation
Complement
Dysregulation
Normally
Functioning Neuron
COR388
Plaque
Alzheimer’s disease Alzheimer’s disease
Tangle
COR388
P. Gingivalis
Gingipain
TNFα
Extracellular
Intracellular
1. Tau is fragmented and aggregated in the AD brain
and by Pg.
2. ApoE is fragmented in the AD brain and by
gingipains.
3. Abeta is overproduced in the AD brain and triggered
by Pg infection in WT mice.
4. Microglia are activated in the AD brain and by Pg.
5. Inflammasomes are activated in the AD brain and by
Pg.
6. Complement is dysregulated in the AD brain and by
gingipains.
7. Neurodegeneration is evident in the AD brain and
caused by Pg gingipains in physiological models
Atuzaginstat (COR388)
Kgp lysine gingipain
inhibitor
Small molecule optimized from proprietary
inhibitor library
• Novel & proprietary small molecule
• Potent: Target IC50 < 50pM
• Selective over 800 human anti-targets
including other cellular proteases
• Orally available, brain penetrant
• Large therapeutic window
Atuzaginstat (COR388) acts upstream of infection
induced Alzheimer’s pathology in wild type mouse
Source: Dominy et al, 2019, Science Advances
0
2,000
4,000
6,000
Co
py #
/ 1
00 n
g D
NA
***
0.00
0.05
0.10
0.15
0.20
pg
/ m
g P
rote
in
***
0.0
0.5
1.0
1.5
2.0
2.5
pg
/ m
g P
rote
in **
0
2,000
4,000
6,000
8,000
10,000
Inte
rneu
ron
s /
mm
3
*
3x oral P.g. / weekCOR388 10 or 30 mg/kg po 2x/day
5 weeks 10 weeks
Mean +/- SEM *p< 0.05,**p<0.01, ***p<0.001
Atuzaginstat Reduces P. gingivalis and Is Efficacious in a
Natural Dog Model of Periodontal Disease
Cessation
of dosing
Source: Aratsu-Kapur et al (2020). Pharmacol Res Perspectives
16
Lysine Gingipain Activity Quantified Using Activity-Based Probes
Cy5
Covalent
Gingipain
Active-site
Inhibitor
Lysine Gingipain Activity Assay
Analysis of in
vitro bacterial
samples
Dominy et al, (2019) Science Advances
Lysine Gingipain Activity Assay
Kgp WB
50kDa -
CAB102 Kgp WB
Aratsu-Kapur et al, (2020) Pharmacol Res Perspectives 8.
Activity-probe analysis
of oral biofluid samples
Cy5 probe
Analysis
of in vivo
samples
17
Atuzaginstat Human Pharmacokinetics in Phase 1
17
• Atuzaginstat absorbed rapidly after oral administration:
- Median Tmax = 0.5-1.5 hours
• Target therapeutic exposure range, predicted from animal models, was achieved with doses as low as 25 mg b.i.d. at steady state:
- Mean Cmax = 25 ng/mL, Mean AUC0-24 178 h*ng/mL
• Good tissue distribution:
- Mean Vd/F = 879 – 1734 L
• Slightly more than linear dose proportionality:
- Slope estimate = 1.7 for Cmax , 1.5 for AUC0-12
• Clearance:
- T1/2 = 4.5 – 4.9 hrs at steady state
- Exposures support BID dosing based on animal models and MOA
• Detected in CSF
• Rat and human 14C-AME studies show no protein adducts
Phase 1 MAD Study in Healthy Older Subjects
Trends To Benefit On Exploratory Cognitive
Measures In Phase 1b Study
Source: Cortexyme Phase 1b study: *p< 0.05, ***p<0.001
Days of treatment Days of treatment Days of treatment
MM
SE
Sco
re
CA
NTA
B c
om
po
site
(Z
sco
re)
Pro
po
rtio
n P
rep
ositio
n: to
tal co
nte
nt
Placebo (n=3)COR388 (n=6)
Winterlight:
Examples of
speech in
75 year old
female with
mild-moderate
AD before and
after
Atuzaginstat
treatment
ApoE fragments are found in AD patient CSF and can be reduced by Atuzaginstat (COR388) treatment
ApoE fragments are found in AD CSF CSF ApoE fragments are reduced in Phase
1b COR388-dosed subjects
Low MW ApoEfragments
Source: Cortexyme Phase 1b study: *p< 0.05Source: Raha et al, 2021 Cell Reports Medicine, submitted
Hum
an C
SF
21
Pivotal P2/3 GAIN Trial Design: Atuzaginstat in Alzheimer’s Disease
• Mild to Moderate: MMSE
12-24
• Ages 55-80
• Stable symptomatic
therapies allowed
• Target N=573
RandomizationScreening
Co-Primary:
ADAS-Cog11 and ADCS-ADL
Secondary:
CDR-SB, MMSE and NPI
Exploratory:
Winterlight, MRI (hippocampal
volume and cortical thickness)
Biomarkers of Pg and
gingipain activity: blood, saliva,
oral biocollections
Biomarkers of Alzheimer’s:
CSF Aβ, tau, p-tau
Markers of disease
modification: MRI volumetric
measures
Endpoints
Key Eligibility Criteria
• Enrollment initiated Apr. 2019; completed Sept. 2020
• Interim analysis in December 2020 successfully
completed with no sample size adjustment
• Top-line data expected Q4 2021
• 233 subjects
• Assessment of pocket depth
and clinical attachment level at
6 and 12 months
Timelines Periodontal REPAIR sub-study
Placebo
Low dose (40 mg BID)
48-week Treatment Period
(Total N=643)
More information: www.gaintrial.com
High dose (80 mg BID)
6-week Safety Follow-up
22
GAIN Baseline Demographics: Population and Stratification as
Expected
Parameter Overall (N=643)
Age at Informed Consent (years) 69.1 (55 – 80)
Sex
Male 278 (43%)
Female 365 (57%)
Race and Ethnicity
Black or African American 42 (7%)
White, Hispanic or Latino 68 (11%)
White, Not Hispanic/Latino 505 (79%)
Other 10 (2%)
Missing 18 (3%)
Parameter Overall (N=643)
Region
North America 447 (70%)
Europe 196 (30%)
MMSE
Moderate >=12 to <=18 324 (50%)
Mild >=19 to <=24 319 (50%)
ApoE4
ApoE4 Carriers 414 (64%)
Non Carriers 229 (36%)
Cholinesterase Inhibitor/Memantine Use
Yes 476 (74%)
No 167 (26%)
Randomization stratified by Mild/Moderate and ApoE4 +/-
Final data to be confirmed post data lock
2323
Central Nervous System (CSF)
Biomarkers
Peripheral Serum/Plasma
Biomarkers
• Biomarkers of P. gingivalis infection, inflammation and neuroinflammation are being assessed
• A subset of these biomarkers at baseline are currently available and will be discussed today
CNS, Peripheral, and Oral Biomarkers in GAIN Trail
Oral Biofluid Collection
Biomarkers
24
Baseline CSF Biomarkers: Ab 42/40, Tau and P-Tau
EUROIMMUN assays; range of control/AD established by EUROIMMUN
Approximately 84% of GAIN subjects have traditional CSF biomarkers of Alzheimer’s Disease
Final data to be confirmed post data lock
25
Elevated vWF, A2M in Majority of GAIN Serum Samples at Baseline
• Cortexyme is analyzing a set of
exploratory serum biomarkers
• Highlighted here:- vWF, a marker of vascular
injury; ULN 106 ug/mL
- A2M, an endogenous protease
inhibitor, ULN 2.3 mg/mL
- Benchmarked against a
normal population for 100
healthy subjects aged 20-50
years (MyriadRBM)
Final data to be confirmed post data lock
26
P. gingivalis specific IgG elevated in serum at baseline indicating
systemic infection
100% of GAIN subjects have
evidence of systemic P. gingivalis
exposure with detectable antibodies;
78% have IgG antibody titers that
correlate with oral periodontal
disease symptoms
Collaboration with H. Hasturk, Forsyth Institute; range and assay from Nobel et al, 2019
Final data to be confirmed post data lock
27
Over 90% of GAIN Subjects in the Periodontal REPAIR
Sub-Study Have Moderate to Severe Periodontal Disease at Baseline
0
1 0
2 0
3 0
4 0
5 0
6 0
7 0
8 0
9 0
1 0 0
% o
f s
ub
jec
ts
N o n e -
M i l d
M o d e r a t e -
S e v e r e
0
4
8
1 2
1 6
2 0
2 4
2 8
3 2
Nu
mb
er
of t
ee
th
N o n e -
M i l d
M o d e r a t e -
S e v e r e
Periodontal Diagnosis Number of teeth%
of
subje
cts
Num
ber
of
teeth
Diagnosis based on Pocket Depth and Clinical Attachment Loss Measures (N=233)
Final data to be confirmed post data lock
28
CSF Analytes: Use Of The CSF/Serum Albumin Index
• This is an index of blood-brain barrier (BBB) integrity,
adjusted for the serum albumin concentration
• This index is increased in BBB dysfunction
• Defined as CSF albumin (mg/L) / serum albumin (g/L)
• CSF/serum albumin index >9 = evidence of BBB loss
of integrity
CSF/Serum Albumin Index
• Utilizing a standard CSF and serum albumin assay,
the majority (98%) of GAIN Trail subjects (mild to
moderate AD) have an index <9, indicating
integrity of the BBB at the time of sample
collection
• This may vary over time, with gender and age
1
1 0
N = 4 7 6
Alb
um
in i
nd
ex
(C
SF
/Se
ru
m)
log
sc
ale
A v e r a g e A l b u m i n I n d e x = 3 . 5
95% CI 3.26-3.77
Final data to be confirmed post data lock
29
Baseline CSF Biomarkers: Serum and CNS Contribution To Levels
1 1 0 1 0 0
0 . 0 1
0 . 1
1
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Ab
eta
ra
tio
(A
b4
2/A
b4
0)
log
sc
ale
r = - 0 . 0 3
N e g l i g i b l e c o r r e l a t i o n
N = 4 6 3
1 1 0 1 0 0
1 0
1 0 0
1 0 0 0
1 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
p1
81
-ta
u(p
g/m
L)
log
sc
ale
r = 0 . 0 4
N e g l i g i b l e c o r r e l a t i o n
N = 4 7 5
1 1 0 1 0 0
1 0 0 0 0
1 0 0 0 0 0
1 0 0 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Co
mp
lem
en
t C
9 (
pg
/mL
)
log
sc
ale
r = 0 . 6 4
M o d e r a t e C o r r e la t i o n
N = 4 5 8
1 1 0 1 0 0
1
1 0
1 0 0
1 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
CS
F a
nti-
Pg
an
tib
od
y (
EU
)
log
sc
ale
r = 0 . 2 2
v e r y w e a k c o r r e l a t i o n
N = 4 7 2
1 1 0 1 0 0
0 . 0 1
0 . 1
1
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Ab
eta
ra
tio
(A
b4
2/A
b4
0)
log
sc
ale
r = - 0 . 0 3
N e g l i g i b l e c o r r e l a t i o n
N = 4 6 3
1 1 0 1 0 0
1 0
1 0 0
1 0 0 0
1 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
p1
81
-ta
u(p
g/m
L)
log
sc
ale
r = 0 . 0 4
N e g l i g i b l e c o r r e l a t i o n
N = 4 7 5
1 1 0 1 0 0
1 0 0 0 0
1 0 0 0 0 0
1 0 0 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Co
mp
lem
en
t C
9 (
pg
/mL
)
log
sc
ale
r = 0 . 6 4
M o d e r a t e C o r r e la t i o n
N = 4 5 8
1 1 0 1 0 0
1
1 0
1 0 0
1 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
CS
F a
nti-
Pg
an
tib
od
y (
EU
)
log
sc
ale
r = 0 . 2 2
v e r y w e a k c o r r e l a t i o n
N = 4 7 2
• Concentration increases in CSF with
increasing albumin index suggesting
minimal central nervous system production
• Concentrations in CSF are independent of the albumin
index suggesting some central nervous system production
as expected
Complement C9 Ab42/Ab40 ratio and p181-tau
Final data to be confirmed post data lock
30
New Data: Baseline CSF Anti-Pg IgG Levels Provide Evidence of
CNS Infection in AD
1 1 0 1 0 0
0 . 0 1
0 . 1
1
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Ab
eta
ra
tio
(A
b4
2/A
b4
0)
log
sc
ale
r = - 0 . 0 3
N e g l i g i b l e c o r r e l a t i o n
N = 4 6 3
1 1 0 1 0 0
1 0
1 0 0
1 0 0 0
1 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
p1
81
-ta
u(p
g/m
L)
log
sc
ale
r = 0 . 0 4
N e g l i g i b l e c o r r e l a t i o n
N = 4 7 5
1 1 0 1 0 0
1 0 0 0 0
1 0 0 0 0 0
1 0 0 0 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l e
Co
mp
lem
en
t C
9 (
pg
/mL
)
log
sc
ale
r = 0 . 6 4
M o d e r a t e C o r r e la t i o n
N = 4 5 8
1 1 0 1 0 0
1
1 0
1 0 0
1 0 0 0
a l b u m i n i n d e x ( C S F / S e r u m )
l o g s c a l eC
SF
an
ti-
Pg
an
tib
od
y (
EU
)
log
sc
ale
r = 0 . 2 2
v e r y w e a k c o r r e l a t i o n
N = 4 7 2
CSF anti-Pg IgG
Collaboration with Hatice Hasturk, DDS PhD, Forsyth Institute
• All subjects with baseline CSF available for
analysis (N=472) were positive for anti-P.
gingivalis IgG in CSF
• Only 2% of subjects have loss of BBB
integrity, as measured by albumin index >9
• Anti-Pg IgG concentration in CSF is largely
independent of the albumin index indicating
central nervous system production in
addition to levels found in serum
• The presence of these antibodies further
supports a direct P. gingivalis infection in
the central nervous system
Final data to be confirmed post data lock
31
Summary
• Data continue to accumulate supporting the gingipain hypothesis of Alzheimer’s, periodontal disease
and other degenerative disorders
• The GAIN trial, has been rigorously designed and implemented to be a key clinical proof of concept
and potentially pivotal trial
• Biomarker data are being used to understand the therapeutic effect of atuzaginstat on key biological
markers of AD and neurodegeneration
• Biomarkers of P. gingivalis infection level, immune response, and gingipain activity are being
assessed to characterize Pg baseline levels and response to treatment
• Baseline data support that this is an appropriate population for testing atuzaginstat for AD- Biomarkers for Aβ, Total tau and p-Tau 181 in CSF
- Pg antibodies in serum and CSF
- Periodontal disease data in the dental REPAIR sub-study
• New data on baseline anti-Pg IgG levels in CSF supports a contribution from a CNS infection
• Topline data will be reported by mid-Nov
32
Acknowledgements
• Advisory Board & other academiccollaborators
• Development Partners
• Clinical trial site personnel
• Study participants and caregivers
• Cortexyme Biomarker team• Shirin Aratsu Kapur• Debasish Raha• Mai Nguyen• Sean Broce• T. Harshani Peiris• Diana Eilerts
• Cortexyme Research and ClinicalDevelopment teams
33
THANK YOU