SecProbe.io

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