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
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

Draft Registration Statement on Form S-1

Prospectus Summary, page 1

1.     We refer to the first paragraph of your Summary, which highlights that
       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
       in some of the cognitive tests...; however, these results should be
interpreted with caution
 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
Management's Discussion and Analysis of Financial Condition and Results of
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
         the presence of P. gingavalis in the brain;
FirstName the causal link between P. gingavalis and Alzheimer's; and
         LastNameCasey C. Lynch
Comapanysuccessful treatment of Alzheimer's disease pathology with gingipain
         NameCortexyme, Inc.
April 2, 2019 Page 2with your COR388 inhibitor.
FirstName LastName
 Casey C. Lynch
FirstName LastNameCasey C. Lynch
Cortexyme, Inc.
Comapany NameCortexyme, Inc.
April 2, 2019
April 3 2019 Page 3
Page 2,
FirstName LastName
5.       Please revise to discuss in greater detail the following preclinical
           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
         results do not provide p-values or address statistical significance.
7.       We note your disclosures on pages 89 and 93 indicating that you have
         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
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.
 Casey C. Lynch
FirstName LastNameCasey C. Lynch
Cortexyme, Inc.
Comapany NameCortexyme, Inc.
April 2, 2019
Page 2,
April 4 2019 Page 4
FirstName LastName
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,
         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,
         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
           Indicate whether WLA analysis was limited to the three measurements
you present.
           Discuss whether FDA has accepted WLA testing as the basis for review
            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.
 Casey C. Lynch
FirstName LastNameCasey C. Lynch
Cortexyme, Inc.
Comapany NameCortexyme, Inc.
April 2, 2019
April 5 2019 Page 5
Page 2,
FirstName LastName
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.

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.
 Casey C. Lynch
FirstName LastNameCasey C. Lynch
Cortexyme, Inc.
Comapany NameCortexyme, Inc.
April 2, 2019
Page 2,
April 6 2019 Page 6
FirstName LastName
       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


                                                        Division of Corporation
                                                        Office of Healthcare &
cc:      Andrew D. Thorpe, Esq.