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1
April 2021
An update and baseline data from the Phase 2/3 GAIN trial of COR388 (atuzaginstat) a novel bacterial virulence factor inhibitor for the treatment of Alzheimer’s Disease
Michael Detke, MD PhD1, Shirin Kapur, PhD1, Marwan Sabbagh, MD2, Mark Ryder, DMD3, Ira Goodman, MD4, Debasish Raha, PhD1, Florian Ermini, PhD1, Mai Nguyen, PhD1, Ursula Haditsch, PhD1, Joanna Bolger1, Dave Hennings, PhD1,
Kim Perry, PhD5, Casey Lynch1, Hatice Hasturk, DDS, PhD6, Leslie J. Holsinger, PhD1, Stephen Dominy, MD1
(1) Cortexyme, South San Francisco, CA; (2) Cleveland Clinic, Las Vegas, NV; (3) UCSF, San Francisco, CA; (4) Bioclinica, Orlando, FL; (5) Innovative Analytics, Portage, MI; (6) Forsyth Forsyth Institute, Cambridge, MA
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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
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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
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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
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Disclaimer
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Disclosures
Drs. Sabbagh, Goodman, Hasturk, Perry and Ryder are consultants for Cortexyme,
compensated for their time (no stock/options).
All other authors are full-time employees of Cortexyme and holders of Cortexyme
stock/options.
Most of the work presented here was funded by Cortexyme, Inc.
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GAIN Trial Overview and Milestones
• GAIN is a double blind, placebo-controlled, randomized 1-year study in mild - moderate AD
patients of the GingipAIN hypothesis of Alzheimer’s.
• Based on the discovery of Porphyromonas Gingivalis (Pg) in the brains AD subjects, this is a
novel mechanism, upstream of immune system activation, proteinopathy, synaptic dysfunction,
and neurodegeneration.
• Ongoing publications and data presentations continue to strengthen evidence for the gingipain
hypothesis; the GAIN trial is designed to be the key clinical test and a potentially pivotal trial.
• Randomization completed Q4 2020. Total enrollment is N=643. N=233 in periodontal REPAIR
sub-study.
• Baseline demographics and biomarkers consistent with appropriate population.
• 90% of patients have moderate-severe periodontal disease at baseline.
• 100% of patients positive for Pg IgG at baseline.
• Topline data expected in Q4 2021 for both AD & Perio.
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
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Atuzaginstat Acts Upstream of Alzheimer’s Induced Pathology
Source: Cortexyme atuzaginstat (COR388) dose response study, Mean +/- SEM *p< 0.05,**p<0.01, ***p<0.001, Science Advances, 2019
Week 1 2 3 4
56 7 8 9 10
0COR388 10 or 30 mg/kg po 2x/day
3x oral P.g. / week
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Efficacious in wild type mouse model for sporadic Alzheimer’s disease
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Atuzaginstat Showed Favorable Trends on Multiple Cognitive Measures