SecProbe.io

CORRESP
 1
 filename1.htm

 CORRESP

 Cyclerion Therapeutics, Inc.
 245 First Street, 18 th Floor
 Cambridge, MA 02142 May 13,
2025 VIA EDGAR Securities and Exchange
Commission Division of Corporation Finance 100 F Street,
N.E. Washington, D.C. 20549

 Attention:
 Doris Stacey Gama

 Re:
 Cyclerion Therapeutics, Inc.
 Registration Statement on Form S-3 (File No. 333-287006)
 Request for Acceleration Ladies and
Gentlemen: Pursuant to Rule 461 of the General Rules and Regulations of the Securities and Exchange Commission promulgated under the Securities Act of
1933, as amended, Cyclerion Therapeutics, Inc., a Massachusetts corporation (the “ Company ”), hereby requests that the effective date for the registration statement referred to above be accelerated so that it will be declared
effective at 4:00 p.m. Eastern Time on May 15, 2025, or as soon as possible thereafter. The Company hereby authorizes William Michener of Ropes & Gray LLP, counsel to the Company, to orally modify or withdraw this request for
acceleration. Please contact William Michener (william.michener@ropesgray.com) / telephone: (617) 951-7247 of
Ropes & Gray LLP as soon as the registration statement has been declared effective. [ Signature page follows ]

 Very truly yours,

 CYCLERION THERAPEUTICS, INC.

 By:

 /s/ Regina Graul

 Name:

 Regina Graul, Ph.D.

 Title:

 President and Chief Executive Officer

 [ Signature Page to
Acceleration Request ]

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 May 12, 2025

Regina Graul
Chief Executive Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18th Floor
Cambridge, MA 02142

 Re: Cyclerion Therapeutics, Inc.
 Registration Statement on Form S-3
 Filed May 6, 2025
 File No. 333-287006
Dear Regina Graul:

 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 Doris Stacey Gama at 202-551-3188 with any questions.

 Sincerely,

 Division of
Corporation Finance
 Office of Life
Sciences
cc: William J. Michener, Esq.
</TEXT>
</DOCUMENT>

CORRESP
1
filename1.htm

CORRESP

 Cyclerion Therapeutics, Inc.

245 First Street, 18th Floor

Cambridge, MA 02142

February 10, 2025

 VIA EDGAR

 Securities and Exchange Commission

 Division of
Corporation Finance

 100 F Street, N.E.

 Washington, D.C.
20549

Attention:

Chris Edwards

Re:

Cyclerion Therapeutics, Inc.

Registration Statement on Form S-3 (File No. 333- 284690)

Request for Acceleration

 Ladies and Gentlemen:

 Pursuant
to Rule 461 of the General Rules and Regulations of the Securities and Exchange Commission promulgated under the Securities Act of 1933, as amended, Cyclerion Therapeutics, Inc., a Massachusetts corporation (the “Company”), hereby
requests that the effective date for the registration statement referred to above be accelerated so that it will be declared effective at 4:00 p.m. Eastern Time on February 12, 2025, or as soon as possible thereafter. The Company hereby
authorizes William Michener of Ropes & Gray LLP, counsel to the Company, to orally modify or withdraw this request for acceleration.

 Please
contact William Michener (william.michener@ropesgray.com) / telephone: (617) 951-7247 of Ropes & Gray LLP as soon as the registration statement has been declared effective.

[Signature page follows]

Very truly yours,

CYCLERION THERAPEUTICS, INC.

By:

/s/ Regina Graul

Name:

Regina Graul, Ph.D.

Title:

President and Chief Executive Officer

 [Signature Page to Acceleration Request]

February 7, 2025
Regina Graul, Ph.D.
President and Chief Executive Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18th Floor
Cambridge, Massachusetts, 02142
Re:Cyclerion Therapeutics, Inc.
Registration Statement on Form S-3
Filed February 4, 2025
File No. 333-284690
Dear Regina Graul Ph.D.:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration. We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Chris Edwards at 202-551-6761 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:William J. Michener

United States securities and exchange commission logo
December 28, 2023
Peter M. Hecht
Chief Executive Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18 Floor
Cambridge , Massachusetts
Re:Cyclerion Therapeutics, Inc.
Form 10-K for the Fiscal Year Ended December 31, 2022
Filed March 22, 2023
File No. 001-38787
Dear Peter M. Hecht:
            We have completed our review of your filings. 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.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
1
filename1.htm

CORRESP

 245 First Street

Riverview II, 18th Floor

 Cambridge,
MA 02142

(857) 327-8778

 info@cyclerion.com

cyclerion.com

 December 12, 2023

 By
EDGAR Submission

 U.S. Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington D.C. 20549

Attn: Ms. Li Xiao and Ms. Angela Connell

 Re:
Cyclerion Therapeutics Inc.

 Form 10-K for the Fiscal Year Ended December 31, 2022

Filed March 22, 2023

 Form 10-Q for the Quarterly Period Ended September 30, 2023

 Filed November 13, 2023

File No. 001-38787

Dear Ms. Li and Ms. Connell:

 Reference is made to a
letter dated November 28, 2023 (the “Comment Letter”) to Peter M. Hecht, the former Chief Executive Officer of Cyclerion Therapeutics, Inc. (the “Company” or “Cyclerion”), setting forth comments of the staff of the
Division of Corporation Finance (the “Staff”) of the U.S. Securities and Exchange Commission (the “Commission”) to the Annual Report on Form 10-K for the year ended December 31, 2022
(the “Annual Report”) and Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2023 (the “Quarterly Report), filed by the Company. As previously announced Peter M.
Hecht resigned as an officer and employee of Cyclerion effective December 1, 2023. Regina Graul, Ph.D. now serves as President of Cyclerion.

 This
letter sets forth the Company’s response to the Staff’s comments. The headings and numbered paragraphs in this letter correspond to the headings and numbered paragraphs in the Comment Letter.

Capitalized terms used but not otherwise defined herein shall have the meanings ascribed to them in the Annual Report or the Quarterly Report.

Form 10-Q for the quarterly period ended September 30, 2023

Notes to the Condensed Consolidated Financial Statements

4. Discontinued Operations, page 14

1.
 You disclose that on May 11, 2023 you sold all of the assets comprising your zagociguat and CY3018
programs (Program Assets) to Tisento Therapeutics Inc. and have presented the operations of the Program Assets as discontinued operations for all periods presented. Please explain to us how you determined that the disposal of these programs results
in a strategic shift in your operations given that you continue to hold other soluble guanylate cyclase (“sGC”) stimulators in your product candidate portfolio.

Company Response

 In evaluating whether the Program
Assets should be presented as discontinued operations, the Company considered the criteria in Financial Accounting Standards Board (“FASB”) Accounting Standards Codification (“ASC”) 205-20-45-1B and determined that it met all the criteria to be presented as discontinued operations for the period ended September 30, 2023.

 245 First Street

Riverview II, 18th Floor

 Cambridge,
MA 02142

(857) 327-8778

info@cyclerion.com

cyclerion.com

 Furthermore, the Company noted the following excerpt from ASC 205-20-45-1C:

 Examples of a strategic shift that has
(or will have) a major effect on an entity’s operations and financial results could include a disposal of a major geographical area, a major line of business, a major equity method investment, or other parts of an entity.

The definition of “strategic shift” in ASC
205-20-45-1B does not include any bright line guidance. Accordingly, significant judgment is required in order to determine
whether a disposal constitutes a strategic shift. When evaluating whether a disposal represents a strategic shift, the Company considered the manner in which management has organized, analyzed and managed its product portfolio; the nature of its
portfolio, their development priorities and objectives; and how management discusses and discloses the nature of its business and operations in its financial statements, press releases, and other supplemental information.

Prior to the sale of the Program Assets, Cyclerion’s portfolio included novel sGC stimulators that modulate a key node in a fundamental signaling network
in both the central nervous system (“CNS”) and the periphery.

 The following table is a high-level summary of Cyclerion’s portfolio assets
prior to the sale:

 Program

 Indication(s)

 Description

 Status

Zagociguat (CNS-penetrant)

MELAS, CIAS, ADV

zagociguat is a CNS-penetrant sGC stimulator that has shown rapid improvements across a range of endpoints reflecting multiple domains of disease activity, including mitochondrial
disease-associated biomarkers.

Sold to Tisento as part of the Asset Purchase Agreement.

CY3018 (CNS-penetrant)

Neuropsychiatric

CY3018 is a CNS-penetrant sGC stimulator in preclinical development that has potential for the treatment of neuropsychiatric diseases and disorders.

Sold to Tisento as part of the Asset Purchase Agreement

Olinciguat (peripheral)

Cardiovascular

olinciguat is a vascular sGC stimulator that the Company intends to out-license for cardiovascular diseases.

Management plans to outlicense olinciguat

Praliciguat (peripheral)

Focal Segmental Glomerulosclerosis (FSGS)

praliciguat is a systemic sGC stimulator that is licensed to Akebia and being advanced in rare kidney disease.

Outlicensed to Akebia

 As referenced in the Company’s October 6, 2022 press release, the Company’s primary focus was on developing
treatments for CNS diseases with CNS penetrant sGC stimulators. While acknowledging all assets within Cyclerion’s portfolio include sGC stimulators, the Program Assets (zagociguat and CY3018) sold to Tisento are uniquely different from the
assets retained by Cyclerion (olinciguat and praliciguat). The Program Assets have high exposure to the CNS (i.e., CNS-penetrant sGC stimulators). In contrast, the retained assets are peripheral sGC

 245 First Street

Riverview II, 18th Floor

 Cambridge,
MA 02142

(857) 327-8778

info@cyclerion.com

cyclerion.com

stimulators. The retained assets are therefore not interchangeable with the Program Assets and do not provide the same benefit in CNS and correspondingly the Program Assets do not provide the
same benefit for systemic/vascular diseases. Additionally, as part of the Asset Purchase Agreement (“APA”), Cyclerion is contractually prohibited from competing for five (5) years from the closing date from developing CNS-penetrant sGC stimulators or working with any Affiliate or Third Party on CNS-penetrant sGC stimulators (Section 6.13(a) of APA). In addition, Cyclerion does not intend to
research CNS-penetrant sGC stimulators in the future. Thus, Cyclerion has strategically shifted out of research and development of CNS-penetrant sGC assets.

After the sale of the Program Assets, the Cyclerion programs being retained are olinciguat and praliciguat which are not CNS focused and are either currently out-licensed (praliciguat) or management plans to out-license (olinciguat). The Company’s prior strategy to conduct research and development on sGC stimulators for CNS
has been discontinued subsequent to the sale of the Program Assets. Cyclerion does not intend to internally pursue research and development or commercialization with any type of sGC assets at this time but intends to utilize royalties and milestones
by out-licensing olinciguat and praliciguat to pursue opportunities with new assets. The Company has shifted its strategy to identify, non-sGC stimulator assets within the CNS therapeutic area to
build a new portfolio. Once the Company identifies new assets outside of the sGC stimulator space, the research and development organization will be built in a
fit-for-purpose way to the appropriate size with the appropriate skillsets. This new approach was evidenced by the Company’s “go forward strategy” as
referenced in the Company’s May 11, 2023 press release.

 The Company’s sale of its Program Assets indicated a strategic shift and based on
the aforementioned discussion and analysis the Company concluded that the sale of these disposed assets and prohibitions against competition under the Asset Purchase Agreement represent a strategic shift in Cyclerion’s operations.

2.
 You disclose that you acquired a 10% equity interest in Tisento Therapeutics Holdings Inc. (Tisento Parent)
with a fair value of $5.3 million and that your investment does not provide you with significant influence over Tisento Parent. Please address the following:

•

 Provide your analysis under ASC 810-10 in determining whether
Tisento Parent is a variable interest entity (VIE), including whether the entity has sufficient equity at risk to finance its activities without additional subordinated financial support.

•

 To the extent that Tisento Parent is determined to be a VIE, provide your analysis under ASC 810-10 supporting your determination that you do not have a controlling financial interest in the VIE. Address the following as part of your response:

•

 Identify the activities of Tisento Parent that most significantly impact its economic performance and
explain how you determined that you do not have the power to direct such activities and therefore do not hold a controlling financial interest.

•

 To the extent that the power is shared among the variable interest holders, clarify whether there is a tie-breaking mechanism in place with respect to key decision making.

•

 With respect to investments held by your CEO and any other related parties, provide an analysis under ASC 810-10-25-42 through 25-44B.

•

 Provide us with a copy of the Asset Purchase Agreement to assist us with our review.

•

 Confirm that you will revise your future filings to provide the
VIE-specific disclosures required by ASC 810-10-50, to the extent applicable.

Company Response

•

 Provide your analysis under ASC 810-10 in determining whether
Tisento Parent is a variable interest entity (VIE), including whether the entity has sufficient equity at risk to finance its activities without additional subordinated financial support.

Cyclerion assessed the accounting for its investment in accordance with
ASC 810-10, Consolidation—Overall. After determining that no scope exception applies under the guidance of ASC 810-10-15-12 and ASC 810-10-15-17, Cyclerion concluded
that it has a variable interest in Tisento Parent through its investment in Tisento Parent common stock. Tisento Parent does not have sufficient equity to finance its activities without additional

 245 First Street

Riverview II, 18th Floor

 Cambridge,
MA 02142

(857) 327-8778

info@cyclerion.com

cyclerion.com

subordinated financial support as Tisento Parent is a startup entity in its early stages of raising funds and will require significant capital to advance its programs to commercial stage.
Therefore, Cyclerion concluded that its investment in Tisento Parent is a variable interest entity (“VIE”) in accordance with
ASC 810-10-15-14(a) and is subject to potential consolidation under the VIE model.

To the extent that Tisento Parent is determined to be a VIE, provide your analysis under ASC 810-10 supporting
your determination that you do not have a controlling financial interest in the VIE. Address the following as part of your response:

a.
 Identify the activities of Tisento Parent that most significantly impact its economic performance and
explain how you determined that you do not have the power to direct such activities and therefore do not hold a controlling financial interest.

b.
 To the extent that the power is shared among the variable interest holders, clarify whether there is a tie-breaking mechanism in place with respect to key decision making.

c.
 With respect to investments held by your CEO and any other related parties, provide an analysis under ASC 810-10-25-42 through 25-44B.

d.
 Provide us with a copy of the Asset Purchase Agreement to assist us with our review.

 Company Response

a.
 Identify the activities of Tisento Parent that most significantly impact its economic performance
and explain how you determined that you do not have the power to direct such activities and therefore do not hold a controlling financial interest.

To evaluate potential consolidation under the variable interest model, Cyclerion (1) evaluated the purpose and design of the VIE and the risks the VIE
was designed to create and pass along to its variable interest holders; (2) identified the activities related to the risks identified in step 1 that most significantly affect the economic performance of the VIE; and (3) identified the
party that makes the significant decisions or controls the activity or activities that most significantly affect the VIE’s economic performance, including whether any other parties have involvement in those decisions (shared power).

Tisento Parent and its subsidiary were initially designed to research and develop novel medicines for diseases with significant unmet medical needs. The
primary risks the VIE was designed to create and pass along to its variable interest holders are the operational and financial risks related to a new business in a developing area of science. More specifically, Tisento Parent and its
subsidiary’s economic performance is dependent on the execution of the research and development activities and future commercialization of its technology. Accordingly, the activities related to these risks that most significantly impact Tisento
Parent and its subsidiary’s economic performance are the decisions relating to the funding, oversight, and execution of research and development activities, which are encapsulated in the operating plan and budget and the personnel of Tisento
Parent and its subsidiary.

 Cyclerion determined the following activities most significantly impact Tisento Parent and its subsidiary’s economic
performance: (1) approval of an operating plan and budget, determining which research and development programs to pursue and how to research and develop the corresponding intellectual property, (2) hiring and firing of management and key
research personnel and (3) determination of management’s compensation.

 To assess which party has the power to direct these activities,
Cyclerion considered Tisento Parent and its subsidiary’s key governance documents, including the articles of incorporation, by-laws, investor rights agreement and voting agreement. Decisions
related to the significant activities that most impact the economic performance of Tisento Parent and its subsidiary noted above are made by the Tisento Parent board of directors on behalf of the equity holders. Although there is an executive team
led by a CEO running the day-to-day operations, the Tisento board has responsibility for the overall direction, supervision and management of Tisento Parent
and its subsidiary.

 245 First Street

Riverview II, 18th Floor

 Cambridge,
MA 02142

(857) 327-8778

info@cyclerion.com

cyclerion.com

 Tisento Parent’s board is comprised of five directors. Two directors are nominated by the preferred
stockholders which are diverse group of preferred shareholders, and no single preferred shareholder has a majority ownership; one CEO director was elected by the common stockholders, which is Peter M. Hecht1; and the remaining two independent directors were designated by agreement of a majority of the other then serving directors. Cyclerion does not have the right to nominate any director.

As noted above, all activities that most significantly impact Tisento Parent and its subsidiary’s economic performance are directed by the Tisento Parent
board and the board approves decisions by a simple majority. Based on the board composition, Cyclerion determined that no one party has control over the Tisento Parent board and power is not shared because the activities that most significantly
affect Tisento Parent and its subsidiary’s economic performance do not require the consent of all of the parties. Rather, all decisions are made by a simple majority vote of the Tisento Parent board. Therefore, because Cyclerion controls no
director of Tisento Parent, Cyclerion cannot unilaterally direct any of the act

United States securities and exchange commission logo
November 28, 2023
Peter M. Hecht
Chief Executive Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18 Floor
Cambridge , Massachusetts
Re:Cyclerion Therapeutics, Inc.
Form 10-K for the Fiscal Year Ended December 31, 2022
Filed March 22, 2023
Form 10-Q for the Quarterly Period Ended September 30, 2023
Filed November 13, 2023
File No. 001-38787
Dear Peter M. Hecht:
            We have limited our review of your filing to the financial statements and related
disclosures and have the following comments.
            Please respond to this letter within ten business days by providing the requested
information or advise us as soon as possible when you will respond. If you do not believe a
comment applies to your facts and circumstances, please tell us why in your response.
            After reviewing your response to this letter, we may have additional comments.
Form 10-Q for the Quarterly Period Ended September 30, 2023
Notes to the Condensed Consolidated Financial Statements
4. Discontinued Operations, page 14
1.You disclose that on May 11, 2023 you sold all of the assets comprising your zagociguat
and CY3018 programs (Program Assets) to Tisento Therapeutics Inc. and have presented
the operations of the Program Assets as discontinued operations for all periods presented.
Please explain to us how you determined that the disposal of these programs results in a
strategic shift in your operations given that you continue to hold other soluble guanylate
cyclase ("sGC") stimulators in your product candidate portfolio.

 FirstName LastNamePeter M. Hecht
 Comapany NameCyclerion Therapeutics, Inc.
 November 28, 2023 Page 2
 FirstName LastName
Peter M. Hecht
Cyclerion Therapeutics, Inc.
November 28, 2023
Page 2
5. Other Investment, page 16
2.You disclose that you acquired a 10% equity interest in Tisento Therapeutics Holdings
Inc.(Tisento Parent) with a fair value of $5.3 million and that your investment does not
provide you with significant influence over Tisento Parent.  Please address the following:
•Provide your analysis under ASC 810-10 in determining whether Tisento Parent is a
variable interest entity (VIE), including whether the entity has sufficient equity at risk
to finance its activities without additional subordinated financial support.
•To the extent that Tisento Parent is determined to be a VIE, provide your analysis
under ASC 810-10 supporting your determination that you do not have a controlling
financial interest in the VIE.  Address the following as part of your response:oIdentify the activities of Tisento Parent that most significantly impact its
economic performance and explain how you determined that you do not have
the power to direct such activities and therefore do not hold a controlling
financial interest.
oTo the extent that the power is shared among the variable interest holders,
clarify whether there is a tie-breaking mechanism in place with respect to key
decision making.
oWith respect to investments held by your CEO and any other related parties,
provide an analysis under ASC 810-10-25-42 through 25-44B.
oProvide us with a copy of the Asset Purchase Agreement to assist us with our
review.
•Confirm that you will revise your future filings to provide the VIE-specific
disclosures required by ASC 810-10-50, to the extent applicable.
            In closing, 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 Li Xiao at 202-551-4391 or Angela Connell at 202-551-3426 with any
questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

United States securities and exchange commission logo
September 7, 2021
Anjeza Gjino
Chief Financial Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18th Floor
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
10-K filed February 25, 2021
File No. 001-38787
Dear Ms. Gjino:
            We have completed our review of your filing.  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.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
1
filename1.htm

    August 27, 2021

    Via EDGAR

    Securities and Exchange Commission

    Division of Corporation Finance

    100 F Street, N.E.

    Washington, D.C. 20549

          Attn:

            Jeanne Baker

    Terence O'Brien

    Division of Corporation Finance

    Office of Life Sciences

          Re:

            Cyclerion Therapeutics, Inc.

    10-K filed February 25, 2021

    File No. 001-38787

    Ladies and Gentlemen:

    On behalf of our client, Cyclerion Therapeutics, Inc. (the “Company”), we submit this letter setting forth the response of the Company to
      the comment provided by the staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) in its comment letter
      dated August 24, 2021 (the “Comment Letter”) with respect to the Annual Report on Form 10-K filed with the Commission by the Company on February 25, 2021.  Concurrently with the filing of
      this letter, the Company has filed Amendment No. 1 on Form 10-K/A (the “Form 10-K/A”) through EDGAR.  For your convenience, we have set forth the comment of the Staff from the Comment Letter
      in bold and italics below and provided our response below the comment.

    Form 10-K for the year ended December 31, 2020

    Exhibit 31, page 1

          1.

            We note the certifications provided in Exhibits 31.1 and 31.2 do not include paragraph 4(b) and the introductory language in paragraph 4 referring to internal control over financial reporting
              after the end of the transition period that allows these omissions. Please amend the filing to provide revised certifications. You may file an abbreviated amendment that is limited to the cover page, explanatory note, signature page and
              paragraphs 1, 2, 4 and 5 of the certification. Refer to Exchange Act Rule 13a-14(a) and Item 601(b)(31) of Regulation S-K. Ensure that the revised certifications refer to the Form 10-K/A and are currently dated. Address this comment as it
              relates to your Form 10-Qs for the quarter ended March 31, 2021 and June 30, 2021.

    Response

    The Company acknowledges the Staff’s comment and has revised the certifications in Exhibits 31.1 and 31.2 of the Form 10-K/A.  The Company acknowledges that it is also addressing the Staff’s comment as it relates to its
      Form 10-Qs for the quarter ended March 31, 2021 and June 30, 2021 by filing Form 10-Q/As for such periods concurrently with the filing of the Form 10-K/A.

    We hope that the foregoing has been responsive to the Staff’s comment and look forward to resolving any outstanding issues as quickly as possible.  Please direct any questions or comments regarding the foregoing to Gary
      J. Simon at 212-837-6770.

            Very truly yours,

            /s/ Gary J. Simon

            Gary J. Simon, Hughes Hubbard & Reed LLP

          cc:

            Anjeza Gjino, Cyclerion Therapeutics, Inc.

United States securities and exchange commission logo
August 24, 2021
Anjeza Gjino
Chief Financial Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18th Floor
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
10-K filed February 25, 2021
File No. 001-38787
Dear Ms. Gjino:
            We have limited our review of your filing to the financial statements and related
disclosures and have the following comment.  In our comment, we may ask you to provide us
with information so we may better understand your disclosure.
            Please respond to this comment within ten business days by providing the requested
information or advise us as soon as possible when you will respond.  If you do not believe our
comment applies to your facts and circumstances, please tell us why in your response.
            After reviewing your response to this comment, we may have additional comments.
Form 10-K for the year ended December 31, 2020
Exhibit 31, page 1
1.We note the certifications provided in Exhibits 31.1 and 31.2 do not include paragraph
4(b) and the introductory language in paragraph 4 referring to internal control over
financial reporting after the end of the transition period that allows these omissions. Please
amend the filing to provide revised certifications. You may file an abbreviated amendment
that is limited to the cover page, explanatory note, signature page and paragraphs 1, 2, 4
and 5 of the certification. Refer to Exchange Act Rule 13a-14(a) and Item 601(b)(31) of
Regulation S-K.  Ensure that the revised certifications refer to the Form 10-K/A and are
currently dated.  Address this comment as it relates to your Form 10-Qs for the quarter
ended March 31, 2021 and June 30, 2021.

            In closing, 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 LastNameAnjeza Gjino
 Comapany NameCyclerion Therapeutics, Inc.
 August 24, 2021 Page 2
 FirstName LastName
Anjeza Gjino
Cyclerion Therapeutics, Inc.
August 24, 2021
Page 2
            You may contact Jeanne Baker at 202-551-3691 or Terence O'Brien at 202-551-
3355 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
1
filename1.htm

    CYCELRION THERAPEUTICS, INC.

    245 First Street, 18th Floor

    Cambridge, MA 02142

    June 21, 2021

    By EDGAR

    Securities and Exchange Commission

    Division of Corporation Finance

    100 F Street, N.E.

    Washington, D.C. 20549

    Attention:  Chris Edwards

            Re:
            Cyclerion Therapeutics, Inc. (the “Company”)

            Registration Statement on Form S-3

              File No. 333-257145

    Ladies and Gentlemen:

    Pursuant to Rule 461 under the Securities Act of 1933, as amended, the Company hereby requests acceleration of the effective date
      of the above referenced Registration Statement to 4:00 p.m., Eastern time, on June 23, 2021, or as soon thereafter as practicable, or at such other time as the Company or its outside counsel, Hughes Hubbard & Reed LLP, request by telephone that
      such Registration Statement be declared effective.

    Please contact Gary J. Simon, of Hughes Hubbard & Reed LLP, special counsel to the Company, at (212) 837-6770, as soon as the
      Registration Statement has been declared effective, or if you have any other questions or concerns regarding this matter.

              Very truly yours,

            CYCLERION THERAPEUTICS, INC.

            By:
            /s/ Anjeza Gjino

            Name:
            Anjeza Gjino

            Title:
            Chief Financial Office

            cc:
            Hughes Hubbard & Reed LLP

United States securities and exchange commission logo
June 21, 2021
Anjeza Gjino
Chief Financial Officer
Cyclerion Therapeutics, Inc.
245 First Street, 18th Floor
Cambridge, Massachusetts, 02142
Re:Cyclerion Therapeutics, Inc.
Registration Statement on Form S-3
Filed June 16, 2021
File No. 333-257145
Dear Ms. Gjino:
            This is to advise you that we have not reviewed and will not review your registration
statement.
            Please refer to Rules 460 and 461 regarding requests for acceleration.  We remind you
that the company and its management are responsible for the accuracy and adequacy of their
disclosures, notwithstanding any review, comments, action or absence of action by the staff.
            Please contact Chris Edwards at 202-551-6761 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Gary J. Simon, Esq.

United States securities and exchange commission logo
August 11, 2020
William Huyett
Chief Financial Officer
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, Massachusetts, 02142
Re:Cyclerion Therapeutics, Inc.
Registration Statement on Form S-3
Filed August 7, 2020
File No. 333-242334
Dear Mr. Huyett:
            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 Margaret Schwartz at 202-551-7153 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
1
filename1.htm

CYCELRION THERAPEUTICS, INC.

301 Binney Street

Cambridge, MA 02142

August 12, 2020

By EDGAR

Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Margaret Schwartz

    Re:
    Cyclerion Therapeutics, Inc. (the “Company”)

    Registration Statement on Form S-3

    File No. 333-242334

Ladies and Gentlemen:

Pursuant to Rule 461 under the Securities
Act of 1933, as amended, the Company hereby requests acceleration of the effective date of the above referenced Registration Statement
to 4:00 p.m., Eastern time, on August 14, 2020, or as soon thereafter as practicable, or at such other time as the Company or its
outside counsel, Hughes Hubbard & Reed LLP, request by telephone that such Registration Statement be declared effective.

Please contact Gary J. Simon, of Hughes
Hubbard & Reed LLP, special counsel to the Company, at (212) 837-6770, as soon as the Registration Statement has been declared
effective, or if you have any other questions or concerns regarding this matter.

    Very truly yours,

    CYCLERION
    THERAPEUTICS, INC.

    By:
    /s/
    William I. Huyett

    Name:
    William I.
    Huyett

    Title:
    Chief Financial Officer

    cc: Hughes Hubbard & Reed LLP

CORRESP
1
filename1.htm

CYCELRION THERAPEUTICS, INC.

301 Binney Street

Cambridge, MA 02142

July 30, 2020

By EDGAR

Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Jason Drory

    Re:
    Cyclerion
Therapeutics, Inc. (the “Company”)

    Registration Statement on Form S-3

    File No. 333-240095

Ladies and Gentlemen:

Pursuant to Rule 461 under the Securities
Act of 1933, as amended, the Company hereby requests acceleration of the effective date of the above referenced Registration Statement
to 4:00 p.m., Eastern time, on July 31, 2020, or as soon thereafter as practicable, or at such other time as the Company or its
outside counsel, Hughes Hubbard & Reed LLP, request by telephone that such Registration Statement be declared effective.

Please contact Gary J. Simon, of Hughes
Hubbard & Reed LLP, special counsel to the Company, at (212) 837-6770, as soon as the Registration Statement has been declared
effective, or if you have any other questions or concerns regarding this matter.

    Very truly yours,

    CYCLERION THERAPEUTICS, INC.

    By:
    /s/ William Huyett

    Name: William Huyett

    Title: Chief Financial Officer

    cc:Hughes Hubbard & Reed LLP

United States securities and exchange commission logo
July 30, 2020
Peter Hecht, Ph.D.
Chief Executive Officer
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, MA, 02142
Re:Cyclerion Therapeutics, Inc.
Registration Statement on Form S-3
Filed July 24, 2020
File No. 333-240095
Dear Dr. Hecht:
            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 L. Drory at 202-551-8342 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Gary J. Simon, Esq.

CORRESP
1
filename1.htm

Cyclerion Therapeutics, Inc.

301 Binney Street

Cambridge, MA  02142

April 22, 2019

VIA EDGAR AND E-MAIL

United States Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549-6010

Attention:  Christine Westbrook

Re:  Cylcerion Therapeutics, Inc. Registration Statement on Form S-1 (Registration File No. 333-230944)

Ladies and Gentlemen:

In accordance with Rule 461 of Regulation C of the General Rules and Regulations under the Securities Act of 1933, as amended, we hereby request acceleration of the effective date of the Registration Statement on Form S-1 (Registration File No. 333-230944) (the “Registration Statement”) of Cyclerion Therapeutics, Inc. (the “Company”). We respectfully request that the Registration Statement become effective as of 4:00 p.m., Eastern time, on April 23, 2019, or as soon as practicable thereafter.  Once the Registration Statement has been declared effective, please orally confirm that event with our counsel, Morgan, Lewis & Bockius LLP, by calling Bryan Keighery at (617) 341-7269.

[Remainder of page intentionally left blank]

Very truly yours,

Cyclerion   Therapeutics, Inc.

By:

/s/ Peter M. Hecht

Peter M. Hecht,

Chief Executive Officer

CC:

Larry Miller, Cyclerion   Therapeutics, Inc.

Laurie A. Cerveny, Morgan, Lewis & Bockius   LLP

Bryan S. Keighery, Morgan, Lewis & Bockius   LLP

[Cyclerion Therapeutics, Inc. — Signature Page to Request for Acceleration]

April 16, 2019
Peter M. Hecht, Ph.D.
Chief Executive Officer
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
Draft Registration Statement on Form S-1
Submitted April 9, 2019
CIK No. 0001755237
Dear Dr. Hecht:
            This is to advise you that we do not intend to review your registration statement.
            We request that you publicly file your registration statement no later than 48 hours prior
to the requested effective date and time. 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 Christine Westbrook at 202-551-5019 with any questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Bryan S. Keighery, Esq.

March 14, 2019
Mark Currie
President
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
Registration Statement on Form 10-12B
Filed on January 28, 2019
File No. 001-38787
Dear Dr. Currie:
            We have completed our review of your filing.  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.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Will Michener, Esq.

CORRESP
1
filename1.htm

Cyclerion Therapeutics, Inc.

301 Binney Street

Cambridge, Massachusetts 02142

March 12, 2019

VIA EDGAR

U.S. Securities and Exchange Commission

Division of Corporation Finance

Office of Healthcare and Insurance

100 F Street, N.E.

Washington, D.C.  20549

Attention:                                         Christine Westbrook / Suzanne Hayes — Legal

Sasha Parikh / Angela Connell — Accounting

Re:                                                                             Acceleration Request for Cyclerion Therapeutics, Inc.

Registration Statement on Form 10

CIK No. 0001755237

Ladies and Gentlemen:

Reference is made to the Registration Statement on Form 10 (File No. 001-38787) (as amended to date, the “Registration Statement”), filed by Cyclerion Therapeutics, Inc. (the “Company”) with the U.S. Securities and Exchange Commission (the “Commission”).

Ironwood Pharmaceuticals, Inc. (“Ironwood”) has set March 19, 2019 as the record date for the distribution of the shares of common stock of the Company, which is scheduled to occur on April 1, 2019. Pursuant to Section 12(d) of the Securities Exchange Act of 1934, as amended, and Rule 12d1-2 promulgated thereunder, the Company hereby requests that the effective date for the Registration Statement be accelerated to 4:00 p.m., Eastern time, on March 14, 2019, or as soon as practicable thereafter.

If the Commission has any questions or comments concerning this letter, or if you require any additional information, please feel free to contact William J. Michener of Ropes & Gray LLP at (617) 951-7247. The Company requests that it be notified of the effectiveness of the Registration Statement by a telephone call to Mr. Michener.

CYCLERION THERAPEUTICS, INC.

/s/ William Huyett

William Huyett

President

December 17, 2018
Mark Currie
President
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
Amendment No. 1 to Draft Registration Statement on Form 10
Submitted on December 6, 2018
CIK 0001755237
Dear Dr. Currie:
            We have reviewed your amended draft registration statement and have the following
comments.  In some of our comments, we may ask you to provide us with information so we
may better understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Amendment No. 1 to Draft Registration Statement on Form 10 submitted December 6, 2018
Exhibit 99.1
Information Statement Summary
Cyclerion
Overview, page 12
1.We note your response to comment 5 and your disclosure that you intend to out license
praliciguat to a “leader in cardiometabolic diseases.” Please revise your disclosure to
remove the implication that you have a prospective agreement with a licensee or
collaboration partner for this product candidate. Alternatively, please tell us the basis for
this statement.

 FirstName LastNameMark Currie
 Comapany NameCyclerion Therapeutics, Inc.
 December 17, 2018 Page 2
 FirstName LastName
Mark Currie
Cyclerion Therapeutics, Inc.
December 17, 2018
Page 2
Unaudited Pro Forma Combined Financial Statements
Notes to Unaudited Pro Forma Combined Financial Data, page 65
2.Regarding pro forma adjustment (C), you include the shares to be issued in the intended
private placement in determining the number of Cyclerion shares of common stock used
to compute basic earnings per share. Please tell us how you determined that the private
placement is factually supportable and directly attributable to the separation transaction.
Please also tell us how you determined that it was appropriate to include these shares in
your pro forma EPS calculation given that the proceeds from the issuance of these shares
are not reflected as an adjustment in your pro forma Statement of Operations.
Business
Praliciguat for Cardiometabolic Diseases
Our Solution, page 96
3.We note your response to comment 8 and your disclosure that results of your Phase 2a
study of praliciguat suggested that patients had improvements in insulin sensitivity and in
endothelial function. Please revise your disclosure to remove the implication that
treatment with praliciguat resulted in the measurements cited.  You may describe any
objective observations from the trials without indicating that praliciguat is responsible for
these observations.
            You may contact Sasha Parikh at 202-551-3627 or Angela Connell at 202-551-3426 if
you have questions regarding comments on the financial statements and related matters.  Please
contact Christine Westbrook at 202-551-5019 or Suzanne Hayes at 202-551-3675 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance
cc:       Will Michener, Esq.

November 5, 2018
Mark Currie
President
Cyclerion Therapeutics, Inc.
301 Binney Street
Cambridge, MA 02142
Re:Cyclerion Therapeutics, Inc.
Draft Registration Statement on Form 10
Submitted on October 9, 2018
CIK 0001755237
Dear Dr. Currie:
            We have reviewed your draft registration statement and have the following comments.  In
some of our comments, we may ask you to provide us with information so we may better
understand your disclosure.
            Please respond to this letter by providing the requested information and either submitting
an amended draft registration statement or publicly filing your registration statement on
EDGAR.  If you do not believe our comments apply to your facts and circumstances or do not
believe an amendment is appropriate, please tell us why in your response.
            After reviewing the information you provide in response to these comments and your
amended draft registration statement or filed registration statement, we may have additional
comments.
Draft Registration Statement on Form 10 submitted on October 9, 2018
Industry and Other Data, page i
1.Please revise your statements that you have verified industry and market data from third
party sources to clarify that you are liable for the information included in the registration
statement.
Cover page, page 1
2.Please revise your disclosure to remove promotional statements concerning Ironwood’s
anticipated profitability, strong revenue growth and expanding margins as these

 FirstName LastNameMark Currie
 Comapany NameCyclerion Therapeutics, Inc.
 November 5, 2018 Page 2
 FirstName LastNameMark Currie
Cyclerion Therapeutics, Inc.
November 5, 2018
Page 2
statements are speculative and inappropriate for you to make. We will not object to an
objective discussion of Ironwood’s continuing business and product portfolio.
Information Statement Summary
Cyclerion
Overview, page 11
3.We note your statement that the presentation in your pipeline development chart
represents ongoing phases of development and does not correspond to the initiation or
completion of a particular phase. Please revise your pipeline development chart so that the
arrows correspond to the current stage of development. As an illustrative example only,
we note that you have not yet completed Phase 2 development for any of your product
candidates. Please revise your disclosure accordingly.
Value-Creating Enablers, page 13
4.We note statements throughout your information statement that imply you will be able to
successfully progress your product candidates to commercialization in a rapid or
accelerated manner and/or mitigate risk of unsuccessful clinical trials. As these statements
are speculative and suggest that investors are afforded protection from loss, please revise
your disclosure here and throughout your information statement to remove these
implications. As a non-exhaustive list of illustrative examples only, we note the following
statements:
•We leverage a diverse cross-disciplinary network of external advisors and experts to
advance our drug candidates quickly and with early, risk-reducing clinical readouts.
•
•The collective experience and singular focus of the team in the biology and
pharmacology of the nitric oxide-cGMP pathway, as well as the medicinal chemical
insights around sGC stimulators, give us unique insights into the mechanisms by
which to realize the therapeutic potential of pharmacologically tailored sGC
stimulation. Further, this allows increasingly rapid discovery and development of
differentiated compounds optimized for their disease target.
•This program structure coupled with our streamlined governance is designed to
support high-velocity decision making and rapid rescaling and redeployment of
resources.
5.We note your description of your "best owner approach" whereby you develop and
commercialize product candidates independently or through a partner depending on which
path you believe will offer the greatest risk-adjusted value for our stockholders and
accelerates global patient access to our drugs.  Please clarify whether you have any
partnerships related to any of your product candidates.  If you do, please describe these
agreement and file them as exhibits to provide as with an analysis supporting your
determination that they are not required to be filed.

 FirstName LastNameMark Currie
 Comapany NameCyclerion Therapeutics, Inc.
 November 5, 2018 Page 3
 FirstName LastName
Mark Currie
Cyclerion Therapeutics, Inc.
November 5, 2018
Page 3
Risks Related to our Business, page 14
6.Please add a bullet point highlighting the risk of competition from marketed products and
product candidates in development, as discussed on page 39.
Risk Factors, page 20
7.Please add a risk factor under an appropriate heading that discusses the risk that you will
be dependent on the intellectual property license agreement with Ironwood. Once known,
please expand your disclosure in the Business section to include all of the material terms
of the license agreement.
Business
Our solution, page 90
8.We note your disclosure that olinciguat has the potential for similar efficacy in SCD
patients. Efficacy determinations are the within sole authority of the FDA.  Please revise
your disclosure to remove the implication that your clinical data shows efficacy. Please
revise similar statements throughout your information statement that refer to your product
candidate’s potential for efficacy or clinical activity. We will not object to an objective
discussion of your observations in clinical and preclinical studies.  However, your
disclosure should not indicate that the treatment resulted in the observations.
            You may contact Sasha Parikh at 202-551-3627 or Angela Connell at 202-551-3426 if
you have questions regarding comments on the financial statements and related matters.  Please
contact Christine Westbrook at 202-551-5019 or Suzanne Hayes at 202-551-3675 with any other
questions.
Sincerely,
Division of Corporation Finance
Office of Healthcare & Insurance