SecProbe.io

April 2, 2019
Casey C. Lynch
Chief Executive Officer
Cortexyme, Inc.
269 East Grand Ave.
South San Francisco, CA 94080
Re:Cortexyme, Inc.
Draft Registration Statement on Form S-1
Submitted March 4, 2019
CIK No. 0001662774
Dear Ms. Lynch:
            We have reviewed your draft registration statement and have the following comments.  In
some of our comments, we may ask you to provide us with information so we may better
understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Draft Registration Statement on Form S-1
Prospectus Summary, page 1
1.We refer to the first paragraph of your Summary, which highlights that Alzheimer’s
patients treated with COR388 showed “positive trends of improvement” across “several”
exploratory cognitive tests commonly used in Alzheimer’s trials.  Please revise your
Summary here and on page 2 to balance your presentation concerning the significance of
the efficacy results demonstrated from testing nine patients.  In this regard, we note that
your CEO’s October 24-27 presentation, concluded, “There was a trend of improvement
in some of the cognitive tests...; however, these results should be interpreted with caution

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 2, 2019 Page 2
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 2, 2019
Page 2

due to the small sample size.”  In addition, we note that your disclosure on page 94
indicates that two of the three conducted tests did not produce statistically significant
results.
Management's Discussion and Analysis of Financial Condition and Results of Operations
Critical Accounting Policies and Significant Judgments and Estimates
Stock-Based Compensation
Common Stock Valuations, page 74
2.Once you have an estimated offering price or range, please explain to us how you
determined the fair value of the common stock underlying your equity issuances and the
reasons for any differences between the recent valuations of your common stock leading
up to the IPO and the estimated offering price. This information will help facilitate our
review of your accounting for equity issuances including stock compensation and
beneficial conversion features.
Results of Operations
Research and Development Expenses, page 76
3.Please revise the disclosure to disaggregate research and development expenses by nature
or type of expense for each period presented.
Business, page 83
4.Given the large number of preclinical tests discussed or referenced in your prospectus,
please consider whether a table briefly identifying these studies and their purpose would
assist investors in understanding your preclinical work and statements, including those
concerning:
•the presence of P. gingavalis in the brain;
•the causal link between P. gingavalis and Alzheimer’s; and
•successful treatment of Alzheimer’s disease pathology with gingipain inhibitors,
including with your COR388 inhibitor.

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 2, 2019 Page 3
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 2, 2019
Page 3
5.Please revise to discuss in greater detail the following preclinical testing:
•the human observational study showing that 100% of 50 mild to moderate Alzheimer’s
patients tested positive using your proprietary test for P. gingivalis DNA fragments in
cerebral spinal fluid (CSF) (pages 2 and 89) and
•your detection of the presence of P. gingavalis DNA from multiple genes, confirming
the presence of bacteria (page 89).
6.At first use, please describe the following terms employed concerning your testing results:
•“demonstrated effects”;
•“positive trends of improvement”;
•“clinically significant trends”;
•“clinically meaningful changes”; and
•“numerical trends of improvement”.

Also, revise your discussions of testing results, where necessary for context, to present p-
values and to clarify whether the results are or are not statistically significant.  For
instance, we note your discussions on pages 94-95 concerning MMSE and CANTAB
results do not provide p-values or address statistical significance.
7.We note your disclosures on pages 89 and 93 indicating that you have developed
proprietary technology to test for the presence of P. gingavalis DNA fragments in the
CSF.  Please tell us, and revise, as applicable, to discuss whether there are challenges or
uncertainties with respect to testing for the presence of P. gingavalis in the human brain.
P. gingivalis and the Role of Gingipains, page 88
8.Please reconcile your disclosure on page 88, which appears to attribute the work to your
collaborators at the University of Auckland, and the second sentence of the prospectus
summary, which highlights “your seminal discovery” observed across multiple studies to
date.  Please note that we may have additional comment after reviewing your response.
P. gingivalis Infection Causes Alzheimer’s Disease Pathology in Mice, page 89
9.We note your statement indicating that the ability to reproduce disease in an infected
animal is an important criterion for demonstrating causation.  Please revise to identify
briefly other criteria typically used to demonstrate causation, or advise.
10.We refer to your disclosure on page 1 highlighting that you have “observed that P.
gingavalis infection causes Alzheimer’s pathology in animal models.”  We note; however,
that your discussion under the heading on page 89 appears limited to discussion of a single
animal model.  In revising this section, please be sure to identify and explain the work that
your team conducted.  Also, identify any other studies or factors that form the basis for
your conclusions concerning causation.

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 2, 2019 Page 4
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 2, 2019
Page 4
Exploratory Cognitive Testing, page 94
11.We note your disclosure on page 2 and elsewhere noting that the study was not “designed
to be powered for significance” on cognitive tests.  Accordingly, please tell us, and revise
the discussion of your cognitive testing on Alzheimer’s patients, as applicable, to explain
the implications of conducting testing and presenting efficacy results where the study was
not designed to be powered for significance.  With reference to your disclosure on page
100 concerning the IND and IRB processes, please tell us whether this exploratory testing
was conducted pursuant to an FDA-authorized IND and whether you submitted the testing
protocols to FDA.  Similarly, please tell us whether an IRB reviewed and approved the
study plan and protocols.
12.Please explain why you chose to test using three measures (MMSE, CANTAB, WLA) but
did not test using ADAS-Cog 11.  In this regard, we refer to your disclosure on page 1 that
ADAS-Cog 11 has served as a key endpoint in supporting regulatory approval of drugs for
Alzheimer's disease as well as your disclosure on page 95 that you have selected mean
change in ADAS-Cog 11 as the primary endpoint for your planned Phase 2/3 GAIN
clinical trial.
13.Please revise your discussion of each of the three measures (MMSE, CANTAB, WLA) to
explain the results in Figure 7 and to demonstrate the numerical trend of improvements or
statistically significant improvement cited.
14.Please revise your discussion of the Winterlight speech-based cognitive assessment
(WLA) to address the following:
•Revise to present the endpoints and results for each of the three WLA measurements
that you highlight.  Here, we note that Figure 7 appears to depict results for only one
measurement, or possibly a portion thereof (i.e., use of prepositions).
•Indicate whether WLA analysis was limited to the three measurements you present.
•Discuss whether FDA has accepted WLA testing as the basis for review and/or
approval of drugs for Alzheimer’s treatment or any drugs treating other diseases,
disorders or conditions that impact cognitive function.  Here, we note your risk factor
disclosure on page 11.

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 2, 2019 Page 5
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 2, 2019
Page 5
Our Planned Phase 2/3 GAIN Clinical Trial of COR388, page 95
15.We note that your discussion on page 102 concerning human clinical studies in support of
an NDA indicates that Phase 2 and Phase 3 are typically conducted in sequential phases.
Please revise to discuss your decision to combine these two phases, including any
attendant challenges.   Also, revise to discuss the current regulatory status of the proposed
GAIN trial.  In this regard, your disclosure on page 11 suggests that FDA acceptance of
your GAIN trial remains pending.
Intellectual Property, page 98
16.Please revise your disclosure regarding your intellectual property to clarify the jurisdiction
in which you hold issued patents and pending applications.
17.We refer to your disclosure on page F-25 concerning a research grant and license
agreement with an unidentified stockholder.  Please revise your intellectual property
section to add disclosure concerning this agreement.  Identify the counterparty, discuss the
subject of the license, and clarify whether the $1.05 million is an annual limitation.  Also,
file the agreement as an Exhibit to the registration statement or explain why it is not
required to be filed pursuant to Item 601(b)(10) of Regulation S-K.
Description of Capital Stock, page 139
18.We note that your current certificate of incorporation provides that the Court of Chancery
of the State of Delaware will be the sole and exclusive forum for any derivative action or
proceeding brought on your behalf.  Please tell us whether the amended and restated
certificate of incorporation that is to be in effect upon closing of the offering will contain a
similar or a modified provision.
General
19.Please provide us proofs of all graphics, visual, or photographic information you will
provide in the printed prospectus prior to its use, for example in a preliminary prospectus.
Please note that we may have comments regarding this material.
20.Please supplementally provide us with copies of all written communications, as defined in
Rule 405 under the Securities Act, that you, or anyone authorized to do so on your behalf,
present to potential investors in reliance on Section 5(d) of the Securities Act, whether or
not they retain copies of the communications.

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 2, 2019 Page 6
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 2, 2019
Page 6
            You may contact Sisi Cheng at 202-551-5004 or Jim Rosenberg at 202-551-3679 if you
have questions regarding comments on the financial statements and related matters.  Please
contact Jeffrey Gabor at 202-551-2544 or Joe McCann at 202-551-6262 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Andrew D. Thorpe, Esq.