SecProbe.io

CORRESP
 1
 filename1.htm

 September
29, 2025

 VIA
EDGAR

 Un i ted
S t a t es S e c urit i es
 a nd Ex c hange Com m iss i on

 Division
of Corporation Finance

 Office
of Life Sciences

 1 0 0
F Street, N.E.

 Washington,
D.C. 20549

 Attention:
 Doris
 Stacey Gama

 Alan
 Campbell

 Re:
 Palisade
 Bio, Inc.

 Draft
 Registration Statement on Form S-1

 Submitted
 July 3, 2025

 CIK
 No. 0001357459

 Ladies
and Gentlemen:

 On
behalf of Palisade Bio, Inc. (the " Company "), and in connection with the filing via EDGAR of its Registration Statement
on Form S-1 (the " Registra t i o n
 S t ate m e n t "),
this letter responds to the comment s e t forth in the letter to the Com p any
dated July 14, 2025 from the sta f f of the Securities and Exchange Commission (the " Staff ").

 For
your convenience, we have repeated and numbered the Staff's comment from the July 14, 2025 letter in italicized print, and t he
Company's response is provided below the comment.

 General

 1.
 We
 note you are offering units with each unit consisting of one share of common stock, one Series 1 warrant and one Series 2 warrant,
 and that the Series 1 warrants will be exercisable until the earlier of (i) the one year anniversary of the Initial Exercise Date
 and (ii) within 30 days of reporting positive clinical data from a cohort of fibrostenotic Crohn's ("FSCD") patients
 in your ongoing Phase 1 study. You also state on page 4 that you have already reported positive results from three cohorts (SAD,
 MAD, FE) of your Phase 1 study on May 27, 2025 and that you plan to initiate an additional exploratory Phase 1b cohort. With respect
 to the Series 1 warrants, please state which cohort(s) trigger the exercise provision, define the "positive" clinical
 data required and discuss whether this exercise provision could be triggered prior to the company obtaining shareholder approval
 for the issuance of the shares underlying the warrants.

 In
response to the Staff's comment, the Company respectfully advises the Staff that because of the new offering structure set forth
in the Registration Statement, and more specifically because the Company is no longer offering units nor is the Company offering any
Series 1 warrants or other securities consisting of any Series 1 warrants, the Company does not believe that this comment is still applicable.

 [Remainder
of page intentionally left blank.]

 *
* * * *

 Securities and Exchange Commission September
 29, 2025 Page 2

 Please
do not hesitate to contact me at (858) 436-8064 if you have any questions or would like addit i onal
information regarding this m a t ter.

 Very
truly yours,

 GUNDERSON
 DETTMER STOUGH

 VILLENEUVE
 FRANKLIN & HACHIGIAN, LLP

 /s/
 Jeffrey C. Thacker

 cc:
 JD
 Finley

 Palisade
 Bio, Inc.

 Ryan
 J. Gunderson

 Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

CORRESP
 1
 filename1.htm

 Ladenburg
Thalmann & Co. Inc.

 640
Fifth Avenue, 4 th Floor

 New
York, New York 10019

 September
29, 2025

 VIA
EDGAR

 U.S.
Securities and Exchange Commission

 Division
of Corporation Finance

 100
F Street, N.E.

 Washington,
DC 20549

 Re:
 Palisade
 Bio, Inc.

 Registration
 Statement on Form S-1 (Registration No. 333-290568)

 Concurrence
 in Acceleration Request

 Ladies
and Gentlemen:

 Ladenburg
Thalmann & Co. Inc. (" Ladenburg "), as representative of the underwriters for the referenced offering, hereby concurs
in the request by Palisade Bio, Inc. that the effective date of the above-referenced registration statement be accelerated to 5:00 p.m.
(Eastern Time), or as soon as practicable thereafter, on September 30, 2025, pursuant to Rule 461 under the Securities Act. Ladenburg
affirms that it is aware of its obligations under the Securities Act in connection with this offering. This concurrence in the Company's
request for acceleration of effectiveness of the Registration Statement supersedes the prior concurrence filed by Ladenburg with respect
to the Registration Statement.

 Very
 truly yours,

 LADENBURG
 THALMANN & CO. INC.

 By:
 /s/
 Nicholas Stergis

 Name:

 Nicholas
 Stergis

 Title:

 Managing
 Director

CORRESP
 1
 filename1.htm

 September
29, 2025

 VIA
EDGAR

 U.S.
Securities and Exchange Commission

 Division
of Corporation Finance

 Mail
Stop 4561

 100
F Street, N.E.

 Washington,
D.C. 20549-3720

 Attention:

 Doris
 Stacey Gama

 Alan
 Campbell

 Re:
 Palisade
 Bio, Inc.

 Registration
 Statement on Form S-1

 Filed
 September 29, 2025

 File
 No. 333-290568

 Request
 for Acceleration of Effective Date

 Requested
 Date:
 September
 30, 2025

 Requested
 Time:
 5:00
 P.M. Eastern Time

 Ladies
and Gentlemen:

 Pursuant
to Rule 461 under the Securities Act of 1933, as amended, Palisade Bio, Inc. (the " Company ") hereby requests that
the above-referenced Registration Statement on Form S-1 (File No. 333-290568) (the " Registration Statement ") be declared
effective at the "Requested Date" and "Requested Time" set forth above or at such later time as the Company or
its counsel may orally request via telephone call to the staff of the Division of Corporation Finance of the Securities and Exchange
Commission. Once the Registration Statement has been declared effective, please orally confirm that event with our counsel, Gunderson
Dettmer Stough Villeneuve Franklin & Hachigian, LLP, by calling Ryan Gunderson at (858) 436-8046. This request for acceleration of
effectiveness of the Registration Statement supersedes the prior request for acceleration filed by the Company with respect to the Registration
Statement.

 [Signature
page follows]

 Securities
and Exchange Commission

 September
29, 2025

 Page
2

 Sincerely,

 Palisade
 Bio, Inc.

 By:
 /s/
 JD Finley

 JD
 Finley

 Chief
 Executive Officer

 Palisade
 Bio, Inc.

 cc:
 Jeffrey
 C. Thacker, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

 Ryan
 J. Gunderson, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

 Michael
 Nertney, Ellenoff Grossman & Schole LLP

CORRESP
 1
 filename1.htm

 Ladenburg
Thalmann & Co. Inc.

 640
Fifth Avenue, 4 th Floor

 New
York, New York 10019

 September
29, 2025

 VIA
EDGAR

 U.S.
Securities and Exchange Commission

 Division
of Corporation Finance

 100
F Street, N.E.

 Washington,
DC 20549

 Re:
 Palisade
 Bio, Inc.

 Registration
 Statement on Form S-1 (Registration No. 333-290568)

 Concurrence
 in Acceleration Request

 Ladies
and Gentlemen:

 Ladenburg
Thalmann & Co. Inc. (" Ladenburg "), as representative of the underwriters for the referenced offering, hereby concurs
in the request by Palisade Bio, Inc. that the effective date of the above-referenced registration statement be accelerated to 9:00
a.m. (Eastern Time), or as soon as practicable thereafter, on October 1, 2025, pursuant to Rule 461 under the Securities Act.
Ladenburg affirms that it is aware of its obligations under the Securities Act in connection with this offering.

 Very
 truly yours,

 LADENBURG
 THALMANN & CO. INC.

 By:
 /s/
 Nicholas Stergis

 Name:

 Nicholas
 Stergis

 Title:

 Managing
 Director

CORRESP
 1
 filename1.htm

 September
29, 2025

 VIA
EDGAR

 U.S.
Securities and Exchange Commission

 Division
of Corporation Finance

 Mail
Stop 4561

 100
F Street, N.E.

 Washington,
D.C. 20549-3720

 Attention:

 Doris
 Stacey Gama

 Alan
 Campbell

 Re:
 Palisade
 Bio, Inc.

 Registration
 Statement on Form S-1

 Filed
 September 29, 2025

 File
 No. 333-290568

 Request
 for Acceleration of Effective Date

 Requested
 Date:
 October
 1, 2025

 Requested
 Time:
 9:00
 A.M. Eastern Time

 Ladies
and Gentlemen:

 Pursuant
to Rule 461 under the Securities Act of 1933, as amended, Palisade Bio, Inc. (the " Company ") hereby requests that
the above-referenced Registration Statement on Form S-1 (File No. 333-290568) (the " Registration Statement ")
be declared effective at the "Requested Date" and "Requested Time" set forth above or at such later time as the
Company or its counsel may orally request via telephone call to the staff of the Division of Corporation Finance of the Securities and
Exchange Commission. Once the Registration Statement has been declared effective, please orally confirm that event with our counsel,
Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP, by calling Ryan Gunderson at (858) 436-8046.

 [Signature
page follows]

 Securities
and Exchange Commission

 September
29, 2025

 Page
2

 Sincerely,

 Palisade
 Bio, Inc.

 By:
 /s/
 JD Finley

 JD
 Finley

 Chief
 Executive Officer

 Palisade
 Bio, Inc.

 cc:
 Jeffrey
 C. Thacker, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

 Ryan
 J. Gunderson, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

 Michael
 Nertney, Ellenoff Grossman & Schole LLP

CORRESP
 1
 filename1.htm

 August
26, 2025

 VIA
EDGAR

 U.S.
Securities and Exchange Commission

 Division
of Corporation Finance

 Mail
Stop 4561

 100
F Street, N.E.

 Washington,
D.C. 20549-3720

 Attention:
Joshua Gorsky

 Re: Palisade Bio, Inc.
 Registration Statement on Form S-3
 Filed
 August 15, 2025

 File
 No. 333-289635

 Ladies
and Gentlemen:

 Pursuant
to Rules 460 and 461 under the Securities Act of 1933, as amended, Palisade Bio, Inc. (the " Company ") hereby requests
that the above-referenced Registration Statement on Form S-1 (File No. 333-289635) (the " Registration Statement ")
be declared effective at 4:00 p.m., Eastern Time on Thursday, August 28, 2025.

 The
Company hereby authorizes Jeffrey Thacker of Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP, counsel to the Company
to orally modify or withdraw this request for acceleration.

 Thank
you for your assistance. If you should have any questions, please contact Jeffrey Thacker of Gunderson Dettmer Stough Villeneuve Franklin
& Hachigian, LLP, counsel to the Company at (858) 436-8064.

 [Signature
page follows]

 Securities
and Exchange Commission

 August
26, 2025

 Page
2

 Sincerely,

 Palisade
Bio, Inc.

 By:
 /s/
 JD Finley

 JD
 Finley

 Chief
 Executive Officer

 Palisade
 Bio, Inc.

 cc: Jeffrey
 C. Thacker, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP
 Ryan
 J. Gunderson, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

 John
 E. Maciejewski, Gunderson Dettmer Stough Villeneuve Franklin & Hachigian, LLP

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 August 21, 2025

J.D. Finley
Chief Executive Officer
Palisade Bio, Inc.
1902 Wright Place, Suite 200
Carlsbad, CA 92008

 Re: Palisade Bio, Inc.
 Registration Statement on Form S-3
 Filed August 15, 2025
 File No. 333-289635
Dear J.D. Finley:

 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 Joshua Gorsky at 202-551-7836 with any questions.

 Sincerely,

 Division of
Corporation Finance
 Office of Life
Sciences
cc: John E. Maciejewski
</TEXT>
</DOCUMENT>

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 July 14, 2025

JD Finley
Chief Executive Officer
Palisade Bio, Inc.
7750 El Camino Real, Suite 2A
Carlsbad, CA 92009

 Re: Palisade Bio, Inc.
 Draft Registration Statement on Form S-1
 Submitted July 3, 2025
 CIK No. 0001357459
Dear JD Finley:

 We have conducted a limited review of your draft registration statement
and have the
following comment.

 Please respond to this letter by providing any requested information
and by publicly
filing your registration statement and non-public draft submission on EDGAR. If
you do not
believe our 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 filed
registration statement, we may have additional comments.

Draft Registration Statement on Form S-1
General

1. We note you are offering units with each unit consisting of one share of
common
 stock, one Series 1 warrant and one Series 2 warrant, and that the
Series 1 warrants
 will be exercisable until the earlier of (i) the one year anniversary of
the Initial
 Exercise Date and (ii) within 30 days of reporting positive clinical
data from a cohort
 of fibrostenotic Crohn's ("FSCD") patients in your ongoing Phase 1
study. You also
 state on page 4 that you have already reported positive results from
three cohorts
 (SAD, MAD, FE) of your Phase 1 study on May 27, 2025 and that you plan
to initiate
 an additional exploratory Phase 1b cohort. With respect to the Series 1
warrants,
 please state which cohort(s) trigger the exercise provision, define the
"positive"
 clinical data required and discuss whether this exercise provision could
be triggered
 prior to the company obtaining shareholder approval for the issuance of
the shares
 July 14, 2025
Page 2

 underlying the warrants.
 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.

 We also remind you that your registration statement must be on file at
least two
business days prior to the requested effective date and time. 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 Doris Stacey Gama at 202-551-3188 or Alan Campbell at
202-551-
4224 with any other questions.

 Sincerely,

 Division of
Corporation Finance
 Office of Life
Sciences
cc: Jeffrey C. Thacker, Esq.
</TEXT>
</DOCUMENT>

CORRESP
1
filename1.htm

Ladenburg
Thalmann & Co. Inc.

640
Fifth Avenue, 4th Floor

New
York, New York 10019

December
12, 2024

VIA
EDGAR

U.S.
Securities and Exchange Commission

Division
of Corporation Finance

100
F Street, N.E.

Washington,
DC 20549

    Re:
    Palisade Bio, Inc.

    Registration Statement on Form S-1 (Registration
    No. 333-282883)

    Concurrence in Acceleration Request

Ladies
and Gentlemen:

Ladenburg
Thalmann & Co. Inc. (“Ladenburg”), as representative of the underwriters for the referenced offering, hereby concurs
in the request by Palisade Bio, Inc. that the effective date of the above-referenced registration statement be accelerated to 12:00 p.m.
(Eastern Time), or as soon as practicable thereafter, on December 12, 2024, pursuant to Rule 461 under the Securities Act. Ladenburg
affirms that it is aware of its obligations under the Securities Act in connection with this offering.

    Very truly yours,

    LADENBURG THALMANN & CO. INC.

    By:
    /s/ Nicholas
    Stergis

    Name:
    Nicholas Stergis

    Title:
    Managing Director

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

December
12, 2024

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:
    Daniel
    Crawford

    Re:
    Palisade
    Bio, Inc. (the “Company”)

    Registration
    Statement on Form S-1

    Originally
    Filed: October 30, 2024, as amended

    File
    No.: 333-282883

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission take
appropriate action to cause the above-referenced Registration Statement on Form S-1 to become effective at 12:00 p.m. Eastern Time on
December 12, 2024, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Raul Silvestre of Silvestre Law Group, P.C. at (818) 597-7552.

    Very
    truly yours,

    PALISADE
    BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

December
11, 2024

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:
    Daniel
    Crawford

    Re:
    Palisade
    Bio, Inc. (the “Company”)

    Withdrawal
    of Acceleration Request – Registration Statement on Form S-1

    Originally
    Filed: October 30, 2024, as amended

    File
    No.: 333-282883

Ladies
and Gentlemen:

Reference
is made to our letter, filed as correspondence via EDGAR on December 10, 2024, in which we requested the acceleration of the effective
date of the above-referenced Registration Statement for Wednesday, December 11, 2024, at 5:30 p.m. Eastern Time, in accordance with Rule
461 under the Securities Act of 1933, as amended. We are no longer requesting that such Registration Statement be declared effective
at this time and we hereby formally withdraw our request for acceleration of the effective date.

If
you have any questions regarding this request, please contact Raul Silvestre of Silvestre Law Group, P.C. at (818) 597-7552.

Very
truly yours,

PALISADE
BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

CORRESP
1
filename1.htm

Ladenburg
Thalmann & Co. Inc.

640
Fifth Avenue, 4th Floor

New
York, New York 10019

December
11, 2024

VIA
EDGAR

U.S.
Securities and Exchange Commission

Division
of Corporation Finance

100
F Street, N.E.

Washington,
DC 20549

    Re:
    Palisade
    Bio, Inc.

    Registration
    Statement on Form S-1 (Registration No. 333-282883)

    Withdrawal
    of Concurrence in Acceleration Request

Ladies
and Gentlemen:

Reference
is made to our letter, filed as correspondence via EDGAR on December 10, 2024, in which we provided concurrence in the request for acceleration
of the effective date of the above-referenced Registration Statement for December 11, 2024, at 5:30 p.m. Eastern Time, in accordance
with Rule 461 under the Securities Act of 1933, as amended. We are no longer requesting that such Registration Statement be declared
effective at this time.

    Very
    truly yours,

    LADENBURG
    THALMANN & CO. INC.

    By:

    /s/
    Nicholas Stergis

    Name:

    Nicholas
    Stergis

    Title:

    Managing
    Director

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

December
10, 2024

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:
    Daniel
    Crawford

    Re:
    Palisade
    Bio, Inc. (the “Company”)

    Registration
    Statement on Form S-1

    Originally
    Filed: October 30, 2024, as amended

    File
    No.: 333-282883

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission take
appropriate action to cause the above-referenced Registration Statement on Form S-1 to become effective at 5:30 p.m. Eastern Time on
December 11, 2024, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Raul Silvestre of Silvestre Law Group, P.C. at (818) 597-7552.

Very
truly yours,

PALISADE
BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

CORRESP
1
filename1.htm

Ladenburg
Thalmann & Co. Inc.

640
Fifth Avenue, 4th Floor

New
York, New York 10019

December
10, 2024

VIA
EDGAR

U.S.
Securities and Exchange Commission

Division
of Corporation Finance

100
F Street, N.E.

Washington,
DC 20549

    Re:
    Palisade
    Bio, Inc.

    Registration
    Statement on Form S-1 (Registration No. 333-282883)

    Concurrence
    in Acceleration Request

Ladies
and Gentlemen:

Ladenburg
Thalmann & Co. Inc. (“Ladenburg”), as representative of the underwriters for the referenced offering, hereby concurs
in the request by Palisade Bio, Inc. that the effective date of the above-referenced registration statement be accelerated to 5:30 p.m.
(Eastern Time), or as soon as practicable thereafter, on December 11, 2024, pursuant to Rule 461 under the Securities Act. Ladenburg
affirms that it is aware of its obligations under the Securities Act in connection with this offering.

    Very truly yours,

    LADENBURG THALMANN & CO. INC.

    By:
    /s/
    Nicholas Stergis

    Name:

    Nicholas
    Stergis

    Title:

    Managing
    Director

November 4, 2024
J.D. Finley
Chief Executive Officer
Palisade Bio, Inc.
7750 El Camino Real, Suite 2A
Carlsbad, CA 92009
Re:Palisade Bio, Inc.
Registration Statement on Form S-1
Filed October 30, 2024
File No. 333-282883
Dear J.D. Finley:
            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:Raul Silvestre, Esq.

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

May
15, 2024

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:

    Jason
    Drory

    Re:

    Palisade
    Bio, Inc. (the “Company”)

    Registration
    Statement on Form S-3

    Originally
    Filed: May 8, 2024

    File
    No.: 333-279222

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission take
appropriate action to cause the above-referenced Registration Statement on Form S-3, to become effective at 4:30 pm Eastern Time on May
17, 2024, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Dennis Gluck of Silvestre Law Group, P.C. at (818) 597-7552.

    Very
truly yours,

    PALISADE
BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

United States securities and exchange commission logo
May 14, 2024
J.D. Finley
Chief Executive Officer
Palisade Bio, Inc.
7750 El Camino Real, Suite 2A
Carlsbad, CA 92009
Re:Palisade Bio, Inc.
Registration Statement on Form S-3
Filed May 8, 2024
File No. 333-279222
Dear J.D. Finley:
            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 Jason Drory at 202-551-8342 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Dennis Gluck

United States securities and exchange commission logo
April 3, 2024
JD Finley
Chief Executive Officer
Palisades Bio, Inc.
7750 El Camino Real, Suite 2A
Carlsbad, California 92009
Re:Palisades Bio, Inc.
Registration Statement on Form S-3
Filed March 29, 2024
File No. 333-278389
Dear JD Finley:
            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 Tamika Sheppard at 202-551-8346 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Raul Silvestre

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

April
3, 2024

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:
    Tamika Sheppard

    Re:
    Palisade Bio, Inc. (the “Company”)

    Registration Statement on Form S-3

    Originally Filed: March 29, 2024

    File No.: 333-278389

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission take
appropriate action to cause the above-referenced Registration Statement on Form S-3, to become effective at 4:30 pm Eastern Time on April
5, 2024, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Dennis Gluck of Silvestre Law Group, P.C. at (818) 597-7552.

Very
truly yours,

PALISADE
BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 2A

Carlsbad,
CA 92009

April
27, 2023

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:
    Tim
    Buchmiller

    Re:
    Palisade
    Bio, Inc. (the “Company”)

    Registration
    Statement on Form S-1

    Originally
    Filed: April 21, 2023, as amended

    File
    No.: 333-271393

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission take
appropriate action to cause the above-referenced Registration Statement on Form S-1, to become effective at 5:00 pm Eastern Time on April
27, 2023, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Dennis Gluck of Silvestre Law Group, P.C. at (818) 597-7552.

Very
truly yours,

PALISADE
BIO, INC.

    /s/ J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

United States securities and exchange commission logo
April 25, 2023
J.D. Finley
Interim Chief Executive Officer
Palisade Bio, Inc.
7750 El Camino Real, Suite 2A
Carlsbad, California 92009
Re:Palisade Bio, Inc.
Registration Statement on Form S-1
Filed April 21, 2023
File No. 333-271393
Dear J.D. Finley:
            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 Tim Buchmiller at (202) 551-3635 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Raul Silvestre, Esq.

CORRESP
1
filename1.htm

Palisade
Bio, Inc.

7750
El Camino Real, Suite 5200

Carlsbad,
CA 92009

January
20, 2023

VIA
EDGAR

United
States Securities and Exchange Commission

Division
of Corporation Finance

100
F. Street, N.E.

Washington,
D.C. 20549

    Attn:

    Lauren Hamill

    Re:

    Palisade Bio, Inc. (the “Company”)

    Registration Statement on Form S-1

    Filed: January 13, 2023

    File No.: 333-269234

Ladies
and Gentlemen:

Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the
“Commission”) take appropriate action to cause the above-referenced Registration Statement on Form S-1, to become effective
at 4:00 pm Eastern Time on January 24, 2023, or as soon thereafter as is practicable.

If
you have any questions regarding this request, please contact Dennis Gluck of Silvestre Law Group, P.C. at (818) 597-7552.

Very
truly yours,

PALISADE
BIO, INC.

    /s/
    J.D. Finley

    J.D.
    Finley

    Chief
    Executive Officer

United States securities and exchange commission logo
January 19, 2023
J.D. Finley
Chief Executive Officer
PALISADE BIO, INC.
7750 El Camino Real, Suite 5200
Carlsbad, CA 92009
Re:PALISADE BIO, INC.
Registration Statement on Form S-1
Filed January 13, 2023
File No. 333-269234
Dear J.D. Finley:
            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:       Dennis Gluck

CORRESP
1
filename1.htm

CORRESP

 PALISADE BIO, INC.

7750 El Camino Real, Suite 5200

Carlsbad, CA 92009

 August 9,
2022

 VIA EDGAR

 Securities and Exchange Commission

 Division of Corporation Finance

 100 F Street, N.E.

Washington, D.C. 20549

Re:
 Palisade Bio, Inc. - Registration Statement – Form S-1

     File No. 333-265769, originally filed
June 22, 2022, as amended

 Ladies and Gentlemen:

Pursuant to Rule 461 under the Securities Act of 1933, as amended, Palisade Bio, Inc. (the “Registrant”) hereby requests
that the effective date of the above-referenced registration statement on Form S-1 (File No. 333-265769) (the “Registration
Statement”) be declared effective on August 10, 2022, at 5:30 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 each of Karen E. Deschaine and Mohammed H. Elayan 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 Karen E. Deschaine of Cooley LLP, counsel
to the Registrant, at (858) 550 6088, or in her absence, Mohammed Elayan at (858) 550 6127.

 Sincerely,

 PALISADE BIO, INC.

By:

 /s/ Thomas M. Hallam

Thomas M. Hallam, Ph.D.

Chief Executive Officer

cc:
 Karen E. Deschaine, Cooley LLP

Mohammed Elayan, Cooley LLP

CORRESP
1
filename1.htm

CORRESP

 Ladenburg Thalmann & Co. Inc.

640 Fifth Avenue, 4th Floor

New York, New York 10019

 August 9, 2022

 VIA FACSIMILE AND EDGAR

 U.S. Securities and
Exchange Commission

 Division of Corporation Finance

Washington, DC 20549

Re:
 Palisade Bio, Inc.

Registration Statement on Form S-1 (Registration
No. 333-265769)

 Concurrence in Acceleration Request

Ladies and Gentlemen:

 Ladenburg
Thalmann & Co. Inc. (“Ladenburg”), as representative of the underwriters for the referenced offering, hereby concurs in the request by Palisade Bio, Inc. that the effective date of the above-referenced registration
statement be accelerated to 5:30 p.m. (Eastern Time), or as soon as practicable thereafter, on August 10, 2022, pursuant to Rule 461 under the Securities Act. Ladenburg affirms that it is aware of its obligations under the Securities Act in
connection with this offering.

Very truly yours,

LADENBURG THALMANN & CO. INC.

By:

 /s/ Nicholas Stergis

Name: Nicholas Stergis

Title: Managing Director

United States securities and exchange commission logo
June 28, 2022
Thomas Hallam, Ph.D.
Chief Executive Officer
Palisade Bio, Inc.
5800 Armada Drive, Suite 210
Carlsbad, California 92008
Re:Palisade Bio, Inc.
Registration Statement on Form S-1
Filed June 22, 2022
File No. 333-265769
Dear Dr. Hallam:
            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 Tyler Howes at 202-551-3370 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine, Esq.

CORRESP
1
filename1.htm

CORRESP

 Palisade Bio, Inc.

5800 Armada Drive, Suite 210

Carlsbad, California 92008

 June 21, 2022

 VIA EDGAR

 United States Securities and Exchange
Commission

 Division of Corporation Finance

 100 F. Street,
N.E.

 Washington, D.C. 20549

 Attn:

 Dorrie Yale

 Re:

 Palisade Bio, Inc. (the “Company”)

 Registration Statement on Form S-1

 Filed: June 14, 2022

 File No.: 333-265570

 Ladies and Gentlemen:

 Pursuant
to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to cause the above-referenced Registration Statement on Form S-1, to become effective at 4:00 pm Eastern Time on June 23, 2022, or as soon thereafter as is practicable.

 If you
have any questions regarding this request, please contact Karen E. Deschaine of Cooley LLP at (858) 550-6088.

Very truly yours,

 PALISADE BIO, INC.

 /s/ Thomas M. Hallam, Ph.D.

Thomas M. Hallam, Ph.D.

Chief Executive Officer

United States securities and exchange commission logo
June 17, 2022
Thomas Hallam
Chief Executive Officer
Palisade Bio, Inc.
5800 Armada Drive, Suite 210
Carlsbad, CA 92008
Re:Palisade Bio, Inc.
Registration Statement on Form S-1
Filed June 14, 2022
File No. 333-265570
Dear Dr. Hallam:
            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 Dorrie Yale at 202-551-8776 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine, Esq

CORRESP
1
filename1.htm

CORRESP

 Palisade Bio, Inc.

5800 Armada Drive, Suite 210

Carlsbad, California 92008

 April 22,
2022

 VIA EDGAR

United States Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, N.E.

 Washington, D.C.
20549

Attn:
 Michael Davis

Laura Crotty

Re:
 Palisade Bio, Inc. (the “Company”)

Registration Statement on Form S-3

Filed: March 18, 2022

File No. 333-263705

Ladies and Gentlemen:

 Pursuant to Rule 461 under the
Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to cause the above-referenced Registration Statement on Form S-3, to become effective at 4:00 p.m. Eastern Time on April 26, 2022 or as soon thereafter as is practicable.

 If
you have any questions regarding this request, please contact Karen E. Deschaine of Cooley LLP at (858) 550-6088.

Very truly yours,

 PALISADE BIO,
INC.

 /s/ Thomas M. Hallam, Ph.D.

Thomas M. Hallam, Ph.D.

Chief Executive Officer

CORRESP
1
filename1.htm

CORRESP

 Palisade Bio, Inc.

5800 Armada Drive, Suite 210

Carlsbad, California 92008

 April 22,
2022

 VIA EDGAR

United States Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, N.E.

 Washington,
D.C. 20549

Attn:
 Michael Davis

 Laura Crotty

Re:
 Palisade Bio, Inc. (the “Company”)

 Registration Statement on Form S-3

 Filed: March 18, 2022

 File No. 333-263709

Ladies and Gentlemen:

 Pursuant to Rule 461 under the
Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to cause the above-referenced Registration Statement on Form S-3, to become effective at 4:00 p.m. Eastern Time on April 26, 2022 or as soon thereafter as is practicable.

If you have any questions regarding this request, please contact Karen E. Deschaine of Cooley LLP at
(858) 550-6088.

 Very truly yours,

PALISADE BIO, INC.

/s/  Thomas M. Hallam, Ph.D.

Thomas M. Hallam, Ph.D.

Chief Executive Officer

United States securities and exchange commission logo
March 24, 2022
Thomas Hallam
Chief Executive Officer
PALISADE BIO, INC.
5800 Armada Drive, Suite 210
Carlsbad, California 92008
Re:PALISADE BIO, INC.
Registration Statement on Form S-3
Filed March 18, 2022
File No. 333-263705
Dear Mr. Hallam:
            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 Michael Davis at 202-551-4385 or Laura Crotty at 202-551-7614 with any
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine

CORRESP
1
filename1.htm

CORRESP

 Palisade Bio, Inc.

5800 Armada Drive, Suite 210

Carlsbad, California 92008

December 3, 2021

 VIA
EDGAR

 United States Securities and Exchange Commission

Division of Corporation Finance

 100 F Street, N.E.

Washington, D.C. 20549

Attn:
 Lauren Hamill

Celeste Murphy

Re:
 Palisade Bio, Inc. (the “Company”)

Amendment No. 1 to

Registration Statement on Form S-3

Filed: November 19, 2021

File No. 333-259747

To Whom It May Concern:

 Pursuant to Rule 461 under the
Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the “Commission”) take appropriate action to cause the above-referenced Amendment No. 1 to Registration
Statement on Form S-3, to become effective at 4:00 p.m. Eastern Time on December 8, 2021 or as soon thereafter as is practicable.

If you have any questions regarding this request, please contact Karen E. Deschaine of Cooley LLP at (858) 550-6088.

 Very truly yours,

 PALISADE
BIO, INC.

 /s/ Thomas M. Hallam, Ph.D.

Thomas M. Hallam, Ph.D.

Chief Executive Officer

United States securities and exchange commission logo
December 2, 2021
Thomas Hallam
Chief Executive Officer
PALISADE BIO, INC.
5800 Armada Drive, Suite 210
Carlsbad, CA
92008
Re:PALISADE BIO, INC.
Amendment No. 1 to
Registration Statement on Form S-3
Filed November 19, 2021
File No. 333-259747
Dear Dr. Hallam:
            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 October 8, 2021 letter.
Amendment No. 1 to Form S-3 filed November 19, 2021
General
1.We note your revisions on page 4 made in response to prior comment 3 that
describe Suzhou’s current limited operations in China.  For the avoidance of doubt, please
revise this disclosure to state, as you have in your response letter, that the Company
believes that all Suzhou operations will cease by March 2022, at the latest.
            Please contact Lauren Hamill at 303-844-1008 or Celeste Murphy at 202-551-3257 with
any questions.

 FirstName LastNameThomas  Hallam
 Comapany NamePALISADE BIO, INC.
 December 2, 2021 Page 2
 FirstName LastName
Thomas  Hallam
PALISADE BIO, INC.
December 2, 2021
Page 2
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine

CORRESP
1
filename1.htm

CORRESP

 KAREN E. DESCHAINE

 +1 858 550 6088

kdeschaine@cooley.com

VIA EDGAR

 November 18, 2021

Securities and Exchange Commission

 Division of Corporation
Finance, Office of Life Sciences

 100 F Street, N.E.

Washington, D.C. 20549

 Attention:
    Lauren Hamill

                     Celeste Murphy

RE:
 Palisade Bio, Inc.

Registration Statement on Form S-3

Filed September 23, 2021

File No. 333-259747

To Whom It May Concern:

 On behalf of Palisade Bio, Inc. (the
“Company”), this letter is being transmitted in response to comments received from the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”), by
letter dated October 8, 2021 (the “Comment Letter”), regarding the Company’s Registration Statement on Form S-3 (the “Registration Statement”). The
text of the Staff’s comments has been included in this letter in italics for your convenience, and we have numbered the paragraphs below to correspond to the numbering of the Comment Letter.

Cover Page

1.
 Please disclose prominently on the prospectus cover page that you are not a Chinese operating company but a
Delaware holding company with operations conducted by your subsidiaries in the U.S. and China and that this structure involves unique risks to investors.

Response:

 The
Company respectfully informs the Staff that that the Company believes that Suzhou Neuralstem Biopharmaceutical Co., Ltd., a wholly-owned subsidiary of the Company organized under the laws of the People’s Republic of China (“Suzhou”),
does not pose any risk to investors due to its limited operations, and therefore does not need to be prominently disclosed on the Cover Page. The Company was originally incorporated in 2001 in the State of Delaware under the name Neuralstem, Inc. In
October 2019, the Company changed its name from Neuralstem, Inc. to Seneca Biopharma, Inc. In April 2021, the Company effected a reverse merger transaction with Leading Biosciences, Inc. (“LBS”), whereby LBS merged into a wholly-owned
subsidiary of the Company. In April 2021, the Company changed its name from Seneca Biopharma, Inc. (“Seneca”) to Palisade Bio, Inc.

 4401 EASTGATE MALL, SAN
DIEGO, CA 92121 T: (858) 550-6000 F: (858) 550-6420 WWW.COOLEY.COM

 In 2013, Seneca commenced an open label, non-GCP
compliant, Phase I safety and dose escalation study to test transplantation of NSI-566 in human subjects for the treatment of motor deficits due to ischemic stroke. The trial was conducted at BaYi Brain
Hospital in Beijing, China and sponsored by Suzhou. Seneca completed dosing the final cohort, for a total of nine subjects, in March 2016. Subjects were monitored through a 24-month observational follow-up period.

 At this time, Suzhou has limited operations and exists for the sole purpose of
conducting observational follow-up for a small group of remaining patients from the completed clinical trial, which it does through the engagement of a consultant. Suzhou has no employees or other
operations. The Company believes that all Suzhou operations shall cease by March 2022, at the latest.

2.
 Provide prominent disclosure about the legal and operational risks associated with being based in or having
the majority of the company’s operations in China. Your disclosure should make clear whether these risks could result in a material change in your operations and/or the value of your common stock or could significantly limit or completely
hinder your ability to offer or continue to offer securities to investors and cause the value of such securities to significantly decline or be worthless. Your disclosure should address how recent statements and regulatory actions by China’s
government, such as those related to the use of variable interest entities and data security or anti-monopoly concerns, has or may impact the company’s ability to conduct its business, accept foreign investments, or list on an U.S. or other
foreign exchange. Your prospectus summary should address, but not necessarily be limited to, the risks highlighted on the prospectus cover page.

Response:

 The Company
respectfully informs the Staff that that the Company is not based in, or have a majority of its operations in, China. At this time, Suzhou has limited operations and exists for the sole purpose of conducting observational follow-up for a small group of remaining patients from the completed clinical trial, which it does through the engagement of a consultant. Suzhou has no employees or other operations. The Company believes that
all Suzhou operations shall cease by March 2022, at the latest. For the foregoing reasons, the Company believes that Suzhou does not pose any risks that could result in a material change in the Company’s operations and/or the value of the
Company’s common stock or could significantly limit or completely hinder the Company’s ability to offer or continue to offer securities to investors and cause the value of such securities to significantly decline or be worthless. The
Company does not have any variable interest entities. Additionally, due to the limited operations of Suzhou described above, the Company does not believe that recent statements and regulatory actions by China’s government, such as those related
to the use of variable interest entities and data security or anti-monopoly concerns, has or may impact the Company’s ability to conduct its business, accept foreign investments, or list on an U.S. or other foreign exchange.

 4401 EASTGATE MALL, SAN
DIEGO, CA 92121 T: (858) 550-6000 F: (858) 550-6420 WWW.COOLEY.COM

 For the foregoing reasons, the Company believes that a prominent disclosure regarding
potential risks associated with Suzhou is unwarranted.

3.
 Clearly disclose how you will refer to the holding company and subsidiaries when providing the disclosure
throughout the document so that it is clear to investors which entity the disclosure is referencing and which subsidiaries or entities are conducting the business operations. Disclose clearly the entity (including the domicile) in which investors
are purchasing their interest.

 Response:

The Company respectfully acknowledges the Staff’s comment and has revised page 4 of the Registration Statement to include a definition for
Suzhou. However, due to the Suzhou’s limited operations, the Company respectfully informs the Staff that it does not believe that Suzhou’s existence will cause investors any confusion as to which entity is conducting the business
operations, and investors will at all times be purchasing their interest in the Company.

 At this time, Suzhou has limited operations and
exists for the sole purpose of conducting observational follow-up for a small group of remaining patients from the completed clinical trial, which it does through the engagement of a consultant. Suzhou
has no employees or other operations. The Company believes that all Suzhou operations shall cease by March 2022, at the latest.

 Prospectus Summary,
page 2

4.
 Please disclose clearly in the prospectus summary that the company uses a structure that involves a
subsidiary based in China and what that entails and provide early in the summary a diagram of the company’s corporate structure, including who the equity ownership interests are of each entity. Identify clearly the entity in which investors are
purchasing their interest and the entities in which the company’s operations are conducted. Describe the relevant relationships between the entities and how this type of corporate structure may affect investors and the value of their
investment.

 Response:

The Company respectfully acknowledges the Staff’s comment and has revised page 4 of the Registration Statement. However, due to the
Suzhou’s limited operations, the Company respectfully informs the Staff that it does not believe that Suzhou’s existence will cause investors any confusion as to which entity is conducting the business operations, and investors will at all
times be purchasing their interest in the Company. Additionally, the Company does not believe that Suzhou’s existence will affect investors or the value of their investment.

 4401 EASTGATE MALL, SAN
DIEGO, CA 92121 T: (858) 550-6000 F: (858) 550-6420 WWW.COOLEY.COM

 At this time, Suzhou has limited operations and exists for the sole purpose of conducting
observational follow-up for a small group of remaining patients from the completed clinical trial, which it does through the engagement of a consultant. Suzhou has no employees or other operations. The
Company believes that all Suzhou operations shall cease by March 2022, at the latest.

5.
 Disclose each permission that you or your subsidiaries are required to obtain from Chinese authorities to
operate and issue these securities to foreign investors. State whether you or your subsidiaries are covered by permissions requirements from the CSRC, CAC or any other entity that is required to approve of you or your subsidiaries’ operations,
and state affirmatively whether you have received all requisite permissions and whether any permissions have been denied.

Response:

 The Company
respectfully advises the Staff that none of the Company or any of its subsidiaries is required to obtain permissions from Chinese authorities to operate or issue securities to foreign investors and the Company is not currently required to obtain
permissions or approvals from the PRC government, including CSRC and CAC, of the Company’s or its subsidiaries’ operations.

6.
 Provide a clear description of how cash is transferred through your organization. Quantify any cash flows
and transfers of other assets by type that have occurred between the holding company and its subsidiaries, and direction of transfer. Quantify any dividends or distributions that a subsidiary has made to the holding company and which entity made
such transfer, and their tax consequences. Similarly quantify dividends or distributions made to U.S. investors, the source, and their tax consequences. Describe any restrictions on foreign exchange and your ability to transfer cash between
entities, across borders, and to U.S. investors. Describe any restrictions and limitations on your ability to distribute earnings from your businesses, including subsidiaries, to the parent company and U.S. investors.

Response:

 The Company
respectfully advises the Staff that it does not generate any revenue at the level of its subsidiary in China and no dividends or distributions are made by such entity to the Delaware parent company. There is no reason why this would change in the
future as the subsidiary in China has very limited operations, limited to the engagement of a consultant to wrap up a clinical trial that was completed in 2016.

The Company has not made any dividend payments or distributions to U.S. investors and clearly discloses that there is no intention to do so in
the Registration Statement.

 4401 EASTGATE MALL, SAN
DIEGO, CA 92121 T: (858) 550-6000 F: (858) 550-6420 WWW.COOLEY.COM

 The Company pays certain expenses to such subsidiary by way of wire transfer from a US-based financial institution on a monthly basis, a practice which is expected to cease not later than March 2022 when the limited patient follow-up work is done in China.

7.
 Disclose that trading in your securities may be prohibited under the Holding Foreign Companies Accountable
Act if the PCAOB determines that it cannot inspect or fully investigate your auditor, and that as a result an exchange may determine to delist your securities.

Response:

 The Company
acknowledges the Staff’s comment and respectfully advises the Staff that the Company is not subject to the Holding Foreign Companies Accountable Act, as the Company’s auditor, BDO LLP, is a reputable auditing firm located in the United
States that may be investigated by the PCAOB.

 Summary of Risk Factors, page 4

8.
 In your summary of risk factors, disclose the risks that your corporate structure and being based in or
having the majority of the company’s operations in China poses to investors. In particular, describe the significant regulatory, liquidity, and enforcement risks with cross-references to more detailed discussion of these risks in the
prospectus. For example, specifically discuss risks arising from the legal system in China, including risks and uncertainties regarding the enforcement of laws and that rules and regulations in China can change quickly with little advance notice;
and the risk that the Chinese government may intervene or influence your operations at any time, or may exert more control over offerings conducted overseas and/or foreign investment in China based issuers, which could result in a material change in
your operations and/or the value of your common stock. Acknowledge any risks that any actions by the Chinese government to exert more oversight and control over offerings that are conducted overseas and/or foreign investment in China-based issuers
could significantly limit or completely hinder your ability to offer or continue to offer securities to investors and cause the value of such securities to significantly decline or be worthless.

Response:

 The Company
respectfully informs the Staff that that the Company is not based in, or have a majority of its operations in, China. As a result of Suzhou’s limited operations, the Company does not believe that there are any regulatory, liquidity, or
enforcement risks. At this time, Suzhou has limited operations and exists for the sole purpose of conducting observational follow-up for a small group of remaining patients from the completed clinical trial,
which it does through the engagement of a consultant. Suzhou has no employees or other operations. The Company believes that all Suzhou operations shall cease by March 2022, at the latest. For the foregoing reasons, the Company believes that any
actions taken by the Chinese government, if any, would not result in a material change in the Company’s operations and/or the value of the Company’s common stock.

 4401 EASTGATE MALL, SAN
DIEGO, CA 92121 T: (858) 550-6000 F: (858) 550-6420 WWW.COOLEY.COM

 Risk Factors, page 8

9.
 Given the Chinese government’s significant oversight and discretion over the conduct of your business,
please revise your risk factors to separately highlight the risk that the Chinese government may intervene or influence your operations at any time, which could result in a material change in your operations and/or the value of your common stock.
Also, given recent statements by the Chinese government indicating an intent to exert more oversight and control over offerings that are conducted overseas and/or foreign investment in China-based issuers, acknowledge the risk that any such action
could significantly limit or completely hinder your ability to offer or continue to offer securities to investors and cause the value of such securities to significantly decline or be worthless.

Response:

 The Company
respectfully informs the Staff that that the due to Suzhou’s limited operations in China, the Chinese government does not have significant oversight and discretion over the conduct of the Company. As a result of Suzhou’s limited
operations, the Company does not believe that there are any regulatory, liquidity, or enforcement risks. At this time, Suzhou has limited operations and exists for the sole purpose of conducting observational
follow-up for a small group of remaining patients from the completed clinical trial, which it does through the engagement of a consultant. Suzhou has no employees or other operations. The Company believes that
all Suzhou operations shall cease by March 2022, at the latest. For the foregoing reasons, the Company believes that any actions taken by the Chinese government, if any, would not result in a material change in the Company’s operations and/or
the value of the Company’s common stock.

 For the foregoing reasons, the Company believes that a prominent disclosure regarding
pote

United States securities and exchange commission logo
October 8, 2021
Thomas Hallam
Chief Executive Officer
PALISADE BIO, INC.
5800 Armada Drive, Suite 210
Carlsbad, CA
92008
Re:PALISADE BIO, INC.
Registration Statement on Form S-3
Filed September 23, 2021
File No. 333-259747
Dear Dr. Hallam:
            We have limited our review of your registration statement to those issues we have
addressed in our 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.
Form S-3 Filed September 23, 2021
Cover Page
1.Please disclose prominently on the prospectus cover page that you are not a Chinese
operating company but a Delaware holding company with operations conducted by your
subsidiaries in the U.S. and China and that this structure involves unique risks to
investors.
2.Provide prominent disclosure about the legal and operational risks associated with being
based in or having the majority of the company’s operations in China. Your disclosure
should make clear whether these risks could result in a material change in your operations
and/or the value of your common stock or could significantly limit or completely hinder

 FirstName LastNameThomas  Hallam
 Comapany NamePALISADE BIO, INC.
 October 8, 2021 Page 2
 FirstName LastNameThomas  Hallam
PALISADE BIO, INC.
October 8, 2021
Page 2
your ability to offer or continue to offer securities to investors and cause the value of such
securities to significantly decline or be worthless. Your disclosure should address how
recent statements and regulatory actions by China’s government, such as those related to
the use of variable interest entities and data security or anti-monopoly concerns, has or
may impact the company’s ability to conduct its business, accept foreign investments, or
list on an U.S. or other foreign exchange. Your prospectus summary should address, but
not necessarily be limited to, the risks highlighted on the prospectus cover page.
3.Clearly disclose how you will refer to the holding company and subsidiaries when
providing the disclosure throughout the document so that it is clear to investors which
entity the disclosure is referencing and which subsidiaries or entities are conducting the
business operations. Disclose clearly the entity (including the domicile) in which investors
are purchasing their interest.
Prospectus Summary, page 2
4.Please disclose clearly in the prospectus summary that the company uses a structure that
involves a subsidiary based in China and what that entails and provide early in the
summary a diagram of the company’s corporate structure, including who the equity
ownership interests are of each entity. Identify clearly the entity in which investors are
purchasing their interest and the entities in which the company’s operations are conducted.
Describe the relevant relationships between the entities and how this type of corporate
structure may affect investors and the value of their investment.
5.Disclose each permission that you or your subsidiaries are required to obtain from Chinese
authorities to operate and issue these securities to foreign investors. State whether you or
your subsidiaries are covered by permissions requirements from the CSRC, CAC or any
other entity that is required to approve of you or your subsidiaries’ operations, and state
affirmatively whether you have received all requisite permissions and whether any
permissions have been denied.
6.Provide a clear description of how cash is transferred through your organization. Quantify
any cash flows and transfers of other assets by type that have occurred between the
holding company and its subsidiaries, and direction of transfer. Quantify any dividends or
distributions that a subsidiary has made to the holding company and which entity made
such transfer, and their tax consequences. Similarly quantify dividends or distributions
made to U.S. investors, the source, and their tax consequences. Describe any restrictions
on foreign exchange and your ability to transfer cash between entities, across borders, and
to U.S. investors. Describe any restrictions and limitations on your ability to distribute
earnings from your businesses, including subsidiaries, to the parent company and U.S.
investors.
7.Disclose that trading in your securities may be prohibited under the Holding Foreign
Companies Accountable Act if the PCAOB determines that it cannot inspect or fully
investigate your auditor, and that as a result an exchange may determine to delist your

 FirstName LastNameThomas  Hallam
 Comapany NamePALISADE BIO, INC.
 October 8, 2021 Page 3
 FirstName LastNameThomas  Hallam
PALISADE BIO, INC.
October 8, 2021
Page 3
securities.
Summary of Risk Factors, page 4
8.In your summary of risk factors, disclose the risks that your corporate structure and
being based in or having the majority of the company’s operations in China poses to
investors. In particular, describe the significant regulatory, liquidity, and enforcement
risks with cross-references to more detailed discussion of these risks in the prospectus. For
example, specifically discuss risks arising from the legal system in China, including risks
and uncertainties regarding the enforcement of laws and that rules and regulations in
China can change quickly with little advance notice; and the risk that the Chinese
government may intervene or influence your operations at any time, or may exert more
control over offerings conducted overseas and/or foreign investment in China based
issuers, which could result in a material change in your operations and/or the value of
your common stock. Acknowledge any risks that any actions by the Chinese government
to exert more oversight and control over offerings that are conducted overseas and/or
foreign investment in China-based issuers could significantly limit or completely hinder
your ability to offer or continue to offer securities to investors and cause the value of
such securities to significantly decline or be worthless.
Risk Factors, page 8
9.Given the Chinese government’s significant oversight and discretion over the conduct of
your business, please revise your risk factors to separately highlight the risk that the
Chinese government may intervene or influence your operations at any time, which
could result in a material change in your operations and/or the value of your common
stock. Also, given recent statements by the Chinese government indicating an intent to
exert more oversight and control over offerings that are conducted overseas and/or foreign
investment in China-based issuers, acknowledge the risk that any such action could
significantly limit or completely hinder your ability to offer or continue to offer securities
to investors and cause the value of such securities to significantly decline or be worthless.
10.In light of recent events indicating greater oversight by the Cyberspace Administration of
China over data security, particularly for companies seeking to list on a foreign exchange,
please revise your disclosure to explain how this oversight impacts your business and your
offering and to what extent you believe that you are compliant with the regulations or
policies that have been issued by the CAC to date.
            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.

 FirstName LastNameThomas  Hallam
 Comapany NamePALISADE BIO, INC.
 October 8, 2021 Page 4
 FirstName LastName
Thomas  Hallam
PALISADE BIO, INC.
October 8, 2021
Page 4
            You may contact Lauren Hamill at 303-844-1008 or Celeste Murphy at 202-551-3257
with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine

CORRESP
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Palisade Bio, Inc.

5800 Armada Drive,
Suite 210

Carlsbad, California
92008

August 6, 2021

Via
Edgar

United States Securities
and Exchange Commission

Division of Corporation
Finance

100 F Street, N.E.

Washington, D.C. 20549

Attn:
Alan Campbell

Re:        Palisade
Bio, Inc. (the “Company”)

Registration Statement
on Form S-3

Filed: July 30, 2021

File
No. 333-258318

Ladies and Gentlemen:

Pursuant to Rule 461
under the Securities Act of 1933, as amended, the Company hereby requests that the Securities and Exchange Commission (the “Commission”)
take appropriate action to cause the above-referenced Registration Statement on Form S-3, to become effective at 4:00 p.m. Eastern Time
on August 10, 2021 or as soon thereafter as is practicable.

If you have any questions
regarding this request, please contact Karen E. Deschaine of Cooley LLP at (858) 550-6088.

Very truly yours,

Palisade
Bio, Inc.

    /s/ Thomas M. Hallam, Ph.D.

    Thomas M. Hallam, Ph.D.

    Chief Executive Officer

United States securities and exchange commission logo
August 5, 2021
Thomas Hallam, Ph.D.
Chief Executive Officer
Palisade Bio, Inc.
5800 Armada Drive, Suite 210
Carlsbad, California 92008
Re:Palisade Bio, Inc.
Registration Statement on Form S-3
Filed July 30, 2021
File No. 333-258318
Dear Dr. Hallam:
            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 Alan Campbell at 202-551-4224 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Karen Deschaine, Esq.

CORRESP
1
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Seneca Biopharma, Inc.

20271 Goldenrod Lane

Germantown, MD 20876

(301) 366-4841

February 10, 2021

VIA EDGAR

Division of Corporation Finance

United States Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549-3628

    Attention:

        Christine Torney

        Kevin Kuhar

        Alan Campbell

        Celeste Murphy

    Re:
    Request for Effectiveness for Seneca Biopharma, Inc.

    Registration Statement on Form S-4 (File No. 333-251659)

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under the Securities Act of 1933,
as amended, Seneca Biopharma, Inc. (the “Registrant”) hereby respectfully requests that the effectiveness of
the above-referenced Registration Statement be accelerated to 4:00 p.m. Eastern Time, on February 11, 2021, or as soon thereafter
as practicable. The Registrant respectfully requests that you notify Raul Silvestre of Silvestre Law Group, P.C. of such effectiveness
by telephone at (818) 597-7552.

If you have any questions or comments regarding the foregoing, please
do not hesitate to contact Mr. Silvestre at the telephone number above.

    Very truly yours,

    Seneca Biopharma, Inc.

    By:

        /s/ Dane Saglio

    Name:

    Dane Saglio

    Title:

    Chief Financial Officer

cc: Raul Silvestre, Silvestre Law Group, P.C.

CORRESP
1
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February 9, 2021

VIA EDGAR AND
BY COURIER

Division of Corporation
Finance

U.S. Securities
and Exchange Commission

100 F Street,
N.E.

Washington, D.C.
20549

Attention: Dane
Saglio

    Re:
    Seneca
    Biopharma, Inc.

    Registration
    Statement on Form S-4

    Filed
    December 23, 2020

    File
    No. 333-251659

Ladies and Gentlemen:

On
behalf of Seneca Biopharma, Inc. (“Seneca”), we respectfully submit this letter in response to the comments of the
staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) in a letter dated February
3, 2021 (the “Comment Letter”) regarding the above referenced Registration Statement on Form S-4 (the “Registration
Statement”). Seneca has also revised the Registration Statement in an Amendment No. 2 (the “Amendment”) as set
forth below in response to the Comment Letter and is filing the Amendment with the Commission concurrently with the submission
of this letter.

The
numbering of the paragraphs below corresponds to the numbering of the Staff’s comments which, for your convenience, we have
incorporated into this response letter in italics. Page references in the text of Seneca’s responses correspond to the page
numbers of the Amendment. Capitalized terms used herein but not defined herein shall have the meanings assigned to them in the
Amendment.

Amendment
No. 1 to Registration Statement on Form S-4

Material
U.S. Federal Income Tax Consequences of the Merger, page 113

1.
We note your response to prior comment 14. However, your revised disclosure states that the Merger "should" qualify
as a reorganization and furthermore continues to assume the material tax consequences at issue (e.g. "Assuming the Merger
constitutes a reorganization...", "If the Merger so qualifies...", etc.). Please revise your prospectus disclosure
to provide a firm conclusion regarding treatment of the transaction under Section 368(a) and remove language stating that it is
intended that, or generally, certain material tax consequences will apply. Please also remove any statement that assumes the material
tax consequences at issue. Refer to Section III of Staff Legal Bulletin No. 19 for guidance.

    February 9, 2021

Page 2

Response:
Seneca respectfully informs the Staff that it believes the current disclosure under the heading “Material U.S. Federal
Income Tax Consequences of the Merger”, beginning on page 113 of the Amendment, complies with Section III of Staff Legal
Bulletin No 19 (the “Bulletin”). The Bulletin explicitly permits counsel may issue a “should” opinion
if there is a lack of authority directly addressing the tax consequences of the transaction and, in general, the disclosure describes
why a “will” opinion cannot be rendered. See Section III.C.4 of the Bulletin.

There
is no definitive authority regarding the treatment of contingent consideration (such as the Milestone Payments) in connection
with a transaction that would otherwise qualify as a “reorganization” for U.S. federal income tax purposes. In Revenue
Procedure 84-42 (the “Revenue Procedure”), the IRS announced that it will not issue favorable letter rulings regarding
the status of a transaction as a “reorganization” where the transaction included contingent stock arrangements unless
certain requirements are satisfied. Such requirements include a 50% threshold on the percentage of contingent stock that may be
issued subsequent to the closing of the transaction. Due to the number of additional shares of Seneca Common Stock that may be
issued as Milestone Payments, the Merger does not satisfy this requirement. Accordingly, due to the lack of definitive authority
regarding the tax treatment of the Milestone Payments, counsel to each of Seneca and LBS rendered a “should” opinion
as to the treatment of the Merger as a “reorganization” for U.S. federal income tax purposes. Furthermore, the disclosure
under the heading “Material U.S. Federal Income Tax Consequences of the Merger - General”, beginning on page
115 of the Amendment, explains such lack of authority, the failure of the Merger to comply with all of the requirements of the
Revenue Procedure, and related risks. As noted above, Seneca believes such disclosure complies with Section III of the Bulletin.

Contingent
Value Rights Agreement, page 144

 1. We
                                         note your response to prior comment 17. Please revise this section to disclose the planned
                                         fees for the CVR Agent and the CVR Holders' Representative.

Response:
Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure as requested on page 146.

* * *

If you have any
questions, or if it would expedite your review in any way, please do not hesitate to contact the undersigned at (818) 597-7552.

We thank the Staff
in advance for its assistance.

    February 9, 2021

Page 3

Sincerely,

/s/ Raul Silvestre

Raul Silvestre

Silvestre Law
Group, P.C.

United States securities and exchange commission logo
February 3, 2021
Dane Saglio
Chief Financial Officer
Seneca Biopharma, Inc.
20271 Goldenrod Lane
Germantown, MD 20876
Re:Seneca Biopharma, Inc.
Amendment No. 1 to Registration Statement on Form S-4
Filed January 26, 2021
File No. 333-251659
Dear Mr. Saglio:
            We have reviewed your 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.
Amendment No. 1 to Registration Statement on Form S-4
Material U.S. Federal Income Tax Consequences of the Merger, page 113
1.We note your response to prior comment 14. However, your revised disclosure states that
the Merger "should" qualify as a reorganization and furthermore continues to assume the
material tax consequences at issue (e.g. "Assuming the Merger constitutes a
reorganization...", "If the Merger so qualifies...", etc.).  Please revise your prospectus
disclosure to provide a firm conclusion regarding treatment of the transaction under
Section 368(a) and remove language stating that it is intended that, or generally, certain
material tax consequences will apply. Please also remove any statement that assumes the
material tax consequences at issue. Refer to Section III of Staff Legal Bulletin No. 19 for
guidance.

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 February 3, 2021 Page 2
 FirstName LastName
Dane Saglio
Seneca Biopharma, Inc.
February 3, 2021
Page 2
Contingent Value Rights Agreement, page 144
2.We note your response to prior comment 17. Please revise this section to disclose the
planned fees for the CVR Agent and the CVR Holders' Representative.
            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.
            You may contact Christine Torney at 202-551-3652 or Kevin Kuhar at 202-551-3662 if
you have questions regarding comments on the financial statements and related matters.  Please
contact Alan Campbell at 202-551-4224 or Celeste Murphy at 202-551-3257 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Raul Silvestre

CORRESP
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January 26, 2021

VIA EDGAR AND BY COURIER

Division of Corporation Finance

U.S. Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C. 20549

Attention: Dane Saglio

    Re:
    Seneca Biopharma, Inc.

    Registration Statement on Form S-4

    Filed December 23, 2020

    File No. 333-251659

Ladies and Gentlemen:

On behalf of Seneca Biopharma, Inc. (“Seneca”), we respectfully
submit this letter in response to the comments of the staff (the “Staff”) of the Securities and Exchange Commission
(the “Commission”) in a letter dated January 19, 2021 (the “Comment Letter”) regarding the above referenced
Registration Statement on Form S-4 (the “Registration Statement”). Seneca has also revised the Registration Statement
in an Amendment No. 1 (the “Amendment”) as set forth below in response to the Comment Letter and is filing the Amendment
with the Commission concurrently with the submission of this letter.

The numbering of the paragraphs below corresponds to the numbering
of the Staff’s comments which, for your convenience, we have incorporated into this response letter in italics. Page references
in the text of Seneca’s responses correspond to the page numbers of the Amendment. Capitalized terms used herein but not
defined herein shall have the meanings assigned to them in the Amendment.

Registration Statement on Form S-4

Questions and Answers About the Merger

What is the Merger?, page 1

 1. Please revise and continue to update your disclosure here and in the Exchange Ratio discussion on pages 122-23 to disclose the
current and/or anticipated status of the Seneca net cash calculation. Please also provide examples of estimated percentage ownership
based on Seneca's level of net cash at the Effective Time.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure as requested on pages 1, 122, and throughout the Amendment.

    January 26, 2021
 Page 2

 2. Please explain to us why you have included two separate calculations of the post-merger combined company ownership at the
bottom of page 1. In particular, please explain why you have only included 50% of the shares subject to the Equity Warrants in
the first calculation as well as in other calculations throughout the document, which state that pre-Merger Seneca equity holders
will hold approximately 26.2% of the combined company (assuming Seneca net cash between $4.5 million and $5.0 million).

Please also update this section to include a cross-reference to the Pre-Merger
Financing discussion that appears later in the document.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised page 1 of the Amendment to clarify that the calculation using an adjusted fully diluted treasury stock method
basis and after giving effect to the Pre-Merger Financing, but including 50% of the shares subject to the Equity Warrants, is the
calculation that was used by Seneca and LBS to determine the Exchange Ratio pursuant to the Merger Agreement. Seneca respectfully
advises the Staff that Seneca disclosed a second calculation on a fully diluted basis, as Seneca believes that this additional
information may help a stockholder more fully understand the capitalization of the combined company.

In addition, Seneca has revised the section to include a cross-reference to
the Pre-Merger Financing discussion that appears later in the document.

 3. Please revise your disclosure here and in the preceding letter to stockholders of Seneca Biopharma, Inc. and Leading BioSciences,
Inc. to disclose the identity of the Investor.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised page 1 of the Amendment and the preceding letter to stockholders of Seneca to disclose the identity of the Investor.

 4. Per your description of the CVR Agreement on page 146, please update your disclosure here and on page 18 to clarify,
if true, that holders of Seneca common stock immediately prior to the effective time will only receive proceeds from Legacy Monetization
Events to the extent that such proceeds exceed $300,000 in the aggregate. Please also revise to confirm whether the up-front payment
of $100,000 received by Seneca for the license NSI-189, as well as any additional proceeds received by Seneca prior to the Effective
Time, will be treated as a Legacy Monetization.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure to clarify
that no distributions will be made from any Legacy Monetization Events unless the proceeds are at least $500,000. Further, we have
clarified that the final distribution will require at least $300,000 in the CVR Escrow which we have also described. Additionally,
we clarified that no distributions will be made to the CVR Holders regarding any funds received prior to the Effective Time, which
would include the $100,000 received by Seneca for the license NSI-189. These changes were made on pages 19, 146 and throughout
the Amendment.

    January 26, 2021
 Page 3

Prospectus Summary

Leading BioSciences, Inc., page 13

 5. Please provide a more detailed, balanced summary of LBS's business including a description of its lead product candidates
and the status of its current clinical programs. Refer to Item 3 of Form S-4.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised the disclosure starting
on page 13 of the Amendment.

 6. Given that LBS has not yet initiated a Phase 2/3 or Phase 3 clinical trial for any of its product candidates, please revise
your statement that LBS is a "late" clinical stage biopharmaceutical company here and on pages 185 and 231.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised pages 185, 231 and throughout the Amendment.

Nasdaq Capital Market Listing, page 24

 7. Please revise your disclosure here and on the cover page to indicate whether the Nasdaq's determination regarding the initial
listing application will be known at the time stockholders are asked to vote on the merger agreement and whether you have had any
discussions with Nasdaq concerning the initial listing application. Please also revise to include a discussion of the potential
consequences to investors, including the ability of investors to buy and sell shares of common stock, if Nasdaq does not approve
the listing application of the combined company, but Seneca and LBS proceed with the merger. Finally, please revise your
disclosure to indicate whether you expect Seneca's current failure to comply with Nasdaq's minimum bid price requirement to
have any impact on the initial listing application of the combined company.

Response: Seneca respectfully acknowledges the Staff’s comment has revised its disclosure to confirm
that shareholders will know the status of the Nasdaq application at the special meeting of Seneca on page 24 and throughout the
Amendment. Additionally, we have added two risk factors regarding the parties moving forward with the merger without approval and
the resulting delisting of Seneca’s Common Stock as well as the impact on investors on page 32. Finally, on January 22, 2021,
Seneca received notice from Nasdaq that it regained compliance with the Nasdaq minimum bid price. Seneca issued a press release
related to regaining compliance on January 25, 2021.

The Merger

Background of the Merger, page 79

 8. To the extent material, please identify the individuals who participated in the meetings and discussions described
in this section. For instance, please identify the representatives of Seneca and LBS who participated negotiation calls on September
25, 2020, October 6, 2020 and October 7, 2020 as well as the representatives who negotiated on calls between November 6, 2020 and
December 15, 2020.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure as requested
on page 79 of the Amendment.

    January 26, 2021
 Page 4

 9. We note your disclosure that you selected Solebury and Hibiscus as your financial advisors. Please provide more details
regarding the selection process for financial advisors, including the qualifications considered.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure as requested on page 79 of the Amendment.

Seneca Reasons for the Merger, page 93

 10. We note your disclosure throughout the document that the Exchange Ratio formula is based upon an LBS valuation of $97.85
million. However, your disclosure on page 103 indicates that Cassel Salpeter's analysis of comparable public companies indicated
an implied equity value reference range for LBS of $58.4-87.6 million and that Cassel Salpeter's analysis of comparable IPOs
indicated an implied equity value reference range for LBS of $58.1-82.9 million.

Please revise your disclosure to discuss the reasons why Seneca's board
determined that a higher LBS valuation is fair to, advisable and in the best interests of Seneca and its stockholders.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure as requested on pages 94 and 102 of the Amendment.

Opinion of the Financial Advisor to the Seneca Transaction Committee

Financial Analysis of Seneca, page 102

 11. Please revise your disclosure to provide the implied equity value reference range for Seneca on an aggregate basis.

Response: Seneca respectfully acknowledges the Staff’s comment
and has consulted with Cassel Salpeter and revised its disclosure as requested on page 102 of the Amendment.

Interests of the Seneca Directors and Executive Officers in the Merger, page 105

 12. Please update your disclosure to discuss whether the report commissioned from Radford -Aon Rewards Consulting, Inc.
included a discussion or recommendation with respect to the compensation payable to the executive officers discussed in this section,
including the compensation that may be paid to executive officers in exchange for the cancellation of their options.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure on page
105 of the Amendment to clarify that AON only calculated 280G thresholds for the executive officers and did not provide a recommendation.

    January 26, 2021
 Page 5

 13. Please define the term "Accrued Obligations."

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure to define “Accrued Obligations” on page 105 of the Amendment.

Material U.S. Federal Income Tax Consequences of the Merger, page 113

 14. Please revise your prospectus disclosure to provide a firm conclusion regarding treatment of the transaction under Section
368(a) and remove language stating that it is intended that, or generally, certain material tax consequences will apply. In addition,
please clearly state that the conclusion is the opinion of counsel. Please also remove any statement that assumes the material
tax consequences at issue (e.g., "If the Merger qualifies as a reorganization within the meaning of Section 368(a) of the
Code"). Refer to Section III of Staff Legal Bulletin No. 19 for guidance.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised pages 7, 21, 115, and 116 of the Amendment.

Agreements Related to the Merger

Pre-Merger Financing, page 142

 15. Please revise your disclosure in the "Securities Purchase Agreement (Equity Financing)" subsection to describe
the circumstances under which the Converted Additional Shares would not be delivered to the Investor by the 136th day following
the Effective Time.

Please also update your disclosure to clarify, if true, that any Converted
Additional Shares not delivered to the Investor from escrow will be distributed to the holders of LBS capital stock at the Effective
Time.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised page 142 of the Amendment to describe the circumstances under which the Converted Additional Shares would
not be delivered to the Investor by the 136th day following the Effective Time and to clarify that such number of Converted Additional
Shares not delivered to the Investor from escrow will be distributed to the Milestone Recipients.

Contingent Value Rights Agreement, page 144

    January 26, 2021
 Page 6

 16. Please revise your disclosure to (i) explain the role of the CVR Agent and (ii) discuss how the CVR Holders' Representative
will be selected. Please also revise to clarify whether Seneca's obligations pursuant to the CVR Agreement will become the obligations
of the combined company following the Effective Time.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure as requested on page 146 of the Amendment.

 17. We note your disclosure that (i) Seneca will be entitled to use all or a portion of the Ongoing Support Funding ($500,000) for
expenses related to a Legacy Monetization, (ii) that Seneca will pay $500,000 (i.e. the entire amount of the Ongoing Support Funding) to
the CVR Holders' Representative at the Effective Time and that (iii) the CVR Holders' Representative will be entitled to be reimbursed
from a segregated escrow account for costs related to any Legacy Monetization.

Please update your disclosure to clarify (A) whether the intent of the arrangement
is that the CVR Holders' Representative's fee will be reduced by amounts used by Seneca for expenses related to a Legacy Monetization
and (B) the amount of funds that will be placed in the segregated escrow account and the identity of the escrow agent.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised its disclosure as requested on pages 145-146.

 18. We note your disclosure that each CVR will entitle its holder to receive a pro rata portion of 80% of the net proceeds from
any Legacy Monetization. We further note that "net proceeds" is defined as gross proceeds less deductions. Please revise
your disclosure to explain how the remaining 20% of net proceeds from any Legacy Monetization will be allocated.

We further note your disclosure on page 146 that the gross proceeds of any
monetization will be reduced by the amount of the Ongoing Support Funding. Please update your disclosure here and in the Q&A
in your document to clarify, if true, that the $500,000 of Ongoing Support Funding must be repaid before the net proceeds of any
Legacy Monetization are distributed to legacy Seneca stockholders.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure with regard
to (i) the remaining 20% of net proceeds on pages 2, 19, 144 and throughout the Amendment and (ii) the Ongoing Support Funding
on pages 145-146.

Description of Seneca's Business

Employees, page 183

    January 26, 2021
 Page 7

 19. Please revise your disclosure here and on page 221 to provide a description of your human capital resources as required
by Item 101(c)(2)(ii) of Regulation S-K.

Response: Seneca respectfully acknowledges the Staff’s comment and has revised its disclosure as requested
on page 183 and on page 221 of the Amendment.

Description of LBS's Business

Overview, page 186

 20. Please update LBS's pipeline chart to clarify whether each of the product candidates in the chart is wholly-owned or licensed
from a third party.

In addition, we note the inclusion of an oral protease inhibitor for
glucose control and autoimmune disease in LBS's pipeline table. Given the status of development and the limited disclosure in the
prospectus regarding these programs it seems premature to highlight theses program prominently in LBS's pipeline table. Accordingly,
please revise to remove these programs from the pipeline table or advise.

Response: Seneca respectfully acknowledges the Staff’s comment
and has revised pages 186 and 232 of the Amendment.

 21. We note the disclosure throughout this section stating that "evidence suggests that digestive enzyme leakage...

United States securities and exchange commission logo
January 19, 2021
Dane Saglio
Chief Financial Officer
Seneca Biopharma, Inc.
20271 Goldenrod Lane
Germantown, MD 20876
Re:Seneca Biopharma, Inc.
Registration Statement on Form S-4
Filed December 23, 2020
File No. 333-251659
Dear Mr. Saglio:
            We have reviewed your 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.
Registration Statement on Form S-4
Questions and Answers About the Merger
What is the Merger?, page 1
1.Please revise and continue to update your disclosure here and in the Exchange Ratio
discussion on pages 122-23 to disclose the current and/or anticipated status of the Seneca
net cash calculation. Please also provide examples of estimated percentage ownership
based on Seneca's level of net cash at the Effective Time.
2.Please explain to us why you have included two separate calculations of the post-merger
combined company ownership at the bottom of page 1. In particular, please explain why
you have only included 50% of the shares subject to the Equity Warrants in the first
calculation as well as in other calculations throughout the document, which state that pre-

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 2
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 2
Merger Seneca equity holders will hold approximately 26.2% of the combined company
(assuming Seneca net cash between $4.5 million and $5.0 million).

Please also update this section to include a cross-reference to the Pre-Merger Financing
discussion that appears later in the document.
3.Please revise your disclosure here and in the preceding letter to stockholders of Seneca
Biopharma, Inc. and Leading BioSciences, Inc. to disclose the identity of the Investor.
4.Per your description of the CVR Agreement on page 146, please update your disclosure
here and on page 18 to clarify, if true, that holders of Seneca common stock immediately
prior to the effective time will only receive proceeds from Legacy Monetization Events to
the extent that such proceeds exceed $300,000 in the aggregate. Please also revise to
confirm whether the up-front payment of $100,000 received by Seneca for the license
NSI-189, as well as any additional proceeds received by Seneca prior to the Effective
Time, will be treated as a Legacy Monetization.
Prospectus Summary
Leading BioSciences , Inc., page 13
5.Please provide a more detailed, balanced summary of LBS's business including a
description of its lead product candidates and the status of its current clinical programs.
Refer to Item 3 of Form S-4.
6.Given that LBS has not yet initiated a Phase 2/3 or Phase 3 clinical trial for any of its
product candidates, please revise your statement that LBS is a "late" clinical stage
biopharmaceutical company here and on pages 185 and 231.
Nasdaq Capital Market Listing , page 24
7.Please revise your disclosure here and on the cover page to indicate whether the Nasdaq's
determination regarding the initial listing application will be known at the time
stockholders are asked to vote on the merger agreement and whether you have had any
discussions with Nasdaq concerning the initial listing application. Please also revise
to include a discussion of the potential consequences to investors, including the ability of
investors to buy and sell shares of common stock, if Nasdaq does not approve the listing
application of the combined company, but Seneca and LBS proceed with the merger.
Finally, please revise your disclosure to indicate whether you expect Seneca's current
failure to comply with Nasdaq's minimum bid price requirement to have any impact on the
initial listing application of the combined company.
The Merger
Background of the Merger, page 79
8.To the extent material, please identify the individuals who participated in the meetings
and discussions described in this section. For instance, please identify the representatives

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 3
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 3
of Seneca and LBS who participated negotiation calls on September 25, 2020, October 6,
2020 and October 7, 2020 as well as the representatives who negotiated on calls between
November 6, 2020 and December 15, 2020.
9.We note your disclosure that you selected Solebury and Hibiscus as your financial
advisors. Please provide more details regarding the selection process for financial
advisors, including the qualifications considered.
Seneca Reasons for the Merger, page 93
10.We note your disclosure throughout the document that the Exchange Ratio formula is
based upon an LBS valuation of $97.85 million. However, your disclosure on page 103
indicates that Cassel Salpeter's analysis of comparable public companies indicated an
implied equity value reference range for LBS of $58.4-87.6 million and that Cassel
Salpeter's analysis of comparable IPOs indicated an implied equity value reference range
for LBS of $58.1-82.9 million.

Please revise your disclosure to discuss the reasons why Seneca's board determined that a
higher LBS valuation is fair to, advisable and in the best interests of Seneca and its
stockholders.
Opinion of the Financial Advisor to the Seneca Transaction Committee
Financial Analysis of Seneca, page 102
11.Please revise your disclosure to provide the implied equity value reference range for
Seneca on an aggregate basis.
Interests of the Seneca Directors and Executive Officers in the Merger, page 105
12.Please update your disclosure to discuss whether the report commissioned from Radford -
Aon Rewards Consulting, Inc. included a discussion or recommendation with respect to
the compensation payable to the executive officers discussed in this section, including the
compensation that may be paid to executive officers in exchange for the cancellation of
their options.
13.Please define the term "Accrued Obligations."
Material U.S. Federal Income Tax Consequences of the Merger, page 113
14.Please revise your prospectus disclosure to provide a firm conclusion regarding treatment
of the transaction under Section 368(a) and remove language stating that it is intended
that, or generally, certain material tax consequences will apply. In addition, please clearly
state that the conclusion is the opinion of counsel. Please also remove any statement that
assumes the material tax consequences at issue (e.g., "If the Merger qualifies as a
reorganization within the meaning of Section 368(a) of the Code"). Refer to Section III of
Staff Legal Bulletin No. 19 for guidance.

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 4
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 4
Agreements Related to the Merger
Pre-Merger Financing, page 142
15.Please revise your disclosure in the "Securities Purchase Agreement (Equity Financing)"
subsection to describe the circumstances under which the Converted Additional Shares
would not be delivered to the Investor by the 136th day following the Effective Time.

Please also update your disclosure to clarify, if true, that any Converted Additional Shares
not delivered to the Investor from escrow will be distributed to the holders of LBS capital
stock at the Effective Time.
Contingent Value Rights Agreement, page 144
16.Please revise your disclosure to (i) explain the role of the CVR Agent and (ii) discuss how
the CVR Holders' Representative will be selected. Please also revise to clarify whether
Seneca's obligations pursuant to the CVR Agreement will become the obligations of the
combined company following the Effective Time.
17.We note your disclosure that (i) Seneca will be entitled to use all or a portion of the
Ongoing Support Funding ($500,000) for expenses related to a Legacy Monetization, (ii)
that Seneca will pay $500,000 (i.e. the entire amount of the Ongoing Support Funding) to
the CVR Holders' Representative at the Effective Time and that (iii) the CVR Holders'
Representative will be entitled to be reimbursed from a segregated escrow account for
costs related to any Legacy Monetization.

Please update your disclosure to clarify (A) whether the intent of the arrangement is that
the CVR Holders' Representative's fee will be reduced by amounts used by Seneca for
expenses related to a Legacy Monetization and (B) the amount of funds that will be placed
in the segregated escrow account and the identity of the escrow agent.
18.We note your disclosure that each CVR will entitle its holder to receive a pro rata portion
of 80% of the net proceeds from any Legacy Monetization. We further note that "net
proceeds" is defined as gross proceeds less deductions. Please revise your disclosure to
explain how the remaining 20% of net proceeds from any Legacy Monetization will be
allocated.

We further note your disclosure on page 146 that the gross proceeds of any monetization
will be reduced by the amount of the Ongoing Support Funding. Please update your
disclosure here and in the Q&A in your document to clarify, if true, that the $500,000 of
Ongoing Support Funding must be repaid before the net proceeds of any Legacy
Monetization are distributed to legacy Seneca stockholders.

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 5
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 5
Description of Seneca's Business
Employees, page 183
19.Please revise your disclosure here and on page 221 to provide a description of your human
capital resources as required by Item 101(c)(2)(ii) of Regulation S-K.
Description of LBS's Business
Overview, page 186
20.Please update LBS's pipeline chart to clarify whether each of the product candidates in the
chart is wholly-owned or licensed from a third party.

In addition, we note the inclusion of an oral protease inhibitor for glucose control and
autoimmune disease in LBS's pipeline table. Given the status of development and the
limited disclosure in the prospectus regarding these programs it seems premature to
highlight theses program prominently in LBS's pipeline table. Accordingly, please revise
to remove these programs from the pipeline table or advise.
21.We note the disclosure throughout this section stating that "evidence suggests that
digestive enzyme leakage...", "genetic evidence supporting the association of proteases...",
"there is building evidence that...", "multiple lines of evidence implicate aberrant protease
activity", etc. Please revise these and similar statements to clearly described where this
evidence was observed and whether it was based on studies or trials conducted by LBS or
by a third party.
Our Strategy, page 187
22.Please update this section, or another part of the Description of LBS's Business as
appropriate, to discuss whether you have identified the first indication(s) for which you
anticipate seeking marketing approval for LB1148 and the clinical trials that you will be
required to conduct to support your initial application(s) for marketing approval.
23.Please remove the statement that LBS intends to "rapidly" develop  LB1148 as well as any
other statements that state or imply that you will be successful in developing and
progressing your product candidates in a rapid or accelerated manner as these statements
are inherently speculative.
24.Please remove here and throughout to remove any statements that LBS's product
candidates are "best-in-class" or "first-in-class" because the term suggests that the product
candidates are effective and likely to be approved by the FDA.  If your use of the term
was designed to convey your belief that your product candidates are based on a
differentiated technology or approach, you may further discuss how your technology or
approach differs from those of your competitors.
25.We note your statements that a "similarly designed" open-label clinical trial provide
evidence that LB1148 can reduce the time to return to bowel function in GI surgery and

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 6
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 6
that three patients treated with LB1148 who were assessed for postoperative adhesions did
not develop postoperative adhesions.

Please balance your disclosure to disclose the stage of these trials, whether the trials were
powered for efficacy, and any relevant limitations. We further note that your disclosure on
page 194 regarding the postoperative adhesions assessment states that the surgeon for one
of the three patients was not an investigator and that postoperative adhesions were not
formally assessed. Please revise your statements on page 187 to reflect the discussion on
page 194.
Unmet Needs in Intestinal Barrier Dysfunction and the Opportunity for LB1148, page 187
26.We note your statement here that LB1148 "is expected to confer multiple benefits" as well
as your statement elsewhere that LB1148 "is expected to improve patient outcomes." We
similarly note your statements that data suggest that LB1148 may prevent postoperative
adhesions in surgical patients, that LB1148 may offer distinguishing benefits for patients
providers and that LB1148 may reduce overall length of stay in both the hospital and ICU
settings. These are just examples.

Please revise your disclosure throughout your prospectus to revise these and similar
statements to eliminate conclusions or predictions that LB1148 is or will be effective as
determinations of efficacy are solely within the authority of the FDA. You may provide a
summary of the objective data from your preclinical studies and clinical trials without
including conclusions related to efficacy.
Clinical Development of LB1148, page 192
27.Please update your disclosure to include a explanation of statistical significance.
CV Surgery Phase 1, LBS-IST-CVS-101, page 192
28.Please update your disclosure to discuss whether the clinical trial of LB1148-Z can be
used to support an eventual NDA filing with the FDA.
PB101, page 200
29.Please revise your disclosure to state whether PB101 is wholly-owned by LBS or in-
licensed. Please also revise your disclosure to clarify whether you conducted the studies
referenced later in this section or if they were conducted by a third-party. Further, please
present more detailed information regarding the studies in animal models that indicate that
PB101 can preserve intestinal issue following intestinal injury. Alternatively, explain to us
why this disclosure would not be material.

Finally, please revise your disclosure to indicate the status of a potential IND filing for
PB101 or explain to us why this would not be practicable.

 FirstName LastNameDane Saglio
 Comapany NameSeneca Biopharma, Inc.
 January 19, 2021 Page 7
 FirstName LastNameDane Saglio
Seneca Biopharma, Inc.
January 19, 2021
Page 7
Protease Activity and IBD, page 201
30.Please revise and simplify your disclosure in the first seven sentences of this paragraph.
Your disclosure should clearly explain the role of proteases and should clearly convey the
potential relationship between protease activity and GI diseases.
Intellectual Property, page 206
31.Please update this section to discuss your IP coverage for PB101.
Co-Development Agreement with Newsoara, page 209
32.Please update your disclosure in this s

United States securities and exchange commission logo
September 22, 2020
Kenneth Carter, Ph.D.
Executive Chairman
Seneca Biopharma, Inc.
20271 Goldenrod Lane, 2nd Floor
Germantown, MD 20876
Re:Seneca Biopharma, Inc.
Registration Statement on Form S-3
Filed September 16, 2020
File No. 333-248848
Dear Dr. Carter:
            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 Ada D. Sarmento at 202-551-3798 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Raul Silvestre, Esq.

CORRESP
1
filename1.htm

SENECA BIOPHARMA, INC.

September 22, 2020

VIA EDGAR

Securities and Exchange Commission

Division of Corporation Finance

100 F. Street, N.E.

Washington, D.C. 20549

    RE:
    Seneca Biopharma, Inc.

    Registration Statement on Form S-3

    Filed September 16, 2020

    File No. 333-248848

Dear Ladies and Gentlemen:

In accordance with Rule 461 under the Securities
Act of 1933, as amended, the undersigned respectfully requests that the effective date of the above-referenced Registration Statement
be accelerated so that the same will become effective at 5:00 PM, Eastern Time on September 23, 2020, or as soon thereafter as
is practicable.

Sincerely,

Seneca BioPharma, Inc.

/s/ Kenneth Carter

Kenneth Carter

Executive Chairman

CORRESP
1
filename1.htm

SENECA BIOPHARMA, INC.

March 30, 2020

Tim Buchmiller

Staff Attorney

Division of Corporate Finance

United States Securities and Exchange Commission

Washington, DC 20549

RE:  Seneca Biopharma, Inc.

    Registration Statement on Form S-3

    Filed February 20, 2020

    File No. 333-236543

Dear Ladies and Gentlemen:

We have been informed telephonically that the Staff has no additional
comments to the above referenced registration statement. Accordingly, Seneca Biopharma, Inc. (“Company”) is requesting
that the above referenced registration statement be declared effective at 4:00 p.m. Eastern Time, on Tuesday, March 31, 2020 or
as soon as practicable thereafter.

In connection with this acceleration request, we hereby acknowledge that:

1.       should the Commission or the staff, acting
pursuant to delegated authority, in declaring the filing effective, such action will not foreclose the Commission from taking any
action with respect to the filing;

2.       the action of the Commission or the staff,
acting pursuant to delegated authority, in declaring the filing effective, will not relieve the Issuer from its full responsibility
for the adequacy and accuracy of the disclosure in the filing; and

3. the Issuer may not assert staff comments and the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Should you require additional information, feel free to contact the undersigned.

Sincerely,

Seneca Biopharma, Inc.

/s/ Kenneth Carter

Kenneth Carter

Executive Chairman

CORRESP
1
filename1.htm

March 27, 2020

Tim Buchmiller

Staff Attorney

Division of Corporate Finance

United States Securities and Exchange Commission

Washington, DC 20549

    RE:
    Seneca Biopharma, Inc.

    Registration Statement on Form S-3

    Filed February 20, 2020

    File No. 333-236543

Dear Ladies and Gentlemen:

We are submitting this letter on behalf of our client, Seneca Biopharma,
Inc. (“Company”) in response to your comments received on February 27, 2020 (“Comment Letter”). The response
utilize the Staff’s comments as the primary guide of this letter. Additionally, based on telephonic conversations with the
Staff, we are also requesting, on behalf of the Company, that the above referenced registration statement be declared effective
at 6:00 a.m. Eastern Time, on Monday, March 30, 2020 or as soon as practicable thereafter.

The Staff’s only comment contained in the Comment Letter is:

Registration Statement on Form S-3 filed February 20, 2020

General

1.       We note that you filed
this registration statement more than 45 days after the end of your fiscal year. As you do not appear to meet the age of financial
statement requirements of Rule 8-08(b) of Regulation S-X, you will need to include your audited financial statements or file and
incorporate by reference your Form 10-K for fiscal year ended December 31, 2019 before we will accelerate the effective date of
your registration statement. For additional guidance, please refer to Section 1220.3 of the Division's Financial Reporting Manual.

 Response: On March 27, 2020, the Company filed its Annual Report on Form 10-K, The Annual Report contains
the Company’s audited financial statements for the fiscal year ended December 31, 2019 (“Financials”). Accordingly,
the Company has filed an amendment to the above reference registration statement on March 27, 2020, which incorporates by reference
the Financials.

On behalf of the Company, we hereby acknowledge that:

 1. should the Commission or the staff, acting pursuant to delegated authority, in declaring the filing
effective, such action will not foreclose the Commission from taking any action with respect to the filing;

 2. the action of the Commission or the staff, acting pursuant to delegated authority, in declaring
the filing effective, will not relieve the Issuer from its full responsibility for the adequacy and accuracy of the disclosure
in the filing; and

 3. the Issuer may not assert staff
comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the
federal securities laws of the United States.

Should you require additional information, feel free to contact
the undersigned at 805.402.7494 or via email at rsilvestre@silvestrelaw.com.

Sincerely,

Silvestre Law Group, P.C.

Raul Silvestre

2

February 27, 2020
Kenneth Carter, PhD
Chief Executive Officer
Seneca Biopharma, Inc.
20271 Goldenrod Lane
Germantown, Maryland 20876
Re:Seneca Biopharma, Inc.
Registration Statement on Form S-3
Filed February 20, 2020
File No. 333-236543
Dear Dr. Carter:
            We have limited our review of your registration statement to those issues we have
addressed in our comment.  In our comment, 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 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 our comment, we may have additional comments.
Registration Statement on Form S-3 filed February 20, 2020
General
1.We note that you filed this registration statement more than 45 days after the end of your
fiscal year.  As you do not appear to meet the age of financial statement requirements of
Rule 8-08(b) of Regulation S-X, you will need to include your audited financial
statements or file and incorporate by reference your Form 10-K for fiscal year ended
December 31, 2019 before we will accelerate the effective date of your registration
statement.  For additional guidance, please refer to Section 1220.3 of the Division's
Financial Reporting Manual.
            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.

 FirstName LastNameKenneth Carter, PhD
 Comapany NameSeneca Biopharma, Inc.
 February 27, 2020 Page 2
 FirstName LastName
Kenneth Carter, PhD
Seneca Biopharma, Inc.
February 27, 2020
Page 2
            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 Tim Buchmiller at (202) 551-3635 or Mary Beth Breslin at (202) 551-
3625 with any other questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Raul Silvestre, Esq.

CORRESP
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July 25, 2019

Office of Healthcare and Insurance

Division of Corporation Finance

United States Securities and Exchange Commission

Washington, DC 20549

RE:  Neuralstem,
                                         Inc.

Registration Statement on Form S-1

Originally Filed June 21, 2019

Amended on July 25, 2019

File No. 333-232273

To Whom it May Concern:

We are in receipt of your letter dated June 27, 2019 advising us
that the above referenced registration statement will not be reviewed. Pursuant to a telephonic conversation between our legal
counsel and the staff, we have been informed that we can request acceleration to become effective at 5:15 p.m. EST, on Thursday
July 25, 2019. Accordingly, please be advised that Neuralstem, Inc. hereby requests that the above referenced registration statement
be declared effective at 5:15 p.m. EST, on Thursday, July 25, 2019 or as soon as practicable thereafter.

We hereby acknowledge that:

 1. should the Commission or the staff, acting pursuant to delegated authority, in declaring the filing
effective, such action will not foreclose the Commission from taking any action with respect to the filing;

 2. the action of the Commission or the staff, acting pursuant to delegated authority, in declaring
the filing effective, will not relieve the Issuer from its full responsibility for the adequacy and accuracy of the disclosure
in the filing; and

 3. The Issuer may not assert staff comments and the declaration of effectiveness as a defense in any
proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Very truly yours,

/s/ Kenneth Carter

Kenneth Carter, PhD

Executive Chairman

June 27, 2019
Kenneth Carter, PhD
Chief Executive Officer
Neuralstem, Inc.
20271 Goldenrod Lane, 2nd Floor
Germantown, MD 20876
Re:Neuralstem, Inc.
Registration Statement on From S-1
Filed June 21, 2019
File No. 333-232273
Dear Dr. Carter:
            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 Tonya K. Aldave at (202) 551-3601 with any questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Raul Silvestre, Esq.

CORRESP
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NEURALSTEM, INC.

July 14, 2017

Ada Sarmento

Office of Healthcare and Insurance

Division of Corporation Finance

United States Securities and Exchange Commission

Washington, DC 20549

    RE:
    Neuralstem, Inc.

    Registration Statement on Form
S-3/A

    Filed July 13, 2017

    File No. 333-219195

Dear Ms. Sarmento:

Pursuant to a telephonic conversation with the Commission stating
that there are no further comments to the above referenced registration statement of Neuralstem, Inc. (“Company”),
the Company hereby requests that the above referenced registration statement be declared effective at 5:00 p.m. EST, on Tuesday,
July 18, 2017, or as soon as practicable thereafter.

We thank you in advance for your time and attention. Should you
wish to further discuss this matter, please do not hesitate to contact me at 301.366.4960 or the Company’s counsel, Raul
Silvestre of Silvestre Law Group, P.C. at 818.597.7552.

We hereby acknowledge that:

 1. should the Commission or the staff, acting pursuant to delegated authority, in declaring the filing
effective, such action will not foreclose the Commission from taking any action with respect to the filing;

 2. the action of the Commission or the staff, acting pursuant to delegated authority, in declaring
the filing effective, will not relieve the Issuer from its full responsibility for the adequacy and accuracy of the disclosure
in the filing; and

 3. The Issuer may not assert staff comments and the declaration of effectiveness as a defense in any
proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Very truly yours,

/s/ Richard Daly

Richard Daly

Chief Executive Officer

1

CORRESP
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NEURALSTEM,
INC.

June 21, 2017

Irene Paik

Office of Healthcare and Insurance

Division of Corporation Finance

United States Securities and Exchange Commission

Washington, DC 20549

RE:  Neuralstem, Inc.

    Registration
Statement on Form S-3

    Filed
June 8, 2017

    File No.
333-218608

Dear Ms. Paik:

We are submitting this letter in response
to your comment letter dated June 20, 2017 regarding the above referenced registration statement of Neuralstem, Inc. (“Company”).
This response will follow the lineal order of your letter and each specific area addressed, utilizing the text of your letter as
the primary guide:

Incorporation of Documents by Reference,
Page 15

 1. Please incorporate by reference the Current Reports on Form 8-K filed on January 6, February 16,
February 22 and March 20, 2017. See Item 12(a)(2) of Form S-3.

 Response: The Company has amended the Registration Statement as requested to comply with your comment.
In addition, we have made conforming changes to page 11 of the warrant exercise prospectus.

Assuming there are no further comments
from the Commission, the Company hereby requests that the above referenced registration statement be declared effective at 5:00
p.m. EST, on Friday June 23, 2017 or as soon as practicable thereafter.

We thank you in advance for your time and
attention. Should you wish to further discuss this matter, please do not hesitate to contact me at 301.366.4960 or the Company’s
counsel, Raul Silvestre of Silvestre Law Group, P.C. at 818.597.7552.

We hereby acknowledge that:

 1. should the Commission or the staff, acting pursuant to delegated authority, in declaring the filing
effective, such action will not foreclose the Commission from taking any action with respect to the filing;

 2. the action of the Commission or the staff, acting pursuant to delegated authority, in declaring
the filing effective, will not relieve the Issuer from its full responsibility for the adequacy and accuracy of the disclosure
in the filing; and

    1

NEURALSTEM,
INC.

 3. The Issuer may not assert staff comments and the declaration of effectiveness as a defense in any
proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Very truly yours,

/s/ Richard Daly

Richard Daly

Chief Executive Officer

2

June 20, 2017
Richard Daly
President, Chief Executive Officer and Chief Financial Officer
Neuralstem, Inc.
20271 Goldenrod Lane, 2nd Floor
Germantown, MD 20876
Neuralstem, Inc.
Registration Statement on Form S-3
Filed June 8, 2017
File No. 333-218608Re:
Dear Mr. Daly:
        We have limited our review of your registration statement to those issues we have
addressed in our comment.
        Please respond to this letter by amending your registration statement and providing the
requested information.  If you do not believe our 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 comment, we may have additional comments.
Form S-3 filed June 8, 2017
Incorporation of Documents by Reference, page 15
Please incorporate by reference the Current Reports on Form 8-K filed on January 6,
February 16, February 22 and March 20, 2017.  See Item 12(a)(2) of Form S-3.1.

Richard Daly
Neuralstem, Inc.
2 PageJune 20, 2017
        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 Irene Paik at (202) 551-6553 with any questions.
Division of Corporation Finance
Office of Healthcare & Insurance
cc: Raul Silvestre, Silvestre Law Group, P.C.

CORRESP
1
filename1.htm

    Unassociated Document

NEURALSTEM, INC.

April 26, 2011

Jeffrey P. Riedler

Assistant Director

Division of Corporation Finance

United States Securities and Exchange Commission

Washington, DC 20549

RE:

Neuralstem, Inc. (“Issuer”)

Registration Statement on Form S-3

Filed March 31, 2011

File No. 333-173221

Dear Mr. Riedler:

Based upon a telephone conversation with your staff, Neuralstem, Inc. (“Company”) is hereby requesting the above referenced registration statement be declared effective at 4:00 p.m. EST, on Tuesday, April 26, 2011 or as soon as practicable thereafter.

We hereby acknowledge that:

·

should the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, such action will not foreclose the Commission from taking any action with respect to the filing;

·

the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the filing effective, will not relieve the Company from its full responsibility for the adequacy and accuracy of the disclosure in the filing; and

·

the Company may not assert staff comments and the declaration of effectiveness as a defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

Very truly yours,

/s/ I. Richard Garr

I. Richard Garr

Chief Executive Officer

April 13, 2011
 I. Richard Garr President and Chief Executive Officer Neuralstem, Inc. 9700 Great Seneca Highway
Rockville, Maryland 20850

Re: Neuralstem, Inc.
  Registration Statement on Form S-3
Filed March 31, 2011
  File No. 333-173221

Dear Mr. Garr:
 We have limited our review of your regist ration statement to your incorporation of
certain documents by reference.  Please amend this section to include the Form 8-K filed
February 15, 2011.
 Please respond to this letter by amending your registration statement and providing the
requested information.  Where you do not believe our 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 re gistration statement and the information you
provide in response to these comments, we may have additional comments.

We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filing to be certain that the filing incl udes the information the Securities Act of 1933 and
all applicable Securities Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disc losure, they are responsible for the accuracy
and adequacy of the disclosures they have made.
Notwithstanding our comments, in the event you request acceleration of  the effective date
of the pending registration statement please pr ovide a written statement from the company
acknowledging that:

• should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose the Co mmission from taking any action with respect
to the filing;

I. Richard Garr Neuralstem, Inc.  April 13, 2011 Page 2

• the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

• the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal
securities laws of the United States.  Please refer to Rules 460 and 461 regarding re quests for acceleration.  We will consider a
written request for acceleration of  the effective date of the regi stration statement as confirmation
of the fact that those reques ting acceleration are aware of thei r respective responsibilities under
the Securities Act of 1933 and the Securities Excha nge Act of 1934 as they relate to the proposed
public offering of the securities specified in th e above registration stat ement.  Please allow
adequate time for us to review any amendment prior to the requested effective date of the
registration statement.
 Please contact Michael Rosenthall at 202-551-3674 or me at 202-551-3715 with any
other questions.
Sincerely,
       Jeffrey P. Riedler
Assistant Director

October 12, 2010

I. Richard Garr
President & Chief Executive Officer
Neuralstem, Inc.
9700 Great Seneca Highway
Rockville, MD 20850

Re: Neuralstem, Inc.  Form 10-K for the Fiscal Year Ended December 31, 2009
Form 10-Q for the Quarterly Period Ended June 30, 2010 File No. 001-33672
 Dear Mr. Garr:

 We have completed our review of your fili ngs and do not have any further comments at
this time.

Sincerely,

Joel Parker
        A c c o u n t i n g  B r a n c h  C h i e f

September 17, 2010

I. Richard Garr
President & Chief Executive Officer
Neuralstem, Inc.
9700 Great Seneca Highway
Rockville, MD 20850

Re: Neuralstem, Inc.  Form 10-K for the Fiscal Year Ended December 31, 2009
Form 10-Q for the Quarterly Period Ended June 30, 2010 File No. 001-33672
 Dear Mr. Garr:

We have limited our review of your filings to  those issues we have addressed in our
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 within ten business days by amending your filing, by
providing the requested information, or by advi sing us when you will provide the requested
response.  If you do not believe a comment applie s to your facts and circumstances or that an
amendment is required, please tell us why in  your response.  Please furnish us a letter on
EDGAR under the form type label CORRESP th at keys your responses to our comments.

After reviewing any amendment and the info rmation provided, we may raise additional
comments.

Form 10-K for the Fiscal Year Ended December 31, 2009

Item 8. Financial Statements and Supplementary Data
Notes to Financial Statements, page 36
1. You disclose on page 7 that you conduct re search and development through research
collaborations.  On the same page, you also  disclose a number of projects for which you
may be required to pay for certain costs a nd expenses incurred in  connection with the
research.  Please provide us proposed revised di sclosure to be included in future filings
that includes the significant terms of your research and de velopment agreements and any
other material agreements w ithin your notes to the fina ncial statements, including the
following:

• Payments made or future obligations unde r the arrangements, in cluding a summary of
events triggering your obligati on and the accounting treatment;
• Length of the agreements; and

I. Richard Garr
Neuralstem, Inc.
September 17, 2010
Page 2

• Termination provisions of the agreements.
 Where uncertainties prevent making a reasonable estimate of the future obligations, explain those uncertainties.
 Note 2. Stockholders’ (Deficit) Equity

Stock Warrants, page 40
2. Please tell us why you believe the fair value you have assigned to the liability classified
warrants complies with GAAP given that a Bl ack-Scholes option pricing model is not
designed to attribute fair va lue to the price protection f eatures of your warrants.
Binomial or lattice models are bett er suited to handle this feature.

Item 11.  Executive Compensation
Employment Agreements and Arrangements and Change-In-Control Arrangements, page 53

3. You describe the employment agreements between the company and CFO John Conron as well as Senior Vice President Thomas Hazel, but do not file these agreements as exhibits to your filing.  Please amend your Fo rm 10-K for the fiscal year ended December
31, 2009 to file these employment agreements as exhibits.
We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filings to be certain that the filings incl ude the information the Secu rities Exchange Act of
1934 and all applicable Exchange Act rules requir e.  Since the company and its management are
in possession of all facts relating to a company’s disclosure, they are responsible for the accuracy
and adequacy of the disclosures they have made.

In responding to our comments, please provi de a written statement from the company
acknowledging that:

• The company is responsible for the adequacy  and accuracy of the disclosure in the
filings;
• Staff comments or changes to disclosure  in response to staff comments do not
foreclose the Commission from taking any action with respect to the filings; and
• The company may not assert staff comments as a defense in any proceeding initiated
by the Commission or any person under the federal securities laws of the United States.

I. Richard Garr
Neuralstem, Inc.
September 17, 2010
Page 3

You may contact Staci Shannon, Staff Account ant, at (202) 551- 3374 or Mary Mast,
Review Accountant, at (202) 551-3613 if you have any questions regarding the processing of
your response, as well as any questions regard ing comments on the financial statements and
related matters.  You may contact Rose Zukin, Staff Attorney, at (202) 551-3239 with questions
on comment four.  In this regard, do not hesitate  to contact me at (202) 551-3679 with any other
questions.
Sincerely,

Jim B. Rosenberg Senior Assistant Chief Accountant

CORRESP
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filename1.htm

    NEURALSTEM,
INC.

    ______________________________________________________

      May 4,
2010

      Jeffrey
P. Riedler

      Assistant
Director

      Division
of Corporation Finance

      Mail Stop
6010

      United
States Securities and Exchange Commission

      Washington,
DC 20549

                    RE:

                Neuralstem,
      Inc. (“Issuer”)

                  Registration
      Statement on Form S-3

                  Initially
      Filed April 9, 2010

                  Amended
      Filed April 27, 2010

                  File
      No. 333-165973

      Dear Mr.
Riedler:

      Based
upon a telephone conversation with your staff, Neuralstem, Inc. is hereby
requesting the above referenced registration statement be declared effective at
1:00 p.m. EST, on Thursday, May 6, 2010 or as soon as practicable
thereafter.

      We hereby
acknowledge that:

                1.

                should
      the Commission or the staff, acting pursuant to delegated authority, in
      declaring the filing effective, such action will not foreclose the
      Commission from taking any action with respect to the
    filing;

                2.

                the
      action of the Commission or the staff, acting pursuant to delegated
      authority, in declaring the filing effective, will not relieve the Issuer
      from its full responsibility for the adequacy and accuracy of the
      disclosure in the filing; and

                3.

                The
      Issuer may not assert staff comments and the declaration of effectiveness
      as a defense in any proceeding initiated by the Commission or any person
      under the federal securities laws of the United
  States.

                Very
      truly yours,

                /s/
      I. Richard Garr

                I.  Richard
      Garr

                Chief
      Executive Officer

Mail Stop 4720          April 19, 2010  I. Richard Garr President and Chief Executive Officer Neuralstem, Inc.  9700 Great Seneca Highway Rockville, MD 20850
 Re: Neuralstem, Inc.
  Registration Statement on Form S-3
  Filed April 9, 2010
  File No. 333-165973
 Dear Mr. Garr:   We have limited our review of your filing to those issues we have addressed in
our comments.  Where indicated, we think you should revise your document in response
to these comments.  If you disagree, we w ill consider your explanation as to why our
comments are inapplicable or a revision is  unnecessary.  Please be as detailed as
necessary in your explanation.  In some of our comments, we may ask you to provide us with information so we may better understand your disclosure.  Af ter reviewing this
information, we may raise additional comments.

 Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure  requirements and to  enhance the overall
disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our comments or any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.
  General

 1. We note your disclosure in footnote 1 to th e registration fee table that pursuant to
Rule 416, the registration statement also covers additional co mmon shares that
may be offered to prevent dilution as a re sult of stock splits, stock dividends or
that may be required for delivery upon exer cise of any warrants as a result of anti-
dilution provisions. Rule 416(a) involves the registration of additional securities
“being offered or issued to prevent di lution resulting from stock splits, stock
dividends or similar transactions.”  Pleas e revise to remove the shares “that may

I. Richard Garr
Neuralstem, Inc.  April 19, 2010 Page 2

be required for delivery upon exercise of any warrants as a result of anti-dilution
provisions” as they do not appear  to be covered by Rule 416.
  Selling Shareholders – Replacement Warrants, page 11

 2. We note that you appear to have conducte d two exchanges of warrants relating to
three classes of warrants.   Please tell us why you do not believe that the
exchanges were subject to Rule 13e-4 relati ng to issuer tender offers.  For further
guidance, refer to the Heritage Entertainment, Inc. lett er, dated April 10,
1987.

* * *
  As appropriate, please amend your regist ration statement in response to these
comments.  You may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cove r letter with your amendment that keys your
responses to our comments and provides any requested information.  Detailed cover
letters greatly facilitate our review.  Please understand that we may have additional comments after reviewing your amendment and responses to our comments.   We urge all persons who are responsible for the accuracy and adequacy of the disclosure in the filing to be certain that the filing includes all in formation required under
the Securities Act of 1933 and that they have  provided all information investors require
for an informed investment decision.  Since the company and its management are in possession of all facts relating to a company’ s disclosure, they are responsible for the
accuracy and adequacy of the disclosures they have made.       Notwithstanding our comments, in the ev ent the company requests acceleration of
the effective date of the pending registration statement, it should furnish a letter, at the time of such request, acknowledging that:
• should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose th e Commission from taking any action with
respect to the filing;
 • the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective,  does not relieve the company from its full responsibility
for the adequacy and accuracy of the disclosure in the filing; and
 • the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the
federal securities laws of the United States.

I. Richard Garr
Neuralstem, Inc.  April 19, 2010 Page 3
 In addition, please be advi sed that the Division of En forcement has access to all
information you provide to the staff of the Di vision of Corporation Finance in connection
with our review of your filing or in response to our comments on your filing.
  We will consider a written request for acceleration of the effective date of the registration statement as conf irmation of the fact that t hose requesting acceleration are
aware of their respective re sponsibilities under the S ecurities Act of 1933 and the
Securities Exchange Act of 1934 as they rela te to the proposed public offering of the
securities specified in the above registration statement.  We will act  on the request and,
pursuant to delegated authority, grant acce leration of the effective date.
  We direct your attention to Rules 460 and 461 regarding requesting acceleration
of a registration statement.  Please allow ad equate time after the filing of any amendment
for further review before submitting a request for acceleration.  Please provide this request at least two business days in a dvance of the requested effective date.
  Please contact Nandini Acharya at (202) 551-3495, Daniel Duchovny, Office of
Mergers and Acquisitions at (202) 551-3619 or  me at (202) 551-3715 with any questions.

Sincerely,
           J e f f r e y  P .  R i e d l e r
        A s s i s t a n t  D i r e c t o r
   cc: Raul Silvestre, Esq.
Silvestre Law Group, P.C.  31200 Via Colinas, Suite 200 Westlake Village, CA 91362

CORRESP
1
filename1.htm

      NEURALSTEM,
INC.

    April 1, 2009

    Jeffrey P. Riedler

    Assistant Director

    Division of Corporation
Finance

    Mail Stop 6010

    United States Securities and Exchange
Commission

    Washington, DC 20549

                RE:

                Neuralstem, Inc. (“Issuer”)

    Registration Statement on Form
S-3

    File No. 333-157079

    Dear Mr. Riedler:

    Based upon a telephone conversation with your staff, Neuralstem, Inc. is hereby requesting
the above referenced registration statement be declared
effective at 1:00 p.m. EST, on Friday, April 3, 2009 or as soon as practicable
thereafter.

    We hereby acknowledge
that:

              1.

              should the Commission or the
      staff, acting pursuant to delegated authority, in declaring the filing
      effective, such action will not foreclose the Commission from taking any
      action with respect to the
filing;

              2.

              the action of the Commission or
      the staff, acting pursuant to delegated authority, in declaring the filing
      effective, will not relieve the Issuer from its full responsibility for
      the adequacy and accuracy of the disclosure in the filing;
      and

              3.

              The Issuer may not assert staff comments and
      the declaration of effectiveness as a defense in any proceeding initiated
      by the Commission or any person under the federal securities laws of the
      United States.

                    Very
      truly yours,

                    /s/ John
      Conron

                    John
      Conron

                    Chief
      Financial Officer

CORRESP
1
filename1.htm

    February 26, 2009

    Jeffrey P. Riedler

    Assistant Director

    Division of Corporation
Finance

    Mail Stop 6010

    United States Securities and Exchange
Commission

    Washington, DC 20549

              RE:

              Neuralstem, Inc. (“Issuer”)

    Registration Statement on Form
S-3

    File No. 333-157079

    Dear Mr. Riedler:

    Based upon a telephone message from your staff, we were informed that the above
referenced registration statement was cleared for
effectiveness.  Please be advised that Neuralstem, Inc. hereby requests that the
registration statement be declared effective at 1:00 p.m. EST, on Monday, March 2, 2009 or as soon as practicable
thereafter.

    We hereby acknowledge
that:

              1.

              should the Commission or the
      staff, acting pursuant to delegated authority, in declaring the filing
      effective, such action will not foreclose the Commission from taking any
      action with respect to the
filing;

              2.

              the action of the Commission or
      the staff, acting pursuant to delegated authority, in declaring the filing
      effective, will not relieve the Issuer from its full responsibility for
      the adequacy and accuracy of the disclosure in the filing;
      and

              3.

              The Issuer may not assert staff comments and
      the declaration of effectiveness as a defense in any proceeding initiated
      by the Commission or any person under the federal securities laws of the
      United
      States.

                  Very
      truly yours,

                  /s/ John
      Conron

                  John
      Conron

                  Chief
      Financial Officer

Mail Stop 6010          February 11, 2009  I. Richard Garr  Chief Executive Officer Neuralstem, Inc. 9700 Great Seneca Highway Rockville, Maryland 20850
 Re: Neuralstem, Inc.
  Registration Statement on Form S-3
  Filed February 2, 2009
  File No. 333-157079
 Dear Mr. Garr:   We have limited our review of your filing to those issues we have addressed in
our comments.  Where indicated, we think you should revise your document in response
to these comments.  If you disagree, we w ill consider your explanation as to why our
comment is inapplicable or a revision is unneces sary.  Please be as detailed as necessary
in your explanation.  In some of our comme nts, we may ask you to provide us with
information so we may better understand your  disclosure.  After reviewing this
information, we may raise additional comments.

 Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure  requirements and to  enhance the overall
disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our comments or any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.
 General

 1. We note your disclosure in footnote 1 to th e registration fee table that pursuant to
Rule 416, the registration statement also covers additional co mmon shares that
may be offered to prevent dilution as a re sult of stock splits, stock dividends or
that may be required for delivery upon exer cise of any warrants as a result of anti-
dilution provisions.  Rule 416(a) involves the registration of additional securities
“being offered or issued to prevent di lution resulting from stock splits, stock
dividends or similar transactions.”  Pleas e revise to remove the shares “that may
be required for delivery upon exercise of any warrants as a result of anti-dilution
provisions” as they do not appear  to be covered by Rule 416.

I. Richard Garr
Neuralstem, Inc. February 11, 2009 Page 2

Incorporation of Certain Info rmation by Reference, page 17

2. Please revise this section to incorpor ate by reference the Form 8-Ks filed on
November 18, 2008, December 3, 2008, December 18, 2008 and January 29, 2009.
 Exhibits, page 20

 3. Please file a copy of your Se ries C Warrant as an exhi bit to this registration
statement.

* * *
  As appropriate, please amend your regist ration statement in response to these
comments.  You may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cove r letter with your amendment that keys your
responses to our comments and provides any requested information.  Detailed cover
letters greatly facilitate our review.  Please understand that we may have additional comments after reviewing your amendmen t and responses to our comments.
  We urge all persons who are responsible for the accuracy and adequacy of the disclosure in the filing to be certain that the filing includes all in formation required under
the Securities Act of 1933 and that they have  provided all information investors require
for an informed investment decision.  Since the company and its management are in possession of all facts relating to a company’ s disclosure, they are responsible for the
accuracy and adequacy of the disclosures they have made.

 Notwithstanding our comments, in the ev ent the company requests acceleration of
the effective date of the pending registration statement, it should furnish a letter, at the time of such request, acknowledging that:
• should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose th e Commission from taking any action with
respect to the filing;
 • the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective,  does not relieve the company from its full responsibility
for the adequacy and accuracy of the disclosure in the filing; and
 • the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the
federal securities laws of the United States.

I. Richard Garr
Neuralstem, Inc. February 11, 2009 Page 3
 In addition, please be advi sed that the Division of En forcement has access to all
information you provide to the staff of the Di vision of Corporation Finance in connection
with our review of your filing or in response to our comments on your filing.
  We will consider a written request for acceleration of the effective date of the registration statement as conf irmation of the fact that t hose requesting acceleration are
aware of their respective re sponsibilities under the S ecurities Act of 1933 and the
Securities Exchange Act of 1934 as they rela te to the proposed public offering of the
securities specified in the above registration statement.  We will act  on the request and,
pursuant to delegated authority, grant acce leration of the effective date.
  We direct your attention to Rules 460 and 461 regarding requesting acceleration
of a registration statement.  Please allow ad equate time after the filing of any amendment
for further review before submitting a request for acceleration.  Please provide this request at least two business days in a dvance of the requested effective date.
  Please contact Jennifer Riegel at ( 202) 551-3575 or me at (202) 551-3715 with
any questions.          S i n c e r e l y ,             J e f f r e y  P .  R i e d l e r          A s s i s t a n t  D i r e c t o r
cc: Raul Silvestre
Law Offices of Raul Silvestre & Associates, APLC
31200 Via Colinas, Suite 200 Westlake Village, CA 91362

Via Facsimile and U.S. Mail
Mail Stop 6010

         December 18, 2008

John Conron
Chief Financial Officer
Neuralstem, Inc.
9700 Great Seneca Highway
Rockville, MD 20850

Re:   Neuralstem, Inc.
 Form 10-KSB for the Fiscal Year Ended December 31, 2007
 Filed March 27, 2008
 File Number:  001-33672

Dear Mr. Conron,

We have completed our review of your Form 10-KSB and have no further
comments at this time.         Sincerely,
     Carlton E. Tartar Accounting Branch Chief

CORRESP
1
filename1.htm

    Unassociated Document

      NEURALSTEM,
INC.

      9700
GREAT SENECA HIGHWAY, SUITE 240

      ROCKVILLE,
MD 20850

      (301)
366-4841

    December
17, 2008

    SENT VIA
EDGAR

    Jim B.
Rosenberg

    Senior
Assistant Chief Accountant

    Telephone
Number: (202) 551-3679

                    RE:

                    Neuralstem,
      Inc.

    Form
10-KSB for the Fiscal Year Ended December 31, 2007

    Filed
March 27, 2008

    File
No. 001-33672

    Dear Mr.
Rosenberg:

    We are
submitting this letter in response to your comments of December 4, 2008, with
respect to Neuralstem, Inc. (“Company”) annual report referenced
above.  This response will follow the lineal order of your letter and
each specific area addressed, utilizing the text of your letter as the primary
guide:

    Form l0-KSB for the fiscal
year ended December 31, 2007

      Report of Independent
Registered Public Accounting Finn, page F-l

              1.

              Please
      confirm that you received a signed audit report by Stegman & Company
      as required by Rule 2-02(a) of Regulation S-X and Rule 232.302 of
      Regulation S-T and tell us whether you will include a signed audit report
      in your future filings.

              Response:

              We are hereby
      confirming that we received a signed audit report from Stegman &
      Company as required by Rule 2-02(a) of Regulation S-X and Rule 232.302 of
      Regulation S-T.  We are also confirming that we will include a
      signed audit report in our future
  filings.

      NEURALSTEM,
INC.

      9700
GREAT SENECA HIGHWAY, SUITE 240

      ROCKVILLE,
MD 20850

      (301)
366-4841

    We hereby
acknowledge that:

                  1.

                  the
      company is responsible for the adequacy and accuracy of the disclosure in
      the filing;

                  2.

                  staff
      comments or changes to disclosure in response to staff comments do not
      foreclose the Commission from taking any action with respect to filing;
      and

                3.

                the
      company may not assert staff comments as a defense in any proceeding
      initiated by the Commission or any person under the federal securities law
      of the United States

                                            Very
truly yours,

                                            /s/
John Conron

                                            John
Conron

                                            Chief
Financial Officer

Via Facsimile and U.S. Mail
Mail Stop 6010

         December 4, 2008

John Conron
Chief Financial Officer
Neuralstem, Inc.
9700 Great Seneca Highway
Rockville, MD 20850

Re:   Neuralstem, Inc.
 Form 10-KSB for the Fiscal Year Ended December 31, 2007
 Filed March 27, 2008
 File Number:  001-33672

Dear Mr. Conron:

We have reviewed your filings and have the following comment. We have limited
our review to your financial statements a nd related disclosures and do not intend to
expand our review to other portions of your documents.  Please provide us the
supplemental information requested below.  After reviewing the information provided,
we may raise additional comments and/or  request that you amend your filing.

 Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure  requirements and to  enhance the overall
disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our  comment or on any other aspect of our
review.  Feel free to call us at the telephone numbers listed at the end of this letter.
Form 10-KSB for the fiscal year ended December 31, 2007

Report of Independent Registered Public Accounting Firm, page F-1
1. Please confirm that you received a signe d audit report by Stegman & Company as
required by Rule 2-02(a) of Regulation S-X and Rule 232.302 of Regulation S-T and
tell us whether you will include a signed  audit report in your future filings.

John Conron
Neuralstem, Inc. December 4, 2008 Page 2
 Please provide us the information request ed within 10 busine ss days or tell us
when you will provide us with a response.  Pl ease furnish a cover le tter with your response
that keys your response to our comment.  De tailed cover letters gr eatly facilitate our
review.  Please furnish your letter on EDGAR under the form type label CORRESP.

 We urge all persons who are responsible  for the accuracy and adequacy of the
disclosure in the filing to be certain that the filing includes all in formation required under
the Securities Exchange Act of 1934 and th at they have provided all information
investors require for an informed invest ment decision.  Since the company and its
management are in possession of all facts re lating to a company’s disclosure, they are
responsible for the accuracy and adequacy of the disclosures they have made.

 In connection with responding to our comment, please provide , in your letter, a
statement from the company acknowledging that:

• the company is responsible for the adequacy and accuracy of the disclosure in
the filing;
• staff comments or changes to disclosure  in response to staff comments do not
foreclose the Commission from taking a ny action with respect to the filing;
and
• the company may not assert staff comme nts as a defense in any proceeding
initiated by the Commission or any pers on under the federal s ecurities laws of
the United States.

 In addition, please be advi sed that the Division of En forcement has access to all
information you provide to the staff of the Divi sion of Corporation Fi nance in our review
of your filing or in response to our comment on your filing.

You may contact Dana Ha rtz, Staff Accountant, at (202) 551-3648 or Don
Abbott, Review Accountant, at (202) 551-3608 if you have any questions regarding the
comment.  In this regard, do not hesi tate to contact me, at (202) 551-3679.

        S i n c e r e l y ,

        J i m  B .  R o s e n b e r g
Senior Assistant Chief
Accountant

Mail Stop 6010         February 5, 2007   Mr. Richard Garr Chief Executive Officer Neuralstem, Inc. 9700 Great Seneca Highway Rockville, MD 20850

Re: Neuralstem, Inc.
 Item 4.01 Form 8-K
Filed February 2, 2007
 File No. 333-132923

Dear Mr. Garr:

We have reviewed your filing and have the following comment.  Where indicated,
we think you should revise your document in response to this comment.  If you disagree,
we will consider your explanation as to why our  comment is inapplicable or a revision is
unnecessary.  Please be as detailed as necessary in your explanation.
  Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure requirements and to enhance the overall disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our  comment or any other aspect of our
review.  Feel free to call us at the telephone number listed at  the end of this letter.
  Item 4.01

1. Please amend the first paragraph of your filing to cover the interim period from
the date of your last audited financial statements through the date your former
accountant was dismissed as required by Item 304(a)(1)(iv) of Regulation S-B.

  As appropriate, please amend your filing a nd respond to this comment within five
business days or tell us when you will respond.  You may wish to provide us with marked copies of the amendment to expedite our re view.  Please furnish a cover letter with your
amendment that keys your responses to our comment and provides any requested

Mr. Richard Garr
Neuralstem, Inc. February 5, 2007 Page 2  information.  Detailed cover le tters greatly facilitate our re view.  Please understand that
we may have additional comments after revi ewing your amendment and responses to our
comment.   We urge all persons who are responsible  for the accuracy and adequacy of the
disclosure in the filing to be certain that the filing includes all in formation required under
the Securities Exchange Act of 1934 and th at they have provided all information
investors require for an informed invest ment decision.  Since the company and its
management are in possession of all facts re lating to a company’s disclosure, they are
responsible for the accuracy and adequacy of the disclosures they have made.
  In connection with responding to our comments, please provide, in writing, a
statement from the company acknowledging that:  ‚ the company is responsible for the adequacy  and accuracy of the disclosure in the
filing;
‚ staff comments or changes to disclosure  in response to staff comments do not
foreclose the Commission from taking any action with respect to the filing; and

‚ the company may not assert staff comments as a defense in any proceeding initiated
by the Commission or any person under the federal securities laws of the United
States.

In addition, please be advise d that the Division of Enfo rcement has access to all
information you provide to the staff of the Divi sion of Corporation Fi nance in our review
of your filing or in response to our comments on your filing.     If you have any questions, please call me at (202) 551-3665.
        S i n c e r e l y ,            J. Todd Sherman        S t a f f  A c c o u n t a n t

CORRESP
1
filename1.htm

      Unassociated Document

    NEURALSTEM,
      INC.

    9700
      GREAT SENECA HIGHWAY, SUITE 240

    ROCKVILLE,
      MD 20850

    (301)
      366-4841

    August
      30, 2006

    VIA
      EDGAR

    Sonia
      Barros

    United
      States Securities and Exchange Commission

    100
      F
      Street, NE

    Washington
      D.C. 20549

            RE:
            NEURALSTEM, INC.

            REGISTRATION STATEMENT ON FORM SB-2

            FILE NUMBER
              333-132923

    Dear
      Ms.
      Barros:

    Based
      upon the conversation between Mr. Mark
      Brunhofer
      of the
      Commission and our attorneys on August 29, 2006, in which Mr. Brunhofer notified
      our attorneys that the foregoing registration statement was cleared for
      effectiveness, please be advised that Neuralstem, Inc. hereby requests that
      the
      registration statement be declared effective at 4:00 pm EST, or as soon as
      practicable thereafter, on Wednesday, August 30, 2006.

    We
      hereby
      acknowledge that:

            1.

              Should
                the Commission or the staff, acting pursuant to delegated authority,
                in
                declaring the filing effective, such action will not foreclose the
                Commission from taking any action with respect to the
                filing.

            2.

              The
                action of the Commission or the staff, acting pursuant to delegated
                authority, in declaring the filing effective, will not relieve Neuralstem,
                Inc. from its full responsibility for the adequacy and accuracy of
                the
                disclosure in the filing.

            3.

              Neuralstem,
                Inc. may not assert staff comments and the declaration of effectiveness
                as
                a defense in any proceeding initiated by the Commission or any person
                under the federal securities laws of the United
                States.

            Very truly yours,

            /s/ Richard Garr

            Richard Garr

              Chief
                Executive Officer

CORRESP
1
filename1.htm

    NEURALSTEM,
      INC.

    9700
      GREAT SENECA HIGHWAY, SUITE 240

    ROCKVILLE,
      MD 20850

    (301)
      366-4841

    August
      29, 2006

    VIA
      EDGAR

    Sonia
      Barros

    United
      States Securities and Exchange Commission

    100
      F
      Street, NE

    Washington
      D.C. 20549

            RE:

              NEURALSTEM,
                INC.

              REGISTRATION
                STATEMENT ON FORM SB-2

              FILE
                NUMBER 333-132923

    Dear
      Ms.
      Barros:

    Based
      upon the conversation between Mr. Mark
      Brunhofer
      of the
      Commission and our attorneys on August 29, 2006, in which Mr. Brunhofer notified
      our attorneys that the foregoing registration statement was cleared for
      effectiveness, please be advised that Neuralstem, Inc. hereby requests that
      the
      registration statement be declared effective no later than by the close of
      business as of Friday, September 1, 2006.

    We
      hereby
      acknowledge that:

            1.

              Should
                the Commission or the staff, acting pursuant to delegated authority,
                in
                declaring the filing effective, such action will not foreclose the
                Commission from taking any action with respect to the
                filing.

            2.

              The
                action of the Commission or the staff, acting pursuant to delegated
                authority, in declaring the filing effective, will not relieve Neuralstem,
                Inc. from its full responsibility for the adequacy and accuracy of
                the
                disclosure in the filing.

            3.

              Neuralstem,
                Inc. may not assert staff comments and the declaration of effectiveness
                as
                a defense in any proceeding initiated by the Commission or any person
                under the federal securities laws of the United
                States.

                Very
      truly
      yours,

                /s/
      Richard
      Garr

                Richard
      Garr

                Chief
      Executive
      Officer

Mail Stop 6010 August 24, 2006
The Corporation Trust Company
1209 Orange Street New Castle County, Wilmington, Delaware 19801

Re: Neuralstem, Inc.
 Amendment No. 4 to Registration Statement on Form SB-2  Filed August 22, 2006  File No. 333-132923

Dear Sir or Madame:

We have reviewed your filing and have the following comments.  Where
indicated, we think you should revise your document in response to these comments.  If you disagree, we will consider your explanation as to why our comment is inapplicable or a revision is unnecessary.  Please be as detailed as necessary in your explanation.  In some of our comments, we may ask you to provide us with supplemental information so we may better understand your disclosure.  After reviewing this information, we may or may not raise additional comments.
Please understand that the purpose of our review process is to assist you in your
compliance with the applicable disclosure requirements and to enhance the overall disclosure in your filing.  We look forward to working with you in these respects.  We welcome any questions you may have about our  comments or on any other aspect of our
review.  Feel free to call us at the telephone numbers listed at the end of this letter.  Financial Information

 Report of Independent Registered Public Accounting Firm, page F-1

 1. Although you represent in response to our previous comment five that your
auditor has modified his consent it does not appear that you have filed this consent.  Please file your auditor’s consent and ensure that it is currently dated and that it references the appropriate dual dating of his audit report.

The Corporation Trust Company
August 24, 2006
Page 2  Preferred Series C Stock, page F-11

 2. The sentence you highlight in response to our previous comment seven indicates
that you believe that your decision to forge the cash consideration related to the options enticed the noteholders to convert their notes.  This sentence does not explain why you were willing to forgo $5 million in cash consideration upon option exercise to entice the noteholders to convert only approximately $1.5 million in notes.  Please revise your disclosure here and in MD&A to clearly indicate your business reason for enticing conversion by forgoing $5 million in potential cash proceeds.
 Interim Financial Statements, page F-17

 Statements of Operations, page F-18

 3. Please revise your presentation and disclosure to address the following comments:
a. Please move your revenue amounts from your operating expenses line
item to the revenues line item.
b. Please clarify whether the three-month periods presented are March or
June.  It appears from the revenue line that the three-month periods may be June as the six-month revenue amounts appear to equal the sum of the three-month revenues presented here plus those from your March disclosures in your third amendment.
c. If you intend to present the three-month periods ended June 30, please
ensure that your six-month numbers equal the totals of your first quarter results, as previously disclosed adjusted for your correction of the registration rights liability in response to our previous comment 10e, and your second quarter results.  In this regard for example, it appears that the total of the first quarter 2006 research and development costs presented in your third amendment of $305,513 plus the $474,593 disclosed here, presumably for the second quarter of 2006, does not equal the six-month total presented of $824,592.  Otherwise, please disclose why you apparently changed your first quarter results as reported in your third amendment.
d. Please ensure that the numbers you present foot.  In this regard, it appears
that the operating and net losses presented for the three-month period in 2005 are the same as those disclosed in your third amendment, even though your revenues and total operating expenses have changed.
e. Please revise your weighted-average shares outstanding for the two
periods presented in 2005.  Otherwise, please explain to us why these amounts are the same as the first quarter 2005 shares presented in your third amendment when you disclose on page II-2 that your preferred shares converted into common shares early in 2005.

The Corporation Trust Company
August 24, 2006
Page 3  Note 4:  Warrant liability and common stock payable, page F-22

 4. Please revise your disclosure added in response to our previous comment 10 to
clearly indicate where in your statement of operations you recorded the $29,815 penalty for common stock and warrants issued under your registration rights agreement.
* * * * *

As appropriate, please amend your filing in response to these comments.  You
may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cover letter with your amendment that keys your responses to our comments and provides any requested supplemental information.  Detailed cover letters greatly facilitate our review.  Please file your cover letter on EDGAR under the form type label CORRESP. Please understand that we may have additional comments after reviewing your amendment and responses to our comments.
We direct your attention to Rules 460 and 461 regarding requesting acceleration
of a registration statement.  Please allow adequate time after the filing of any amendment for further review before submitting a request for acceleration.  Please provide this request at least two business days in advance of the requested effective date.
You may contact Mark Brunhofer at (202) 551-3638 or Kevin Woody at (202)
551-3629 if you have questions regarding comments on the financial statements and related matters.  Please contact Sonia Ba rros at (202) 551-3655 or me at (202) 551-3710
with any other questions.

        S i n c e r e l y ,              J e f f r e y  P .  R i e d l e r          A s s i s t a n t  D i r e c t o r   cc: Raul Silvestre
Law Offices of Raul Silvestre & Associates, APLC 31200 Via Colinas, Suite 200 Westlake Village, CA 91362

CORRESP
1
filename1.htm

    Sonia
      Barros

    Division
      of Corporation Finance

    Telephone
      Number: (202) 551-3655

    Telecopier
      Number: (202) 772-9217

            RE:

              Neuralstem,
                Inc.

    Amendment
      No. 3
      to Registration Statement on Form SB-2

    Filed
      August 10, 2006

    File
      No. 333-132923

    Dear
      Ms.
      Barros:

    We
      are
      submitting this letter in response to your comments of August 15, 2006.
The
      following are our proposed responses to be included in our fourth amendment
      to
      the SB2 for
      Neuralstem, Inc. I will forward under separate cover the actually proposed
      change. This correspondence will follow the lineal order of your letter and
      each
      specific area addressed, utilizing the text of your letter as the primary
      guide:

    Management’s
      Discussion and Analysis and Plan of Operation, pages
      23-28

              11.

              We
                note your response to our prior comment 5 and reissue that comment.
                We
                refer to your statement on page 24 that you “anticipate that [you] will
                approach market makers in order for them to quote [your] securities” and
                that “in the event [your] securities become quoted, [you] will be subject
                to the periodic reporting requirements of the Securities Act of 1934.”
                These statements are currently inaccurate. Your securities do not
                have to
                be “quoted for you to be subject to the periodic reporting requirements
                of
                the Securities Exchange Act of 1934. Once his registration statement
                becomes effective, you will be subject to the periodic reporting
                requirements of the Securities Exchange Act of 1934, whether or not
                your
                securities are quoted. In addition, the market makers are not the
                quotation medium. The OTCBB would be the quotation medium. Market
                Makers
                may apply to have your securities quoted on the OTCBB. Please revise
                your
                disclosure accordingly.

    Proposed
      Response: We
      have removed the reference to our securities being quoted and have revised
      the
      disclosure to accurately state that we will be subject to the reporting
      requirements of the Exchange Act upon the registration statement becoming
      effective.

    Signatures

              11.

              We
                note your response to our prior comment 7 and reissue that comment.
                You
                revised signatures still do not comply with the signatures requirements
                of
                Form SB-2. Please revise Mr. Garr’s third signature to indicate he is also
                the company’s principal accounting officer and signing for himself in that
                capacity. In addition, please note that his second signature on behalf
                of
                the company is unnecessary, unless required by the company’s governing
                documents.

    Proposed
      Response: We
      have clearly indicated that Mr. Garr is signing in his capacity as the principal
      accounting officers.

    Interim
      Financial Statements, page F-17

    Note
      4: Registration Rights Liability, page F-21

              11.

              We
                acknowledge your response to our previous comment 17. Please address
                the
                following additional comments:

              a.

              Please
                revise your registration rights disclosure here and on page 46 to
                clearly
                indicate that your one percent for each 30-day period penalties are
                prorated for partial periods as indicated in Section 8(c) of your
                Subscription Agreement for your March private
                placement.

    Proposed
      Response: We
      have revised the disclosure to clearly indicate that the penalties are prorated
      for partial periods.

              b.

              Please
                explain to us how you calculated the 33,000 shares of common stock
                to be
                issued under the registration rights as a result of your late filing
                of
                your initial registration statement on Form SB-2. It would appear
                that a
                1% penalty on 5 million shares would be 50,000 shares issuable per
                30-day
                period. Based on the February 23, 2006 private placement closing
                date you
                disclose it appears that the most days you can accrue as of March
                31, 2006
                is six days. A six day penalty would appear to be only 10,000 shares
                while
                a total nine day penalty would appear to be 15,000 shares, based
                on the
                April 3, 2006 filing date. Additionally, please clarify your disclosures
                to indicate that the penalty starts to be assessed subsequent to
                the
                initial 30-day grace period.

    Proposed
      Response: We
      have clarified our disclosure to indicate that we have already accrued a penalty
      of 9 days and that the penalty starts to be assessed subsequent to the initial
      30 day-grace period.

    Exhibits,
      page II-4

              11.

              We
                acknowledge your response to our previous comment 10. It appears
                that you
                list your investment agreement with Regal One as both Exhibits 4.6
                and
                4.17. Please confirm to us that the only difference between the two
                agreements is that Exhibit 4.6 is unexecuted. If true, please revise
                your
                Exhibit list to remove the unexecuted document. Please explain to
                us any
                other differences between the two documents and revise your Exhibit
                list
                to clarify why two agreements are
                necessary.

    Proposed
      Response: We have removed the reference to Exhibit 4.6 from the Exhibit Table.
      We are also confirming that the only difference between the two agreements
      is
      the inclusion of signatures.

Mail Stop 6010 August 15, 2006

The Corporation Trust Company
1209 Orange Street
New Castle County, Wilmington, Delaware 19801

Re: Neuralstem, Inc.
 Amendment No. 3 to Registration Statement on Form SB-2
 Filed August 10, 2006
 File No. 333-132923

Dear Sir or Madame:

We have reviewed your filing and have the following comments.  Where
indicated, we think you should revise your document in response to these comments.  If
you disagree, we will consider your explanation as to why our comment is inapplicable
or a revision is unnecessary.  Please be as detailed as necessary in your explanation.  In some of our comments, we may ask you to provide us with supplemental information so
we may better understand your disclosure.  After reviewing this information, we may or
may not raise additional comments.

Please understand that the purpose of our review process is to assist you in your
compliance with the applicable disclosure requirements and to enhance the overall
disclosure in your filing.  We look forward to working with you in these respects.  We
welcome any questions you may have about our comments or on any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.

Management's Discussion and Analysis and Plan of Operation, pages 23-28
1. We note your response to our prior comment 5 and reissue that comment.  We refer to your statement on page 24 that you “anticipate that [you] will approach
market makers in order for them to quote [your] securities” and that “in the event
[your] securities become quoted, [you] will be subject to the periodic reporting requirements of the Securities Act of 1934.”   These statements are currently
inaccurate.  Your securities do not have to be “quoted for you to be subject to the
periodic reporting requirements of the Securities Exchange Act of 1934.  Once this registration statement becomes effective, you will be subject to the periodic reporting
requirements of the Securities Exchange Act of 1934, whether or not your securities
are quoted.  In addition, the market makers are not the quotation medium.  The

The Corporation Trust Com pany
August 15, 2006
Page 2

OTCBB would be the quotation medium.  Market makers may apply to have your securities quoted on the OTCBB.  Please revise your disclosure accordingly.

Signatures
2. We note your response to our prior comment 7 and reissue that comment.  Your revised signatures still do not comply with the signature requirements of Form SB-2.
Please revise Mr. Garr’s third signature to indicate he is also the company’s principal
accounting officer and signing for himself in  that capacity.  In addition, please note
that his second signature on behalf of the company is unnecessary, unless required by
the company’s governing documents.

Financial Information

General
3. Please revise your filing to include updated financial statements and financial
disclosures through June 30, 2006 as required by Item 310(g) of Regulation S-B.

Managements Discussion and Analysis

Results of Operations, page 25
4. Please revise your disclosure regarding other expenses incurred in 2004 to discuss the
charge you added in response to our previous comment 12 related to your options issued to acquire Series C preferred stock.

Financial Information

Report of Independent Registered Public Accounting Firm
5. Although your auditor modified the date of his report to be consistent with that
identified in his consent in response to our previous comment eight, the date of the report does not appear to cover the restatement adjustment you recorded in response
to our previous comment 12.  Please have your auditor update his report to a date after you identified and recorded your additional restatement adjustments and modify
his consent as appropriate.  Please have your auditor currently date his consent.

Statements of Stockholders’ Deficit, page F-4

The Corporation Trust Com pany
August 15, 2006
Page 3

6. Although you continue to indicate in response to our previous comment nine, that you
removed reference to “Interest on notes receivable from stockholders,” this line item
is still in your statement of stockholders’ deficit.  Please remove this line item from
your statement.

Preferred Series C Stock, page F-11
7. Although you indicate in response to our previous comment 13, that you have revised
your disclosure to indicate why you decided to forego the cash consideration related
to the exercise price of the Series C preferred stock options, we are unable to locate
your revised disclosure.  Please tell us the exact location of your revised disclosure or revise your disclosure to clearly indicate why you enticed your note holders to
convert their notes to preferred stock.

Recent Sales of Unregistered Securities, page II-1
8. We acknowledge your response to our previous comment 16a.  It appears that you
still indicate on page F-10 that the warrants issued to Regal One in September 2005 are options.  Please revise your disclosure to consistently reflect these instruments.
9. We acknowledge your response to our previous comment 16b. Although you
represent that the 200,000 warrants issued to Mr. Westeich were issued in connection with the sale of common stock your disclosure on page II-3 clearly indicates that Mr.
Westeich converted a note to common stock and that you issued these warrants as additional compensation.  Your disclosure in footnote 8 to the table on page 31
clearly indicates that these warrants were issued in connection with the settlement of
a note.  Please revise your accounting to reflect the fair value of these warrants as an induced conversion expense under SFAS 84 or tell us in detail why you continue to
believe that these warrants were issued in connection with a cash sale of stock when
this sale is not apparently disclosed in Part II.  In any regard, as previously requested, please revise your financial statement footnotes to disclose the existence of and your
accounting for these warrants or tell us where you have added this disclosure in the
financial statement footnotes.

Interim Financial Statements, page F-17

Note 4:  Registration Rights Liability, page F-21
10. We acknowledge your response to our previous comment 17.  Please address the
following additional comments:
a. Please revise your registration rights disclosure here and on page 46 to clearly indicate that your one percent for each 30-day period penalties are prorated for
partial periods as indicated in Section 8(c) of your Subscription Agreement for
your March private placement.

The Corporation Trust Com pany
August 15, 2006
Page 4

b. Please explain to us how you calculated the 33,000 shares of common stock to be issued under the registration rights as a result of your late filing of your initial
registration statement on Form SB-2.  It would appear that a 1% penalty on 5
million shares would be 50,000 shares issuable per 30-day period.  Based on the February 23, 2006 private placement closing date you disclose it appears that the
most days you can accrue as of March 31, 2006 is six days.  A six day penalty
would appear to be only 10,000 shares while a total nine day penalty would appear to be 15,000 shares, based on the April 3, 2006 filing date.  Additionally,
please clarify your disclosures to indicate that the penalty starts to be assessed
subsequent to the initial 30-day grace period.
c. In addition to the disclosures included with regards to the shares of common stock issuable as of March 31, 2006 as a result of the registration rights agreement,
please disclose the number of warrants that you were obligated to issue on March
31, 2006 and the total amount due on April 3, 2006.
d. Although you indicate in response to previous comment 17c that you have reflected the shares returned or returnable from Regal One in your financial
statements, your statement of stockholders’ equity on page F-19 does not reflect
this transaction.  In addition, your footnote disclosure does not address this transaction.  Please revise your accounting and disclosure to reflect the returned
or returnable shares from Regal One as of March 31, 2006 and disclose the total
amount of shares returned through your April 3, 2006 filing date.
e. Based upon the additional disclosures you include in response to comment 17b, the $2,385,216 liability appears to accrue penalties that have not yet been
incurred.  Therefore, please reverse this liability and reflect the 2.5 million class
A warrants and 2.5 million class B warrants issued and outstanding as liabilities under paragraphs 14-18 of EITF 00-19 or tell us why this accounting treatment is
inappropriate.  In this regard, please allocate the net proceeds from your March
private placement first to the fair value of these warrants with the remainder to the common stock.  Please reflect the value allocated to the warrants as a liability
upon issuance and mark this liability to market at each period with the change in
value recorded through your income statement.  Please ensure you include the warrants issued or issuable as identified in part c. above in your liability at March
31, 2006.

Exhibits, page II-4
11. We acknowledge your response to our previous comment 10.  It appears that you list
your investment agreement with Regal One as both Exhibits 4.6 and 4.17.  Please confirm to us that the only difference between the two agreements is that Exhibit 4.6
is unexecuted.  If true, please revise your Exhibit list to remove the unexecuted document.  Please explain to us any other differences between the two documents and
revise your Exhibit list to clarify why two agreements are necessary.
* * * * *

The Corporation Trust Com pany
August 15, 2006
Page 5

As appropriate, please amend your filing in response to these comments.  You
may wish to provide us with marked copies of the amendment to expedite our review.
Please furnish a cover letter with your amendment that keys your responses to our
comments and provides any requested supplemental information.  Detailed cover letters greatly facilitate our review.  Please file your cover letter on EDGAR under the form type
label CORRESP. Please understand that we may have additional comments after
reviewing your amendment and responses to our comments.

We direct your attention to Rules 460 and 461 regarding requesting acceleration
of a registration statement.  Please allow adequate time after the filing of any amendment
for further review before submitting a request for acceleration.  Please provide this
request at least two business days in advance of the requested effective date.

You may contact Mark Brunhofer at (202) 551-3638 or Kevin Woody at (202)
551-3629 if you have questions regarding comments on the financial statements and
related matters.  Please contact Sonia Ba rros at (202) 551-3655 or me at (202) 551-3710
with any other questions.

        S i n c e r e l y ,

        J e f f r e y  P .  R i e d l e r
        A s s i s t a n t  D i r e c t o r

cc: Raul Silvestre
Law Offices of Raul Silvestre & Associates, APLC
31200 Via Colinas, Suite 200
Westlake Village, CA 91362

Mail Stop 6010 August 4, 2006

The Corporation Trust Company
1209 Orange Street
New Castle County, Wilmington, Delaware 19801

Re: Neuralstem, Inc.
 Amendment No. 2 to Registration Statement on Form SB-2
 Filed July 26, 2006
 File No. 333-132923

Dear Sir or Madame:

We have reviewed your filing and have the following comments.  Where
indicated, we think you should revise your document in response to these comments.  If
you disagree, we will consider your explanation as to why our comment is inapplicable or a revision is unnecessary.  Please be as detailed as necessary in your explanation.  In some of our comments, we may ask you to provide us with supplemental information so we may better understand your disclosure.  After reviewing this information, we may or may not raise additional comments.

Please understand that the purpose of our review process is to assist you in your
compliance with the applicable disclosure requirements and to enhance the overall disclosure in your filing.  We look forward to working with you in these respects.  We welcome any questions you may have about our comments or on any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.

Risk Factors, pages 6-12

“We intend to rely upon the third-party FDA-approved manufacturers for our stem cells .
. . .”  Page 9
1. We note your response to our prior comment 29 and your statement in this risk factor that you will rely on third-party FDA-approved manufacturers for your stem cells in the future.  As you currently have an agreement with Charles River Laboratories for the manufacturing and storage of stem cells, please revise this risk factor to address this agreement and any specific risks arising from such agreement.

The Corporation Trust Company
August 4, 2006
Page 2

Our Business, pages 13-22

General
2. We note your response to our prior comment 18 and reissue that comment in part.  Please revise your disclosure to how your cells are “purified.”

Our Grants, page 17
3. We note your response to our prior comment 24 and reissue that comment in part.  Please revise your disclosure with respect to the NIH grant to describe amounts received to date and any stipulations and conditions to the full funding of the grant.

Our Intellectual Property Licensed to Others, pages 17-18
4. We note your response to our prior comment 26 and reissue that comment in part.  For license agreements with each of A-TCP and BRM, please also describe the obligations/rights to defend and the term and termination provisions.

Management's Discussion and Analysis  and Plan of Operation, pages 23-28
5. On page 24 you refer to a possible “listing” of your common stock on the OTCBB.  Please note that the OTCBB is not an issuer listing service, market or exchange and your company and securities cannot be approved for listing on the OTCBB.  Only Market Makers can apply to quote your securities on the OTCBB.  Please revise your disclosure to clarify this statement.

Selling Shareholders, pages 35-45
6. We note your response to our prior comment 41 and reissue that comment in part.  For each selling stockholder who is an affiliate of a broker-dealer, please revise the prospectus to also state that such selling stockholder purchased or will purchase the securities in the ordinary course of business, or alternatively, state that these persons are underwriters within the meaning of the Securities Act of 1933.

Signatures
7. We note your response to our prior comment 58 and reissue that comment in part.  Your revised signatures, however, still do not comply with the signature requirements of Form SB-2.  Please revise Mr. Garr’s second signature to indicate he is also the company’s principal accounting officer.

The Corporation Trust Company
August 4, 2006
Page 3

Financial Information

Report of Independent Registered Public Accounting Firm
8. The audit report date is not consistent with the dates as listed in your auditor’s consent filed as Exhibit 23.2.  Please have your auditor revise his audit report or consent as appropriate.

Statements of Stockholders’ Deficit, page F-4
9. Although you indicate in response to our previous comment 46, that you removed reference to notes receivable from stockholders’, this line item is still in your statement of stockholders’ deficit.  Please remove this line item from your statement.

Note 2: Stockholders’ Deficit

Common Stock, page F-10
10. We acknowledge your response to our previous comment 47.  Please explain to us why the document you identify as a non-execute d draft of the agreement erroneously
filed as Exhibit 10.8 to your initial Form SB-2 filing appears to be executed while the new agreement filed as Exhibit 4.6 of your first amendment is not executed.

Preferred Series A & B Stock, page F-10
11. We acknowledge your response to our previous comment 48.  We continue to believe that the conversion rate of your Series A and B preferred stock is 3.3333 shares of preferred stock to receive one share of common stock, not three shares of preferred stock to receive one share of common stock.  An original conversion rate of one-for-one with a three-for-10 reverse stock split results in a post-split rate of 0.3 common shares for each preferred share.  This in turn equates to 0.9 common shares for three preferred shares or one common share for 3.3333 shares of preferred stock.  Please revise your disclosure to reflect this revised conversion rate.  If you indeed issued the common stock based on a one-for-three conversion ratio and are unable to recover these shares from your former preferred shareholders, please revise your accounting and disclosure to reflect the shares issued in excess of the one-for-3.3333 conversion ratio as a dividend to the preferred stock holders, or explain to us in detail why the one-for-three conversion ratio is appropriate.

Preferred Series C Stock, page F-11
12. We acknowledge your response to our previous comment 49.  We do not believe that an expected option life of one year and a volatility of 1% are reasonable assumptions given an apparent five year life of the option and the early stage of your company’s

The Corporation Trust Company
August 4, 2006
Page 4

life cycle.  Please revise your accounting and disclosure for the options issued in connection with the Series C preferred stock to reflect reasonable assumptions for expected life and volatility or explain to us in detail why these assumptions are reasonable.
13. We acknowledge that your decision to forego the cash consideration related to the exercise price of the Series C preferred stock options enticed the noteholders to convert their notes.  Please revise the disclosure you added in response to our previous comment 50 to clearly indicate w hy you enticed your noteholders to convert
their notes to preferred stock.

Stock Options, page F-12
14. We acknowledge your response to comment 51.  Please revise your disclosure to provide the pro forma information required by paragraph 45c of SFAS 123.  In addition, please revise your March 31, 2006 interim financial statements to indicate how you adopted SFAS 123R on January 1, 2006.  If true, please disclose that you continue to follow the intrinsic value model of APB 25 for those awards issued and unmodified prior to the adoption of SFAS 123R as permitted by paragraph 83 of the new guidance.

Common stock payable for 226,000 unissued shares of common stock, page F-13
15. Please revise the disclosure added in response to our previous comment 44a to clearly disclose why these shares were unissued as of December 31, 2005 and apparently remain issued through the date of your filing.

Recent Sales of Unregistered Securities, page II-1
16. We acknowledge your response to our previous comment 55.  Please address the following additional comments:
a. You continue to use the terms options and warrants interchangeably.  This is confusing as it is unclear whether two separate instruments exist.  As examples, on pages 31 and II-2 you indicate that 1,000,000 warrants were issued to Regal One in September 2005, while on page F-10 you appear to indicate that these instruments are options.  On pages 32 and II-3 you indicate that 200,000 options were issued to Mr. Westeich, while on pages 31 and F-4 you appear to indicate that these instruments are warrants.  In addition, in the warrant disclosure on page F-12 you indicate that you issued 1,599,000 options to consultants in 2005.  Please revise your disclosures throughout your filing to properly and consistently classify your instruments as either options or warrants.
b. As previously requested in comment 55b, please revise your financial statement footnotes to disclose your accounting for the 200,000 options or

The Corporation Trust Company
August 4, 2006
Page 5

warrants issued to Mr. Westeich or tell us where you have added this disclosure.  In addition, it appears that these options or warrants were issued to induce the conversion of a note.  If you have not reflected the fair value of these options or warrants as an induced conversion expense, please revise your financial statements and disclosure to do so, or tell us why this accounting is not appropriate.  Please see SFAS 84.

Interim Financial Statements, page F-17

Note 2: Stockholders’ Equity, page F-21
17. We acknowledge your response to our previous comment 54.  Please address the following additional comments:
a. It does not appear that you have accounted for the 33,333 common shares issued or issuable as a result of your late filing of this registration statement as disclosed on page 46.  Please revise your financial statements and disclosure to indicate your accounting for these shares as previously requested.
b. It appears that the warrants issued in conjunction with your 2006 private placement may be liabilities under paragraphs 14-18 of EITF 00-19.  Please revise your accounting and disclosure to reflect these warrants as liabilities or tell us why your registration rights do not result in liability treatment and provide to us your complete analysis of all the provisions of EITF 00-19.
c. Please revise your registration rights disclosure starting on page 45 to disclose the provision to cancel shares held by Regal One if you do not meet the filing and effectiveness date deadlines.  In addition, please revise your accounting and disclosure to reflect any shares of Regal One cancelled or tell us why no such shares were cancelled.

* * * * *

As appropriate, please amend your filing in response to these comments.  You
may wish to provide us with marked copies of the amendment to expedite our review.  Please furnish a cover letter with your amendment that keys your responses to our comments and provides any requested supplemental information.  Detailed cover letters greatly facilitate our review.  Please file your cover letter on EDGAR under the form type label CORRESP. Please understand that we may have additional comments after reviewing your amendment and responses to our comments.

We direct your attention to Rules 460 and 461 regarding requesting acceleration

The Corporation Trust Company
August 4, 2006
Page 6

of a registration statement.  Please allow adequate time after the filing of any amendment for further review before submitting a request for acceleration.  Please provide this request at least two business days in advance of the requested effective date.

You may contact Mark Brunhofer at (202) 551-3638 or Kevin Woody at (202)
551-3629 if you have questions regarding comments on the financial statements and related matters.  Please contact Sonia Ba rros at (202) 551-3655 or me at (202) 551-3715
with any other questions.

        S i n c e r e l y ,

        J e f f r e y  P .  R i e d l e r
        A s s i s t a n t  D i r e c t o r

cc: Raul Silvestre
Law Offices of Raul Silvestre & Associates, APLC
31200 Via Colinas, Suite 200
Westlake Village, CA 91362

Mail Stop 6010 July 5, 2006

The Corporation Trust Company
1209 Orange Street
New Castle County, Wilmington, Delaware 19801

Re: Neuralstem, Inc.
 Amendment No. 1 to Registration Statement on Form SB-2
 Filed June 21, 2006
 File No. 333-132923

Dear Sir or Madame:

We have reviewed your filing and have the following comments.  Where
indicated, we think you should revise your document in response to these comments.  If
you disagree, we will consider your explanation as to why our comment is inapplicable or a revision is unnecessary.  Please be as detailed as necessary in your explanation.  In some of our comments, we may ask you to provide us with supplemental information so we may better understand your disclosure.  After reviewing this information, we may or may not raise additional comments.

Please understand that the purpose of our review process is to assist you in your
compliance with the applicable disclosure requirements and to enhance the overall disclosure in your filing.  We look forward to working with you in these respects.  We welcome any questions you may have about our comments or on any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.

General
1. We note your response to our prior comment 2 and reissue that comment in part.  As there is currently no market for your common shares you must set a price at which the selling shareholders will offer the shares until a market develops.  Please revise your disclosure on the prospectus cover page and in the Plan of Distribution accordingly.  Your revised disclosure should state that “The selling shareholders will sell at a price of $x.xx  per share until our shares are quoted on the OTC Bulletin Board and thereafter at prevailing market prices or privately negotiated prices.”

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 2
2. Please revise your filing to include updated financial statements and financial disclosures through March 31, 2006 as required by Item 310(g) of Regulation S-B.

Prospectus Cover Page
3. We note your response to our prior comment 7 and reissue that comment.  Please limit the cover page to one page and to the information that is required by Item 501 of Regulation S-B.  Your cover page still contains superfluous information such as the bullets that describe the instruments under which the common share are issuable and the statement regarding how the selling shareholders may sell their shares.

Risk Factors, pages 7-16

General
4. Throughout the risk factor section you refer to “proceeds from this Offering.”  We note, however, that this is a secondary offering and the company will not receive the proceeds from the sale of any shares registered, other than from the exercise price of warrants.  Please clarify if you are referring to proceeds from the exercise of the warrants or delete this statement.
5. Please move the risk factors “The Company relies on stem cell technologies . . . .” and “Inability to complete pre-clinical and clinical testing . . . .” to the subsection for “Risks Relating to the Company’s Stage of Development” as these risk factors relate to the company’s development.

The Company will need to raise additional capital . . . ., page 7
6. We note your statement that your current working capital will be sufficient to satisfy contemplated cash requirements for approximately 18 months.  Please revise this risk factor to quantify your current working capital.
7. We also note that the above statement is inconsistent with the statement on page 33 in your MD&A that your available cash and expected income will be sufficient to finance most of your current activities for at least six to eight months from the date of the financial statements.  Please revise your disclosure so that these statements are consistent.

Inability to complete pre-clinical and clinical testing . . . ., page 9
8. Please revise this risk factor to disclose the company’s current stage of development.  We note that you have yet to file an IND with the FDA.

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 3
Potential and actual legislation and regulation . . . ., page 10
9. We note your response to our prior comment 25 and reissue that comment.  Please expand your discussion to explain what you mean by “certain pharmaceutical research methods or products resulting from them.”
10. We note your response to our prior comment 26 and reissue that comment.  We note your statement that your cells are not “embryonic stem cells” but that any future or additional government-imposed restrictions on embryonic stem cells may adversely impact your business.  Please expand your discussion to explain why that is the case and how your stem cells differ from embryonic stem cells.

The Company may depend on its collaborators . . . ., page 11
11. We note your response to our prior comment 28 and reissue that comment.  Please expand your discussion in this risk factor to name any current key collaborators, licensors or licensees and to discuss any specific risks related to your agreements with and dependence upon those parties.

The Company’s reliance on the activities of its non-employee consultants, research
institutions, and scientific contractors . . . ., page 12
12. We note your response to our prior comment 29 and reissue that comment.  Please expand your discussion in this risk factor to name any key non-employee consultants, research institutions, and scientific contractors and to discuss any specific risks related to your agreements with and dependence upon those parties.

There is no public market . . . ., page 14
13. We note your response to our prior comment 23 and reissue that comment.  Please expand your discussion in this risk factor to explain that your stock is not traded on an exchange or on the OTCBB and that this is your initial registration.  Please also explain that even if it is listed on the OTCBB, the trading volume may be limited, making it difficult for an investor to sell shares.
14. In addition, we note various statements in this risk factor that appear to be inapplicable to this registration statement, e.g. an investment in “Units,” the right to participate in a contemplated public registration and no assurances that a public registration will ever be effected.  Please revise this risk factor so that it relates to this registration.

The Company has identified significant weaknesses . . . ., page 15

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 4
15. We note your response to our prior comment 16 and reissue that comment.  Your statement that you have “found deficiencies or weaknesses with the timely reporting of transactions and the documentation thereof” is vague and does not provide insight into the nature of the significant deficiencies and material weaknesses that you have identified.  Please revise your disclosure to elaborate on the nature of the significant deficiencies and material weaknesses that you have identified.

There will be a continuation of management control.  Page 16
16. This risk factor as currently written appears to apply to a previous offering as it refers to the purchase of “Units” in the offering.  Please revise the risk factor to delete such references.
17. Please also revise the risk factor to address the risks associated with the fact that your two officers and directors and certain princi pal stockholders have significant control
over the company.

Our Business, pages 17-28

General
18. Please revise your disclosure to provide a complete explanation of your technology.
Throughout the prospectus, you make claims  about what your technology does, but
you not describe the technology itself.  For example, on page 19 you explain that your technology “allows for the isolation of human neural stem cells” and “allows for cells to grow in cultured dishes” but you do not describe your technology.  In addition, on page 18 you state that you “have developed proprietary and reproducible processes to identify, isolate, purify, expand, control the cells differentiation in mature functioning human neurons . . . .” and that “the cells are purified . . . .”  Please revise your disclosure to describe your “processes” and how your cells are “purified.”
19. We note your response to our prior comment 48 and reissue that comment.  You no longer make any statements about where and with whom you complete the basic work of growing cells.  Please revise your disclosure to describe if you complete this work in-house or if you have outsourced it to universities and research labs.  If you have outsourced it, describe the terms of any material arrangements and file the written agreements as exhibits to the registration statement.

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 5
Our History, page 17
20. Please revise your disclosure to restor e your explanation of why you changed your
business plan from genomics and drug discovery to neural stem cells.

Potential Markets, page 19
21. We note that your current research programs are targeting only three of the potential markets you have listed in this section, Parkinson’s, spinal-cord injuries and Amyotrophic Lateral Sclerosis.  While you may target these other markets at some time in the future, your disclosure of market size should be limited to your current potential markets.  Please revise to delete the statements regarding market size as they relate to the other potential markets.

Our Research and Programs, page 20
22. In the previous version of your prospectus, you referred to six research collaborations, but in this version you only refer to four.  If you believe your research programs with University of Florida and Rush-Presbyterian are no longer material, please supplementally provide us an explanation.  If they are still material, then please describe all material terms and file any research agreements as exhibits to the registration statement.
23. We note your response to our prior comment 50 and reissue that comment.  Please revise your disclosure to describe all material terms of each material research program and collaboration and file any relevant agreements as exhibits, to the extent you have not already done so.  For each agreement, please disclose:

• Each parties obligations, including, but not limited to, research and development funding obligations and obligations to defend patents;
• Fees paid to date, including upfront payments, annual payments, royalties and milestone payments,
• Aggregate potential milestone payments;
• Existence of royalty provisions;
• Term and termination provisions.
Please revise your disclosure here and in the financial statement footnotes to specifically indicate the payments you have made under your collaboration agreements and those that you are expected to make in the future.  If appropriate, please disclose the nature of any contingent payments you may make.  In addition, please revise your MD&A to discuss the impact of future collaboration obligations on your liquidity and capital resources.

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 6
Grants, page 21
24. We note your response to our prior comment 60 and reissue the comment.  Please revise your disclosure with respect to the NIH grant to summarize the material terms of the grant.  At a minimum, your description should include the material obligations, amounts received to date, any stipulations and the conditions under which the grant may be refundable.
25. In addition, we note that your prior disclosure also referred to a $1 million grant from NIH related to diabetes and in your MD&A you refer to a federal grant program sponsored by the Defense Advanced Research Projects Agency.  Are these grants still outstanding?  If so, please also summarize the material terms of the grants and file the grant agreements as exhibits to the registration statement.

Our Intellectual Property Licensed to Others, pages 21-22
26. For each material license agreement, please also describe the obligations/rights to defend and termination provisions.
27. For your license with High Med, please expand your disclosure to briefly describe the technology that is the subject of the license.
28. Please revise your disclosure to explain what you mean by “technology for use in developing suitable assay(s) for screening compounds to treat Ataxia-Telangiectasia.”

Manufacturing, page 22
29. Please revise your disclosure to disclose the current status of your arrangements with your manufacturer Charles River Laboratories.  In the risk factor disclosure on page 12 you state that you intend to rely on third party manufacturers in the future.  This disclosure in this section, however, suggests that you have a current arrangement with Charles River.
30. In addition, we note that you have filed your agreement with Charles River as an exhibit to the registration statement.  Please describe the material terms of this material agreement in the prospectus.
31. We acknowledge your response to our previous comment 57 related to your Ischmeic Spastic Paraplegia clinical trials.  Although you have removed all disclosure related to these trials, it appears based on your prior disclosure that you have engaged a contractor to manufacture the clinical supply for these anticipated trials.  Please explain to us whether you have any material commitments to this contract

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 7
manufacturer.  If you do, please disclose these commitments in your financial statement footnotes and in the liquidity discussion of your MD&A.

Our Intellectual Property, pages 22-24
32. You state that you maintain a “disciplined patent policy.”  Please revise your disclosure to describe your policy and to explain how it is “disciplined.”

Government Regulation, pages 25-27
33. We note your reference to FDA rules for “registration of establishments that engage in the recovery, screening, testing, processing, storage or distribution of human cells, tissues, and cellular and tissue-based products, and for the listing of such products.”  Please revise your disclosure to indicate whether you have registered with the FDA
pursuant to these rules or where you are in the registration process.  If you have not registered, please explain why.

Management's Discussion and Analysis  and Plan of Operation, pages 28-33
34. We note your response to our prior comment 34 and are unable to locate your revised disclosure in the MD&A regarding the number and type (i.e. research, administrative, marketing or other) of personnel you expect to hire and any known expected expenditures in hiring such personnel.  Please revise your disclosure to provide this information.

Results of Operations, pages 29-33
35. We note your response to our prior comment 72 and reissue that comment.  Item 303(b)(1)(vi) requires you to discuss the material changes from period to period in the line items of your financial statements.  The amounts referenced in this section do not appear to match the line items presented in your financial statements.  Please revise your disclosure to explain how these amounts differ from the line items in the financial statements.
36. We note your response to our prior comment 73 and reissue that comment.  Please revise your MD&A so that there is more focus on analysis as required by our recent MD&A Release No. 33-8350; 34-48960; FR-72 (December 19, 2003).  In that release, we explained that “MD&A requires  . . . an ‘analysis’ of known material
trends, events, demands, commitments and uncertainties.  MD&A should not be merely a restatement of financial statement information in a narrative form. . . . A thorough analysis often will involve discussing both the intermediate effects of those matters and the reasons underlying those intermediate effects.”  For example, you

The Corporation Trust Company
Neuralstem, Inc.
July 5, 2006
Page 8
should explain what led t

CORRESP
1
filename1.htm

    Sonia
      Barros

    Division
      of Corporation Finance

    Telephone
      Number: (202) 551-3655

    Telecopier
      Number: (202) 772-9217

    Registration
      Statement on Form SB-2, filed April 3, 2005 File No.
      333-132923

    Dear
      Ms. Barros:

    We
      are submitting this letter in response to your comments of April 28, 2006,
      along
      with the Amended Form SB-2 for Neuralstem, Inc. This response will follow the
      lineal order of your letter and each specific area addressed, utilizing the
      text
      of your letter as the primary guide:

    Form
      SB-2

    Calculation
      of Registration Fee

              1.

              Please
                delete the reference to Rule 457(c). Rule 457(c) applies to exchange
                traded securities or over-the-counter securities. The company's securities
                are not currently traded on an exchange or
                over-the-counter.

    Response: We
      have deleted the reference to rule 457(c) and updated the disclosure.

    Prospectus

    General

              2.

              As
                there is currently no market for your common shares you must set
                a price
                at which the selling shareholders will offer the shares until a market
                develops. Please revise your disclosure on the prospectus cover page
                and
                in the Plan of Distribution accordingly. Your revised disclosure
                should
                state that "The Selling shareholders will sell at a price of $x.xx
                per
                share until our shares are quoted on the OTC Bulletin Board and thereafter
                at prevailing market prices or privately negotiated prices." In addition,
                please also rcvise your calculation of the registration fee, to the
                extent
                applicable, to base your registration fee on your set
                price

    Response:
      The company has recalculated the registration fee in compliance with Rule
      457.

              3.

              We
                note an article published in market wire on March 13, 2006 which
                states
                that Regal One's Chairman and CEO, Dr. Malcolm Currie, has agreed
                to serve
                on the company's board, Since Dr. Currie has been "chosen to become"
                a
                director, please revise your disclosure to provide the information
                required by Item 401 of Regulation S-B as it relates to Dr.
                Currie.

    Response:
       We
      have revised our disclosure to provide the information required by Item 401
      as
      it relates to Dr. Currie.

        1

              4.

              The
                forepart of your prospectus uses jargon and technical terms. For
                example,
                these words and phrases appear in the forepart of your
                prospectus:

    "regenerative
      medicine"

    "billion
      billion times (60 doublings or 1018)”

    "controlled
      differentiation"

    "human
      neurons and glia"

    “optimize
      its tissue acquisition"

    "proof-of-principle
      data"

    "neurogenic
      compounds"

    Please
      replace all technical language and jargon with language that can be understood
      by persons who do not work in your industry. Alternately, if you cannot find
      substitute language without changing the meaning, provide an explanation of
      the
      term where you first use it. See Rule 421(d)(2)(ii) of Regulation
      C.

    Response:
      All
      technical language has been deleted and substituted with wording to be
      understood by a person who does not work in our industry.

              5.

              Please
                revise your disclosure to provide a complete and consistent description
                of
                your current licenses. On page 5 you state that you have out-licensed
                lead
                compounds for further development toward various CNS diseases. On
                page 22
                you refer to compounds discovered under your program with the Department
                of Defense that have been licensed out for development. Are the licenses
                referenced on pages 5 and 22 the same? To whom have you licensed
                these
                compounds? On page 35 you mention a license agreement with an SA
                company
                substantially owned by one of your officers. In your description
                of
                business, please describe the material terms of each license, including,
                but not limited to the parties to the license, the payment provisions,
                the
                existence of royalty provisions, exclusivity provisions,
                obligations/rights to defend, and termination provisions. Please
                also file
                the license agreements as
                exhibits.

    Response:
      We have clearly identified all licenses and have limited them to the section
      entitled “Our Intellectual Property Licensed to Others.” We have also filed our
      licensing agreements as exhibits.

              6.

              Please
                revise your disclosure to provide a complete and consistent description
                of
                your grants. On page 22, you refer to a Department of Defense contact
                that
                was cancelled in 2002. On page 23, you state that your small molecule
                program was funded by a grant from the Department of Defense. Is
                this
                grant the same as the contract you refer to on page 22? On page 33
                you
                refer to $310,000 in grant and other revenue for the drug development
                program. From whom did you receive this grant revenue? Have you described
                this grant in the prospectus? In your description of business, please
                describe the material terms of each grant, including, but not limited
                to
                the aggregate amounts, stipulations and terms. Please also file any
                relevant agreements as
                exhibits.

    Response:
      We have clearly defined our one existing grant and included it in its own
      section including any material terms thereof, entitled “Our Grants.” We have
      also filed the grant as an exhibit.

        2

    Prospectus
      Cover Page

              7.

              Please
                limit the
                cover page to the information that is required by Item 501 of Regulation
                S-B. Your cover page contains superfluous information such as the
                statement that the selling shareholders may be deemed underwriters,
                who
                will bear the expenses of the registration and the proceeds to be
                received
                from the exercise of warrants. You may describe this other information
                in
                the prospectus offering
                summary.

    Response:
      The superfluous information has been removed from the Cover Page and the
      information has been limited to that required by Item 501.

              8.

              In
                addition, in the section of the prospectus that you choose to describe
                who
                will bear the expenses of the registration, please clarify the disclosure.
                Your disclosure here contains inconsistent
                statements. The statement in the last paragraph states that the company
                will bear the expenses. The statement in the third paragraph states
                that
                Regal One Corporation will bear the
                expenses.

    Response:
      We have updated the table regarding the expenses associated with the
      registration statement expenses.

    9. Further,
      please clarify what you mean by "BDC,"

    Response:
      We have deleted all reference to BDC.

              10.

              Your
                statement that a listing on the OTC BB "may occur" is inappropriate.
                Please revise this
                statement to explain that market makers may make listing applications
                for
                your stock once your registration statement becomes
                effective.

    Response:
      Revised as suggested.

    Recent
      Developments,

              11.

              Please
                revise the prospectus to describe the terms of the February and March
                2006
                private placements and to describe the material
                terms of the related agreements and file the agreements as exhibits
                to the
                registration statement. We may have additional comments after we
                have had
                an opportunity to review
                them.

    Response:
      We have deleted the recent development section as it is not required.

        3

    Risk
      Factors. page 7

    General

              12.

              Please
                delete the statement "Our business is subject to various risks, included
                but not limited to those described below." Your
                risk factor section should describe all material
                risks.

    Response:
      The sentence has been deleted.

              13.

              Please
                revise each subheading to ensure it reflects the risk that
                you
                discuss in the text. Many of your subheadings currently merely state
                a
                fact about your business, such as "There is
                no public market for the Company's securities" and "The Company needs
                to
                improve its financial control procedures." State in your subheadings
                the
                risks that result from the facts or
                uncertainties.

    Response:
       The
      subheadings have been revised to identify the specific risk clarified in the
      text below the heading.

              14.

              We
                note you have or plan to outsource the manufacturing of cGMP cells
                for
                your future ISP human clinical trials. Please add a risk factor that
                addresses the risks relating to your reliance on such a
                manufacturer.

    Response:
      We have added a disclosure regarding our risk relating to reliance on an
      outsource manufacturer.

              15.

              We
                note that you have 75,000,000 shares of authorized common stock
                and
                only 23,338,876 shares are currently issued and outstanding and you
                have
                assumed that only 33,468,876 shares will be issued and outstanding
                after
                the offering. Please also add a risk factor that addresses the risks
                of
                having such a large number of authorized but unissued common stock,
                including the risks
                that your management may issue additional stock without further
                stockholder appioval, thereby causing dilution of current company
                stockholders

    Response:  We
      have added a disclosure the address the risk of having such a large amount
      of
      shares authorized but unissued.

              16.

              In
                separate risk factors on pages 7 and 11 you indicate that you have
                identified significant deficiencies and material weaknesses in your
                internal controls over financial reporting. Please revise your disclosure
                here or in
                MD&A to elaborate on the nature of the significant deficiencies and
                material weaknesses that you have
                identified,

    Response:
      We have revised our disclosure contained in the risk factors to more full
      identify the weaknesses we have identified.

    Risks
      Relating to the Corporation

              17.

              It
                appears that you are addressing three separate risks in the first
                risk
                factor on page 7. The first
                relates to the risks related to your limited operating history which
                should be moved to the second risk factor that discusses your short
                operating history. The second relates to the risks related to being
                a
                company in the preclinical stage of development. The third relates
                to
                the risks related to ethically sensitive and controversial issues.
                Please
                revise your disclosure to separate this risk factor accordingly with
                appropriate subheadings for each risk
                factor.

        4

    Response:
      We have revised our risk factors with regard to the Company in their entirety
      to
      provide better disclosure.

              18.

              Please
                revise the risk factor related to ethically sensitive and controversial
                issues to describe the
                nature of the ethically sensitive and controversial
                issues.

    Response:
      We have eliminated the risk factor relating to ethical sensitivity as we do
      not
      feel it is a material risk at this early stage as we have no products.

    The
      Company has a short operating history.., page 7

              19.

              Please
                revise this risk factor to disclose your net losses for the two most
                recent fiscal years and any subsequent interim
                periods.

    Response:
      We have removed the section describing our short operating history and included
      a more detailed discussion in the section entitled: “Since the Company has a
      limited operating history and has significantly shifted its operations and
      strategies since inception, you cannot rely upon the Company’s limited
      historical performance to make an investment decision. “

              20.

              Please
                revise this risk factor to describe your limited sources of revenue.

    Response:
      Please see response to comment 19.

    The
      Company will require substantial additional funding....page
      7

              21.

              Please
                incorporate into this discussion the rate at which you are currently
                burning cash on a monthly
                basis.

    Response:
      The company has revised its disclosure to provide information with regard to
      monthly burn rate.

              22.

              Please
                revise to quantify and disclose your current anticipated needs for
                additional financing.

    Response:
      We have revised our disclosure regarding anticipated needs for additional
      financing. Please see response to common 21.

    There
      is no public market ... page 7

              23.

              Please
                expand your discussion in this risk factor to explain that your stock
                is
                not traded on an exchange or on the OTCBB and that this is your initial
                registration. Please also explain that even if it is listed on the
                OTCBB,
                the trading volume may be limited, making it difficult for an investor
                to
                sell shares.

Mail Stop 6010 April 28, 2006

The Corporation Trust Company
1209 Orange Street
New Castle County, Wilmington, Delaware 19801

Re: Neuralstem, Inc.
 Registration Statement on Form SB-2, filed April 3, 2005
 File No. 333-132923

Dear Sir or Madame:

We have reviewed your filing and have th e following comments.  Where indicated, we
think you should revise your documents in response  to these comments.  If you disagree, we will
consider your explanation as to why our commen t is inapplicable or a revision is unnecessary.
Please be as detailed as necessary  in your explanation.  In some of our comments, we may ask you
to provide us with supplemental information so we may better understand your disclosure.  After
reviewing this information, we may or  may not raise additional comments.

Please understand that the purpose of our review process is to  assist you in your compliance
with the applicable disclosure requirements and to enhance the ove rall disclosure in your filing.
We look forward to working with you in these re spects.  We welcome any questions you may have
about our comments or on any other aspect of our review.  Feel free to call us at the telephone
numbers listed at the end of this letter.

Form SB-2

Calculation of Registration Fee
1. Please delete the reference to Rule 457(c).  Rule 457(c) applies to exchange traded
securities or over-the-counter se curities.  The company’s secur ities are not currently traded
on an exchange or over-the-counter.

Prospectus

General
2. As there is currently no market for your comm on shares you must set a price at which the
selling shareholders will offer the shares unt il a market develops.  Please revise your
disclosure on the prospectus cover page and in  the Plan of Distribut ion accordingly.  Your

The Corporation Trust Company
April 28, 2006
Page 2

revised disclosure should state that “The sell ing shareholders will sell at a price of $x.xx
per share until our shares are quoted on the OTC Bulletin Board and thereafter at prevailing
market prices or privately negotiated prices .”  In addition, plea se also revise your
calculation of the registration fee, to the exte nt applicable, to base  your registration fee on
your set price.
3. We note an article published in market wire on March 13, 2006 which states that Regal One's Chairman and CEO, Dr. Malcolm Curri e, has agreed to serve on the company’s
board.  Since Dr. Currie has been “chosen to become” a director, please revise your
disclosure to provide the info rmation required by Item 401 of Re gulation S-B as it relates to
Dr. Currie.
4. The forepart of your prospectus uses jargon a nd technical terms.  Fo r example, these words
and phrases appear in the fo repart of your prospectus:
• “regenerative medicine”
• “billion billion times (60 doublings or 1018)”
• “controlled differentiation”
• “human neurons and glia”
• “optimize its tissue acquisition”
• “proof-of-principle data”
• “neurogenic compounds”

Please replace all technical language and jar gon with language that can be understood by
persons who do not work in your industry. Alternately, if you cannot find substitute
language without changing the meaning, prove an  explanation of the term where you first
use it. See Rule 421(d)(2 )(ii) of Regulation C.
5. Please revise your disclosure to provide a co mplete and consistent description of your
current licenses.  On page 5 you state that you have out-licensed lead  compounds for further
development toward various CNS diseases.  On page 22 you refer to compounds discovered under your program with the Department of De fense that have been licensed out for
development.  Are the licenses referenced on pages 5 and 22 the same?  To whom have you
licensed these compounds?  On page 35 you me ntion a license agre ement with an 8A
company substantially owned by one of your o fficers.  In your description of business,
please describe the material terms of each license , including, but not limited to the parties to
the license, the payment provisions, the exis tence of royalty provisions, exclusivity
provisions, obligations/r ights to defend, and termination provisions.  Please also file the
license agreements as exhibits.
6. Please revise your disclosure to provide a co mplete and consistent description of your
grants.  On page 22, you refer to a Department  of Defense contact that was cancelled in
2002.  On page 23, you state that your small mo lecule program was funded by a grant from
the Department of Defense.  Is this grant the same as the contract you refer to on page 22?
On page 33 you refer to $310,000 in grant and other revenue for the drug development

The Corporation Trust Company
April 28, 2006
Page 3

program.  From whom did you receive this gran t revenue?  Have you described this grant in
the prospectus?  In your descri ption of business, please descri be the material terms of each
grant, including, but not limite d to the aggregate amounts, stipulations and term.  Please
also file any relevant agreements as exhibits.

Prospectus Cover Page
7. Please limit the cover page to the information that is requi red by Item 501 of Regulation S-
B.  Your cover page contains superfluous info rmation such as the stat ement that the selling
shareholders may be deemed underwriters, who will bear the expenses of the registration
and the proceeds to be received from the exercise  of warrants.  You ma y describe this other
information in the prospectus offering summary.
8. In addition, in the section of the prospectus that you choose to describe who will bear the
expenses of the registration, pl ease clarify the disclosure.  Yo ur disclosure here contains
inconsistent statements.  The statement in th e first paragraph states that the company will
bear the expenses.  The statement in the third paragraph states that  Regal One Corporation
will bear the expenses.
9. Further, please clarify what you mean by “BDC.”
10. Your statement that a listing on the OTCBB “m ay occur” is inappropriate.  Please revise
this statement to explain that market makers  may make listing applications for your stock
once your registration statement becomes effective.

Recent Developments, page 5
11. Please revise the prospectus to describe th e terms of the February and March 2006 private
placements and to describe the material term s of the related agreements and file the
agreements as exhibits to the registration statement.  We may have additional comments
after we have had an opportunity to review them.

Risk Factors, page 7

General

12. Please delete the statement “Our business is subject to various risks, included but not
limited to those described below.”  Your risk factor section should de scribe all material
risks.
13. Please revise each subheading to ensure it reflects the risk that you discuss in the text.  Many of your subheadings currently merely state a fact about your business, such as “There
is no public market for the Company’s securiti es” and “The Company needs to improve its

The Corporation Trust Company
April 28, 2006
Page 4

financial control procedures.”  State in your subheadings the ri sks that result from the facts
or uncertainties.
14. We note you have or plan to outsource the manuf acturing of cGMP cells for your future ISP
human clinical trials.  Please add a risk factor that addres ses the risks relating to your
reliance on such a manufacturer.
15. We note that you have 75,000,000 shares of authorized common stock and only 23,338,876
shares are currently issued and outsta nding and you have assumed that only 33,468,876
shares will be issued and outstanding after the offering.  Please also a dd a risk factor that
addresses the risks of havi ng such a large number of authorized but unissued common
stock, including the risks that your management may issue additional stock without further stockholder approval, thereby causing dilution of current company stockholders.
16. In separate risk factors on pages 7 and 11 you indicate that you have identified significant
deficiencies and material weaknesses in your in ternal controls over fi nancial reporting.
Please revise your disclosure here or in MD&A to elaborate on the natu re of the significant
deficiencies and material weakne sses that you have identified.

Risks Relating to the Company’s Stage of Development, page 7

17. It appears that you are a ddressing three separate risks in the first risk factor on page 7.  The
first relates to the risks related to your lim ited operating history which should be moved to
the second risk factor that discusses your short operating hist ory.  The second relates to the
risks related to being a company in the preclinical stage of de velopment.  The third relates
to the risks related to ethically sensitive and controversial issues .  Please revise your
disclosure to separate this risk factor accordi ngly with appropriate subheadings for each risk
factor.

18. Please revise the risk factor related to ethically  sensitive and controvers ial issues to describe
the nature of the ethically sens itive and controversial issues.

The Company has a short operati ng history . . . ., page 7

19. Please revise this risk factor to disclose your net losses for the two most recent fiscal years
and any subsequent interim periods.

20. Please revise this risk fa ctor to describe your limited sources of revenue.

The Company will require substantial additional funding . . . ., page 7

21. Please incorporate into this discussion the rate at which you are cu rrently burning cash on a
monthly basis.

The Corporation Trust Company
April 28, 2006
Page 5

22. Please revise to quantify and disclose your  current anticipated needs for additional
financing.

There is no public market . . . ., page 7

23. Please expand your discussion in this risk factor  to explain that your stock is not traded on
an exchange or on the OTCBB and that this is your initial registration.  Please also explain that even if it is listed on the OTCBB,  the trading volume may be limited, making it
difficult for an investor to sell shares.

Risks Relating to Govern ment Regulation, page 8

24. Please provide a subheading for the first risk factor on page 8 relating to the company’s
intellectual property and patents.  In addition, please expand th is discussion to address the
risks related to pending patent applications and any other inte llectual property material to
your business.

Potential and actual legislation and regulation . . . ., page 8

25. Please expand your discussion in explain what you mean by “certain pharmaceutical research methods or products resulting from them.”

26. We note your statement that your cells are not “e mbryonic stem cells” but that any future or
additional government-imposed restrictions on embryonic stem cells may adversely impact your business.  Please expand your discussion to explain why that is the case and how your
stem cells differ from embryonic stem cells.  We  also note your disclosure on page 31 that
the cell line for your product candidate ISP has b een derived from a “single fetal spinal cord
tissue.”

Because the Company or its collaborators must  obtain regulatory appr oval . . . ., pages 8-9

27. Please address in a separate risk factor any mate rial risks to your business related to the use
and disposal of hazardous or potentially hazardous substances.  The risk factor should address whether you carry insurance for the us e and disposal of hazardous or potentially
hazardous substances and the cost of su ch insurance to you if material.

The Company may depend on its co llaborators . . . ., page 9

28. Please expand your discussion to name any current  key collaborators, li censors or licensees
and to discuss any specific risks related to your agreements with and dependence upon those
parties.

The Corporation Trust Company
April 28, 2006
Page 6

The Company’s reliance on the activ ities of its non-employee consulta nts, research institutions, and
scientific contractors . . . ., pages 9-10

29. Please expand your discussion to name any key non-employee consultants, research
institutions, and scientific c ontractors and to discuss any sp ecific risks related to your
agreements with and dependence upon those parties.

The Company’s products may be expensive to manufacture . . . ., page 10

30. Please expand your discussion to explain why th e company’s products may be significantly
more expensive to manufacture than most ot her drugs currently on the market today.

The Company depends on key personnel . . . ., page 11
31. Please name your “key personnel” and their pos itions with the company.  In addition, we
note that you refer to “key executive officers an d “scientific officers.”  It appears, however,
that you only have two key personnel and th ey are your sole employees and executive
officers.  Please revise your disclosure to clarify.
32. To the extent that you have experienced problems attracting and retaining any “key
personnel” in the recent past, please revise to describe these problems.  Additionally, if any
“key personnel” have plans to retire or l eave your company or terminate their agreement
with the company in the near future, pleas e revise the discussion to disclose this
information.
33. Please state whether you maintain employment contracts with “key personnel” and disclose
the term and termination provisions of the same if applicable.
34. Please revise to disclose the number and type (i.e. research, administrative, marketing or other) of personnel you expect to hire and to the extent practicable, please quantify any
known expected expenditures in hiring such personnel.
35. Please state if you maintain key person insurance on any of your key personnel.

Selling Stockholders, pages 13-16
36. Please tell us whether any selling shareholder is  a broker-dealer or an affiliate of a broker-
dealer.  We may have further comments.
37. For each selling shareholder that is neither  a natural person nor a publicly registered
company, revise to disclose the natural person(s) that have voting and dispositive rights.
38. You are registering for resale 8,072,000 shares  of your common stock that are already
issued and 8,130,000 shares of your common stock that are issuable pursuant to outstanding

The Corporation Trust Company
April 28, 2006
Page 7

warrants.  The selling stockholder table, how ever, lists 7,436,000 shares already issued and
8,155,000 shares issuable pursuant to warrants.  Please revise the table to correct these
discrepancies.  The selling stockholder table s hould identify the exact number of shares that
you are registering.
39. Please revise the table in this section to disclose the percenta ge (if one percent or more) of
shares owned by each selling stockholder as of the date of the prospectus and before the offering.
40. Please also revise the table in  this section to disclose th e amount and percentage (if one
percent or more) of shares that will be ow ned by each selling stockholder after the offering.
41. We refer to your disclosure in footnote (1) to  the table and have the following comments:
• You refer to 175 to 600 shareholders of Regal One who are selling sh areholders in this
offering.  Generally, you must identify all se lling shareholders in a resale registration
statement.  Since the dividend will occur after the effectiveness of the registration
statement as you indicate on page 35, it appears that you will be unable to identify all of
the selling shareholders before effectiveness.  Pl ease revise the disclosure at this time to
provide a separate line item in the table for the unknown shareholders of Regal One who are selling shareholders in this offering.  You will then need to file a post-effective amendment to name these selling sharehol ders.  Please revise your prospectus to
indicate that you will file such post-effective amendment.  Selling shareholders must be named before they can sell pursuant to the registration statement.
• You refer to a total of 1,847,287 shares , but