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 Quince Therapeutics, Inc.
 611 Gateway Boulevard, Suite 273
 South San Francisco, CA 94080 August 1,
2025 United States Securities and Exchange Commission
 Division of Corporation Finance 100 F Street, N.E.
 Washington, D.C. 20549

 RE:
 Quince Therapeutics, Inc.
 Registration Statement on Form S-3
 File No. 333-288971
 Ladies and Gentlemen: Quince Therapeutics, Inc.
(the “ Registrant ”) hereby requests that the U.S. Securities and Exchange Commission (the “ Commission ”) take appropriate action to cause the above-referenced Registration Statement on Form S-3 to become effective on August 5, 2025, at 4:00 p.m., Eastern Time, or as soon thereafter as is practicable or at such later time as the Registrant may orally request via telephone call to the staff of the
Commission. The Registrant hereby authorizes Gordon Ho of Cooley LLP, counsel to the Registrant, to make such request on its behalf. Once
the Registration Statement has been declared effective, please orally confirm that event with Gordon Ho of Cooley LLP, counsel to the Registrant, at (650) 843-5190.

 Very truly yours,

 QUINCE THERAPEUTICS, INC.

 By:

 / S / B RENDAN H ANNAH

 Name:

 Brendan Hannah

 Title:

 Chief Business Officer and Chief Operating Officer

 cc:
 Gordon Ho, Cooley LLP

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 August 1, 2025

Dr. Dirk Thye
Chief Executive Officer, Chief Medical Officer and Director
Quince Therapeutics, Inc.
611 Gateway Boulevard, Suite 273
South San Francisco, CA 94080

 Re: Quince Therapeutics, Inc.
 Registration Statement on Form S-3
 Filed July 25, 2025
 File No. 333-288971
Dear Dr. Dirk Thye:

 This is to advise you that we have not reviewed and will not review your
registration
statement.

 Please refer to Rules 460 and 461 regarding requests for acceleration.
We remind you
that the company and its management are responsible for the accuracy and
adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action
by the staff.

 Please contact Daniel Crawford at 202-551-7767 with any questions.

 Sincerely,

 Division of
Corporation Finance
 Office of Life
Sciences
cc: Gordon Ho, Esq.
</TEXT>
</DOCUMENT>

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Document

Quince Therapeutics, Inc.

611 Gateway Boulevard, Suite 273

 South San Francisco, CA 94080

December 23, 2024

Via EDGAR

U.S. Securities and Exchange Commission

Division of Corporation Finance

100 F. Street N.E.

Washington, D.C. 20549-3010

Attention: Daniel Crawford

RE:     Quince Therapeutics, Inc.

Registration Statement on Form S-3

Filed December 18, 2024

File No. 333-283897

Ladies and Gentlemen:

Quince Therapeutics, Inc. (the “Registrant”) hereby requests that the U.S. Securities and Exchange Commission (the “Commission”) take appropriate action to cause the above-referenced Registration Statement on Form S-3 to become effective on Thursday, December 26, 2024, at 4:00 p.m., Eastern Time, or as soon thereafter as is practicable or at such later time as the Registrant may orally request via telephone call to the staff of the Commission. The Registrant hereby authorizes Gordon Ho of Cooley LLP, counsel to the Registrant, to make such request on its behalf.

Once the Registration Statement has been declared effective, please orally confirm that event with Gordon Ho of Cooley LLP, counsel to the Registrant, at (650) 843-5190.

[Signature Page Follows]

Very truly yours,

Quince Therapeutics, Inc.

By:    /s/ Brendan Hannah

Name:    Brendan Hannah

Title:    Chief Business Officer and Chief Operating Officer

cc:    Gordon Ho, Cooley LLP

December 23, 2024
Dirk Thye, M.D.
Chief Executive Officer and Chief Medical Officer
Quince Therapeutics, Inc.
611 Gateway Boulevard, Suite 273
South San Francisco, CA 94080
Re:Quince Therapeutics, Inc.
Registration Statement on Form S-3
Filed December 18, 2024
File No. 333-283897
Dear Dirk Thye M.D.:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Daniel Crawford at 202-551-7767 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Gordon K. Ho, Esq.

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 269 East Grand Ave.

South San Francisco, CA 94080

 April 9, 2020

 VIA EDGAR

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, D.C. 20549

 Attn: Chris Edwards, Office of
Life Sciences

Re:

 Cortexyme, Inc.

 Registration
Statement on Form S-1

 Filed April 7, 2020

File No. 333-237594

REQUEST FOR ACCELERATION OF EFFECTIVENESS

 Acceleration Request

Requested Date:

April 13, 2020

Requested Time:

4:00 p.m. Eastern Time

 Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under the Securities Act of 1933, as amended, Cortexyme, Inc. (the “Company”)
hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to declare the Company’s Registration Statement on Form S-1 (File
No. 333-237594) effective at the “Requested Date” and “Requested Time” set forth above or as soon thereafter as practicable.

The Company hereby authorizes Niki Fang, who is an attorney with the Company’s outside legal counsel, Orrick, Herrington &
Sutcliffe LLP, to orally modify or withdraw this request for acceleration.

 The Company requests that it be notified of such effectiveness
by a telephone call to Ms. Fang at (415) 773-5540.

 [Signature page follows]

Sincerely,

CORTEXYME, INC.

By:

/s/ Christopher Lowe

Name: Christopher Lowe

Title: Chief Financial Officer

cc:
 Casey C. Lynch, Cortexyme Inc.

Ted Monohon, Cortexyme Inc.

Scott M. Iyama, Esq., Orrick, Herrington & Sutcliffe LLP

Niki Fang, Esq., Orrick, Herrington & Sutcliffe LLP

April 8, 2020
Casey C. Lynch
President and Chief Executive Officer
Cortexyme, Inc.
269 East Grand Ave.
South San Francisco, CA 94080
Re:Cortexyme, Inc.
Registration Statement of Form S-1
Filed April 7, 2020
File No. 333-237594
Dear Ms. Lynch:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Chris Edwards at (202) 551-6761 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Niki Fang, Esq.

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 Merrill Lynch, Pierce, Fenner & Smith

  Incorporated

 One Bryant Park

New York, New York 10036

 Credit Suisse Securities (USA) LLC

 Eleven Madison Avenue

 New York, New York 10010

May 6, 2019

 VIA EDGAR

Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attn:

Suzanne Hayes

Jeffrey Gabor

Joseph McCann

 Re: Cortexyme, Inc. Acceleration Request

Acceleration Request

 Requested Date: May 8, 2019

 Requested Time: 3:30 p.m. Eastern Time

 Ladies
and Gentlemen:

 In accordance with Rule 461 under the Securities Act of 1933, as amended (the “Act”), we, as representatives of the
several underwriters, hereby join in the request of Cortexyme, Inc. (the “Company”) for acceleration of the effective date of the Registration Statement on Form S-1 (File No. 333-230853), as amended, requesting effectiveness as of 3:30 p.m., Eastern Time, on May 8, 2019, or at such later time as the Company or its outside counsel, Orrick, Herrington &
Sutcliffe LLP, may request via telephone call to the staff of the Division of Corporation Finance of the Securities and Exchange Commission.

 Pursuant to
Rule 460 under the Act, we, as representatives of the several underwriters, wish to advise you that between April 29, 2019 through the date hereof we have distributed approximately 1,280 copies of the Company’s preliminary prospectus dated
April 29, 2019 to prospective underwriters, dealers, institutional investors and others.

 We, the undersigned, as representatives of the several
underwriters, have complied and will comply, and we have been informed by the participating underwriters that they have complied and will comply, with the requirements of Rule 15c2-8 under the Securities
Exchange Act of 1934, as amended.

 [Signature page follows]

Very truly yours,

MERRILL LYNCH, PIERCE, FENNER & SMITH

INCORPORATED

By:

 /s/ Charles Newton

                      Authorized Signatory

CREDIT SUISSE SECURITIES (USA) LLC

By:

 /s/ John Hoffman

                      Authorized Signatory

 [Signature Page to
Underwriters’ Acceleration Request]

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 May 6, 2019

 VIA
EDGAR

 U.S. Securities and Exchange Commission

 100
F Street, N.E.

 Washington, D.C. 20549

Attn:
 Suzanne Hayes

 Jeffrey Gabor

 Joseph McCann

Re:
 Cortexyme, Inc. Acceleration Request

Acceleration Request

Requested Date:

May 8, 2019

Requested Time:

3:30 p.m. Eastern Time

 Ladies and Gentlemen:

Cortexyme, Inc. (the “Company”) hereby requests that the Securities and Exchange Commission (the
“Commission”) take appropriate action to declare the Company’s Registration Statement on Form S-1 (File No. 333-230853), as amended, effective at the “Requested Date” and “Requested Time” set
forth above or as soon thereafter as practicable.

 The Company hereby authorizes Andrew D. Thorpe or Peter M. Lamb, both of whom are
attorneys with the Company’s outside legal counsel, Orrick, Herrington & Sutcliffe LLP, to orally modify or withdraw this request for acceleration.

The Company requests that it be notified of such effectiveness by a telephone call to Mr. Thorpe at (415) 773-5970, or in his absence,
Mr. Lamb at (650) 289-7117.

269 East Grand Ave.

 South San
Francisco, CA 94080

 Sincerely,

CORTEXYME, INC.

 By:

 /s/ Casey C. Lynch

Name: Casey C. Lynch

Title: President and Chief Executive Officer

cc:
 Chris Lowe, Cortexyme, Inc.

 Andrew D. Thorpe, Orrick, Herrington & Sutcliffe, LLP

 Peter M. Lamb, Orrick, Herrington & Sutcliffe, LLP

 Brian J. Cuneo, Latham & Watkins LLP

 B. Shayne Kennedy LLP, Latham & Watkins LLP

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 Orrick, Herrington & Sutcliffe LLP

1000 Marsh Road

Menlo Park, CA 94025-1015

 +1 650 614 7400

orrick.com

Andrew D. Thorpe

E athorpe@orrick.com

D +1 415 773 5970

 April 29, 2019

 VIA
EDGAR

 Suzanne Hayes

 Assistant Director, Office of
Healthcare & Insurance

 Division of Corporation Finance

United States Securities and Exchange Commission

 100 F Street,
N.E.

 Washington, DC 20549

Re:
 Cortexyme, Inc.

Draft Registration Statement on Form S-1

Submitted March 4, 2019

 CIK
No. 0001662774

 Dear Ms. Hayes:

 On behalf of our
client, Corteyxme, Inc. (the “Company”), we submit this letter to the Staff of the Securities and Exchange Commission (the “Commission”) with respect to the above referenced Registration Statement on Form S-1 (the “Registration Statement”). Set forth below is the Company’s supplemental response to Comment No. 2 in the letter from the staff of the Division of Corporation Finance (the
“Staff”) of the Commission in its letter dated April 2, 2019. The page references set forth in the Company’s responses below are to the Registration Statement.

 Suzanne Hayes

Assistant Director

 April 29, 2019

 Page
 2

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.

 Prior Response to the Staff
pursuant to the letter dated April 12, 2019:

 The Company confirms that once an estimated IPO price is available, it
will provide the Staff an explanation to progressively bridge the fair value per share determination in each valuation to the estimated IPO price per share.

Supplemental Response:

 To assist the
Staff in its evaluation of stock compensation disclosures and certain other matters in the Registration Statement, the Company advises the Staff that, considering information currently available and current market conditions based in part on input
received from its underwriters, the Company currently estimates a price range of $16.00 to $18.00 per share for the initial public offering (“IPO”) of the Company’s Common Stock, $0.001 par value per share (which is referred to in the
Registration Statement as the Company’s “common stock”). This per share price range reflects a reverse split of the Company’s common stock whereby each outstanding share will be exchanged for 0.367647 of a share (the
“Reverse Stock Split”), which the Company expects to reflect in the preliminary prospectus prior to the commencement of the roadshow. For consistency with the Registration Statement expected to be filed prior to commencement of the
roadshow, all data in this letter is reflected on a post-split basis. For clarity, the Company advises the Staff that, given the volatility of the public trading market and the uncertainty of the timing of the offering, the Company and the
underwriters have not yet agreed to a final price range for the offering, and the Company has not yet conclusively determined the size or ratio of the split of the common stock referred to above. Accordingly, the information in this letter provided
to the Staff is for illustrative purposes only and may differ in the actual preliminary prospectus for the offering.

 We confirm on behalf
of the Company that, prior to circulating copies of the preliminary prospectus in connection with the offering, the Company will file a pre-effective amendment to the Registration Statement that will include
the actual price range that complies with the Staff’s interpretation regarding the parameters of a bona fide price range.

 Suzanne Hayes

Assistant Director

 April 29, 2019

 Page
 3

 To facilitate the Staff’s review, we have included the table below, which is a complete
list of all grants of options to purchase the Company’s common stock made since January 1, 2018:

Grant date

Number of shares
of common stock
underlying options
granted

Exercise
price per
share of
common
stock

Estimated fair
value per share
of common
stock

 January 11, 2018

110,287

$
0.46

$
0.46

 July 25, 2018

51,469

$
2.23

$
2.23

 October 30, 2018

669,297

$
2.23

$
2.23

 November 28, 2018

485,289

$
2.23

$
2.23

 February 6, 2019

382,350

$
6.91

$
6.91

 February 28, 2019

14,705

$
6.91

$
6.91

 April 17, 2019

128,673

$
11.32

$
11.32

 As stated in the Registration Statement, the Company recognizes stock-based compensation expense based on the
estimated fair value of stock-based payment awards on the date of grant using the Black-Scholes option-pricing model (“OPM”). The Company uses the straight-line attribution method for recognizing compensation expense over the requisite
service period, which is generally the vesting period of the respective awards, and has elected to recognize the actual forfeitures by reducing the employee stock-based compensation expense in the same period as the forfeitures occur.

Stock-based compensation expense related to stock options granted to employees is measured at the date of grant based on the estimated fair
value of the award. Stock-based compensation expense related to stock options granted to non-employees is recognized based on the vesting date fair value of awards as the stock options are earned. The Company
recognizes the fair value of stock options granted to non-employees as stock-based compensation expense over the period in which the related services are received. Stock-based compensation expense related to
the restricted stock is recognized based on the vesting date fair value of the stock using the Black-Scholes pricing model.

Common Stock Valuations

As set forth in more detail on pages 76-78 of the Registration Statement, as there has been no public
market for the Company’s equity instruments to date, the estimated fair value of shares of the Company’s common stock has been determined by the Company’s Board of Directors (the “Board”) as of the grant date, with input
from management, considering the Company’s most recently available independent third-party valuation of the Company’s common stock and the Board’s assessment of additional objective and subjective factors that it believed were
relevant and which may have changed between the effective date of the most recent valuation and the date of the grant. Following is a discussion of the specific independent third-party valuations reviewed by the Board in establishing the fair market
value for each grant date.

 Under the OPM, the Board determined that the Company’s common stock had a per share value of $0.46 as of
November 30, 2017. As a private company, the analysis provided for a discount for lack of marketability (“DLOM”) of 35% as of November 30, 2017.

 Suzanne Hayes

Assistant Director

 April 29, 2019

 Page
 4

 Under the OPM, the Board determined that the Company’s common stock had a per share
value of $2.23 as of June 15, 2018. As a private company, the analysis provided for a discount for lack of marketability (“DLOM”) of 40% as of June 15, 2018.

Under the OPM, the Board determined that the Company’s common stock had a per share value of $2.23 as of October 31, 2018. As a
private company, the analysis provided for a DLOM of 40% as of October 31, 2018.

 Under Probability-Weighted Expected Return Method,
or PWERM and the OPM, the Board determined that the Company’s common stock had a per share value of $6.91 as of December 31, 2018. As a private company, the analysis provided for a DLOM of 20.76% as of December 31, 2018.

Under PWERM and the OPM, the Board determined that the Company’s common stock had a per share value of $11.32 as of March 31, 2019.
As a private company, the analysis provided for a DLOM of 13.54% as of March 31, 2019.

 The independent third-party valuations with
valuation dates of November 30, 2017, June 15, 2018, October 31, 2018, December 31, 2018, and March 31, 2019 weighted OPM and PWERM values based on multiple factors, including discussions with management regarding expected
exit outcomes. The per share fair value of the Company’s common stock under the OPM ($0.46) accounted for 100% of the valuation calculation for the valuation prepared as of November 30, 2017, resulting in a per share fair value of the
Company’s common stock of $0.46 as of November 30, 2017. The per share fair value of the Company’s common stock under the OPM ($2.23) accounted for 100% of the valuation calculation for the valuation prepared as of June 15, 2018,
resulting in a per share fair value of the Company’s common stock of $2.23 as of June 15, 2018. The per share fair value of the Company’s common stock under the OPM ($2.23) accounted for 100% of the valuation calculation for the
valuation prepared as of October 31, 2018, resulting in a per share fair value of the Company’s common stock of $2.23 as of October 31, 2018. The per share fair value of the Company’s common stock under the OPM ($1.24) and PWERM
($5.67) accounted for 18% and 82% of the valuation calculation, respectively, for the valuation prepared as of December 31, 2018, resulting in a per share fair value of the Company’s common stock of $6.91 as of December 31, 2018. The
per share fair value of the Company’s common stock under the OPM ($0.61) and PWERM ($10.71) accounted for 5.4% and 94.6% of the valuation calculation, respectively, for the valuation prepared as of March 31, 2019, resulting in a per share
fair value of the Company’s common stock of $11.32 as of March 31, 2019. As a private company, the analysis provided for a DLOM of 35% under the OPM for the valuation prepared as of November 30, 2017, a DLOM of 40% under the OPM for
the valuations prepared as of June 15, 2018 and October 31, 2018 and a DLOM of 20.76% and 13.54% under PWERM and the OPM for the valuations prepared as of December 31, 2018 and March 31, 2019, respectively, all of which is
accounted for in the per share fair values in this paragraph.

 The fair value determinations described above have been adjusted to reflect
the Reverse Stock Split, with the ultimate fair value amount for each date reflected as an adjustment to the respective fair value on each date rather than the individual components that combined together for the fair value on each date.

 Suzanne Hayes

Assistant Director

 April 29, 2019

 Page
 5

 Comparison of Estimated Offering Price Range and Recent Fair Value Determinations

 The anticipated price range for this offering was determined with reference to several quantitative and qualitative factors,
each of which contributed to the difference between the Company’s most recent valuation of its common stock as of December 31, 2018 of $6.91, and as of March 31, 2019 of $11.32, and the $17.00 midpoint of the anticipated offering
price range of $16.00 to $18.00 per share. Specifically, the Company believes that the difference between the fair value of its common stock determined on March 31, 2019 and the midpoint of the anticipated offering price range for this offering
is primarily the result of the following factors and events:

•

 The difference between the valuation as of December 31, 2018 and March 31, 2019 is attributable to a
number of significant business achievements between those two dates. First, the Company has made significant progress related to its Phase 2/3 clinical trial, which was launched on April 12, 2019. Second, the Company commenced the IPO process
after December 31, 2018, and the probability of an IPO exit increased between the two valuation dates. Finally, in January 2019, the Company published its pre-clinical and clinical data in a peer reviewed
medical journal, which may have raised the Company’s profile in the marketplace.

•

 A substantial amount of the difference in value between the March 31, 2019 common stock valuation of $11.32
per share and the midpoint of the offering price range of $17.00 per share is attributable to the fact that the public offering price does not factor in a DLOM. The anticipated price range for this offering necessarily assumes that the IPO has
occurred and that a public market for the Company’s common stock has been created, and, therefore, excludes any DLOM of the Company’s common stock, which was appropriately taken into account in the Company’s Board of Directors’
determination of the fair value of the Company’s common stock as of March 31, 2019. Stated differently, the anticipated offering price range effectively assigns a probability of 100% to an IPO outcome. The anticipated price range for this
offering is based only upon a scenario in which the Company completes this offering and is not probability weighted, in contrast to the Company’s prior valuations of common stock, which had to consider multiple potential outcomes, some of which
would have resulted in a lower value of the Company’s common stock than in an IPO. Accordingly, without any DLOM factored into the valuation, the Company’s March 31, 2019 common stock valuation would have been $16.51 per share, which
is within the anticipated public offering price range.

•

 The holders of the Company’s redeemable convertible preferred stock currently enjoy substantial economic
rights and preferences over the holders of its common stock. In particular, the holders of redeemable convertible preferred stock are entitled to receive liquidation payments prior to holders of common stock in the event of any liquidation,
dissolution or wind up of the Company. In addition, holders of the Company’s redeemable convertible preferred stock are entitled to receive dividends prior to any dividends declared or paid on any shares of the Company’s common stock. The
holders of redeemable convertible preferred stock also have anti-dilution protection under certain circumstances and special voting rights. The anticipated price range assumes the conversion of the Company’s redeemable convertible preferred
stock upon the completion of its IPO, and therefore, the corresponding elimination of the preferences and rights enjoyed by the holders of such redeemable convertible preferred stock. The anticipated elimination of the preferences and rights upon an
IPO results in an increased common stock valuation for the anticipated price range.

•

 The proceeds of a successful IPO would substantially strengthen the Company’s balance sheet by increasing
its cash resources. In addition, the completion of this offering would provide the Company with readier access to the public debt and equity markets. These projected improvements in the Company’s financial position influenced the increased
common stock valuation indicated by the midpoint of the anticipated price range.

•

 The price that investors may be willing to pay in this offering may take into account factors that have not been
expressly considered in the Company’s prior valuations as a private company, and are not objectively determinable and that valuation models are not able to quantify.

Conclusion

The Company has historically determined the fair value of its common stock consistent with the guidance set forth in the American Institute of
Certified Public Accountants Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (the “AICPA Practice Guide”), including, specifically, its use of the hybrid method using a
probability weighting of

 Suzanne Hayes

Assistant Director

 April 29, 2019

 Page
 6

the OPM and PWERM scenarios, which is an accepted valuation method under the AICPA Practice Guide. The Company believes that the probability weighting of each potential liquidity event used in
its fair value analysis was reasonable at the time, in light of the Company’s stage of development, including the status of its research and development efforts and

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 April 29, 2019

Via EDGAR

 Orrick, Herrington & Sutcliffe
LLP

 1000 Marsh Road

Menlo Park, CA 94025-1015

+1 650 614 7400

orrick.com

 Suzanne Hayes

 Assistant
Director, Office of Healthcare & Insurance

 Division of Corporation Finance

United States Securities and Exchange Commission

 100 F Street,
N.E.

 Washington, DC 20549

Re:
 Cortexyme, Inc.

Draft Registration Statement on Form S-1

Submitted March 4, 2019

 CIK
No. 0001662774

 Dear Ms. Hayes:

 On behalf of our
client, Cortexyme, Inc. (the “Company”), we submit this letter to the Staff of the Securities and Exchange Commission (the “Commission”) with respect to the above referenced Draft Registration Statement on Form S-1 (the “Draft Registration Statement”). Set forth below are the Company’s responses to the comments contained in the Staff’s letter dated April 25, 2019. The Staff’s
comments are repeated below in bold face type and followed by the Company’s responses in regular type. Concurrent with this letter, the Company is filing its Registration Statement on Form S-1/A (the
“Registration Statement”), which incorporates the Company’s responses to the Staff’s comments. The page references set forth in the Company’s responses below are to the Registration Statement. For the Staff’s reference,
we have included both a clean copy of the Registration Statement and a copy marked to show all changes from the version filed on April 16, 2019.

Amendment No. 1 to Registration Statement on Form S-1 Filed April 16, 2019

Summary of Our Clinical and Preclinical Data, page 86

1.
 We note your revisions in response to prior comment 4. Please revise the descriptions of the fifth
and sixth studies to indicate the type of cells studied. Also tell us where in the prospectus you discuss the final study referenced in the table.

Response:

 In response to the Staff’s
comment, the Company has revised the table on pages 88 and 89 of the prospectus to reference human SH-SY5Y cells, which is a neuroblastoma cell line from human neural tissue commonly used in neuroscience
research, that was used in the fifth study. In the same table, the Company clarified that the sixth study is a mouse brain study.

 The
final study is discussed in the prospectus on pages 95 and 100 of the prospectus. On page 95, the prospectus states, “However, among the identified gingipain substrates we have documented, tau is a target of gingipain proteolysis and
potentially contributes to the development and toxicity of tau tangles.” In addition, on page 100 of the prospectus, the Company discussed how ApoE, a target for gingipains, can be proteolytically cleaved into peptides consistent with those
identified by other researchers in the brain and by the Company in the cerebral spinal fluid, or CSF, of Alzheimer’s patients. In the Alzheimer’s patients treated with COR388, fragments of ApoE in the CSF were reduced compared to placebo.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 29, 2019

  Page
 2

 Exploratory Cognitive Testing, page 99

2.
 We note your response to prior comment 14 and note your revisions in this section and in the Summary. Please
tell us whether the three WLA measurements you present are the only WLA parameters that you consider to be key measurements for indicating the presence and severity of Alzheimer’s disease. In your response, tell us about the WLA testing that
you will conduct in your Phase 2/3 GAIN trial, including whether all 35 markers will be assessed.

 Response:

The Company’s Phase 1b clinical trial was an exploratory study to look for the drug effects of COR388 with appropriate statistical
methods, as noted on page 101 of the prospectus. Accordingly, the Company analyzed 35 speech parameters using Winterlight’s technology. Because WLA is a relatively new platform, there is limited evidence indicating which of the 35 parameters
are best for measuring the cognitive impairment in Alzheimer’s patients, and the effects of Alzheimer’s investigational treatments. It is a common technique in early clinical development to include a large number of readouts for the
purpose of identifying those with a signal to include in future studies. Correcting for multiple analyses, using statistical methods such as the conservative Bonferonni correction, as discussed in the Registration Statement, is important in order to
control for Type 1 error, or the increased chance of seeing significance on any single measure the more measures that are conducted. Standard statistics as well as Bonferonni corrected statistics are generally reported as the Company has done in the
Registration Statement.

 The three WLA measurements that the Company discusses in detail in the prospectus might not be the only
measurements for indicating the presence and severity of Alzheimer’s disease. The Company reports in detail on the three “key parameters” in its Phase 1b study because those parameters: (i) are clearly identified in the
scientific literature as some of the most important parameters in Alzheimer’s disease; (ii) impact communication and daily functions of Alzheimer’s disease patients (please see improvement in a patient’s communication in the
example below); and (iii) were shown to be useful in measuring the effects of COR388. The 32 other parameters that were not discussed in detail in the prospectus either showed trends of improvement that were not statistically significant, or
showed no meaningful changes over the course of the study. Additionally, the placebo group did not show any statistically significant improvements in any of the 35 measures.

In response to the Staff’s comment, the Company has amended page 101 of the prospectus to include additional description of the results.

 The statistical analysis plan for including WLA parameters in the GAIN study is still being finalized, but the Company intends to focus
only on the key parameters identified as useful for measuring potential effects of COR388 on Alzheimer’s disease. In response to the Staff’s comment, the Company has amended page 101 of the prospectus to clarify that the Company will not
include all 35 WLA parameters in the statistical analysis plan for the GAIN trial.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 29, 2019

  Page
 3

 Example

Winterlight: Examples of speech in 75-year-old female with
moderate AD before and after COR388 treatment.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 29, 2019

  Page
 4

 We appreciate your time and attention to the Company’s responses to the Staff’s comments. Should
you have any additional questions or concerns, please call me at (415) 773-5970.

 Very truly yours,

/s/ Andrew D. Thorpe

 Andrew D. Thorpe

cc:
 Casey C. Lynch, Cortexyme, Inc.

Christopher Lowe, Cortexyme, Inc.

Kristin Gafric, Esq., Cortexyme, Inc.

Scott Iyama, Esq., Orrick, Herrington & Sutcliffe LLP

Peter Lamb, Esq., Orrick, Herrington & Sutcliffe LLP

Brian J. Cuneo, Esq., Latham & Watkins LLP

B. Shayne Kennedy, Esq., Latham & Watkins LLP

Ross McAloon, Esq., Latham & Watkins LLP

Jeffrey Gabor, Esq., Securities & Exchange Commission

Joseph McCann, Esq., Securities & Exchange Commission

April 25, 2019
Casey C. Lynch
Chief Executive Officer
Cortexyme, Inc.
269 East Grand Ave.
South San Francisco, CA 94080
Re:Cortexyme, Inc.
Amendment No. 1 to Registration Statement on Form S-1
Filed April 16, 2019
File No. 333-230853
Dear Ms. Lynch:
            We have reviewed your amended 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 amending your registration statement and providing the
requested information.  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 any amendment to your registration statement and the information you
provide in response to these comments, we may have additional comments.  Unless we note
otherwise, our references to prior comments are to comments in our April 2, 2019 letter.
Amendment No. 1 to Registration Statement on Form S-1 Filed April 16, 2019
Summary of Our Clinical and Preclinical Data, page 86
1.We note your revisions in response to prior comment 4.  Please revise the descriptions of
the fifth and sixth studies to indicate the type of cells studied.  Also tell us where in the
prospectus you discuss the final study referenced in the table.

 FirstName LastNameCasey C. Lynch
 Comapany NameCortexyme, Inc.
 April 25, 2019 Page 2
 FirstName LastName
Casey C. Lynch
Cortexyme, Inc.
April 25, 2019
Page 2
Exploratory Cognitive Testing, page 99
2.We note your response to prior comment 14 and note your revisions in this section and in
the Summary.  Please tell us whether the three WLA measurements you present are the
only WLA parameters that you consider to be key measurements for indicating the

presence and severity of Alzheimer's disease.  In your response, tell us about the WLA
testing that you will conduct in your Phase 2/3 GAIN trial, including whether all 35
markers will be assessed.
            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.

CORRESP
1
filename1.htm

CORRESP

 April 12, 2019

Via EDGAR

 Orrick, Herrington & Sutcliffe LLP

1000 Marsh Road

 Menlo Park, CA 94025-1015

 +1 650 614 7400

 orrick.com

 Suzanne Hayes

 Assistant
Director, Office of Healthcare & Insurance

 Division of Corporation Finance

United States Securities and Exchange Commission

 100 F Street,
N.E.

 Washington, DC 20549

Re:

Cortexyme, Inc.
Draft Registration Statement on Form S-1
Submitted March 4, 2019
CIK No. 0001662774

 Dear Ms. Hayes:

 On behalf
of our client, Cortexyme, Inc. (the “Company”), we submit this letter to the Staff of the Securities and Exchange Commission (the “Commission”) with respect to the above referenced Draft Registration Statement on Form S-1 (the “Draft Registration Statement”). Set forth below are the Company’s responses to the comments contained in the Staff’s letter dated April 2, 2019. The Staff’s comments
are repeated below in bold face type and followed by the Company’s responses in regular type. Concurrent with this letter, the Company is filing its Registration Statement on Form S-1 (the
“Registration Statement”), which incorporates the Company’s responses to the Staff’s comments. The page references set forth in the Company’s responses below are to the Registration Statement. For the Staff’s reference,
we have included both a clean copy of the Registration Statement and a copy marked to show all changes from the version confidentially submitted on March 4, 2019.

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 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.

 Response:

In response to the Staff’s comment, the Company has revised the prospectus Summary and throughout the Business Section to include the
requested disclosure. In addition, we amended the pertinent risk factor on pages 15 and 16 of the prospectus.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 2

 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.

 Response:

The Company confirms that once an estimated IPO price is available, it will provide the Staff an explanation to progressively bridge the fair
value per share determination in each valuation to the estimated IPO price per share.

 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.

 Response:

In response to the Staff’s comment, the Company has revised page 78 of the prospectus to include the requested disclosure.

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. gingivalis in the brain;

•

 the causal link between P. gingivalis and Alzheimer’s; and

•

 successful treatment of Alzheimer’s disease pathology with gingipain inhibitors, including with your
COR388 inhibitor.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 3

 Response:

In response to the Staff’s comment, the Company has revised pages 87 and 88 of the prospectus to include the requested disclosure.

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. gingivalis DNA from multiple genes, confirming the
presence of bacteria (page 89).

 Response:

In response to the Staff’s comment, the Company has revised pages 3 and 92 of the prospectus to include the requested disclosure.

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.

Response:

 The Company respectfully
acknowledges the Staff’s comment, and advises the Staff that the Company has elected to remove the terms “demonstrated effects,” “positive trends of improvement,” “clinically meaningful” and “numerical trends
of improvement,” and the disclosure on pages 2, 15, 85, 86, 95, 96, 97 and 99 have been modified accordingly. In addition, the phrase “clinically significant trends” was eliminated on pages 2, 15, 16, 85, 86 and 96, and the Company
added more specificity on the clinical results from its Phase 1a and 1b clinical trials under the section entitled “Our COR388 Clinical Results.”

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 4

7.
 We note your disclosures on pages 89 and 93 indicating that you have developed proprietary technology
to test for the presence of P. gingivalis 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. gingivalis in the human brain.

 Response:

The Company respectfully advises the Staff that it has developed a method to assess the presence of P. gingivalis DNA in human cerebral
spinal fluid, or CSF, because there are no currently available methods to sample human brain tissue for bacterial DNA from live subjects and no imaging technology currently available for the detection of the bacteria in the brain of live subjects.
The detection of multiple bacterial genes in human brain tissue using quantitative polymerase chain reaction, or qPCR, as well as the detection of gingipain proteins by immunohistochemical, or IHC, analysis was all completed on available postmortem
brain tissue samples. In the process of developing this method of detection in CSF, which can be obtained using a lumbar puncture from subjects under a clinical protocol, the Company identified that the bacterial DNA found in CSF was fragmented and
was not composed of intact bacterial genomic DNA. The Company also identified that levels were low enough to require a highly sensitive PCR methodology.

Challenges inherent in the detection of CSF and unique from the detection in postmortem brain tissue include: The DNA found is fragmented and
represents a fraction of the genomic bacterial DNA present in the whole brain; because the DNA is fragmented it is a qualitative measure of the presence of a central nervous system infection and, while specific amounts of DNA can be identified in a
specified volume of CSF, the Company cannot currently correlate it to a specific amount of bacteria present in whole brain tissue; the level of fragmented DNA is small and isolation of small amounts of DNA is subject to high variability; CSF is a
biofluid that turns over regularly and will contain DNA that has been released or shed with a recent known timeframe. However, CSF has an advantage in that it circulates throughout the entire brain and, as such, represents not just a small sampling
of one area of the brain, but a representation of bacterial DNA present throughout the brain tissue. CSF is also readily available with a significant volume that can be sampled from subjects in a clinical trial setting before and after treatment.

 In response to the Staff’s comment, the Company has revised pages 92 and 98 of the prospectus to include the requested disclosure.

 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.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 5

 Response:

In response to the Staff’s comment, while the Company believes that it was the first to discover P. gingivalis and gingipains in
the brain, other researchers have also identified P. gingivalis in the brain, and published their findings. As such, the Company has revised pages 1, 72 and 85 of the prospectus to change all references to “our” seminal discovery to
“the” seminal discovery.

 The Company respectfully advises the Staff that certain researchers at the University of Auckland are
referenced as co-authors, together with the Company, of the paper published in the peer reviewed journal, Science Advances, that was cited in the prospectus. In response to the Staff’s
comment, the Company has revised page 91 of the prospectus to clarify that the statements from that paper are attributable to the Company. The prospectus refers to two other independently conducted academic studies that were published in peer
reviewed journals that are publicly available without a subscription.1

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.

Response:

 In response to the
Staff’s comment, the Company has revised page 92 of the prospectus to include disclosure of the criteria that supports a causal relationship between P. gingivalis and Alzheimer’s disease.

10.
 We refer to your disclosure on page 1 highlighting that you have “observed that
P. gingivalis 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.

 Response:

 In
response to the Staff’s comment, the Company has revised pages 92 and 93 of the prospectus to include the requested disclosure.

1
 Illievski, V., Zuchowska, P., Green, S., Toth, P., Ragozzino, M., et al. “Chronic oral application of a
periodontal pathogen results in brain inflammation, neurodegeneration and amyloid beta production in wild type mice.” PLoS ONE. October 2018; Poole, S., Singhrao, S., Kesavalu, L., Curtis, M., Crean, S. “Determining the Presence of
Periodontopathic Virulence Factors in Short-Term Postmortem Alzheimer’s Disease Brain Tissue.” Journal of Alzheimer’s Disease. Volume 36, Number 4, August 2013.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 6

 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.

Response:

 The Company respectfully
acknowledges the Staff’s comment. The Company respectfully advises the Staff that standard Phase 1 studies have a primary goal of assessing for any safety signals, and, because the safety is not known a priori, Phase 1 studies are not
constructed or designed to be powered to assess statistical significance for any endpoints. The Company further advises the Staff that, despite safety being the primary analysis for a Phase 1 study, it is also standard practice in the industry to
include and examine other measures (often referred to “exploratory endpoints”) whose result does not bear on the primary safety measure, to assess activity of the product candidate being evaluated. The assessments of the cognitive
endpoints in the Company’s Phase 1a/1b study were exploratory in nature, and, as customary, were designed to assess for potential signals of efficacy, and their approximate magnitude, to guide the design of future, more definitive studies. All non-primary outcome measures (e.g., non-safety related) are conducted, assessed and communicated in standard practice. There was an open IND
(“FDA-authorized”) for COR388, the protocols were submitted to the FDA, and they were reviewed and approved by IRBs, all of which are standard practice.

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.

 Response:

 The
Company respectfully advises the Staff’s that it did not select ADAS-Cog in the Phase I exploratory cognitive testing because ADAS-Cog is inherently highly variable
and, as such, typically requires large numbers of patients to provide reliable data. Accordingly, ADAS-Cog would not be an appropriate measure in Phase I exploratory testing. MMSE is typically used as a
screening tool to categorize Alzheimer’s disease patients as mild, moderate or severe and therefore this test was necessarily included at baseline and therefore used at study endpoints. CANTAB and WLA were selected because they are thought to
be more sensitive to changes in smaller studies, in part because they are computerized and thus less variable.

 Suzanne Hayes

 SEC Division
of Corporation Finance

 April 12, 2019

  Page
 7

13.
 Please revise your discussion of each of the three measures (MMSE, CANTAB, WLA) to explain the results in
Figure 7 a

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.