S-1MEF

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As filed with the Securities and Exchange Commission on November 5, 2013

Registration No. 333-        

SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

FORM S-1
REGISTRATION STATEMENT
UNDER
THE SECURITIES ACT OF 1933

KARYOPHARM THERAPEUTICS INC.
(Exact Name of Registrant as Specified in its Charter)

Delaware
(State or Other Jurisdiction of
Incorporation or Organization) 2834
(Primary Standard Industrial
Classification Code Number) 26-3931704
(I.R.S. Employer
Identification Number)

2 Mercer Road
Natick, MA 01760
(508) 975-4820
(Address, Including Zip Code, and Telephone Number, Including Area Code, of Registrant's Principal Executive Offices)

Michael G. Kauffman, M.D., Ph.D.
Chief Executive Officer
Karyopharm Therapeutics Inc.
2 Mercer Road
Natick, MA 01760
(508) 975-4820
(Name, Address, Including Zip Code, and Telephone Number, Including Area Code, of Agent for Service)

Copies to:
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	Patrick O'Brien, Esq. Ropes & Gray LLP Prudential Tower 800 Boylston Street Boston, MA 02199 Telephone: (617) 951-7000

Approximate date of commencement of proposed sale to the public:
As soon as practicable after this Registration Statement becomes effective.

         If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, check the following box.    o

         If this Form is filed to register additional securities for an offering pursuant Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    ý 333-191584

         If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    o

         If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.    o

         Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting company. See the definitions of "large accelerated filer," "accelerated filer" and "smaller reporting company" in Rule 12b-2 of the Exchange Act. (Check one):

Large accelerated filer o Accelerated filer o Non-accelerated filer ý
(Do not check if a
smaller reporting company) Smaller reporting company o

CALCULATION OF REGISTRATION FEE

Title of each class of securities to be registered	Amount to be registered(1)	Proposed maximum offering price per share(2)	Proposed maximum aggregate offering price(2)	Amount of registration fee
Common Stock, $0.0001 par value per share	1,303,333 shares	$16.00	$20,853,328	$2,685.91

(1)

Includes 170,000 shares which the Underwriters have the option to purchase from the Company to cover over-allotments, if any.

(2)

Estimated in accordance with Rule 457(a) of the Securities Act of 1933 solely on the basis of $16.00, the Price to the Public set forth on the cover page of the Registrant's Prospectus dated November 5, 2013 relating to its initial public offering pursuant to the Company's Registration Statement on Form S-1 (File No. 333-191584).

EXPLANATORY NOTE AND INCORPORATION BY REFERENCE

        This registration statement is being filed with respect to the registration of additional shares of common stock, par value $0.0001 per share, of Karyopharm Therapeutics Inc., a Delaware corporation, pursuant to Rule 462(b) under the Securities Act of 1933, as amended. The contents of the earlier registration statement on Form S-1(File No. 333-191584), which was declared effective by the Commission on November 5, 2013, are incorporated in this registration statement by reference.

        The required opinions and consents are listed on an Exhibit Index attached hereto and filed herewith.

SIGNATURES

        Pursuant to the requirements of the Securities Act of 1933, the Registrant has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Natick, Commonwealth of Massachusetts, on this 5^th day of November, 2013.

KARYOPHARM THERAPEUTICS INC.
By:	/s/ MICHAEL G. KAUFFMAN Michael G. Kauffman, M.D., Ph.D. Chief Executive Officer

        Pursuant to the requirements of the Securities Act of 1933, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated.

Signature			Title	Date
/s/ MICHAEL G. KAUFFMAN Michael G. Kauffman, M.D., Ph.D.			President and Chief Executive Officer, Chief Medical Officer and Director (principal executive officer)	November 5, 2013
/s/ PAUL BRANNELLY Paul Brannelly			Senior Vice President, Finance and Administration, Secretary and Treasurer (principal financial and accounting officer)	November 5, 2013
/s/ * Garen G. Bohlin			Director	November 5, 2013
/s/ * Barry E. Greene			Director	November 5, 2013
/s/ * Deepa R. Pakianathan, Ph.D.			Director	November 5, 2013
/s/ * Mansoor Raza Mirza, M.D.			Director	November 5, 2013
/s/ * Kenneth E. Weg			Director	November 5, 2013
*By:	/s/ PAUL BRANNELLY
	Name:	Paul Brannelly
	Title:	Attorney-in-Fact

EXHIBIT INDEX

Exhibit No.			Description
	5.1		Opinion of Wilmer Cutler Pickering Hale and Dorr LLP
	23.1		Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1)
	23.2		Consent of McGladrey LLP
	24.1	*	Powers of Attorney

*

Filed as Exhibit 24.1 to the Registrant's Registration Statement on Form S-1 (File No. 333-191584) filed with the Commission on October 4, 2013.

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EXPLANATORY NOTE AND INCORPORATION BY REFERENCE
SIGNATURES
EXHIBIT INDEX

EX-5.1

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Exhibit 5.1

WILMERHALE

November 5, 2013

Karyopharm Therapeutics Inc.
2 Mercer Road
Natick, MA 01760

Re:

Rule 462(b) Registration Statement on Form S-1

Ladies and Gentlemen:

        We have acted as counsel to you in connection with your filing of (i) a Registration Statement on Form S-1 (File No. 333-191584) (the "Initial Registration Statement") with the Securities and Exchange Commission (the "Commission") under the Securities Act of 1933, as amended (the "Securities Act") and (ii) a second registration statement on Form S-1 filed pursuant to Rule 462(b) of the Securities Act (the "462(b) Registration Statement," and together with the Initial Registration Statement, the "Registration Statement"). This opinion letter is furnished to you in connection with your filing of the 462(b) Registration Statement, relating to the registration of 1,303,333 shares of Common Stock, $0.0001 par value per share (the "Shares"), of Karyopharm Therapeutics Inc., a Delaware corporation (the "Company"), including 170,000 Shares issuable upon exercise of an over-allotment option granted by the Company.

        The Shares are to be sold by the Company pursuant to an underwriting agreement (the "Underwriting Agreement") to be entered into by and among the Company and the several underwriters named in Schedule A thereto, for whom Merrill Lynch, Pierce, Fenner & Smith Incorporated and Leerink Swann LLC are acting as representatives, the form of which has been filed as Exhibit 1.1 to the Registration Statement.

        We are acting as counsel for the Company in connection with the issue and sale by the Company of the Shares. We have examined signed copies of the Registration Statement as filed with the Commission. We have also examined and relied upon the Underwriting Agreement, minutes of meetings of the stockholders and the Board of Directors of the Company as provided to us by the Company, stock record books of the Company as provided to us by the Company, the Certificate of Incorporation and By-Laws of the Company, each as restated and/or amended to date, and such other documents as we have deemed necessary for purposes of rendering the opinions hereinafter set forth.

        In our examination of the foregoing documents, we have assumed the genuineness of all signatures, the authenticity of all documents submitted to us as originals, the conformity to original documents of all documents submitted to us as copies, the authenticity of the originals of such latter documents and the legal competence of all signatories to such documents.

        We express no opinion herein as to the laws of any state or jurisdiction other than the state laws of the Commonwealth of Massachusetts, the General Corporation Law of the State of Delaware and the federal laws of the United States of America.

        Based upon and subject to the foregoing, we are of the opinion that the Shares have been duly authorized for issuance and, when the Shares are issued and paid for in accordance with the terms and conditions of the Underwriting Agreement, the Shares will be validly issued, fully paid and nonassessable.

Wilmer Cutler Pickering Hale and Dorr LLP, 850 Winter Street, Waltham, MA 02451

Beijing    Berlin    Boston    Brussels    Frankfurt     London    Los Angeles    New York    Oxford    Palo Alto    Waltham    Washington

        Please note that we are opining only as to the matters expressly set forth herein, and no opinion should be inferred as to any other matters. This opinion is based upon currently existing statutes, rules, regulations and judicial decisions, and we disclaim any obligation to advise you of any change in any of these sources of law or subsequent legal or factual developments which might affect any matters or opinions set forth herein.

        We hereby consent to the filing of this opinion with the Commission as an exhibit to the 462(b) Registration Statement in accordance with the requirements of Item 601(b)(5) of Regulation S-K under the Securities Act and to the use of our name in the Registration Statement and in the related Prospectus under the caption "Legal Matters." In giving such consent, we do not hereby admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act or the rules and regulations of the Commission.

Very truly yours,

WILMER CUTLER PICKERING
HALE AND DORR LLP

By:
	/s/ JOSHUA D. FOX Joshua D. Fox, a Partner

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Exhibit 5.1

EX-23.2

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Exhibit 23.2

Consent of Independent Registered Public Accounting Firm

        We consent to the incorporation by reference in this Registration Statement on Form S-1 of Karyopharm Therapeutics Inc. filed pursuant to Rule 462(b) of the Securities Act of 1933, as amended, of our report dated September 4, 2013, except for Note 11, as to which the date is October 25, 2013, relating to our audits of the consolidated financial statements, appearing in the Prospectus, which is a part of the Registration Statement (Form S-1 No. 333-191584) declared effective on November 5, 2013.

        We also consent to the reference to our firm under the caption "Experts" in such Prospectus.

/s/ McGladrey LLP

Boston, Massachusetts
November 5, 2013

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Exhibit 23.2