SecProbe.io

CORRESP
 1
 filename1.htm

 A lto
Neuroscience , Inc.

 650 Castro Street, Suite 450
Mountain View, CA 94041

 April 17, 2026

 Via EDGAR

 U.S. Securities and Exchange Commission

 Division of Corporation Finance

 100 F Street, N.E.

 Washington, D.C. 20549

 Attn:
 Lauren S. Hamill

 Re:
 A lto Neuroscience, Inc.

 Registration Statement on Form S-3 (File No. 333-294974)

 Request for Acceleration of Effective Date

 Ms. Hamill,

 In accordance with Rule 461 under the Securities Act of 1933, as amended,
the undersigned registrant (the " Registrant ") hereby requests that the Securities and Exchange Commission (the
" Commission ") take appropriate action to cause the above-referenced Registration Statement on Form S-3 (File
No. 333-294974) (the " Registration Statement ") to become effective on April 20, 2026, at 4:00 p.m. Eastern Time,
or as soon thereafter as is practicable, or at such other time as the Registrant or its legal counsel, Cooley LLP, may request by telephone
to the staff of the Commission. The Registrant hereby authorizes each of Courtney M.W. Tygesson and Madison A. Jones of Cooley LLP to
make such a request on its behalf.

 Once the Registration Statement has been declared effective, please
confirm that event with Courtney M.W. Tygesson of Cooley LLP, counsel to the Registrant, at (312) 881-6680 or ctygesson@cooley.com, or
in her absence, Madison A. Jones, at (202) 728-7087 or madison.jones@cooley.com.

 [Signature page follows]

 Very truly yours,

 Alto Neuroscience, Inc.

 By:
 /s/ Nicholas C. Smith

 Nicholas C. Smith

 Chief Financial Officer

 cc:

 Amit Etkin, M.D., Ph.D., Alto Neuroscience, Inc.
 Erin R. McQuade, Alto Neuroscience, Inc.
 Divakar Gupta, Cooley LLP

 Courtney M.W. Tygesson, Cooley LLP

 Madison A. Jones, Cooley LLP

 Signature Page to Company Acceleration Request
– S-3

April 16, 2026
Amit Etkin
Chief Executive Officer
Alto Neuroscience, Inc.
650 Castro St, Suite 450
Mountain View, CA 94041
Re:Alto Neuroscience, Inc.
Registration Statement on Form S-3
Filed April 10, 2026
File No. 333-294974
Dear Amit Etkin:
            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 Lauren Hamill at 303-844-1008 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:Courtney Tygesson

CORRESP
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 A lto
Neuroscience , INC.

 650 Castro Street, Suite 450
Mountain View, CA 94041

 December 8, 2025

 Via EDGAR

 U.S. Securities and Exchange Commission

 Division of Corporation Finance

 100 F Street, N.E.

 Washington, D.C. 20549

 Attn: Tyler
Howes

 Re:

 A lto Neuroscience, Inc.

 Registration Statement on Form S-3 (File No. 333-291834)

 Request for Acceleration of Effective Date

 Mr. Howes:

 In accordance with Rule 461 under the Securities Act of 1933, as amended,
the undersigned registrant (the " Registrant ") hereby requests that the Securities and Exchange Commission (the
" Commission ") take appropriate action to cause the above-referenced Registration Statement on Form S-3 (File
No. 333-291834) (the " Registration Statement ") to become effective on December 10, 2025, at 4:00 p.m. Eastern
Time, or as soon thereafter as is practicable, or at such other time as the Registrant or its legal counsel, Cooley LLP, may request by
telephone to the staff of the Commission. The Registrant hereby authorizes each of Courtney M.W. Tygesson and Madison A. Jones of Cooley
LLP to make such a request on its behalf.

 Once the Registration Statement has been declared effective, please
confirm that event with Courtney M.W. Tygesson of Cooley LLP, counsel to the Registrant, at (312) 881-6680 or ctygesson@cooley.com, or
in her absence, Madison A. Jones, at (202) 728-7087 or madison.jones@cooley.com.

 [Signature page follows]

 Very truly yours,

 Alto Neuroscience, Inc.

 By:

 /s/ Nicholas C. Smith

 Nicholas C. Smith

 Chief Financial Officer

 cc:

 Amit Etkin, M.D., Ph.D., Alto Neuroscience, Inc.
 Erin R. McQuade, Alto Neuroscience, Inc.
 Divakar Gupta, Cooley LLP

 Courtney M.W. Tygesson, Cooley LLP

 Madison A. Jones, Cooley LLP

CORRESP
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CORRESP

 ALTO NEUROSCIENCE, INC.

650 Castro Street, Suite 450

Mountain View, California 94041

 February 7,
2025

 Via EDGAR

 U.S. Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street,
N.E.

 Washington, D.C. 20549

 Attn: Daniel Crawford

Re:
 Alto Neuroscience, Inc.

Registration Statement on Form S-3 (File
No. 333-284667)

 Request for Acceleration of Effective Date

Daniel Crawford:

 In accordance with Rule 461 under the
Securities Act of 1933, as amended, the undersigned registrant (the “Registrant”) hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to cause the
above-referenced Registration Statement on Form S-3 (File No. 333-284667) (the “Registration Statement”) to become effective on
February 11, 2025, at 4:00 p.m. Eastern Time, or as soon thereafter as is practicable, or at such other time as the Registrant or its legal counsel, Cooley LLP, may request by telephone to the staff of the Commission. The Registrant hereby
authorizes each of Courtney M.W. Tygesson and Madison A. Jones of Cooley LLP to make such a request on its behalf.

 Once the Registration Statement has
been declared effective, please confirm that event with Courtney M.W. Tygesson of Cooley LLP, counsel to the Registrant, at (312) 881-6680 or ctygesson@cooley.com, or in her absence, Madison A. Jones at (202) 728-7087 or madison.jones@cooley.com.

 [Signature page follows]

Very truly yours,

Alto Neuroscience, Inc.

By:

 /s/ Nicholas Smith

Nicholas Smith

Chief Financial Officer

cc:

Amit Etkin, Alto Neuroscience, Inc.

Erin McQuade, Alto Neuroscience, Inc.

Divakar Gupta, Cooley LLP

Christina Roupas, Cooley LLP

Courtney M.W. Tygesson, Cooley LLP

Madison A. Jones, Cooley LLP

 Signature Page to Company Acceleration Request – S-3

February 7, 2025
Amit Etkin, M.D., Ph.D.
President and Chief Executive Officer
Alto Neuroscience, Inc.
650 Castro Street, Suite 450
Mountain View, CA 94041
Re:Alto Neuroscience, Inc.
Registration Statement on Form S-3
Filed February 3, 2025
File No. 333-284667
Dear Amit Etkin M.D., Ph.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:Madison Jones, Esq.

CORRESP
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CORRESP

 January 30, 2024

VIA EDGAR

 U.S. Securities and Exchange Commission

 Division of Corporation Finance

 Office of Life Sciences

 100 F Street, N.E.

 Washington, D.C. 20549

Attn: Lauren Hamill, Tim Buchmiller, Li Xiao, Mary Mast

Re:
 Alto Neuroscience, Inc.

Registration Statement on Form S-1, as amended

File No. 333-276495

Acceleration Request

Requested Date: Thursday, February 1, 2024

Requested Time: 4:30 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 Alto Neuroscience, Inc. (the “Company”) for acceleration of the
effective time of the above-referenced Registration Statement, requesting effectiveness as of 4:30 P.M., Eastern Time, on February 1, 2024, or at such later time as the Company or its outside counsel, Cooley 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, please
be advised that we will take reasonable steps to secure adequate distribution of the preliminary prospectus to underwriters, dealers, institutions and others, prior to the requested effective time of the Registration Statement.

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,

 JEFFERIES LLC

COWEN & COMPANY, LLC

 STIFEL, NICOLAUS &
COMPANY, INCORPORATED

As representatives of the underwriters

JEFFERIES LLC

By:

/s/ Michael Brinkman

Name:

Michael Brinkman

Title:

Managing Director & Joint U.S. Head

of Biopharmaceuticals

COWEN & COMPANY, LLC

By:

/s/ Bill Follis

Name:

Bill Follis

Title:

Managing Director

STIFEL, NICOLAUS & COMPANY, INCORPORATED

By:

/s/ Nick Oust

Name:

Nick Oust

Title:

Managing Director

 [Signature Page to Underwriters’ Acceleration Request]

CORRESP
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CORRESP

 Alto Neuroscience, Inc.

369 South San Antonio Road

 Los
Altos, CA 94022

 January 30, 2024

 VIA EDGAR

 U.S. Securities and Exchange Commission

 Division
of Corporation Finance

 Office of Life Sciences

 100 F
Street, N.E.

 Washington, D.C. 20549

 Attn: Lauren Hamill,
Tim Buchmiller, Li Xiao, Mary Mast

 Re: Alto Neuroscience, Inc.

Registration Statement on Form S-1, as amended (File
No. 333-276495)

 Request for Acceleration of Effective Date

Ladies and Gentlemen:

 Pursuant to Rule 461 of the General Rules
and Regulations under the Securities Act of 1933, as amended, Alto Neuroscience, Inc. (the “Company”) hereby requests that the U.S. Securities and Exchange Commission (the “Commission”) accelerate the effective date
of the above-referenced Registration Statement on Form S-1 (as amended to date, the “Registration Statement”) and declare the Registration Statement effective as of 4:30 p.m. Eastern time, on
February 1, 2024, or as soon thereafter as possible, or at such other time as its legal counsel, Cooley LLP, may request by telephone to the staff of the Commission.

Once the Registration Statement has been declared effective, please orally confirm that event with Divakar Gupta of Cooley LLP at (212) 479-6474 or, in his absence, Christina Roupas of Cooley LLP at (312) 881-6670.

Under separate cover, you will receive today a letter from the managing underwriters of the proposed offering joining in the Company’s request for
acceleration of the effectiveness of the Registration Statement.

Very truly yours,

 Alto Neuroscience, Inc.

/s/ Amit Etkin

By:

 Amit Etkin, M.D., Ph.D.

Title:

 President and Chief Executive Officer

 cc: Nicholas Smith, Alto Neuroscience, Inc.

Erin McQuade, Alto Neuroscience, Inc.

 Divakar Gupta, Cooley LLP

 Christina Roupas, Cooley LLP

 Courtney Tygesson, Cooley LLP

 Laurie Bauer, Cooley LLP

 Nathan Ajiashvili,
Latham & Watkins LLP

 Christopher Lueking, Latham & Watkins LLP

Ross McAloon, Latham & Watkins LLP

CORRESP
1
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CORRESP

 Divakar Gupta

 +1 212 479 6474

dgupta@cooley.com

VIA EDGAR

 January 25, 2024

 U.S.
Securities and Exchange Commission

 Division of Corporation Finance

Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

Attn:
 Lauren Hamill

 Tim Buchmiller

 Li Xiao

 Mary Mast

Re:
 Alto Neuroscience, Inc.

 Correspondence filed January 19, 2024

 File No. 333-276495

Ladies and Gentlemen:

 On behalf of Alto Neuroscience, Inc. (the
“Company”), in response to a discussion with the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) on January 25, 2024 regarding the
Staff’s comment letter dated January 23, 2024 (the “Comment Letter”), relating to the Company’s correspondence submitted to the Commission on January 19, 2024 and January 24, 2024 pertaining to the
Registration Statement on Form S-1 (the “Registration Statement”), we are submitting this supplemental letter to further address Comment No. 1 of the Comment Letter. For the
convenience of the Staff, we have incorporated the relevant text of Comment No. 1 in italicized type into this letter, which is followed by the Company’s response with respect to such portion of Comment No. 1 of the Comment Letter.

 Staff Comment

 Correspondence filed
January 19, 2024

 General

1.
 We have read your response to our prior comment number 38 in our letter dated December 19, 2023. Please
address the following:

 …

•

 Please clarify how you are determining the enterprise value for the November 20, 2023
valuation.

 Cooley LLP 55 Hudson Yards New
York, NY 10001

 T:+1 212 479 6000 f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 25, 2024

 Page Two

 Response: In response to the Staff’s comment, the Company advises the Staff that it determined
the enterprise value for the November 20, 2023 Valuation using a market-based approach, taking into account the Series C convertible preferred stock financing as an arms-length transaction with new investors in the Company and applying an
increase in value aligned with recent biotechnology company IPOs. This methodology resulted in an enterprise value within the preliminary price range proposed for the IPO. To determine the fair market value of the common stock, the Company then used
a backsolve method assuming a weighting between an IPO scenario and a non-IPO scenario based on the likelihood of each determined at the time. This valuation methodology, consistent with all historical
valuation approaches by the Company, is consistent with the guidelines for determining fair market value outlined in the outlined in the American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of
Privately-Held-Company Equity Securities Issued as Compensation.

 The Company further advises the Staff that it intends to include disclosure in an
amendment to the Registration Statement consistent with the foregoing explanation.

 *    *    *

 Cooley LLP 55 Hudson
Yards New York, NY 10001

 T:+1 212 479 6000 f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 25, 2024

 Page Three

 Please contact me at (212) 479-6474 with any questions or further
comments regarding the Company’s response to the Staff’s comment.

 Sincerely,

/s/ Divakar Gupta

 Divakar Gupta

 Cooley LLP

cc:
 Amit Etkin, M.D., Ph.D., Alto Neuroscience, Inc.

Nicholas Smith, Alto Neuroscience, Inc.

Erin McQuade, Alto Neuroscience, Inc.

Christina Roupas, Cooley LLP

Courtney Tygesson, Cooley LLP

Laurie Bauer, Cooley LLP

 Nathan
Ajiashvili, Latham & Watkins LLP

 Christopher Lueking, Latham & Watkins LLP

Ross McAloon, Latham & Watkins LLP

 Cooley LLP 55 Hudson
Yards New York, NY 10001

 T:+1 212 479 6000 f:+1 212 479 6275 cooley.com

CORRESP
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CORRESP

 Divakar Gupta

 +1 212 479 6474

dgupta@cooley.com

 VIA EDGAR

 January 24, 2024

 U.S.
Securities and Exchange Commission

 Division of Corporation Finance

Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

Attn:
 Lauren Hamill

Tim Buchmiller

 Li Xiao

Mary Mast

Re:
 Alto Neuroscience, Inc.

Correspondence filed January 19, 2024

File No. 333-276495

Ladies and Gentlemen:

 On behalf of Alto Neuroscience, Inc.
(the “Company”), in response to comments from the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) received by letter dated January 23,
2024 (the “Comment Letter”), relating to the Company’s correspondence submitted to the Commission on January 19, 2024 pertaining to the Registration Statement on Form S-1 (the
“Registration Statement”), we are submitting this supplemental letter to further address Comment No. 1 of the Comment Letter. For the convenience of the Staff, we have incorporated the text of Comment No. 1 in
italicized type into this letter, which is followed by the Company’s response with respect to each bullet of Comment No. 1 of the Comment Letter.

Staff Comment

 Correspondence filed
January 19, 2024

 General

1.
 We have read your response to our prior comment number 38 in our letter dated December 19, 2023. Please
address the following:

•

 Tell us the circumstances that resulted in the repricing of options in April 2023 and if the repricing
occurred after internal discussions relating to a possible IPO.

 Response: In response to the Staff’s comment, the
Company respectfully advises the Staff that the repricing of options to purchase 1,658,667 shares of the Company’s common stock, par value $0.001 per share (the “Common Stock”) occurred in April 2023 following the
closing of the final tranche of the Company’s Series B convertible preferred stock financing (the “Series B Preferred Stock Financing”) in January 2023, which represented 42% of the total Series B Preferred Stock
Financing and a 10% reduction in the price per share of the Series B Preferred Stock relative to earlier tranches of the financing. The Board of Directors of the Company (the “Board”) determined the fair value of the Common
Stock at the time of

 Cooley LLP 55 Hudson Yards New York, NY 10001

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 U.S. Securities and Exchange Commission

January 24, 2024

 Page Two

the repricing to be $2.80 per share based on a number of factors, including the independent third-party valuation of the Common Stock as of December 31, 2022 (the
“December 31, 2022 Valuation”). At the time of the December 31, 2022 Valuation and the subsequent repricing, no internal discussions regarding a possible initial public offering
(“IPO”) had occurred and there had been no steps undertaken to commence an IPO process.

•

 Tell us the vesting period for each of the option grants since January 1, 2023. If any of
the grants vest upon the IPO, please tell us why any additional stock compensation using the mid-point of the IPO price, would not be material to the company’s results of operations.

 Response: In response to the Staff’s comment, the Company respectfully advises the Staff that the Company has granted the
following stock option awards since January 1, 2023:

Date of Grant

Numbers of
Shares Subject
to Stock
Options Granted

Exercise Price
Per Share of
Common Stock

Estimated Fair
Value Per Share
of Common
Stock at Grant
Date

Vesting Terms

 April 14, 2023

1,572,271

$
2.80

$
2.80

(2)

 April 19, 2023

1,658,667
(1)

$
2.80

$
2.80

(2)

 July 12, 2023

67,000

$
2.80

$
2.80

(2)

 October 12, 2023

343,500

$
2.80

$
2.80

(2)

 December 20, 2023

1,975,000

$
2.38

$
2.38

(2)(3)

(1)
 Previously granted options to purchase an aggregate of 1,658,667 shares of Common Stock were repriced on
April 19, 2023 to provide for an exercise price of $2.80 per share. The Company treated the repricing as a modification of terms of the options outstanding. Please see page F-48 of the Registration
Statement for further information regarding the repricing.

(2)
 This stock option vests over a period of four years, with 25% of the shares of Common Stock underlying the
option vesting on the one year anniversary of the applicable vesting commencement date, and 1/48 of the shares of Common Stock underlying the option vesting on a monthly basis thereafter, subject to continued service through each vesting date.

(3)
 An aggregate of 433,333 of these stock options vests upon completion of the Company’s IPO.

•

 Clarify the conversion ratio of the preferred stock issuance on November 20, 2023 and
explain to us why, given the proximity to the IPO process, the fair value of the common stock was not comparable to the fair value of the preferred stock at that time. Tell us what discussions occurred with the preferred stock investors relating to
the timing of your anticipated IPO.

 Response: In response to the Staff’s comment, the Company advises the Staff that
the Series C convertible preferred stock (the “Series C Preferred Stock”) issued on November 20, 2023 converts on a one-for-one basis into
Common Stock. Notwithstanding the conversion ratio, the Company and the Board believed it was appropriate for the fair market value of the Common Stock and the Series C Preferred Stock to be different for a variety of reasons, including the report
of the independent third-party valuation of the Common Stock as of November 20, 2023 (the “November 20, 2023 Valuation”). While the Company held an organizational meeting for an IPO on
October 20, 2023, the Company’s management continued to believe an IPO was unlikely during the foreseeable future as a result of then-ongoing adverse macroeconomic conditions, including specifically in the market for biotechnology
companies at that time. In addition, the Company received investor feedback during the financing of the Series C Preferred Stock (the “Series C Preferred Stock Financing”) that further led management to believe that there was
a low probability of a successful IPO in the foreseeable future. Furthermore, following its receipt of the proceeds from the Series C Preferred Stock Financing, the Company viewed its cash and cash equivalents on hand as sufficient to progress
through data readouts of ongoing clinical trials of its two leading product candidates. As a result,

 Cooley LLP 55 Hudson
Yards New York, NY 10001

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 U.S. Securities and Exchange Commission

January 24, 2024

 Page Three

management viewed the IPO as an opportunistic transaction that it would undertake only in the event that market conditions improved significantly during the limited period of 2024 before data
from the Company’s trials would become available. In its discussions with investors in the Series C Preferred Stock Financing, the Company addressed that it would continue to evaluate future capital-raising transactions, including an IPO
subject to significantly improved market conditions. However, the Company had no explicit discussions with new investors regarding the timing of the IPO, nor did it communicate that the Company had already commenced an IPO process.

In light of the above factors and the substantial economic rights and preferences of holders of Series C preferred stock over the holders of Common Stock, the
Company believes the discount in the fair value of the Common Stock relative to the fair value of the Series C convertible preferred stock was justified at the time of the November 20, 2023 Valuation.

•

 Tell us when the November 20, 2023 valuation report was issued and why the valuation did
not use a higher weighting for the IPO scenario given the proximity to filing your registration statement and the ongoing IPO process.

Response: In response to the Staff’s comment, the Company respectfully advises the Staff that November 20, 2023 Valuation was officially
issued in January 2024, and a draft form of such report was taken into account by the Board in determining the fair value of the Company’s common stock at the time of the December 20, 2023 stock option grants. The Company furthermore
confirms that there were no changes between the draft report and the final report of the November 20, 2023 Valuation.

 Furthermore, at the time of
the November 20, 2023 Valuation, the Company still viewed the possibility of completing an IPO as unlikely, including as a result of the various factors discussed above such as then-ongoing adverse conditions in the market for biotechnology
companies and investor feedback relating to the Series C Preferred Stock Financing that limited management’s confidence in the possibility of a successful IPO during the foreseeable future.

•

 You state on page 6 that you did not initiate an IPO process in the period from January 2023 through October
2023. However you state on page 7 that you evaluated going public in the first half of 2024, including holding an organizational meeting for a potential IPO on October 20, 2023. Please tell us when internal discussions of the IPO
began and when your first meeting relating to the IPO occurred.

 Response: In response to the Staff’s comment, the
Company respectfully advises the Staff that any evaluation regarding a potential IPO to occur in the first half of 2024 related to conversations among the management team regarding the theoretical possibility of commencing an IPO process in the
event the Company was successful in completing its then-proposed Series C convertible preferred stock financing. However, such conversations did not reference specific details regarding a potential IPO, nor did the Company take any formal actions
toward the commencement of an IPO process at such time due to then-ongoing adverse market conditions affecting the biotechnology industry, including the global geopolitical environment, high interest rates and the after-market stock performance of
many of the companies that went public in 2023. In light of the receipt of a term sheet relating to the Series C Preferred Financing and ongoing progress in the Company’s clinical programs, the Board first discussed the timing of a potential
IPO during a meeting of the Board on October 12, 2023. The first meeting relating to the IPO then occurred with the organizational meeting on October 20, 2023.

 Cooley LLP 55 Hudson
Yards New York, NY 10001

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 U.S. Securities and Exchange Commission

January 24, 2024

 Page Four

•

 Tell us why the exercise price of the December 20, 2023 options was lowered from the
previous grants in the year given the market conditions, the preferred stock issuance price per share on November 20, 2023, and the stage of your IPO process, including receipt of comments relating to your initial registration
statement.

 Response: In response to the Staff’s comment, the Company advises the Staff that the decrease in exercise
price of the December 20, 2023 option grants relative to earlier grants in 2023 was primarily based on the completion of its Series C Preferred Stock Financing at a price of $4.7132 per share, which represented a 21.4% decrease from the closing
price of $6.00 per share received in the Series B Preferred Stock Financing. At the time of the November 20, 2023 Valuation and the closing of the Series C Preferred Stock Financing, market conditions remained challenging for biotechnology
companies, including for a number of biotechnology companies that had recently completed an IPO and whose stocks were trading at below their IPO issuance price. Accordingly and as discussed in additional detail in the Company’s responses above,
the Company viewed the possibility of completing an IPO at the time of the November 20, 2023 Valuation as unlikely. Furthermore, while the Company conducted “testing the waters” meetings with potential investors in reliance on
Section 5(d) of the Securities Act of 1933, as amended, from November 27, 2023 through December 20, 2023, the Company had not received sufficient feedback to date to support advancement of the IPO as of the date of the
December 20, 2023 option grants. Therefore, at the time of such option grants, the Company continued to believe the likelihood of conducting an IPO remained low. The Company’s optimism in completing the IPO increased shortly following
these grants, first as a result of the announcement on December 22, 2023 of the acquisition of a competitor of the Company in the neuropsychiatric drug field. Later, following additional testing the waters meetings between January 8-11, 2024 with potential investors, the Company became confident based on investor feedback that it had sufficient investor interest to proceed with the IPO and at a potential valuation that would be acceptable to
the Company’s current investors and the Board.

•

 Tell us why the DLOM at November 20, 2023 was not significantly below the DLOM for the
December 31, 2022 valuation, given the ongoing IPO process. In addition, tell us why the DLOM would be the same for both the sale and IPO scenarios.

Response: In response to the Staff’s comment, the Company directs the Staff to its responses above regarding the factors affecting the
November 20, 2023 Valuation. The Company further advises the Staff that a change in the DLOM for the sale and IPO scenarios would not result in a material difference in the price per share of Common Stock in the November 20, 2023
Valuation.

•

 Please clarify how you are determining the enterprise value for the November 20, 2023
valuation.

 Cooley LLP 55 Hudson
Yards New York, NY 10001

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 U.S. Securities and Exchange Commission

January 24, 2024

 Page Five

 Response: In response to the Staff’s comment, the Company advises the Staff that it determined
the enterprise value for the November 20, 2023 Valuation based on the valuation of the Company following the Series C Preferred Stock Financing, multiplied by 1.25. The Company believes this increase was reasonable based on a review of
comparable companies in the biotechnology industry, and represented a potentially aggressive increase in valuation from the Series C Preferred Stock Financing as current step-up metrics in the biotechnology
space into an IPO is averaging 1.2x.

 Disclosure in the Registration Statement on Form S-1

In light of the Comment Letter and the Company’s discussion with the Staff on January 24, 2024, the Company respectfully advises the Staff that it
intends to revise the disclosure within the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies and Significant Judgments and Estimates— Determination
of the Fair Value of Common Stock” in an amendment to the Registration Statement, by placing the following language between the fourth paragraph and fifth paragraphs of the section as currently included in the Registration Statement:

***

 Common Stock Valuations
and Stock Option Grants in 2023

 We have granted the following stock option awards since January 1, 2023:

 Date of Grant

Numbers of
Shares Subject
to Stock
Options Granted

Exercise
Price Per
Share of
Common
Stock

Estimated
Fair Value Per
Share of
Common
Stock at
Grant Date

 April 14, 2023

1,572,271

$
2.80

$
2.80

 April 19, 2023

1,658,667
(1)

$
2.80

$
2.80

 July 12, 2023

67,000

$
2.80

$
2.80

 October 12, 2023

343,500

$
2.80

$
2.80

 December 20, 2023

1,975,000

$
2.38

$
2.38

(1)
 Previously granted options to purchase an aggregate of 1,658,667 shares of Common Stock were repriced on
April 19, 2023 to provide for an exercise price of $2.80 per share. We treated the repricing as a modification of terms of the options outstanding. Please see Note 6 to our unaudited condensed consolidated financial statements included
elsewhere in this prospectus for further information regarding the repricing.

 Other

United States securities and exchange commission logo
January 23, 2024
Amit Etkin
Chief Executive Officer
Alto Neuroscience, Inc.
369 South San Antonio Road
Los Altos, CA 94022
Re:Alto Neuroscience, Inc.
Correspondence filed January 19, 2024
File No. 333-276495
Dear Amit Etkin:
            We have reviewed your correspondence dated January 19, 2024 pertaining to your
registration statement on Form S-1 filed January 12, 2024 and have the following comment.
            Please respond to this letter by amending your registration statement and providing the
requested information. If you do not believe a comment applies 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 this letter, we may have additional comments.
Correspondence filed January 19, 2024
General
1.We have read your response to our prior comment number 38 in our letter dated
December 19, 2023. Please address the following:
•Tell us the circumstances that resulted in the repricing of options in April 2023 and if
the repricing occurred after internal discussions relating to a possible IPO.
•Tell us the vesting period for each of the option grants since January 1, 2023. If any
of the grants vest upon the IPO, please tell us why any additional stock compensation
using the mid-point of the IPO price, would not be material to the company's results
of operations.
•Clarify the conversion ratio of the preferred stock issuance on November 20, 2023
and explain to us why, given the proximity to the IPO process, the fair value of the
common stock was not comparable to the fair value of the preferred stock at that
time. Tell us what discussions occurred with the preferred stock investors relating to
the timing of your anticipated IPO.

 FirstName LastNameAmit  Etkin
 Comapany NameAlto Neuroscience, Inc.
 January 23, 2024 Page 2
 FirstName LastName
Amit  Etkin
Alto Neuroscience, Inc.
January 23, 2024
Page 2
•Tell us when the November 20, 2023 valuation report was issued and why the
valuation did not use a higher weighting for the IPO scenario given the proximity to
filing your registration statement and the ongoing IPO process.
•You state on page 6 that you did not initiate an IPO process in the period from
January 2023 through October 2023. However you state on page 7 that you evaluated
going public in the first half of 2024, including holding an organizational meeting for
a potential IPO on October 20, 2023. Please tell us when internal discussions of the
IPO began and when your first meeting relating to the IPO occurred.
•Tell us why the exercise price of the December 20, 2023 options was lowered from
the previous grants in the year given the market conditions, the preferred stock
issuance price per share on November 20, 2023, and the stage of your IPO process,
including receipt of comments relating to your initial registration statement.
•Tell us why the DLOM at November 20, 2023 was not significantly below the
DLOM for the December 31, 2022 valuation, given the ongoing IPO process. In
addition, tell us why the DLOM would be the same for both the sale and IPO
scenarios.
•Please clarify how you are determining the enterprise value for the November 20,
2023 valuation.
            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.
            Refer to Rules 460 and 461 regarding requests for acceleration. Please allow adequate
time for us to review any amendment prior to the requested effective date of the registration
statement.
            Please contact Li Xiao at 202-551-4391 or Mary Mast at 202-551-3613 if you have
questions regarding comments on the financial statements and related matters. Please contact
Lauren Sprague Hamill at 303-844-1008 or Tim Buchmiller at 202-551-3635 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Divakar Gupta, Esq.

CORRESP
1
filename1.htm

CORRESP

 Divakar Gupta

 +1 212 479 6474

dgupta@cooley.com

VIA EDGAR

 *FOIA Confidential Treatment Request*

Confidential Treatment Requested by Alto Neuroscience, Inc.

in connection with its Registration Statement on Form S-1 (File
No. 333-276495)

 January 19, 2024

U.S. Securities and Exchange Commission

 Division of Corporation
Finance

 Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

Attn:
 Lauren Hamill

Tim Buchmiller

 Li Xiao

Mary Mast

Re:
 Alto Neuroscience, Inc.

Registration Statement on Form S-1

January 12, 2024

File No. 333-276495

Ladies and Gentlemen:

 On behalf of Alto
Neuroscience, Inc. (the “Company”), in response to comments from the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) received by letter
dated December 19, 2023 (the “Comment Letter”), relating to the Company’s draft Registration Statement on Form S-1 confidentially submitted to the Commission on
November 22, 2023 (the “DRS”), and which was subsequently updated by the Company with a Registration Statement on Form S-1 filed with the Commission on January 12, 2024 (the
“Registration Statement”), we are submitting this supplemental letter to further address Comment No. 38 of the Comment Letter. For the convenience of the Staff, we have incorporated the text of Comment No. 38 into
this letter.

 Due to the commercially sensitive nature of information contained in this letter, this submission is accompanied by the
Company’s request for confidential treatment for selected portions of this letter. The Company has filed a separate letter with the Office of Freedom of Information and Privacy Act Operations in connection with the confidential treatment
request pursuant to Rule 83 of the Commission’s Rules on Information and Requests (17 C.F.R. § 200.83).

 Cooley
LLP     55 Hudson Yards     New York, NY     10001

 T:+1 212 479
6000     f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 19, 2024

 Page Two

 Staff Comment

Unaudited Condensed Consolidated Financial Statements as of and for the Nine Months Ended September 30, 2023 and 2022

Note 2. Summary of Significant Accounting Policies and Basis of Presentation 6. Stock Based Plans, page F-46

38.
 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. Please discuss with the staff how to submit your response.

 Response:

Preliminary Price Range

 The
Company respectfully advises the Staff that the Company currently expects a price range of approximately $[***] to $[***] per share (the “Preliminary Price Range”) for the initial public offering
(“IPO”) of the Company’s common stock, par value $0.001 per share (the “Common Stock”), which Preliminary Price Range does not reflect the impact of a reverse stock split of the Common Stock that
the Company anticipates may be effected prior to the filing of, and reflected in, an amendment to the Registration Statement to be filed prior to the commencement of the Company’s road show (the “Reverse Stock Split”).
The share and per share numbers in this letter are presented on a pre-Reverse Stock Split basis. This Preliminary Price Range implies a pre-money equity valuation for
the Company of $[***] million to $[***] million.

 The Preliminary Price Range is based in part upon the Company’s prospects,
prospects for the biotechnology industry generally, the general condition of the securities markets and the recent market prices of, and the demand for, publicly traded shares of generally comparable companies in the biotechnology industry, as well
as input received from Jefferies LLC, Cowen and Company, LLC, and Stifel, Nicolaus & Company, Incorporated, the representatives of the several underwriters for the Company’s IPO (the “Representatives”). The
Company notes that, as is typical in IPOs, the Preliminary Price Range for the Company’s IPO was not derived using a formal determination of fair value or single valuation methodology but was determined by discussions among the Company and the
Representatives based on a variety of considerations and methodologies, including the assessment of the aforementioned factors.

 The
Company will include a narrower bona fide price range of the Common Stock, as adjusted for the Reverse Stock Split, in an amendment to the Registration Statement that will be filed prior to the commencement of the Company’s road show. However,
the parameters of the bona fide price range will be subject to then-current market conditions, continuing discussions with the Representatives and material business developments impacting the Company, and, due to the volatility in the securities
markets, in particular the volatility experienced in the market by recent IPO issuers, there is a possibility that the bona fide price range for the IPO may fall outside of the Preliminary Price Range. In any event, the Company confirms to the Staff
that the bona fide price range will comply with Item 501(b)(3) of Regulation S-K and C&DI 134.04.

 FOIA Confidential
Treatment Requested by Alto Neuroscience, Inc.

 Cooley LLP     55 Hudson Yards     New York,
NY     10001

 T:+1 212 479 6000     f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 19, 2024

 Page Three

 Common Stock Valuation Methodologies

As there has been no public market for the Common Stock to date, the Company’s board of directors (the “Board”)
has determined the estimated fair value of the Common Stock for purposes of granting equity awards, as of the date of each option grant, with input from management, considering (i) the Company’s most recent arm’s length sales of its
convertible preferred stock, (ii) the most recent third-party valuation of its Common Stock, and (iii) the Board’s assessment of additional objective and subjective factors that the Board believed were relevant and which may have
changed from the date of the most recent third-party valuation through the date of the grant. The Board considered various objective and subjective factors to determine the estimated fair value of the Common Stock as of each grant date, including:

•

 the prices of the Company’s convertible preferred stock sold to outside investors in arm’s length
transactions and the rights, preferences, and privileges of the Company’s convertible preferred stock as compared to those of the Common Stock, including liquidation and redemption preferences of the Company’s convertible preferred stock;

•

 the progress of the Company’s research and development programs, including the status and results of
clinical trials for the Company’s product candidates, development of the Company’s Precision Psychiatry Platform for the discovery and evaluation of potential brain-based biomarkers, and progress of the Company’s development and
manufacturing processes;

•

 the Company’s stage of development and business strategy, and material risks related to the Company’s
business;

•

 the hiring of key personnel and management;

•

 external market conditions affecting the biotechnology industry, and trends within the biotechnology industry;

•

 the Company’s financial position, including cash on hand, and historical and forecasted performance and
results of operations;

•

 the lack of an active public market for the Common Stock and the Company’s convertible preferred stock;

•

 the likelihood of achieving a liquidity event for the holders of Common Stock, such as an IPO or a sale of the
Company, given prevailing market conditions;

•

 the achievement of enterprise milestones, including entering into collaboration and license agreements;

•

 the analysis of IPOs and the market performance of similar companies in the biotechnology industry; and

•

 the economy in general.

The third-party valuations of the Common Stock that the Board considered in making its determinations were prepared in accordance with the
American Institute of Certified Public Accountants’ Accounting and Valuation Guide, Valuation of Privately-Held-Company Equity Securities Issued as Compensation (the “Practice Aid”), which prescribes several
valuation approaches for determining the value of an enterprise, such as the cost, market and income approaches, and various methodologies for allocating the value of an enterprise to its capital structure and specifically its common stock.

 FOIA Confidential
Treatment Requested by Alto Neuroscience, Inc.

 Cooley LLP     55 Hudson Yards     New York,
NY     10001

 T:+1 212 479 6000     f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 19, 2024

 Page Four

 In accordance with the Practice Aid, the Company considered the following methods for
allocating the enterprise value across its classes and series of capital stock to determine the estimated fair value of the Common Stock at each valuation date.

•

 Option Pricing Method (“OPM”). The OPM estimates the value of the
Common Stock using the various inputs in the Black-Scholes option pricing model. The OPM treats the rights of the holders of Common Stock as equivalent to that of call options on any value of the enterprise above certain break points of value
based upon the liquidation preferences of the holders of the Company’s convertible preferred stock, as well as their rights to participation, and the stock prices of the outstanding options. Thus, the value of the Common Stock can be determined
by estimating the value of its portion of each of these call option rights. Under this method, the Common Stock has value only if the funds available for distribution to stockholders exceed the value of the liquidation preference at the time of a
liquidity event, such as a merger or sale.

•

 Probability-Weighted Expected Return Method (“PWERM”). The PWERM is a
scenario-based analysis that estimates the value per share based on the probability-weighted present value of expected future investment returns, considering each of the possible outcomes considered by the Company, as well as the economic and
control rights of each share class.

•

 Hybrid Method (“Hybrid Method”). The Hybrid Method is a weighted-average
method that combines both OPM and PWERM. Weighting allocations are assigned to the OPM and PWERM methods factoring in possible future liquidity events.

To support the Board in determining the estimated fair value of the Common Stock as the Company sought to obtain better visibility into the
timing of a potential IPO, but accounting for uncertainty around the Company’s value should an IPO not occur, the OPM was utilized for the independent third-party valuation of the Common Stock as of December 31, 2022 (the
“December 31, 2022 Valuation”) and the Hybrid Method was utilized for the independent third party valuation of the Common Stock as of November 20, 2023 (the
“November 20, 2023 Valuation” and together with the December 31, 2022 Valuation, the “Valuations”), each as discussed below. The OPM and Hybrid Method are commonly
used in these situations and such use is consistent with guidance from the Practice Aid. In the Company’s case, the Hybrid Method incorporated two scenarios: (1) a sale scenario where the allocation of total equity value was performed
using the OPM, and (2) an IPO scenario where all outstanding shares of the Company’s convertible preferred stock were assumed to be mandatorily converted into shares of Common Stock. In addition, given the Common Stock represents a non-marketable equity interest in a private enterprise, an adjustment to the preliminary value estimates was made in each of the sale and IPO scenario to account for the lack of liquidity. This adjustment is
commonly referred to as a discount for lack of marketability (“DLOM”).

 At each grant date, the Board evaluated
any recent events and their potential impact on the estimated fair value per share of the Common Stock. For grants of awards made on dates for which there was no contemporaneous independent third-party valuation, the Board determined the estimated
fair value of the Common Stock on the date of grant taking into consideration the most recent valuation report as well as other pertinent information available to it at the time of the grant.

 FOIA Confidential
Treatment Requested by Alto Neuroscience, Inc.

 Cooley LLP     55 Hudson Yards     New York,
NY     10001

 T:+1 212 479 6000     f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 19, 2024

 Page Five

 Common Stock Valuations and Stock Option Grants

The Company granted the following stock option awards since January 1, 2023:

 Date of Grant

Numbers of
Shares Subject to
Stock Options
Granted

Exercise Price Per
Share of Common
Stock

Estimated Fair
Value Per Share of
Common Stock at
Grant Date

April 14, 2023

[
***]

$
[
***]

$
[
***]

April 19, 2023

[
***](1)

$
[
***]

$
[
***]

July 12, 2023

[
***]

$
[
***]

$
[
***]

October 12, 2023

[
***]

$
[
***]

$
[
***]

December 20, 2023

[
***]

$
[
***]

$
[
***]

(1)
 Previously granted options to purchase an aggregate of [***] shares of Common Stock were repriced on
April 19, 2023 to provide for an exercise price of $[***] per share. The Company treated the repricing as a modification of terms of the options outstanding. Please see page F-48 of the Registration
Statement for further information regarding the repricing.

 Other than the foregoing, there were no other equity
incentive awards granted by the Company since January 1, 2023.

 December 31, 2022 Valuation – April 14, 2023, July 12, 2023,
and October 12, 2023 Stock Option Grants and April 19, 2023 Repricing:

 On April 14, 2023, July 12, 2023, and
October 12, 2023, the Company granted stock options to purchase a total of [***] shares of Common Stock at an exercise price of $[***] per share. In addition, on April 19, 2023, the Company repriced previously granted outstanding options
to purchase an aggregated [***] shares of Common Stock to an exercise price of $[***] per share. The Board determined the fair value of the Common Stock at the time of each of the grants and at the time of the repricing to be $[***] per share based
on a number of factors, including the December 31, 2022 Valuation.

 For the December 31, 2022 Valuation, the fair value of the
Common Stock was estimated using the OPM. There were only 16 biotech IPOs in 2022 as compared to 98 in 2021. In addition, the Company had not yet given serious consideration to conducting an IPO, nor undertaken meaningful preparation toward an IPO.
Based on the overall lack of IPOs, and the Company’s actions to date, the Company determined that there was no likelihood of a near-term IPO.

The total equity values in the sale scenario were estimated using the backsolve method (the “Backsolve
Method”) as of January 26, 2023, the date of the final closing of the Series B convertible preferred stock financing (the “Series B Preferred Stock Financing”), and then rolled backwards to the valuation
date of December 31, 2022. The final sale and closing of the Series B Preferred Stock Financing was $25 million, or 42% of the total Series B Preferred Stock Financing, and was transacted with a new investor. The terms of the Series B
Preferred Stock Financing were known as of December 31, 2022 and deemed effective at that date.

 FOIA Confidential
Treatment Requested by Alto Neuroscience, Inc.

 Cooley LLP     55 Hudson Yards     New York,
NY     10001

 T:+1 212 479 6000     f:+1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 19, 2024

 Page Six

 For purposes of the December 31, 2022 Valuation, the OPM reflected the Company’s
issuance and sale of 9,876,955 shares of Ser

CORRESP
1
filename1.htm

CORRESP

Divakar Gupta

 T: (212) 479-6474

dgupta@cooley.com

Via EDGAR

 January 12, 2024

 U.S.
Securities and Exchange Commission

 Division of Corporation Finance

Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

Attention:
 Lauren Hamill

Tim Buchmiller

 Li Xiao

Mary Mast

Re:
 Alto Neuroscience, Inc.

Amendment No. 1 to Draft Registration Statement on Form S-1

Submitted December 28, 2023

CIK No. 0001999480

 Ladies and
Gentlemen:

 On behalf of Alto Neuroscience, Inc. (the “Company”), the following information is submitted in response to the
comments received from the staff (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) by letter dated January 9, 2024 (the “Comment Letter”)
regarding the above-referenced Amendment No. 1 to the draft Registration Statement on Form S-1, as confidentially submitted to the Commission on December 28, 2023. Concurrently with the submission of
this response letter, the Company is filing a revised Registration Statement on Form S-1 (the “Registration Statement”) with the Commission. In addition to addressing the comments
raised by the Staff in the Comment Letter, the Company has included other revisions and updates to its disclosure in the Registration Statement.

 For the
convenience of the Staff, the numbering of the paragraphs below corresponds to the numbering of the respective comment in the Comment Letter, the text of which we have incorporated into this response letter for convenience in italicized type and
which is followed by the Company’s response. In the responses below, page number references are to the Registration Statement.

 Amendment
No. 1 to Draft Registration Statement on Form S-1 Submitted December 28, 2023

 Prospectus
Summary

 Overview, page 1

1.
 We note your response to prior comment 3, which we reissue in part.

•

 Please describe, where appropriate, each of the discussions you have had with the FDA regarding your novel
approach to the discovery and development of your product candidates using your Platform, as well as any material outcomes of such discussions.

•

 Explain whether you are basing your current expectation that you may be required to develop and obtain FDA
approval of a companion diagnostic for any of your product candidates upon your prior discussions with the FDA. Also, please describe when you expect to know more definitively the FDA’s views on this subject and how such views may affect your
plans.

 Cooley LLP 55 Hudson Yards New York, NY 10001

t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 12, 2024

 Page Two

 Response: The Company respectfully advises the Staff that its discussions with the FDA concerning its
approach to developing its product candidates have occurred in the ordinary course of its clinical development process, including through submissions of clinical trial protocols and written feedback in response to meeting requests. In response to
the Staff’s comment, the Company has revised the disclosure on pages 2 and 125 of the Registration Statement and has added disclosure on page 145 of the Registration Statement to provide additional detail concerning its material
interactions with the FDA.

 Additionally, in response to the Staff’s comment, the Company has revised the disclosure on pages 2, 8, 9, 26, and 125 of
the Registration Statement to indicate that the Company expects to initiate discussions with the FDA concerning the development of companion diagnostics at its end of Phase 2 meetings with respect to ALTO-100
and ALTO-300.

2.
 We note your revisions in response to prior comment 5, which we reissue. Please further revise the
disclosure on pages 1, 103, and 123 to include the information contained in your response to prior comment 5 in your letter dated December 28, 2023 concerning your goal to ultimately provide treatments, if approved, that are
tailored to specific patient populations and explain how this might allow you to avoid the current lengthy paradigm of treating psychiatric patients.

Response: In response to the Staff’s comment, the Company has revised the disclosure on pages 1, 104, and 124 of the Registration Statement.

Our Pipeline, page 3

3.
 We note your revisions in response to prior comment 7, which we reissue in part. Please revise your
disclosure on pages 4, 104, and 125 to clarify whether or not the Company’s representatives have had any interaction to date with the FDA regarding its willingness to accept foreign clinical trial data underpinning the recently submitted IND
covering ALTO-203 in MDD. Also, please revise the Prospectus Summary to disclose the risk that the FDA or comparable regulators may not accept earlier clinical data generated abroad, in which case you may need
to conduct additional clinical trials, as referenced in your risk factor on page 31.

 Response: In response to the
Staff’s comment, the Company has revised the disclosure on pages 4, 105, and 126 of the Registration Statement.

4.
 We note your revisions in response to prior comment 13, which we reissue in part. Please further revise your
discussion of the clinical development of your ALTO-202 program here and in the Business section where appropriate to disclose the following information with respect to any material clinical trials that third
parties conducted:

•

 The trial design;

•

 The number of participants in the trial;

•

 The primary and secondary endpoints as well as the results as they relate to those endpoints; and

•

 The occurrence of any series adverse events.

 Cooley LLP 55 Hudson
Yards New York, NY 10001

 t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 12, 2024

 Page Three

 Additionally, please include a description of any material development activities you have conducted to
date since licensing ALTO-202, relevant clinical work conducted or in process, and the remaining steps to develop and commercialize the product and disclose when you plan to initiate a Phase 2 trial for ALTO-202 and expect to report data from that trial.

 Response: In response to the Staff’s comment, the
Company has revised the disclosure on page 158 of the Registration Statement. The Company respectfully advises the Staff that the Company is currently in the process of planning the next phase of clinical development for ALTO-202, which the Company expects to be informed by the outcomes of its ongoing Phase 2b trials of ALTO-100 and ALTO-300.

Risk Factor Summary, page 8

5.
 Consistent with your disclosure on page 162 and elsewhere, please revise your summary risk and risk factor
disclosure where appropriate to highlight that issued patents covering the composition of ALTO-202 are due to retire in 2024 (compound) and 2035 (polymorph) and patents covering the composition of ALTO-203 in 2027.

 Response: In response to the Staff’s comment, the Company has
revised the disclosure on pages 9, 48, and 63 of the Registration Statement.

 Business

ALTO-101 Biological Rationale, page 151

6.
 We note your response stating that you have revised disclosure on page 152 to ensure that the graphics
included are legible. However, we observe that the revisions are not sufficient to render your disclosures easily readable without magnification, as certain text remains too small to be clear. Please further review and revise as appropriate.

 Response: In response to the Staff’s comment, the Company has revised the graphic on page 153 as well as other
graphics throughout the Registration Statement to make them more easily readable.

 * * *

 Cooley LLP 55 Hudson
Yards New York, NY 10001

 t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

 U.S. Securities and Exchange Commission

January 12, 2024

 Page Four

 Please contact me at (212) 479-6474 with any questions or further
comments regarding the Company’s response to the Staff’s comments.

Sincerely,

/s/ Divakar Gupta

Divakar Gupta

cc:
 Amit Etkin, M.D., Ph.D., Alto Neuroscience, Inc.

Nicholas Smith, Alto Neuroscience, Inc.

Erin McQuade, Alto Neuroscience, Inc.

Christina Roupas, Cooley LLP

Courtney Tygesson, Cooley LLP

Laurie Bauer, Cooley LLP

 Nathan
Ajiashvili, Latham & Watkins LLP

 Christopher Lueking, Latham & Watkins LLP

Ross McAloon, Latham & Watkins LLP

 Cooley LLP 55 Hudson
Yards New York, NY 10001

 t: +1 212 479 6000 f: +1 212 479 6275 cooley.com

United States securities and exchange commission logo
January 9, 2024
Amit Etkin
Chief Executive Officer
Alto Neuroscience, Inc.
369 South San Antonio Road
Los Altos, CA 94022
Re:Alto Neuroscience, Inc.
Amendment No. 1 to Draft Registration Statement on Form S-1
Submitted December 28, 2023
CIK No. 0001999480
Dear Amit Etkin:
            We have reviewed your amended draft registration statement and have the following
comments.
            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 a comment applies 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 this letter and your amended
draft registration statement or filed registration statement, we may have additional comments.
Amendment No. 1 to Draft Registration Statement on Form S-1
Prospectus Summary
Overview, page 1
1.We note your response to prior comment 3, which we reissue in part.
•Please describe, where appropriate, each of the discussions you have had with the
FDA regarding your novel approach to the discovery and development of your
product candidates using your Platform, as well as any material outcomes of such
discussions.
•Explain whether you are basing your current expectation that you may be required to
develop and obtain FDA approval of a companion diagnostic for any of your product
candidates upon your prior discussions with the FDA.  Also, please describe when
you expect to know more definitively the FDA's views on this subject and how such
views may affect your plans.

 FirstName LastNameAmit  Etkin
 Comapany NameAlto Neuroscience, Inc.
 January 9, 2024 Page 2
 FirstName LastNameAmit  Etkin
Alto Neuroscience, Inc.
January 9, 2024
Page 2
2.We note your revisions in response to prior comment 5, which we reissue. Please further
revise the disclosure on pages 1, 103, and 123 to include the information contained in your
response to prior comment 5 in your letter dated December 28, 2023 concerning your goal
to ultimately provide treatments, if approved, that are tailored to specific patient
populations and explain how this might allow you to avoid the current lengthy paradigm
of treating psychiatric patients.
Our Pipeline, page 3
3.We note your revisions in response to prior comment 7, which we reissue in part.  Please
revise your disclosure on pages 4, 104, and 125 to clarify whether or not the Company's
representatives have had any interaction to date with the FDA regarding its willingness to
accept foreign clinical trial data underpinning the recently submitted IND covering
ALTO-203 in MDD. Also, please revise the Prospectus Summary to disclose the risk that
the FDA or comparable regulators may not accept earlier clinical data generated abroad,
in which case you may need to conduct additional clinical trials, as referenced in your risk
factor on page 31.
4.We note your revisions in response to prior comment 13, which we reissue in part. Please
further revise your discussion of the clinical development of your ALTO-202 program
here and in the Business section where appropriate to disclose the following information
with respect to any material clinical trials that third parties conducted:
•the trial design;
•the number of participants in the trial;
•the primary and secondary endpoints as well as the results as they relate to those
endpoints; and
•the occurrence of any serious adverse events.

Additionally, please include a description of any material development activities you have
conducted to date since licensing ALTO-202, relevant clinical work conducted or in
process, and the remaining steps to develop and commercialize the product and disclose
when you plan to initiate a Phase 2 trial for ALTO-202 and expect to report data from that
trial.
Risk Factor Summary, page 8
5.Consistent with your disclosure on page 162 and elsewhere, please revise your summary
risk and risk factor disclosure where appropriate to highlight that issued patents covering
the composition of ALTO-202 are due to retire in 2024 (compound) and 2035
(polymorph) and patents covering the composition of ALTO-203 in 2027.
Business
ALTO-101 Biological Rationale, page 151
6.We note your response stating that you have revised disclosure on page 152 to ensure that
the graphics included are legible. However, we observe that the revisions are not sufficient

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 January 9, 2024 Page 3
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Amit  Etkin
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January 9, 2024
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to render your disclosures easily readable without magnification, as certain text remains
too small to be clear.  Please further review and revise as appropriate.
            Please contact Li Xiao at 202-551-4391 or Mary Mast at 202-551-3613 if you have
questions regarding comments on the financial statements and related matters. Please contact
Lauren Hamill at 303-844-1008 or Tim Buchmiller at 202-551-3635 with any other questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Divakar Gupta

United States securities and exchange commission logo
December 19, 2023
Amit Etkin
Chief Executive Officer
Alto Neuroscience, Inc.
369 South San Antonio Road
Los Altos, CA 94022
Re:Alto Neuroscience, Inc.
Draft Registration Statement on Form S-1
Submitted November 22, 2023
CIK No. 0001999480
Dear Amit Etkin:
            We have reviewed your draft registration statement and have the following comments.
            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 a comment applies 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 this letter and your amended
draft registration statement or filed registration statement, we may have additional comments.
Draft Registration Statement on Form S-1 Submitted November 22, 2023
Prospectus Summary
Overview, page 1
1.Here and throughout the registration statement, please revise to disclose how you define
"late-stage" or remove statements that any of your product candidates are in "late-stage"
clinical trials, as these statements may imply that your products are farther along in the
development process than they actually are.
2.We note that a key element of your strategy is to build and expand your pipeline of
product candidates, including through your "differentiated biomarker-based approach"
that relies heavily on insights derived from your proprietary Precision Psychiatry Platform
(the "Platform").  Here and where appropriate throughout the prospectus, please expand
your discussion of your Platform to describe how it was built and how it grows. For
instance, discuss the scope of your data repository and explain whether lines of data are

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added through third-party data sets or libraries.  Also, address the "scalable" nature of
your Platform.  To the extent that the scalability of the Platform is currently aspirational,
please so state.
3.Please balance your discussion of your Platform and biomarkers-based approach to
matching potential drug responders with therapeutic product candidates.  Explain that
such approach is unproven and disclose, if true, that you anticipate that you will be
required to develop and obtain FDA approval of a companion diagnostic for such
therapeutic product candidates. Disclose whether or not you have had any conversations
with or received any input from the FDA to date regarding the use of your Platform and/or
your biomarkers-based approach to product development, and if so, describe the
outcome of such discussions.
4.We note your statements of belief that your Platform-driven approach to developing
therapeutics will enable you to improve upon the high failure rates of late-stage clinical
trials and improve your product candidates’ probability of clinical success. Please balance
these and other statements in your Summary by prominently highlighting that:
•your Platform is unproven and clinical evidence to support your approach is
preliminary and limited at this time;
•there can be no guarantee that your candidates will have an increased chance of
approval.
Make conforming revisions throughout, including in the Business section, as appropriate.
5.We note disclosure in the prospectus summary, in the section beginning on page 125,
and in other places throughout the prospectus regarding your pursuit of a strategy to match
patients to the right medication "quickly" or to quickly find patient populations more
likely to respond to a particular product candidate. Please revise these and any similar
disclosures throughout the prospectus to remove any implication that you will be
successful in obtaining necessary regulatory approvals or commercializing your product
candidates in a rapid or accelerated manner, as such statements are speculative given your
current stage of development. You may state, if true, that your goal is to develop drug
candidates more efficiently than current industry standards.
6.We note your disclosure at the end of the second paragraph on page 1 that you estimate
one or both of two independent biomarkers are present in approximately three-quarters of
the overall MDD population. We also note your disclosure in the table on page 2 that
30%-60% of patients are likely to be biomarker positive. Please revise your disclosure so
that investors can better understand how to reconcile these different percentages.
Our Pipeline, page 3
7.It appears that your current pipeline consists of clinical-stage assets that have been
acquired or in-licensed, and that in certain cases the originators of such candidates
progressed your candidates through certain phases of clinical development.  Please add
footnotes to your pipeline table to show which columns relate to work conducted by the
company and which, if any, relate to the work of third parties.  Also, as appropriate, please

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disclose where third party clinical trials were conducted and discuss any interaction the
company has had with the FDA regarding its ability to rely on such trial data in the event
any trials were not conducted in the United States.
8.To the extent that your product candidates were previously known by different names
prior to being acquired or in-licensed by your company, please revise your disclosure to
include these names.
9.We note that you disclose the potential timing of clinical trials you expect to initiate
without addressing whether you have active INDs for your clinical-stage candidates in
each indication you are studying.  Please revise to clarify.  If you do not have active INDs
for each candidate and indication, please disclose when you plan to submit INDs.

10.With respect to your study of ALTO-100 for PTSD:
•Please remove the reference in the pipeline table, and any other similar references
throughout the prospectus, to ALTO-100 for PTSD being "Phase 2b/3 ready" to
remove any implication that the FDA has signed off on a registrational trial for any of
your product candidates in any indication.
•If true, include a footnote to the table disclosing, as you have on page 4, that your
plans to continue study of ALTO-100 for PTSD are dependent upon generating
positive Phase 2b data from the ongoing trial of ALTO-100 for patients with MDD.
Clarify that there is no guarantee that the results from the ongoing trial will be
positive.
11.Please revise the narrative disclosure supporting the pipeline table appearing on pages 3
and 100 to support your statement that each of ALTO-101, ALTO-203 and ALTO-202 are
"Phase 2 ready."  In this regard, we note that it is unclear from your disclosure whether
you have active INDs for your product candidates in the indications you state you are
currently pursuing.
ALTO-101, page 5
12.Please revise this section to explain, if true, that ALTO-101 is being developed as a
combination product due its patch formulation.  Explain the implications of combination
product status with respect to the regulatory approval process.  Disclose whether or
not you have had any conversations with or received any input from the FDA to date
regarding the patch formulation of ALTO-101, and if so, describe the outcome of such
discussions.
Other Pipeline Programs, page 5
13.We note that the prospectus contains minimal discussion of your ALTO-202 program, and
as such, it is not clear why this program is sufficiently material to your current operations
to warrant being highlighted in the pipeline table appearing on pages 3 and 100.  To the
extent that ALTO-202 is currently material to your business, please expand your

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disclosure here and in your Business section to provide a more fulsome discussion of
that program, including a description of development activities you have conducted to
date, relevant clinical work conducted or in process, and the remaining steps to develop
and commercialize the product.  In this regard, your disclosure concerning clinical
work should support the positioning of the progress arrow in your pipeline table.

Risk Factor Summary, page 6
14.We note your disclosure on page 145 that you have reformulated ALTO-101 in a
transdermal patch formulation, as well as your disclosure on page 162 regarding the
regulation of patch formulations of drugs as combination products in the United States.  If
material, please add summary risk and risk factor disclosure discussing any risks or
challenges related to your development of ALTO-101 and/or the approval process if the
FDA may consider ALTO-101 to be a drug/device combination product.
15.Consistent with your disclosure on page 153, please revise your summary risk and risk
factor disclosure where appropriate to highlight that issued patents covering the
composition of ALTO-100, one of your lead product candidates, are due to retire in 2024
and patents covering the method of its manufacturing are due to expire in 2030.
16.We note your disclosure on page 148 with respect to the license agreement with Stanford
University that your rights under the Licensed Patents are exclusive until December 2029,
at which time it will become non-exclusive, and that your rights under the Licensed
Technology are non-exclusive. Please include related disclosure in your risk factor
summary and risk factor disclosure.
Our amended and restated certificate of incorporation will provide..., page 82
17.Since you state that the exclusive forum provision will apply to claims under the
Securities Act, please revise here and in the Choice of Forum section on page 211 to state
that investors cannot waive compliance with the federal securities laws and the rules and
regulations thereunder. In that regard, we note that Section 22 of the Securities Act creates
concurrent jurisdiction for federal and state courts over all suits brought to enforce any
duty or liability created by the Securities Act or the rules and regulations thereunder.

Capitalization, page 93
18.Please revise to include your term loan as shown on your September 30, 2023 balance
sheet at F-35 as part of your capitalization table. Also revise to double-underline your cash
and cash equivalent balance so it is clear that cash and cash equivalent is not part of your
total capitalization.
Business
Our Team, page 123

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19.We note the references to your "scientific advisory board."  If material, please include
disclosure in the appropriate section or sections of your prospectus that:
•Describes the role or function of your scientific advisory board;
•Describes the composition of such board; and
•Describes the material provisions of any advisory contracts between advisory board
members and the Company, including how such board members are compensated.  In
this regard, we note disclosure on page 69 that seemingly indicates that you have
entered into advisory agreements with certain physicians who are paid, in part, in the
form of stock or stock options.
Our Differentiated Approach and Capabilities, page 125
20.You state:  "We believe developing product candidates for biomarker-characterized
patient populations and likely drug responders could improve efficacy within such
populations, enabling us to conduct smaller more cost-efficient trials without sacrificing
statistical power."  Please place this and any similar statements in context by disclosing
that the FDA or other regulatory authorities may disagree with your clinical trial designs
and interpretation of data or may not permit you to reduce the number of patients
required.  Please also revise to clarify whether the FDA has permitted you to reduce the
number of patients in your currently active trials.

Methodical Approach to Curate Product Candidates, page 126
21.Conclusions regarding the safety or efficacy of your drug candidates are solely within the
authority of the FDA and comparable regulatory bodies. As such, please remove or revise
the following statement on page 126, and any similar statements throughout:  "We have
focused on acquiring or in-licensing novel chemical entities with favorable safety results,
clear biological rationale, and preliminary pharmacodynamic data indicative of potential
efficacy in biomarker-characterized patient groups."
Our Approach to Biomarker Discovery and Managing Development Risk, page 128
22.You state that to power your biomarker approach, you run larger trials than typical Phase
1 or Phase 2a trials for CNS product candidates.  Revise to provide examples of the size of
completed Phase 1 or Phase 2a trials you have conducted for your product candidates as
well as the "typical" size of such trials for CNS product candidates.
23.Please revise the graphic on page 128 as follows:
•Define references to "bio +," "bio -," and "PBO; and
•In right-most column labeled "Phase 2B/3," please revise the reference to "establish
efficacy in Bio +" and to "Efficacy: Drug > PBO in Bio+" to remove any implication
that your process for discovery and development will demonstrate the efficacy of any
of your product candidates.  In this regard, we note that determinations of efficacy are
solely within the authority of the FDA or equivalent foreign regulator.

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2) Biomarker Validation - "Test" Data, page 129
24.You state:  "We believe the independent prospective validation not only directly
demonstrates the robustness of the biomarkers we identify, but also increases the
probability of success for our pivotal clinical development plan, representing substantially
more knowledge about a product candidate than is typical at that stage of CNS drug
development."  Please explain what you mean by "pivotal clinical development plan" and
explain the basis for your belief.  Where appropriate, disclose whether or not you have
discussed your clinical study plans and designs with the FDA, and if so, describe the
outcome of such discussions.
Our Product Candidates
ALTO-100
Data from Prior ALTO-100 Clinical Trials in MDD, page 130
25.Please revise this section to explain who completed the multiple preclinical models of
ALTO-100 referenced on page 132.  Also, please identify the "originator" that studied
ALTO-100 in two previous clinical trials for patients with MDD, when such trials were
completed, and disclose the primary and secondary endpoints of such studies as well as
the results as they relate to those endpoints.
ALTO-101, page 143
26.You state on page 143 that ALTO-101 has been studied across multiple Phase 1 trials, in
which the product candidate demonstrated human brain penetration and was well
tolerated. Please revise to clarify the number of such prior Phase 1 trials conducted by
third parties, and when such trials were conducted.
ALTO-101 Phase 1 Clinical Data, page 144
27.It appears based on your disclosure that prior to your acquisition of ALTO-101, this
product candidate was studied in a human positron emission tomography study and a total
of nine Phase 1 trials involving healthy subjects and Parkinson's disease patients.  Please
revise to explain whether you intend to rely on such prior PET study and Phase 1
clinical trial data to suppor