SecProbe.io

CORRESP
 1
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 CORRESP

 May 12, 2026
 VIA EDGAR SUBMISSION Securities and Exchange
Commission Division of Corporation Finance, Office of Life Sciences
 100 F Street, NE Washington, DC 20549
 Attention: Alan Campbell

 Re:

 Karyopharm Therapeutics Inc.

 Registration Statement on Form S-3
 Filed May 4, 2026 File
 No. 333-295535 Request for Acceleration
 Ladies and Gentlemen: Pursuant
to Rule 461 under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Registration Statement on Form
 S-3 (File No. 333-295535), so that it may become effective at 4:30 p.m., Eastern Time, on May 14, 2026, or as soon as practicable thereafter, or at such later
time as the Registrant or its counsel may orally request via telephone call to the staff.

 Very truly yours,
 KARYOPHARM THERAPEUTICS INC.

 By:

 /s/ Michael Mano

 Name:

 Michael Mano

 Title:

 Executive Vice President, Chief Legal Officer and Secretary

 cc:

 Jason Kropp, Sidley Austin LLP

 Craig Hilts, Sidley Austin LLP

CORRESP
 1
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 CORRESP

 May 12, 2026
 VIA EDGAR SUBMISSION Securities and Exchange
Commission Division of Corporation Finance, Office of Life Sciences
 100 F Street, NE Washington, DC 20549
 Attention: Alan Campbell

 Re:

 Karyopharm Therapeutics Inc.

 Registration Statement on Form S-3
 Filed May 4, 2026 File
 No. 333-295533 Request for Acceleration
 Ladies and Gentlemen: Pursuant
to Rule 461 under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Registration Statement on Form
 S-3 (File No. 333-295533), so that it may become effective at 4:30 p.m., Eastern Time, on May 14, 2026, or as soon as practicable thereafter, or at such later
time as the Registrant or its counsel may orally request via telephone call to the staff.

 Very truly yours,
 KARYOPHARM THERAPEUTICS INC.

 By:

 /s/ Michael Mano

 Name:

 Michael Mano

 Title:

 Executive Vice President, Chief Legal Officer and Secretary

 cc:

 Jason Kropp, Sidley Austin LLP

 Craig Hilts, Sidley Austin LLP

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 May 7, 2026

Richard Paulson
President and Chief Executive Officer
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459

 Re: Karyopharm Therapeutics Inc.
 Registration Statement on Form S-3
 Filed May 4, 2026
 File No. 333-295533
Dear Richard Paulson:

 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: Craig Hilts
</TEXT>
</DOCUMENT>

<DOCUMENT>
<TYPE>TEXT-EXTRACT
<SEQUENCE>2
<FILENAME>filename2.txt
<TEXT>
 May 7, 2026

Richard Paulson
President and Chief Executive Officer
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459

 Re: Karyopharm Therapeutics Inc.
 Registration Statement on Form S-3
 Filed May 4, 2026
 File No. 333-295535
Dear Richard Paulson:

 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: Craig Hilts
</TEXT>
</DOCUMENT>

CORRESP
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CORRESP

 June 5, 2024

VIA EDGAR SUBMISSION

 Securities and Exchange
Commission

 Division of Corporation Finance, Office of Life Sciences

100 F Street, NE

 Washington, DC 20549

Attention: Chris Edwards

Re:
 Karyopharm Therapeutics Inc.

Registration Statement on Form S-3

Filed May 30, 2024

 File No. 333-279833

 Request for Acceleration

Ladies and Gentlemen:

 Pursuant to Rule 461 under the Securities
Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Registration Statement on Form S-3 (File No. 333- 279833), so
that it may become effective at 4:30 p.m., Eastern Time, on June 7, 2024, or as soon as practicable thereafter, or at such later time as the Registrant or its counsel may orally request via telephone call to the staff.

 Very truly yours,

KARYOPHARM THERAPEUTICS INC.

By:

/s/ Michael Mano

Name:

Michael Mano

Title:

Senior Vice President, General Counsel and Secretary

cc:
 Jason Kropp, Wilmer Cutler Pickering Hale and Dorr LLP

Craig Hilts, Wilmer Cutler Pickering Hale and Dorr LLP

United States securities and exchange commission logo
June 3, 2024
Richard Paulson
President and Chief Executive Officer
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459
Re:Karyopharm Therapeutics Inc.
Registration Statement on Form S-3
Filed May 30, 2024
File No. 333-279833
Dear Richard Paulson:
            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:       Craig Hilts

United States securities and exchange commission logo
April 18, 2024
Michael Mason
EVP, Chief Financial Officer and Treasurer
Karyopharm Therapeutics Inc.
85 Wells Ave., 2nd Floor
Newton, MA 02459
Re:Karyopharm Therapeutics Inc.
Form 10-K for the year ended December 31, 2023
Filed February 29, 2024
File No. 001-36167
Dear Michael Mason:
            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
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CORRESP

 April 3, 2024

 By
Electronic Submission

 Securities and Exchange Commission

Division of Corporation Finance

 Office of Life Sciences

100 F Street, N.E.

 Washington, DC 20549

Attention: Sasha Parikh and Kevin Vaughn

Re:
 Karyopharm Therapeutics Inc.

Form 10-K for the fiscal year ended December 31, 2023

Filed February 29, 2024

File No. 001-36167

Ladies and Gentlemen:

 Karyopharm Therapeutics Inc. (the
“Company” or “we”) is responding to the comments of the staff (the “Staff”) of the Securities and Exchange Commission contained in the Staff’s letter dated March 21, 2024 (the
“Comment Letter”), relating to the above referenced Form 10-K for the fiscal year ended December 31, 2023. For convenience, the Company’s responses below are keyed to the numbering
of the comments and the headings used in the Comment Letter.

 Form 10-K filed February 29, 2024

Management’s Discussion and Analysis of Financial Condition and Results of Operations, page 99

1. Please revise your future filings to address the following:

•

 Revise to clearly disclose the extent to which you track any of your research and development (R&D)
expenses on a program-by-program basis.

•

 To the extent you track any R&D expenses by program, revise to separately quantify those amounts.

•

 Please provide us with your proposed disclosures.

Response: The Company respectfully acknowledges the Staff’s comment and advises the Staff that in future filings, the Company will
disclose expenses incurred for research and development (“R&D”) on a program-by-program basis for the Company’s core programs to the extent such spend
is attributable to such specific program. The Company

 incurs external clinical trial and related expenses and tracks these costs by program. The
Company also incurs unallocated R&D costs that are tracked in the aggregate and not by program. As such, the only R&D costs that the Company tracks by program are external clinical trial and related expenses incurred for a specific program.

 In respect to the Staff’s comment, the Company will include a breakdown of R&D expenses consistent with the following tabular and
narrative disclosure in the Management Discussion and Analysis of Financial Condition and Results of Operations section of its Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q filed with the Commission commencing with its Quarterly Report on Form 10-Q for the quarter ended March 31, 2024.

“Research and Development Expenses (in thousands, except for percentages)

For the Three Months Ended March 31,

2024

2023

$ Change

% Change

 Clinical trial and related costs:

 Selinexor in multiple myeloma

 Selinexor in endometrial cancer

 Selinexor in myelofibrosis

 Other programs

 Non-program specific clinical trial and related costs

 Total clinical trial and related costs

 Unallocated costs:

 Personnel

 Consulting, professional and other

 Stock-based compensation

 Total unallocated costs

 Total research and development expenses

 At any one time, we have a number of ongoing clinical development programs that we are conducting
independently or in collaboration with third parties. We track our external clinical trial and related costs on a program-by-program basis. Our major programs include
our three core clinical development programs in multiple myeloma, endometrial cancer and myelofibrosis. To the extent that external clinical trial and related costs are not attributable to a major program, they are included in “Other
programs” and to the extent external clinical trial and related costs cannot be allocated to a specific program, they are included in “Non-program specific clinical trial and related costs.” We
also have unallocated R&D costs, which we do not track on a program-by-program basis. These costs represent costs that are incurred across multiple programs or to
support our general R&D operations.

 2

 The [increase/decrease] in research and development expenses for the [Period]
was primarily due to [insert explanations].”

 If you have any further questions or comments, or if you require any additional information,
please contact the undersigned by telephone at (617) 658-0600. Thank you for your assistance.

Very truly yours,

 /s/ Michael Mason

Michael Mason

Chief Financial Officer

cc:
 Richard Paulson, President and Chief Executive Officer, Karyopharm Therapeutics Inc.

Mike Mano, Senior Vice President and General Counsel, Karyopharm Therapeutics Inc.

Jason L. Kropp, Wilmer Cutler Pickering Hale and Dorr LLP

 3

United States securities and exchange commission logo
March 21, 2024
Michael Mason
EVP, Chief Financial Officer and Treasurer
Karyopharm Therapeutics Inc.
85 Wells Ave., 2nd Floor
Newton, MA 02459
Re:Karyopharm Therapeutics Inc.
Form 10-K for the year ended December 31, 2023
Filed February 29, 2024
File No. 001-36167
Dear Michael Mason:
            We have limited our review of your filing to the financial statements and related
disclosures and have the following comment(s).
            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-K filed February 29, 2024
Management's Discussion and Analysis of Financial Condition and Results of Operations, page
99
1.Please revise your future filings to address the following:
•Revise to clearly disclose the extent to which you track any of your research and
development (R&D) expenses on a program-by-program basis.
•To the extent you track any R&D expenses by program, revise to separately quantify
those amounts.
•Please provide us with your proposed disclosures.
            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 Sasha Parikh at 202-551-3627 or Kevin Vaughn at 202-551-3494 with any
questions.

 FirstName LastNameMichael Mason
 Comapany NameKaryopharm Therapeutics Inc.
 March 21, 2024 Page 2
 FirstName LastName
Michael Mason
Karyopharm Therapeutics Inc.
March 21, 2024
Page 2
Sincerely,
Division of Corporation Finance
Office of Life Sciences

CORRESP
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CORRESP

 May 3, 2023

VIA EDGAR SUBMISSION

 Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street, NE

 Washington, DC 20549

 Attention:
Arzhang Navai

Re:
 Karyopharm Therapeutics Inc.

Registration Statement on Form S-3

File No. 333-269846

Request for Acceleration

 Ladies and
Gentlemen:

 Pursuant to Rule 461 under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests
acceleration of the effective date of its Registration Statement on Form S-3 (File No. 333-269846), so that it may become effective at 4:30 p.m., Eastern Time,
on May 5, 2023, or as soon as practicable thereafter, or at such later time as the Registrant or its counsel may orally request via telephone call to the staff.

Very truly yours,

/s/ KARYOPHARM THERAPEUTICS INC.

By:

 /s/ Michael Mano

Name: Michael Mano

Title: Senior Vice President and General Counsel

cc:
 Jason Kropp, Wilmer Cutler Pickering Hale and Dorr LLP

Craig Hilts, Wilmer Cutler Pickering Hale and Dorr LLP

United States securities and exchange commission logo
February 21, 2023
Michael Mano
Senior Vice President and General Counsel
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459
Re:Karyopharm Therapeutics Inc.
Registration Statement on Form S-3
Filed February 17, 2023
File No. 333-269846
Dear Michael Mano:
            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 Arzhang Navai at 202-551-4676 with any questions.
Sincerely,
Division of Corporation Finance
Office of Life Sciences
cc:       Craig Hilts

CORRESP
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Acceleration Request

 December 29, 2022

VIA EDGAR SUBMISSION

 Securities and Exchange
Commission

 Division of Corporation Finance

 100 F Street, NE

 Washington, DC 20549

 Attention: Tim Buchmiller

Re:
 Karyopharm Therapeutics Inc.

Registration Statement on Form S-3

File No. 333-268991

Request for Acceleration

 Ladies and
Gentlemen:

 Pursuant to Rule 461 under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests
acceleration of the effective date of its Registration Statement on Form S-3 (File No. 333-268991), so that it may become effective at 4:30 p.m., Eastern Time, on
January 3, 2023, or as soon as practicable thereafter, or at such later time as the Registrant or its counsel may orally request via telephone call to the staff.

 Very truly yours,

 KARYOPHARM THERAPEUTICS INC.

By:

/s/ Michael Mano

 Name:

 Michael Mano

 Title:

 Senior Vice President and General Counsel

cc:
 Jason Kropp, Wilmer Cutler Pickering Hale and Dorr LLP

Craig Hilts, Wilmer Cutler Pickering Hale and Dorr LLP

United States securities and exchange commission logo
December 28, 2022
Richard Paulson
President and Chief Executive Officer
Karyopharm Therapeutics Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459
Re:Karyopharm Therapeutics Inc.
Registration Statement on Form S-3
Filed December 23, 2022
File No. 333-268991
Dear Richard Paulson:
            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:       Craig Hilts, Esq.

CORRESP
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CORRESP

 KARYOPHARM THERAPEUTICS INC.

85 WELLS AVENUE, SECOND FLOOR

NEWTON, MA 02459

 April 22,
2019

 Via EDGAR

 Securities and Exchange Commission

 Division of Corporation Finance

 100 F Street, N.E.

Washington, D.C. 20549

Re:
 Karyopharm Therapeutics Inc.

 Post-Effective Amendment No. 2 to Form S-3 Registration Statement

 File No. 333-226038

 Request for Acceleration

Ladies and Gentlemen:

 Pursuant to Rule 461 promulgated
under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Post-Effective Amendment No. 2 to Form
S-3 Registration Statement (File No. 333-226038), so that it may become effective at 4:00 p.m. Eastern time on April 24, 2019, or as soon thereafter as
practicable.

 Very truly yours,

Karyopharm Therapeutics Inc.

By:

/s/ Christopher B. Primiano

 Name:

 Title:

 Christopher B. Primiano

 Executive Vice
President, Chief Business Officer, General Counsel and Secretary

CORRESP
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CORRESP

 KARYOPHARM THERAPEUTICS INC.

85 WELLS AVENUE, SECOND FLOOR

NEWTON, MA 02459

February 13, 2018

 Via EDGAR

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Re:
Karyopharm Therapeutics Inc.

 Registration Statement on Form
S-3

 File No. 333-222726

Request for Acceleration

 Ladies and Gentlemen:

 Pursuant to Rule 461 promulgated under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”)
hereby requests acceleration of the effective date of its Registration Statement on Form S-3 (File No. 333-222726), so that it may become effective at
4:00 p.m. Eastern time on February 15, 2018, or as soon thereafter as practicable.

Very truly yours,

Karyopharm Therapeutics Inc.

By:

 /s/ Christopher B. Primiano

Name:

Christopher B. Primiano

Title:

Executive Vice President, Chief Business Officer,

General Counsel and Secretary

CORRESP
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CORRESP

 KARYOPHARM THERAPEUTICS INC.

85 WELLS AVENUE, SECOND FLOOR

NEWTON, MA 02459

February 13, 2018

 Via EDGAR

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Re:
Karyopharm Therapeutics Inc.

Registration Statement on Form S-3

File No. 333-222726

Request for Acceleration

 Ladies and Gentlemen:

Karyopharm Therapeutics Inc. (the “Registrant”) hereby withdraws its earlier request dated the date hereof requesting acceleration of the
effective date of its Registration Statement on Form S-3 (File No. 333-222726) (the “Registration Statement”) to February 15, 2018.

Pursuant to Rule 461 promulgated under the Securities Act of 1933, as amended, the Registrant hereby requests acceleration of the effective date of the
Registration Statement so that it may become effective at 4:00 p.m. Eastern time on February 14, 2018, or as soon thereafter as practicable.

Very truly yours,

 Karyopharm Therapeutics Inc.

By:

 /s/ Christopher B. Primiano

Name:

Christopher B. Primiano

Title:

 Executive Vice President, Chief Business Officer,

General Counsel and Secretary

CORRESP
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CORRESP

 KARYOPHARM THERAPEUTICS INC.

 85 WELLS AVENUE, SECOND FLOOR

 NEWTON, MA 02459

November 29, 2016

 Via EDGAR

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Re:
Karyopharm Therapeutics Inc.

 Registration Statement on Form S-3

File No. 333-214489

 Request
for Acceleration

 Ladies and Gentlemen:

 Pursuant to
Rule 461 promulgated under the Securities Act of 1933, as amended, Karyopharm Therapeutics, Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Registration Statement on Form S-3 (File
No. 333-214489) (the “Registration Statement”), so that it may become effective at 4:00 p.m. Eastern time on December 1, 2016, or as soon thereafter as practicable.

Very truly yours,

Karyopharm Therapeutics Inc.

 By:

/s/ Christopher B. Primiano

 Name:

Christopher B. Primiano

 Title:

Senior Vice President, Corporate Development,

General Counsel and Secretary

Mail Stop 4546

November 18, 2016

Michael G. Kauffman, M.D., Ph.D.
Chief Executive Officer
Karyopharm Therapeutics  Inc.
85 Wells Avenue, 2nd Floor
Newton, MA 02459

Re: Karyopharm Therapeutics Inc.
  Registration Statement on Form S-3
Filed  November 8, 2016
  File No.  333-214489

Dear Dr. Kauffman :

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 Scot Foley at (202) 551 -3383 or Mary Beth Breslin at (202) 551 -3625  with
any questions.

Sincerely,

 /s/ Mary Beth Breslin for

Suzanne Hayes
Assistant Director
        Office of Healthcare and Insurance

cc:  Steven D. Singer, Esq.

CORRESP
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CORRESP

 Karyopharm Therapeutics Inc.

85 Wells Avenue, 2nd Floor

 Newton,
MA 02459

 May 2, 2016

 VIA EDGAR

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, D.C. 20549

Re:
Karyopharm Therapeutics Inc.

 Post-Effective Amendment No. 2 to Registration Statement on
Form S-3

 File No. 333-201366

Request for Acceleration

 Ladies and
Gentlemen:

 Pursuant to Rule 461 promulgated under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the
“Registrant”) hereby requests acceleration of the effective date of its Post-Effective Amendment No. 2 to Registration Statement on Form S-3 (File No. 333-201366) (the “Registration Statement”), so that it may become
effective at 4:00 p.m. Eastern Time on May 4, 2016, or as soon thereafter as practicable.

 The Registrant hereby acknowledges that:

(i)
should the Securities and Exchange Commission (the “Commission”) or the staff, acting pursuant to delegated authority, declare the Registration Statement effective, it does not foreclose the Commission from
taking any action with respect to the Registration Statement;

(ii)
the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the Registration Statement effective, does not relieve the Registrant from its full responsibility for the adequacy and
accuracy of the disclosure in the Registration Statement; and

(iii)
the Registrant 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,

KARYOPHARM THERAPEUTICS INC.

By:

 /s/ Christopher B. Primiano

Christopher B. Primiano

Senior Vice President, Corporate Development, General Counsel and Secretary

November 4, 2013

Via E -mail
Michael G. Kauffman, M.D., Ph.D.
Chief Executive Officer
Karyopharm Therapeutics Inc.
2 Mercer Road
Natick, MA 01760

Re: Karyopharm  Therapeutics Inc.
Amendment No. 1 to Registration Statement on Form S -1
Filed October 28, 2013
  File No. 333-191584

Dear Dr. Kaufman :

We have reviewed your  amendment and related correspondence filed October 28, 2013
and we have the following comments.

Please respond to this letter by amending your registration statement and providing the
requested informati on.  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.

Capitalization, page 51

1. Please explain how the share amounts shown in the section (ii) (a) through (d) aggregate
to 19,114,241 shares and are consistent with the amounts shown in the relevant caption
disclosure on p age 52.

Dilution, page 54

2. Please explain how you computed the historical net tangible book value per share of
($14.50 per share), pro forma net tangible book value per share of $2.74 per share and
pro forma net tangible book value per share adjusted f or the planned offering of $4.95 per
share. In particular, explain how you determined the shares amounts used in each of these
calculations and how these share amounts are consistent with corresponding disclosure in
the section, Capitalization, and the con solidated statement of convertible preferred stock
and stockholders’ equity.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
November 4, 2013
Page 2

3. Please explain how the amount of shares purchased by existing shareholders of
21,864,198 shares, disclosed on page 55, is consistent with the corresponding amount at
June 30, 2 013 on page F -5.

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 the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.   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 event you request acceleratio n of the effective date
of the pending regist ration statement please provide  a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does not for eclose 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, 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 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.

Please refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of  1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to review any amendment prior to the requested effective date o f the
registration statement.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
November 4, 2013
Page 3

You may c ontact Frank Wyman  at (202) 551 -3660  or Joel Parker at (202) 551 -3651  if
you have questions regarding comments on the financial statements and related matters.  Please
contact Scot Foley  at (202) 551 -3383, Bryan Pitko at (202) 551 -3203 or me at (202) 551 -3715
with any other questions.

Sincerely,

 /s/ Bryan J. Pitko for

Jeffrey P. Riedler
Assistant Director

cc: Steven D. Singer, Esq.
Joshua D. Fox, Esq.
Wilmer Cutler Pickering Hale and Dorr  LLP
60 State Street
Boston, MA 02109

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November 4,   2013

Joshua D. Fox

+1 781 966 2007 (t)

+1 781 966 2100 (f)

Securities   and Exchange Commission

joshua.fox@wilmerhale.com

Division   of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Attention: Jeffrey P. Riedler

Re:              Karyopharm Therapeutics Inc.
 Amendment No. 1 to Registration Statement on Form S-1
 Filed October 28, 2013
 File No. 333-191584

Ladies and Gentlemen:

On behalf of Karyopharm Therapeutics Inc. (the “Company”), we are responding to the comments contained in the letter dated November 4, 2013 (the “Comment Letter”) from Jeffrey P. Riedler of the Staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”), relating to the above referenced Amendment No. 1 to Registration Statement on Form S-1.

The responses set forth below are based upon information provided to Wilmer Cutler Pickering Hale and Dorr LLP by the Company.  The responses are keyed to the numbering of the comments and the headings used in the Comment Letter.

On behalf of the Company, we advise you as follows:

Capitalization, page 51

1.                                      Please explain how the share amounts shown in the section (ii) (a) through (d) aggregate to 19,114,241 shares and are consistent with the amounts shown in the relevant caption disclosure on page 52.

Response:                                        The Company advises the Staff that the number of shares of common stock to be issued upon conversion of the preferred stock (19,114,241), as set forth on Page 51 of Amendment No. 1 to the Registration Statement, reflects the number of shares of preferred stock outstanding as of June 30, 2013, as well as the number of shares of preferred stock issued by the company thereafter which are reflected in clauses (a) through (d) on page 51, after taking into account the 1 for 3.3 reverse stock split of the common stock effected on October 25, 2013. Pursuant to the terms of the Company’s charter, the conversion ratio for the preferred stock was adjusted as a result of the reverse stock split. Accordingly, upon

consummation of the offering, the outstanding preferred stock will automatically convert into 19,114,241 shares of common stock.

Dilution, page 54

2.                                      Please explain how you computed the historical net tangible book value per share of ($14.50 per share), pro forma net tangible book value per share of $2.74 per share and pro forma net tangible book value per share adjusted for the planned offering of $4.95 per share. In particular, explain how you determined the shares amounts used in each of these calculations and how these share amounts are consistent with corresponding disclosure in the section, Capitalization, and the consolidated statement of convertible preferred stock and stockholders’ equity.

Response:                                        The Company advises the Staff that:

·                  the number of shares used to calculate the historical net tangible book value per share consists of the shares of common stock outstanding as of June 30, 2013 (2,450,510), plus the shares of unvested restricted stock outstanding as of June 30, 2013 (287,326), which are considered outstanding shares for purposes of this calculation;

·                  the number of shares used to calculate the pro forma net tangible book value per share consists of the shares of common stock outstanding as of June 30, 2013 (2,450,510), plus the shares of unvested restricted stock outstanding as of June 30, 2013 (287,326), plus the shares of common stock issued upon settlement of the special participation stock (adjusted to reflect the reverse stock split) (12,121) and the shares of common stock issuable upon conversion of the preferred stock (on an as-converted, post-reverse stock split basis) (19,114,241); and

·                  the number of shares used to calculate the pro forma as adjusted net tangible book value per share consists of the total calculated in the prior bullet plus the shares being offered in this offering (5,666,667).

3.                                      Please explain how the amount of shares purchased by existing shareholders of 21,864,198 shares, disclosed on page 55, is consistent with the corresponding amount at June 30, 2013 on page F-5.

Response:                                        The Company advises the Staff that the number of shares of common stock outstanding on a pro forma basis as of June 30, 2013 as disclosed on page F-5 does not include 287,326 shares of unvested restricted stock outstanding at June 30, 2013 since unvested restricted stock is not

2

considered outstanding for accounting purposes. The number of shares outstanding on page 55 of Amendment No. 1 includes the 287,326 shares of unvested restricted stock, as they are considered outstanding for legal purposes.

If you have any further questions or comments, or if you require any additional information, please contact the undersigned at (781) 966-2007 or Steven D. Singer at (212) 295-6307.  Thank you for your assistance.

Sincerely,

/s/   Joshua D. Fox

Joshua   D. Fox

cc:                    Steven D. Singer, Wilmer Cutler Pickering Hale and Dorr LLP
 Michael G. Kauffman, M.D., Ph.D., Karyopharm Therapeutics Inc.
 Paul Brannelly, Karyopharm Therapeutics Inc.

3

CORRESP
1
filename1.htm

November 1, 2013

Securities and Exchange Commission

100 F Street, N.E.

Washington, D.C.  20549

Re:                             Karyopharm Therapeutics Inc.

Registration Statement on Form S-1 (SEC File No. 333-191584)

Ladies and Gentlemen:

In connection with the above-referenced Registration Statement, and pursuant to Rule 461 under the Securities Act of 1933, as amended (the “Act”), we hereby join in the request of Karyopharm Therapeutics Inc. that the effective date of the Registration Statement be accelerated so that it will be declared effective at 4:00 p.m., New York City time, on November 5, 2013 or as soon thereafter as practicable.

Pursuant to Rule 460 under the Act, we wish to advise you that we have distributed approximately 2,133 copies of the Preliminary Prospectus dated October 28, 2013 (the “Preliminary Prospectus”) through the date hereof, to underwriters, dealers, institutions and others.

In connection with the Preliminary Prospectus distribution for the above-reference issue, the prospective underwriters have confirmed that they are complying with the 48-hour requirement as promulgated by Rule 15c2-8 under the Securities Exchange Act of 1934, as amended.

[Remainder of page intentionally left blank]

Very truly yours,

MERRILL LYNCH, PIERCE,   FENNER & SMITH

INCORPORATED

LEERINK SWANN LLC

By:

MERRILL LYNCH, PIERCE, FENNER & SMITH

INCORPORATED

By:

/s/ Michele A. H. Allong

Name:

Michele A. H. Allong

Title:

Authorized Signatory

For themselves and as Representatives of the other Underwriters.

[Signature Page to Karyopharm Therapeutics Inc. S-1 Acceleration Request]

CORRESP
1
filename1.htm

KARYOPHARM THERAPEUTICS INC.

2 Mercer Road

Natick, MA 01760

November 1, 2013

VIA EDGAR

Securities and Exchange Commission

Division of Corporation Finance

100 F Street, N.E.

Washington, D.C. 20549

Re:                             Karyopharm Therapeutics Inc.

Registration Statement on Form S-1

File No. 333-191584

Request for Acceleration

Ladies and Gentlemen:

Pursuant to Rule 461 promulgated under the Securities Act of 1933, as amended, Karyopharm Therapeutics Inc. (the “Registrant”) hereby requests acceleration of the effective date of its Registration Statement on Form S-1 (File No. 333-191584), as amended (the “Registration Statement”), so that it may become effective at 4:00 p.m. Eastern time on November 5, 2013, or as soon thereafter as practicable, or at such later time as the Registrant or its counsel may orally request via telephone call to the staff of the Securities and Exchange Commission (the “Commission”).

The Registrant hereby acknowledges that:

(i)            should the Commission or the staff, acting pursuant to delegated authority, declare the Registration Statement effective, it does not foreclose the Commission from taking any action with respect to the Registration Statement;

(ii)           the action of the Commission or the staff, acting pursuant to delegated authority, in declaring the Registration Statement effective, does not relieve the Registrant from its full responsibility for the adequacy and accuracy of the disclosure in the Registration Statement; and

(iii)          the Registrant 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.

[Signature page follows]

Very   truly yours,

KARYOPHARM   THERAPEUTICS INC.

By:

/s/   Paul Brannelly

Paul   Brannelly

Senior   Vice President, Finance and Administration

2

October 2 4, 2013

Via E -mail
Michael G. Kauffman, M.D., Ph.D.
Chief Executive Officer
Karyopharm Therapeutics Inc.
2 Mercer Road
Natick, MA 01760

Re: Karyopharm  Therapeutics Inc.
Registration Statement on Form S -1
Response dated October 18, 2013
  File No. 333-191584

Dear Dr. Kaufman :

We have reviewed your correspondence filed on October 18, 2013 and have the
following comments.  Please respond to this letter by providing the requested information .  If
you do not believe our comments apply to your facts and circumstances, please tell us why in
your response.

After reviewing the information you provide in response to these  comments , we may
have  additional comments.

Management’s Discussion and Analysis of Financial Condition and Results of Operations
Critical Accounting Policies and Estimates
Share -Based Compensation, page 62

1. It is unclear how you have sufficiently addressed the qua ntitative or qualitative
components in our initial comment in your discussion of each significant factor
contributing to the difference between the latest common stock valuation and the
estimated IPO price, considering the significant increase in fair value from the  September
24, 2013 price to the midpoint of your IPO price range.  Please revise your disclosure to
further support this increase and quantify the impact that the following items had on your
increased valuation:

 The enrollment of 22 additional patients i n clinical trials of Selinexor;

 The receipt of updated clinical data;

 The agreement with Fast Forward LLC; and

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2 4, 2013
Page 2

  The 65% weighting of your IPO scenario.

2. You cite improved capital market conditions for companies in your industry as a reason
for the increase  in fair value, reflected in the  estimated IPO price .  Please explain to us
why you were unaware of this information and presumably did not include it in your
September 24, 2013 common stock valuation.

3. During the three months ended September 30, 2 013, you granted an additional 3,959,000
options to employees and 140,500 options to non -employees per page F -22.  Please
include these options in your tabular disclosure on page 63.

4. We will further evaluate your accounting for stock compensation and rel ated disclosures,
once you have finalized an estimated offering price range and disclosed this information in a
subsequent amendment to your Registration Statement .

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 the information the Securities Act of 193 3 and
all applicable Securities  Act rules require.   Since the company and its management are in
possession of all facts relating to a company’s disclosure, they a re 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 regist ration statement please provide  a written statement from the company
acknowledging that:

 should the Commission or the staff, acting pursuant to delegated authority, declare the
filing effective, it does 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, 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 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.

Please refer to Rules 460 and 461 regarding requests for  acceleration .  We will consider a
written request for acceleration of the effective date of the registration statement as confirmation
of the fact that those requesting acceleration are aware of their respective responsibilities under
the Securities Act of  1933 and the Securities Exchange Act of 1934 as they relate to the proposed
public offering of the securities specified in the above registration statement.  Please allow
adequate time  for us to review any amendment prior to the requested effective date o f the
registration statement.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2 4, 2013
Page 3

 You may c ontact Frank Wyman  at (202) 551 -3660  or Joel Parker at (202) 551 -3651  if
you have questions regarding comments on the financial statements and related matters.  Please
contact Scot Foley  at (202) 551 -3383, Bryan  Pitko at (202) 551 -3203 or me at (202) 551 -3715
with any other questions.

Sincerely,

 /s/ Bryan J. Pitko for

Jeffrey P. Riedler
Assistant Director

cc: Steven D. Singer, Esq.
Joshua D. Fox, Esq.
Wilmer Cutler Pickering Hale and Dorr  LLP
60 State Street
Boston, MA 02109
Telephone: (617)  526-6000

CORRESP
1
filename1.htm

FOIA CONFIDENTIAL TREATMENT REQUEST

Joshua D. Fox

+1 781 966 2007 (t)

The entity requesting confidential treatment is:

+1 781 966 2100 (f)

Karyopharm Therapeutics Inc.

joshua.fox@wilmerhale.com

2 Mercer Road

Natick, MA 01760

Attn: Michael G. Kauffman, M.D., Ph.D.

Chief Executive Officer

(508) 975-4820

October 18, 2013

VIA EDGAR SUBMISSION

Securities and Exchange Commission

Division of Corporation Finance

100 F Street, NE
 Mail Stop 6010
 Washington, DC 20549-6010
  Attention:  Jeffrey P. Riedler

Re:              Karyopharm Therapeutics Inc.
 Registration Statement on Form S-1
  File No. 333-191584

Ladies and Gentlemen:

On behalf of Karyopharm Therapeutics Inc. (the “Company”), set forth below is additional information to supplement the Company’s prior response to comment 18 contained in the letter dated October 2, 2013 (the “Letter”) from Jeffrey P. Riedler of the Staff (the “Staff”) of the Securities and Exchange Commission (the “Commission”) to Michael G. Kauffman, the Company’s Chief Executive Officer, with respect to the Registration Statement referenced above (the “Registration Statement”).  The supplemental response set forth below is based upon information provided to Wilmer Cutler Pickering Hale and Dorr LLP by the Company.

On behalf of the Company, we advise you as follows:

18.               We will further evaluate your accounting for stock compensation and related disclosure once you have disclosed an estimated offering price.  Please expand your disclosure to address the following:

·                  Once you can reasonably estimate the IPO price, qualitiatively and quantitiatively discuss each significant factor contributing to the difference between each valuation and the estimated IPO price;

·                  Continue to update your disclosure for all equity related transactions through the effectiveness date of the registration statement; and

·                  Please revise your disclosure to present the intrinisic value of outstanding vested and unvested options as of the most recent balance sheet date based on the estimated IPO price.

Rule 83 Confidential Treatment Request by Karyopharm Therapeutics Inc.

Request #1

Response:             In response to the Staff’s comment in the first bullet above, and to provide additional context and further information for the Staff’s consideration, the Company supplementally advises the Staff that the Company currently anticipates that the price range for this offering will be within the range of $[**] to $[**] per share (before giving effect to a reverse stock split that the Company plans to implement prior to effectiveness of the Registration Statement). This price range is based on a number of factors, including the Company’s prospects and the history of and prospects for the Company’s industry, the general condition of the securities markets, the recent market prices of, and the demand for, publicly-traded common stock of generally similar companies and preliminary discussions with the underwriters regarding potential valuations of the Company. The actual price range to be included in a subsequent amendment to the Registration Statement (which will comply with the Staff’s interpretation regarding the parameters of a bona fide price range) has not yet been determined and remains subject to adjustment based on factors outside of the Company’s control. However, the Company believes that the foregoing indicative price range will not be subject to significant change.

Karyopharm Therapeutics Inc. respectfully requests that the information contained in this response be treated as confidential information and that the Commission provide timely notice to Michael G. Kauffman, M.D., Ph.D., Chief Executive Officer, Karyopharm Therapeutics Inc., 2 Mercer Road, Natick, MA 01760, telephone (508) 975-4820, before it permits any disclosure of the bracketed information contained in Request #1.

Once the estimated price range for this offering has been determined, the Company will reflect in a subsequent amendment to the Registration Statement an additional list of significant factors contributing to any difference between the most recent common stock valuation and the midpoint of the estimated price

2

range for this offering. The Company expects that such disclosure would be generally consistent with the following disclosure, which was included, in substantial part, on pages 72 to 74 of the Registration Statement filed by the Company with the Commission on October 4, 2013.

Rule 83 Confidential Treatment Request by Karyopharm Therapeutics Inc.

Request #2

“In consultation with the underwriters for this offering, we determined the estimated price range for this offering, as set forth on the cover page of this prospectus.  The midpoint of the price range is $[**] per share. In comparison, our estimate of the fair value of our common stock was $1.71 per share as of September 24, 2013. We note that, as is typical in IPOs, the estimated price range for this offering was not derived using a formal determination of fair value, but was determined by negotiation between us and the underwriters. Among the factors that were considered in setting this range were the following:

Karyopharm Therapeutics Inc. respectfully requests that the information contained in this response be treated as confidential information and that the Commission provide timely notice to Michael G. Kauffman, M.D., Ph.D., Chief Executive Officer, Karyopharm Therapeutics Inc., 2 Mercer Road, Natick, MA 01760, telephone (508) 975-4820, before it permits any disclosure of the bracketed information contained in Request #2.

·                  an analysis of the typical valuation ranges seen in recent IPOs for companies in our industry;

·                  the general condition of the securities markets and the recent market prices of, and the demand for, publicly traded common stock of generally comparable companies;

·                  an assumption that there would be a receptive public trading market for pre-commercial biotechnology companies such as us; and

·                  an assumption that there would be sufficient demand for our common stock to support an offering of the size contemplated by this prospectus.

The midpoint of the estimated price range for this offering reflects a significant increase over the estimated valuation as of September 24, 2013 of $1.71 per share. Investors should be aware of this difference and recognize that the price range for this offering is in excess of our prior valuations. Further, investors are cautioned not to place undue reliance on the valuation methodologies discussed above as an indicator of future stock prices. We believe the difference may be due to the following factors:

3

·                  We received positive feedback from potential investors in connection with our “testing-the-waters” meetings;

·                  We enrolled 22 additional patients in our clinical trials of Selinexor;

·                  After September 24, 2013, we received incremental updated clinical data as of September 20, 2013, which confirmed and expanded data previously received in our studies;

·                  After September 24, 2013, we received incremental updated data about the number of patients remaining on study between August 20, 2013 and September 20, 2013, thereby increasing the average days on study for our patients;

·                  We entered into an agreement with Fast Forward LLC, a not-for-profit subsidiary of the National Multiple Sclerosis Society, to explore the application of our SINE compounds in multiple sclerosis, demonstrating potential third party validation of the applicability of our SINE compounds in indications outside of oncology;

·                  We added research and development staff to our organization to support our preclinical and clinical trials;

·                  We have taken several steps towards the completion of an initial public offering, including:

·                  On October 4, 2013, we publicly filed our registration statement with the Commission;

·                  Our board of directors established a pricing committee in connection with this offering and, in anticipation of this offering, approved a certificate of amendment to our certificate of incorporation in order to effect a reverse stock split of our common stock;

·                  Our board of directors approved our certificate of incorporation, bylaws, committee charters and various governance policies that will become effective upon the closing of this offering; and

·                  We added Garen G. Bohlin to our board of directors, a director with significant experience on the boards of directors of publicly traded biopharmaceutical companies, including as an “audit committee financial expert”;

·                  The contemporaneous valuation prepared as of September 24, 2013 contained multiple liquidity scenarios, including an initial public offering to which we assigned a probability weighting of 65%. However, the consideration of different scenarios accounts for some but not all of the difference between the initial public offering price and the valuation as of September 24, 2013;

·                  Improved capital market conditions for companies in our industry, as evidenced by a recent increase in the number of public offerings by such

4

companies and in the initial public offering valuations of such companies compared to the valuations in their most recent pre-IPO equity financing;

·                  The initial offering price range necessarily assumes that this offering has occurred, a public market for our common stock has been created and that our preferred stock has converted into common stock in connection with this offering and, therefore, excludes the marketability or illiquidity discounts associated with the timing or likelihood of an initial public offering, the superior rights and preferences of our preferred stock and the alternative scenarios considered in the contemporaneous valuations over the past two years. Our September 24, 2013 valuation included an illiquidity discount of 0% in the IPO scenario and 30% in the OPM scenario;

·                  In the public markets we believe there are investors who may apply more qualitative and subjective valuation criteria to certain of our clinical assets than the valuation methods applied in our valuations, although there can be no assurance that this will in fact be the case. As described above, as a private company we used a more quantitative methodology to determine the fair value of our common stock and this methodology differs from the methodology used to determine the estimated price range for this offering. The estimated price range for this offering was not derived using a formal determination of fair value, but rather was determined by negotiation between us and the underwriters. In particular, the estimate of fair value of our common stock as of September 24, 2013 was not a factor in setting the estimated price range for this offering; and

·                  The price that investors are willing to pay in this offering, for which the price range is intended to serve as an estimate, may take into account other things that have not been expressly considered in our prior valuations, are not objectively determinable and that valuation models are not able to quantify.

Investors should be cautioned that the midpoint of the price range set forth on the cover of this prospectus does not necessarily represent the fair value of our common stock, but rather reflects an estimate of the offer price determined in consultation with the underwriters.

There are significant judgments and estimates inherent in the determination of these valuations. These judgments and estimates include assumptions regarding our future performance, including the successful enrollment and completion of our clinical studies as well as the determination of the appropriate valuation methods. If we had made different assumptions, our stock-based compensation expense could have been different. The foregoing valuation methodologies are not

5

the only methodologies available and they will not be used to value our common stock once this offering is complete. We cannot make assurances as to any particular valuation for our common stock. Accordingly, investors are cautioned not to place undue reliance on the foregoing valuation methodologies as an indicator of future stock prices.”

In response to the Staff’s comment in the second bullet above, and as set forth in the response letter submitted by the Company to the Staff on October 4, 2013, the Company has reflected equity related transactions through October 4, 2013 in the Registration Statement filed with the Commission on such date, and undertakes that it will update such disclosure through the effectiveness of the Registration Statement.

Rule 83 Confidential Treatment Request by Karyopharm Therapeutics Inc.

Request #3

In response to the Staff’s comment in the third bullet above, the Company supplementally advises the Staff that, based on the Company’s estimated price range for this offering of $[**] to $[**] per share, the intrinsic value of outstanding vested and unvested options as of June 30, 2013, the most recent balance sheet date, were $[**] and $[**], respectively.  The Company undertakes that it will provide the intrinsic value of outstanding vested and unvested options as of the most recent balance sheet date at such time as the Company includes a bona fide price range for this offering in its prospectus.

Karyopharm Therapeutics Inc. respectfully requests that the information contained in this response be treated as confidential information and that the Commission provide timely notice to Michael G. Kauffman, M.D., Ph.D., Chief Executive Officer, Karyopharm Therapeutics Inc., 2 Mercer Road, Natick, MA 01760, telephone (508) 975-4820, before it permits any disclosure of the bracketed information contained in Request #3.

If you have any further questions or comments, or if you require additional information, please contact the undersigned by telephone at (781) 966-2007  or electronically at joshua.fox@wilmerhale.com.  Thank you for your assistance.

6

Very   truly yours,

/s/   Joshua D. Fox

Joshua   D. Fox

cc:                    Michael G. Kauffman, M.D., Ph.D.
 Paul Brannelly

Office of Freedom of Information and Privacy Act Operations

Securities and Exchange Commission

100 F Street N.E., Mail Stop 2736

Washington, D.C. 20549

7

October 2, 2013

Via E -mail
Michael G. Kauffman, M.D., Ph.D.
Chief Executive Officer
Karyopharm Therapeutics Inc.
2 Mercer Road
Natick, MA 01760

Re: Karyopharm Therapeutics Inc.
Draft Registration Statement on Form S -1
Submitted September 5, 2015
  CIK No. 0001503802

Dear Dr. Kaufman :

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 registra tion statement or filed registration statement,  we may have  additional
comments.

General

1. We note that you have s ubmitted an applic ation f or confidential treat ment relating to one
of your exhibits.  Please be adv ised that comments to this application, if any, will be sent
under separate cover and that a ny such com ments must be resolved prior to our acting on
any acceleration request relating to your registration state ment.

2. Please confirm  that the graphics included  in your registration state ment are the only
graphics you will u se in your prospectus.  If those are not the only graphics, please
provide any additional graphics  prior to t heir use for our review.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2, 2013
Page 2

 3. Please supple mentally provide us with copies of all writ ten communications,  as defined
in Rule 405 under the Securities A ct, that you, or anyone authorized to do so on your
behalf, present to potential inv estors in reliance on Section 5(d) of the Securities Act,
whether or not they retain copies of the communic ations. Si milarly, please
supple mentally provide us  with any research reports about you that are published or
distributed in reli ance upon Section 2(a)( 3) of the Securities Act of 1933 added by
Section 105(a) of t he Jumpstart Our Business Startups Act by any broker or dealer that is
participating or will participate in your offering.

Prospectus Summary
Overview, page 1

4. Please revise your summary to include the percentage of total patients with relapsed
and/or refractory acute myeloid leukemia who experienced complete remission or stable
disease.

5. Please indicate here that your first Phase 1 clinical trial relating to ad vanced
hematological malignancies has three arms, and list the indications for each arm

6. Here, and in your Business discussion, please explain how your planned clinical trial for
Selinexor will qualify as both a Phase 2 and Phase 3 clinical trial.

Risks A ssociated with Our Business, page 5

7. In your first bullet point, please include the amount of your accumulated deficit to date.

8. In your sixth bullet point, please  note that both adverse events and serious adverse
events have been experienced by patients in your clinical trials for Selinexor including
several which have been determined to relate to the use of Selinexor.

9. In your eighth bullet point, please  clarify that you have applied for but have not yet been
granted any patents in relation to your key  drug candidates.

Risk Factors

“We will need substantial additional funding …,” page 12

10. Please include an estimate of the capital you believe you will require for the remainder
of this fiscal year and the next complete fiscal year.

“Product liability lawsuits against us could cause us to incur substantial liabilities…,” page 24

11. Please revise your risk fac tor discussion to identify the amount  of clinical trial liability
insurance coverage you maintain.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2, 2013
Page 3

 “Third p arties may initi ate legal proceedings alleging th at we are in fringing their intellectual
property rights . . .,” page 31

12. Please indicate in this risk factor whether or not any such litigation is currently
pending against you and/or whether you have ever been held by a court of co mpetent
jurisd iction to have infringed  on a third party’s i ntellectual rights.

“We may be subject to clai ms that our e mployees have wrongfully used or disclosed alleged
trade secrets of their former employers,” page 31

13. Please incl ude in t his risk factor examples of an y such claims that has been filed
against you or any of your founders,  scientific advisor s, directors  and/or executive
officers.

 “We will incur increased costs as a result of operating as a public company . . .,” page 45

14. In this risk factor, please include, to t he exte nt practicable, an  estimate of the  annual costs
associated with being a public co mpany.

Use of Proceeds, page 48

15. Please bifurcate the approximate amount of net proceeds you intend to allocate to the
Phase 2/3 clinical trials of Seline xor and the amount you intend to allocate to Selinexor’s
Phase 2 trials for the two solid tumor indications.

Industry and Other Data, page 50

16. Please revise your prospectus to remove your statements that you have not independently
verified market and in dustry and competitive position date from third -party sources and
that internal company research and estimates and market definitions have not been
verified by any independent source.  It is not appropriate to directly or indirectly disclaim
liability for information in the registration statement.

Dilution, page 54

17. Your historical net tangible book value as of June 30, 2013 appears to be a def icit.  Please
revise your disclosure or tell why your presentation is appropriate.

Management’s Discussion and Analysis of Financial Condition and Results of Operations
Critical Accounting Policies and Estimates
Share -Based Compensation, page 62

18. We will further evaluate your accounting for stock compensation and related disclosure
once you have disclosed an estima ted offering price.  Please expand your disclosure to
address the following:

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2, 2013
Page 4

  Once you can reasonably estimate the IPO price, qualitatively and quantitatively
discuss each significant factor contributing to the difference between each
valuation and the est imated IPO price;

 Continue to update your disclosure for all equity related transactions  through the
effectiveness dat e of the registration statement; and

 Please revise your disclosure to present the intrinsic value of outstanding vested
and unvested options as of the most recent balance sheet date based on the
estimated IPO price.

Business
Our Drug Candidates, page 86

19. Please indicate in your disclosure when you filed the Investigational New Drug
application(s) for Selinexor and the various indications it is being developed to treat.

20. We note your disclosure that Selinexor  has been generally well -tolerated despite the
occurrence of a number of adverse and serious adverse events in your Phase 1 clinical
trials.  In light of the occurrence and frequency of these events, please revise your
disclosure to provide your basis for the conclusion that Selinexor has generally been
well-tolerated.

Adva nced Hematological Malignancies, page 86

21. We note that your disclosure, as currently written, only provides examples of complete
response and partial response for chronic lymphocytic l eukemia . Please revise your
disclosure to identify what results qualify as a CR, PR, MR, and SD under the
“commonly accepted evaluation criteria” for each indication tested in arm 1 of your
Phase I trial for h ematological  malignancies . Please also discuss the results constituting
progressive disease for each indication.

Intellectual Property, page 100

22. Please identify the three foreign jurisdictions in which you have pending patent
applications for Selinexor.

Management, page 119

23. We note that the biographical information provided for Drs. Kauffman and Shacham
discusses  their employment at Epix Pharmaceuticals, Inc. which underwent liquidation
proceedings in 2009.  If a  petition under the federal bankruptcy laws or any state
insolvency  law was filed by or against, or a receiver, fiscal agent or similar officer was
appointed by a court for Epix, please revise the biographical information for Drs.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2, 2013
Page 5

 Kauffman and Shacham to provide this information.  Please refer to requirements of Item
401(f)(1) of Regulation S -K.

Narrative Disclosure to Summary Compensation Tab le, page 127
Annual Performance -based Cash Incentives , page 127

24. Please revise your disclosure to provide a description of the material terms of your annual
performance -based cash incentive program including any formula or criteria applied to
determine the amount paid to Drs. Kauffman and Shacham.  Please also highlight the
specific corporate and individual performance that led the board to award the cash
incentive payments paid.

Shares Eligible for Future Sale
Lock -Up Agreements, page 152

25. Please file a copy of the form  lock-agree ment as an exhibit to your registration
statement.  If it is to be filed as an exhibit to your underwriting agree ment, please
confirm  this for us.

Note 2. Summary of S ignificant Accounting Policies
Principles of Consolidation , page F -9

26. Please tell us and disclose where you have recorded the non -controlling interest for NPM.

If you intend to respond to these comments with an amended draft registration st atement ,
please submit it and any associated correspondence in accordance with the guidance we provide
in the Division’s October 11, 2012 announcement on the SEC website at
http://www.sec.gov/divisions/corpfin/cfannouncements/drsfilingprocedures101512.htm .

Please keep in mind that we may publicly post filing review correspondence in
accordance with our December 1, 2011 policy
(http://www.sec.gov/divisions/corpfin/cfannouncements/edgarcorrespondence.htm ).  If you
intend to use Rule 83 (17 CFR 200.83) to req uest confidential treatment of information in the
correspondence you submit on EDGAR, please properly mark that information in each of your
confidential submissions to us so we do not repeat or refer to that information in our comment
letters to you.

Michael G. Kaufman, M.D., Ph.D.
Karyopharm Therapeutics Inc.
October 2, 2013
Page 6

 You may c ontact Frank Wyman  at (202) 551 -3660  or Joel Parker at (202) 551 -3651  if
you have questions regarding comments on the financial statements and related matters.  Please
contact Scot Foley  at (202) 551 -3383, Bryan Pitko at (202) 551 -3203 or me at (202) 551 -3715
with any other questions.

Sincerely,

 /s/ Bryan J. Pitko for

Jeffrey P. Riedler
Assistant Director

cc: Steven D. Singer, Esq.
Joshua D. Fox, Esq.
Wilmer Cutler Pickering Hale and Dorr  LLP
60 State Street
Boston, MA 02109