SecProbe.io

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