Cortexyme : Corporate Overview December 2021

Investor Presentation

December 2021

1

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 an individual's investment objectives, or that the investor 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. Cortexyme recommends that investors independently evaluate specific investments and strategies.

2

Evidence Based Approach Focused Upstream

Disruptive MOA

Lead Asset in

Alzheimer's

Phase 3

Expanding Evidence Base

Growing Pipeline

Strong Capital Position

• Atuzaginstat is a proprietary, oral, small molecule with an MOA upstream of neurodegeneration
• Gingipain inhibitor blocks downstream effects of P. gingivalis infection as a driver of Alzheimer's progression
• Novel therapeutic class with supporting clinical data
• Recently completed GAIN Trial supports mechanism of action
• Therapeutic dose, safety profile, and responder population established
• Phase 3 GAIN2 Trial start up and regulatory engagement Q1 2022
• Expanding evidence base with animal causation and human clinical studies
• Data supports expansion into other indications, including Parkinson's disease and periodontal disease
• COR588 is a lysine gingipain inhibitor that began Phase 1 in Q3 2021, data expected H1 2022
• Arginine gingipain inhibitor COR852 advancing to IND enabling studies in 2022
• 3CLpro inhibitor COR803/COR817 advancing to IND enabling studies in 2022
• $140.1M in cash, equivalents, and short-term investments (as of September 30, 2021)
• Fully funded through 2023 to advance through multiple clinical and regulatory milestones

3

Expanding Pipeline

Molecule	Target	Indication		Development Stage
Pre-clinical	Phase 1	Phase 2	Phase 3
	Lysine gingipain inhibitor	Alzheimer's disease
Atuzaginstat
(COR388)
	Lysine gingipain inhibitor	Parkinson's disease
		Periodontal and other
COR588	Lysine gingipain inhibitor	P. gingivalis driven
		disease
COR803/	CL3 Pro inhibitor	COVID-19 and other
COR817	coronaviruses
COR852	Arginine gingipain	Undisclosed
inhibitor
Undisclosed	Undisclosed	Undisclosed

4

Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease

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

Alzheimer's Amyloid-b is an antimicrobial peptide: a review of the evidence

Gosztyla, M.G., Brothers, H.M., Robinson, S.R. (2018). Journal

of Alzheimer's Disease, 64(4), 1495- 1506.

The Alzheimer's Disease-Associated

Amyloid β-Protein Is an Antimicrobial

Peptide

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

Antimicrobial Properties of

Amyloid Peptides

Bruce L. Kagan, Hyunbum Jang, Ricardo Capone,

Fernando Teran Arce, Srinivasan Ramachandran,

Ratnesh Lal, and Ruth Nussinov

"Could

Alzheimer's Stem From

Infections? It makes sense, experts

say"

Periodontal Disease and Incident

Dementia: The Atherosclerosis Risk

in Communities Study (ARIC)

Ryan T. Demmer, Faye L. Norby, Kamakshi

Lakshminarayan, Keenan A. Walker, James S. Pankow, Aaron R. Folsom, Thomas Mosley, Jim Beck, Pamela L. Lutsey

Tooth loss, dementia and neuropathology in the Nun Study

Pamela Sparks Stein, DMD; Mark Desrosiers, PhD; Sara Jean Donegan, SSND, DDS; Juan F. Yepes, DDS, MD, MPH; Richard J. Kryscio, PhD

Periodontal disease associates with higher brain amyloid load in normal elderly

Angela R. Kamer, Elizabeth Pirraglia, Wai Tsui, Henry Rusinek, Shankar Vallabhajosula, Lisa Mosconi, Li Yi, Pauline McHugh, Ronald G. Craig, Spencer

Tooth loss and Periodontal Disease Predict Poor Cognitive Function in Older Men

Elizabeth Krall Kaye, PhD, Aileen Valencia, BS, Nivine Baba, MA, Avron Spiro, III, PhD, Thomas Dietrich, DMD, and Raul I. Garcia, DMD

Serum antibodies to periodontal pathogens are a risk factor for

Alzheimer's disease

Pamela Sparks Stein, Michelle J. Steffen, Charles Smith, Gregory Jicha, Jeffrey L. Ebersole, Erin Abner, and Dolph Dawson III