85 Wells Avenue, Newton, Massachusetts 02459

NOTICE OF ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON FRIDAY, MAY 22, 2015TUESDAY, JUNE 19, 2018

Dear Stockholder:

You are cordially invited to our 20152018 Annual Meeting of Stockholders (the “Annual Meeting”) on Friday, May 22, 2015,Tuesday, June 19, 2018, beginning at 8:00 a.m., Eastern time, at our headquarters, 85 Wells Avenue, Newton, Massachusetts 02459, for the following purposes:

1. To elect two directorsone Class II director to serve as Class II directors for a three-year term to expire at the 20182021 annual meeting of stockholders;

2. To consider and vote upon the ratification of the selection of Ernst & Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2015;2018; and

3. To transactconsider and vote upon such other business as may be properly brought before the meeting or any adjournment or postponement thereof.

Instead of mailing a printed copy of our proxy materials to all of our stockholders, we provide access to these materials via the Internet. This reduces the amount of paper necessary to produce these materials as well as the costs associated with mailing these materials to all stockholders. Accordingly, on or about April 7, 2015,27, 2018, we will begin mailing a Notice of Internet Availability of Proxy Materials, or Notice, to all stockholders of record on our books at the close of business on March 26, 2015, the record date for the Annual Meeting, and will post our proxy materials on the website referenced in the Notice. As more fully described in the Notice, stockholders may choose to access our proxy materials on the website referred to in the Notice or may request to receive a printed set of our proxy materials. In addition, the Notice and website provide information regarding how you may request to receive proxy materials in printed form by mail, or electronically by email, on an ongoing basis.

If you are a stockholder of record, you may vote in one of the following ways:

If your shares are held in “street name,” meaning that they are held for your account by a broker or other nominee, you will receive instructions from the holder of record that you must follow for your shares to be voted.

Our Board of Directors has fixed the close of business on April 23, 2018 as the record date for the determination of stockholders entitled to notice of, and to vote at, the Annual Meeting and any adjournment or postponement thereof.

Whether or not you plan to attend the Annual Meeting in person, we urge you to take the time to vote your shares.

By Order of the Board of Directors,

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

Chief Executive Officer

Newton, Massachusetts

April 7, 201527, 2018

TABLE OF CONTENTS

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85 Wells Avenue, Newton, Massachusetts 02459

PROXY STATEMENT FOR THE 20152018 ANNUAL MEETING OF STOCKHOLDERS

TO BE HELD ON FRIDAY, MAY 22, 2015TUESDAY, JUNE 19, 2018

The board of directors of Karyopharm Therapeutics Inc. (which we also refer to as “Karyopharm” or “the Company”) is soliciting the enclosed proxyproxies for use at the 20152018 annual meeting of stockholders, or the Annual Meeting, to be held at the company’sour headquarters, 85 Wells Avenue, Newton, Massachusetts 02459, on May 22, 2015June 19, 2018 at 8:00 a.m., localEastern time.

Important Notice Regarding the Availability of Proxy Materials for the Annual Meeting of

Stockholders to be Held on May 22, 2015:June 19, 2018:

This proxy statement and our annual report are available electronically at www.proxyvote.com.www.proxyvote.com.

On or about April 7, 2015,27, 2018, we mailedbegan mailing a Notice of Internet Availability of Proxy Materials, or Notice, to our stockholders (other than those who previously requested electronic or paper delivery of proxy materials), directing stockholders to a website where they can access our proxy materials, including this proxy statement and our Annual Report on Form10-K, and view instructions on how to vote online or by telephone. If you would prefer to receive a paper copy of our proxy materials, please follow the instructions included in the Notice. If you have previously elected to receive our proxy materials electronically, you will continue to receive access to those materials viae-mail unless you elect otherwise.

EXPLANATORY NOTE

We are an “emerging growth company” under applicable federal securities laws and therefore permitted to take advantage of certain reduced public company reporting requirements. As an emerging growth company, we provide in this proxy statement the scaled disclosure permitted under the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, including the compensation disclosures required of a “smaller reporting company,” as that term is defined in Rule12b-2 promulgated under the Securities Exchange Act of 1934, as amended, or the Exchange Act. In addition, as an emerging growth company, we are not required to conduct votes seeking approval, on an advisory basis, of the compensation of our named executive officers or the frequency with which such votes must be conducted. We will remain an “emerging growth company” until the earliest of (i) the last day of the fiscal year in which we have total annual gross revenues of $1$1.07 billion or more; (ii) December 31, 2018; (iii) the date on which we have issued more than $1 billion in nonconvertible debt during the previous three years; or (iv) the date on which we are deemed to be a large accelerated filer under the rules of the Securities and Exchange Commission, or SEC.

GENERAL INFORMATION ABOUT THE ANNUAL MEETING AND VOTING

Why did you send me thisthese proxy statement?materials?

We are providing these proxy materials because our board of directors is soliciting your proxy to vote at the Annual Meeting. This proxy statement summarizes information related to your vote at the Annual Meeting. All

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stockholders who find it convenient to do so are cordially invited to attend the Annual Meeting in person. However, you do not need to attend the meeting to vote your shares. Instead, you may simply complete, sign and returnvote your shares as described in further detail in the enclosed proxy card.answer to the question “How do I vote?” below.

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The Notice of Annual Meeting, proxy statement, and voting instructions, together with our Annual Report on Form10-K for the year ended December 31, 2014,2017, will be made available to each stockholder entitled to vote starting on or about April 7, 2015.27, 2018. These materials are available for viewing, printing and downloading on the Internet at www.proxyvote.com.

Who can vote at the Annual Meeting and what are the voting rights of such stockholders?

Only stockholders who owned our common stock on March 26, 2015April 23, 2018 are entitled to vote at the Annual Meeting. On this record date, there were 35,682,76049,691,328 shares of our common stock outstanding.outstanding (each of which entitles its holder to one vote per share). Common stock is our only class of stock outstanding.

What is the purpose of the Annual Meeting?

At the Annual Meeting, stockholders will consider and vote on the following matters:

Stockholders will also act on any other business that may properly come before the meeting, or any adjournment thereof.

How many votes do I have?

Each share of our common stock that you own as of March 26, 2015April 23, 2018 entitles you to one vote.

How do I vote?

If you are the“record holder” “record holder” of your shares, meaning that you own your shares in your own name and not through a bank, brokerage firm or other nominee, you may vote:

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If your shares are held in“street name,” meaning they are held for your account by a bank, brokerage firm, or other nominee, you may vote:

If you hold your shares of our common stock in multiple accounts, you should vote your shares as described above for each account.account.

Can I revoke or change my vote?

If your shares are registered directly in your name, you may revoke your proxy and change your vote at any time before the Annual Meeting. To do so, you must do one of the following:

If your shares are held in “street name,” you may submit new voting instructions with a later date by contacting your bank, brokerage firm, or other nominee. You may also vote in person at the Annual Meeting, which will have the effect of revoking any previously submitted voting instructions, if you obtain a legal proxy as described in the answer to the question “How do I vote?” above.

Will my shares be voted if I do not return my proxy?proxy or do not provide specific voting instructions in the proxy card or voting instruction form that I submit?

If your shares are registered directly in your name,your shares will not be voted if you do not vote over the Internet, by telephone, by returning your proxy by mail, or by ballot at the Annual Meeting. If you submit a proxy card without giving specific voting instructions on one or more matters listed in the notice for the Annual

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Meeting, your shares will be voted as recommended by our board of directors on such matters, and as the proxyholders may determine in their discretion how to vote with respect to any other matters properly presented for a vote at the Annual Meeting.

If your shares are held in “street “street name,” your brokerage firm may under certain circumstances vote your shares if you do not timely return your voting instructions.Brokers can vote their customers’ unvoted shares on discretionary matters but cannot vote such shares onnon-discretionary matters. If you do not timely return voting instructions to your brokerage firm to vote your shares, your brokerage firm may, on discretionary matters, either vote your shares or leave your shares unvoted.

Proposal 1, election of directors,director, is anon-discretionary matter.If you do not instruct your brokerage firm how to vote with respect to this proposal, your brokerage firm may not vote with respect to this proposal, and those shares that would have otherwise been entitled to be voted will be counted as“broker

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non-votes.” “Brokernon-votes” are shares that are held in “street name” by a bank or brokerage firm that indicates on its proxy that it does not have or did not exercise discretionary authority to vote on a particular matter. Proposal 2, ratification of the selection of our independent registered public accounting firm, is considered a discretionary matter, and your brokerage firm will be able to vote on this proposal even if it does not timely receive instructions from you, so long as it holds your shares in its name. We encourage you to timely provide voting instructions to your brokerage firm or other nominee. This ensures that your shares will be voted at the Annual Meeting according to your instructions. You should receive directions from your brokerage firm or other nominee about how to submit your voting instructions to them.

How many shares must be represented to hold the Annual Meeting?

A majority in voting power of our shares of common stock outstanding at the record date must be present in person or represented by proxy to hold the Annual Meeting and conduct business. This is called a quorum. For purposes of determining whether a quorum exists, we count as present any shares that are voted over the Internet, by telephone, by completing and submitting a proxy by mail, or that are represented in person at the meeting. Further, for purposes of establishing a quorum, we will count as present shares that a stockholder holds even if the stockholder votes to abstain or only votes on one of the proposals. In addition, we will count as present shares held in “street name” by banks, brokerage firms, or nominees who indicate on their proxies that they do not have discretionary authority to vote those shares on Proposal 1, or brokernon-votes. If a quorum is not present, we expect to adjourn the Annual Meeting until we obtain a quorum.

The presence at the Annual Meeting, in person or by proxy, of holders representing a majority of our outstanding common stock as of March 26, 2015,April 23, 2018, or 17,841,38149,691,328 shares, constitutes a quorum at the Annual Meeting, permitting us to conduct the business of the Annual Meeting.

What vote is required to approve each matter and how are votes counted?

Proposal 1—Election of DirectorsDirector

The two nomineesnominee for director to receive the highest number of votes FOR election will be elected as directors.a Class II director. This is called a plurality.Proposal 1 is anon-discretionary matter. Therefore, if your shares are held by your brokerage firm in “street name” and you do not timely provide voting instructions with respect to your shares, your brokerage firm cannot vote your shares on Proposal 1. Shares held in “street name” by banks, brokerage firms, or nominees who indicate on their proxies that they do not have authority to vote the shares on Proposal 1 will not be counted as votes FOR or WITHHELD from anythe nominee. As a result, such “brokernon-votes” will have no effect on the voting on Proposal 1. You may:

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Votes that are withheld will not be included in the vote tally for the election of directorsdirector and will not affect the results of the vote.

Proposal 2—Ratification of Selection of Independent Registered Public Accounting Firm

To approve Proposal 2, stockholders holding a majority of the votes cast on the matter must vote FOR the proposal.Proposal 2 is considered a discretionary matter. If your shares are held by your brokerage firm in “street name” and you do not timely provide voting instructions with respect to your shares, your brokerage firm may vote your unvoted shares on Proposal 2. If you ABSTAIN from voting on Proposal 2, your shares will not be voted FOR or AGAINST the proposal and will also not be counted as votes cast or shares voting on the proposal. As a result, voting to ABSTAIN will have no effect on the outcome of Proposal 2.

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Although stockholder approvalratification of our audit committee’s selection of Ernst & Young LLP as our independent registered public accounting firm for the year ending December 31, 20152018 is not required, we believe that it is advisable to give stockholders an opportunity to ratify this selection. If this proposal is not approved at the annual meeting,Annual Meeting, our audit committee will reconsider its selection of Ernst & Young LLP as our independent registered public accounting firm for the year ending December 31, 2015.2018.

How does the board of directors recommend that I vote on the proposals?

Our board of directors recommends that you vote:

Are there other matters to be voted on at the Annual Meeting?

We do not know of any matters that may come before the Annual Meeting other than the election of two membersone member of our board of directors and the ratification of the selection of our independent registered public accounting firm. If any other matters are properly presented at the Annual Meeting, the persons named in the accompanying proxy intend to vote, or otherwise act, in accordance with their judgment on the matter.

Who is paying the costs of soliciting these proxies?

We will pay all of the costs of soliciting proxies. Our directors, officers, and other employees may solicit proxies in person or by mail, telephone, fax or email. We will pay our directors, officers, and other employees no additional compensation for these services. We do not currently plan to hire a proxy solicitor to help us solicit proxies, although we reserve the right to do so. We will ask banks, brokerage firms, and other nominees to forward these proxy materials to their principals and to obtain authority to execute proxies. We will then reimburse them for their expenses. Our costs for forwarding proxy materials will not be significant.

How do I obtain an Annual Report on Form10-K?

If you would like a copy of our Annual Report on Form10-K for the year ended

December 31, 20142017 that we filed with the SEC, we will send you one without charge. Please

write to: Karyopharm Therapeutics Inc.

85 Wells Avenue

Newton, Massachusetts 02459

Attn: Investor Relations

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All of our SEC filings are also available free of charge under the heading “Financials & Filings—SEC Filings” in the “Investors” section of our website at www.karyopharm.com.

How can I find out the results of the voting at the annual meeting?Annual Meeting?

Preliminary voting results will be announced at the Annual Meeting. Final voting results will be tallied by the inspector of election and published in a current report on Form8-K to be filed with the SEC within four business days after the Annual Meeting.

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PROPOSAL 1:

ELECTION OF DIRECTORSDIRECTOR

Our board of directors is divided into three classes, with one class of our directors standing for election each year to serve for a three-year term. Directors for each class are elected at the annual meeting of stockholders held in the year in which the term for their class expires and hold office until their resignation or removal or until their successors are duly elected and qualified. In accordance with our certificate of incorporation and bylaws, our board of directors may fill existing vacancies on the board of directors by appointment.

Kenneth E. Weg, a Class II director who has served on our board of directors since February 2013 and whose term is scheduled to expire at the Annual Meeting, will not stand forre-election. We are deeply grateful for the enormous contributions that Mr. Weg has made to our company and board of directors.

The term of office of our other Class II directors,director, Deepika R. Pakianathan, Ph.D. and Kenneth E. Weg,, will expire at the Annual Meeting. Accordingly, the nomineesnominee for Class II directorsdirector for election at the Annual Meeting areis Dr. Pakianathan and Mr. Weg.Pakianathan. If Dr. Pakianathan and Mr. Weg areis elected at the Annual Meeting, each such individualshe will be elected to serve for a three-year term that will expire at our 20182021 annual meeting of stockholders and until such individual’sher successor is duly elected and qualified.

If no contrary indication is made, proxies in the accompanying form are to be voted for Dr. Pakianathan, and Mr. Weg or in the event that either Dr. Pakianathan and Mr. Weg is not a candidate or is unable to serve as a director at the time of the election (which is not currently expected), for any nominee who is designated by our board of directors to fill the vacancy.

Our board of directors currently consists of eight members. Effective upon the election of director at the Annual Meeting, our board of directors will be reduced to seven members.

We have no formal policy regarding board diversity, but our Corporate Governance Guidelines provide that the background and qualifications of the members of our board of directors considered as a group should provide a significant breadth of experience, knowledge, and ability to assist our board of directors in fulfilling its responsibilities. Our priority in selection of board members is identification of members who will further the interests of our stockholders through his or her established record of professional accomplishment, the ability to contribute positively to the collaborative culture among board members, knowledge of our business, understanding of the competitive landscape and adherence to high ethical standards. Certain individual qualifications and skills of our directors that contribute to our board of directors’ effectiveness as a whole are described in the following paragraphs.

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Information Regarding Directors

The information set forth below as to the directors and nomineesnominee for director has been furnished to us by the directors and nomineesnominee for director:

NomineesNominee for Election to the Board of Directors

For a Three-Year Term Expiring at the

20182021 Annual Meeting of Stockholders (Class II)

Deepika R. Pakianathan, Ph.D.Dr. Pakianathan has served as a member of our board of directors since April 2013. Since 2001, Dr. Pakianathan has been a Managing Member at Delphi Ventures, a venture capital firm focused on biotechnology and medical device investments, and leads the firm’s biotechnology investment activities. From 1998 to 2001, Dr. Pakianathan was a senior biotechnology banker at JPMorgan, a global investment bank, from 1997 to 1998, she was a Research analyst covering biotech at Genesis Merchant Group and from 1993 to 1997 she was a post-doctoral research scientist at Genentech. Dr. Pakianathan serves on the boards of directors of Alexza Pharmaceuticals,Alder Biopharmaceuticals, Inc., a public biopharmaceutical company, where she serves as a member of its compensation and nominating and governance committees, Alder Biopharmaceuticals, Inc., a

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public biopharmaceutical company, where she serves as a member of its compensation and audit committees,committee, OncoMed Pharmaceuticals, Inc., a public biopharmaceutical company, where she serves as a member of its audit and compensation committees and Calithera Biosciences, Inc., a public biopharmaceutical company, where she serves as the lead independent director and is a member of its auditcompensation committee and chair of its nominating and governance committees.committee. From 2004 to 2016, Dr. Pakianathan served on the board of directors of Alexza Pharmaceuticals, Inc., from 2009 to February 2013, Dr. Pakianathan served on the board of directors of PTC Therapeutics, Inc., and from 2007 to 2012, Dr. Pakianathan served on the board of directors of Relypsa, Inc., each a public biopharmaceutical company. Dr. Pakianathan received a B.Sc. from the University of Bombay, India, a M.Sc. from The Cancer Research Institute at the University of Bombay, India, and an M.S. and Ph.D. from Wake Forest University. We believe Dr. Pakianathan’s qualifications to serve on our board of directors include her experience as a venture capital investor in, and director of, multiple biotechnology companies, as well as her experience as a biotechnology investment banker, research analyst and research scientist.

Kenneth E. Weg.Mr. Weg has served as a member of our board of directors since February 2013. He has over 35 years of experience in the pharmaceutical industry with global biopharmaceutical companies Bristol-Myers Squibb Company and Merck & Co., Inc. From 1993 to 1998, he was President, Worldwide Medicines Group of Bristol-Myers Squibb, responsible for all ethical pharmaceuticals and over-the-counter medicines on a global basis. Mr. Weg also served as Vice-Chairman of the Board of Bristol-Myers Squibb from 1993 to 1998. He retired from Bristol-Myers Squibb in February 2001. From January 2002 to August 2013, Mr. Weg served as a director of AVEO Pharmaceuticals, Inc., a public biotechnology company. Mr. Weg also served as non-Executive Chairman of Millennium Pharmaceuticals until that company was acquired by Takeda, Inc. in 2008. In addition, he has served as founder and Chairman of Metamark Genetics Inc., a private biotechnology company, since 2005. He holds a B.A. in English Literature from Dartmouth College and an M.B.A. from Columbia University. We believe Mr. Weg’s qualifications to serve on our board of directors include his extensive leadership experience in the global pharmaceutical industry, including his extensive executive leadership at Bristol-Myers Squibb, and his experience as a member of the boards of directors of multiple biopharmaceutical companies.

Recommendation of the Board of Directors

OUR BOARD OF DIRECTORS UNANIMOUSLY RECOMMENDS THAT THE STOCKHOLDERS VOTE FOR THE ELECTION OF DR. DEEPIKA R. PAKIANATHAN AND MR. KENNETH E. WEG.

Members of the Board of Directors Continuing in Office

Term Expiring at the

20162019 Annual Meeting of Stockholders (Class III)

Garen G. Bohlin.Mr. Bohlin has served as a member of our board of directors since October 2013. Since April 2012, Mr. Bohlin has focused exclusively on service on boards of directors and consulting. From January2010 until his retirement in April 2012, he served as Executive Vice President of Constellation Pharmaceuticals, Inc., a biopharmaceutical company, where his responsibilities included consummating option-to-acquire and pre-negotiated merger agreementshe served as a part-time business partner with Genentech.the Chief Executive Officer. Prior to Constellation Pharmaceuticals, Mr. Bohlin served as Chief Operating Officer of Sirtris Pharmaceuticals, Inc., a biotechnology company, from January 2006 to December 2009, where he played key roles in the overall management of Sirtris, its initial public offering and the sale of the company to

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GlaxoSmithKline. Mr. Bohlin was the founding Chief Executive Officer of Syntonix Pharmaceuticals, Inc., a biopharmaceutical company, from 1999 through December 2008, where heplayed a key role in the overall management of Syntonix, positioning it for an eventual sale to Biogen Idec. Prior

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toPriorto Syntonix, Mr. Bohlin was Executive Vice President of Genetics Institute, Inc., a biotechnology company, where he played a key role in overall management, its initial public offering and its sale to American Home Products/Wyeth, and a partner at Arthur Andersen & Co., a public accounting and consulting organization. Mr. Bohlin serves on the boards of directors and audit committees of Collegium Pharmaceutical, Inc., Tetraphase Pharmaceuticals, Inc. and Proteon Pharmaceuticals,Therapeutics, Inc., each a public biopharmaceutical company. He previously served as a director of several private and public biotechnology companies. Mr. Bolin also serves on the board of directors and audit committee of Collegium Pharmaceutical, Inc., a private biotechnology company. HeBohlin holds a B.S. in Accounting from the University of Illinois. We believe Mr. Bohlin’s qualifications to serve on our board of directors include his extensive industry and board experience, including his audit committee experience, with publicly traded and privately held biotechnology companies.

Mikael Dolsten, M.D., Ph.D.Dr. Dolsten was elected to ourhas served as a member of the board of directors onsince March 31, 2015. He has served as the President of Worldwide Research and Development and Executive Vice President of Pfizer Inc., a biopharmaceutical company, since December 2010. Dr. Dolsten served as President of Worldwide Research and Development and Senior Vice President of Pfizer Inc. from May 2010 until December 2010 and President of Pfizer BioTherapeutics Research & Development Group and Senior Vice President of Pfizer Inc. from October 2009 until May 2010. From June 2008 to October 2009, Dr. Dolsten served as Senior Vice President of Wyeth, a biopharmaceutical company that was acquired by Pfizer Inc. in October 2009, and President, Wyeth Research from June 2008 to October 2009. Prior to joining Wyeth, Dr. Dolsten was a Private Equity Partner at Orbimed Advisors, LLC and Executive Vice President, Head of Pharma Research at Boehringer Ingelheim, a pharmaceutical company. Dr. Dolsten also previously held research leadership positions at AstraZeneca, Pharmacia and Upjohn. We believe Dr. Dolsten’s qualifications to serve on our board of directors include his depth of experience leading pharmaceutical research and development teams at large public companies. He is widely recognized as a leader within the medical research and drug development community and this level of expertise is significant to our board of directors as we continue to advance our clinical development pipeline and initiate additional clinical trials.

Michael G. Kauffman, M.D., Ph.D. Dr. Kauffman has served as Karyopharm’s Chief Executive Officer since January 2011 and has been one of our directors since 2008. Dr. Kauffmanco-founded Karyopharm with Dr. Sharon Shacham in 2008 and served as our President from January 2011 to December 2013 and as Chief Medical Officer from December 2012 to December 2013. Prior to joining Karyopharm, he was Chief Medical Officer of Onyx Pharmaceuticals Inc., a biopharmaceutical company, from November 2009 to December 2010. From November 2008 to November 2009, Dr. Kauffman was Chief Medical Officer of Proteolix Inc., which was acquired by Onyx Pharmaceuticals. At Proteolix, he led the development of Kyprolis^® (carfilzomib), a novel proteasome inhibitor approved in refractory myeloma by the FDAFood and Drug Administration in July 2012. Dr. Kauffman was an operating partner at Bessemer Venture Partners from 2006 to 2008, where he led investments in biotechnology companies. From 2006 to 2008, he was President and Chief Executive Officer of Epix Pharmaceuticals, Inc., a biopharmaceutical company that underwent liquidation proceedings through an assignment for the benefit of creditors under Massachusetts law in 2009. Dr. Kauffman was President and Chief Executive Officer of Predix Pharmaceuticals, Inc., a private biopharmaceutical company focused on G protein-coupled receptors (GPCR), from 2002 until its merger into Epix Pharmaceuticals in 2006. In that role, he led the merger of Predix Pharmaceuticals and Epix Pharmaceuticals, oversaw the discovery and development of four new clinical candidates and led collaboration transactions with Amgen and GlaxoSmithKline. From March 2000 to September 2002, Dr. Kauffman was Vice President, Clinical at Millennium Pharmaceuticals, Inc., a biopharmaceutical company, where he led the VELCADEVelcade^® development program. From September 1997 to March 2000, Dr. Kauffman held a number of senior positions at Millennium Predictive Medicine, Inc., a biopharmaceutical company and a subsidiary of Millennium Pharmaceuticals, where he led the discovery and development of novel molecular diagnostics for major cancers, including melanoma and led transactions with Becton-Dickenson and Bristol Myers Squibb. From August 1995 to September 1997, Dr. Kauffman held a number of senior positions at Biogen Idec, Inc., a biopharmaceutical company, where he led the clinical

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development of anti-CD40L antibodies in autoimmune and inflammatory diseases, and acted as the main medical advisor to the Biogen business development group. Dr. Kauffman currently serves on the board of directors, nominating and compensationgovernance committee and research and development committee of VerastemInfinity Pharmaceuticals, Inc., a public biopharmaceutical company, and on the board of directors and the

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compensation committee of Metamark GeneticsVerastem Inc., also a private molecular diagnosticspublic biopharmaceutical company. Dr. Kauffman previously served on the board of directors and compensation and audit committees of Zalicus Inc., a biotechnology company. Dr. Kauffman received his B.A. in Biochemistry from Amherst College and his M.D. and Ph.D. from Johns Hopkins Medical School, and he trained in internal medicine and rheumatology at Beth Israel Hospital (now Beth Israel Deaconess Medical Center) and Massachusetts General Hospitals.Hospital. He is board certified in internal medicine. We believe Dr. Kauffman’s qualifications to serve on our board of directors include his extensive experience in the healthcare industry as well his extensive knowledge of our company and its business since inception through service in multiple executive leadership positions and as a member of our board.

Term Expiring at the

20172020 Annual Meeting of Stockholders (Class I)

J. Scott Garland. Mr. Garland has served as a member of our board of directors since November 2014. Mr. Garland has been the President of Relypsa Inc., a biopharmaceutical company, since April 2017 and was Senior Vice President and Chief Commercial Officer at Relypsa Inc., a publicly-traded biopharmaceutical company since November, 2014.from October 2014 to April 2017. Prior to Relypsa, Mr. Garland served as Executive Vice President and Chief Commercial Officer of Exelixis, Inc., a biopharmaceutical company focused on developing and commercializing cancer treatments, from October 2011 to October 2014. Prior to joining Exelixis, from April 2002 to October 2011, Mr. Garland held positions at Genentech, Inc., most recently serving as Vice President of Genentech’s Avastin^® franchise, where he led the U.S. sales and marketing efforts for the drug. Prior to that position, he served as Vice President, Hematology Marketing and Sales, overseeing the Rituxan^® franchise and as a Director on the Tarceva^® franchise. From July 1997 to April 2002, Mr. Garland held several positions within the sales and marketing division of Amgen, Inc. and from July 1991 to July 1995, he served as a professional sales representative at Merck & Co., Inc. Mr. Garland has an M.B.A. from Duke University’s Fuqua School of Business and a B.A. from California Polytechnic University (San Luis Obispo). We believe Mr. Garland’s qualifications to serve on our board of directors include his more than 20 years of sales, marketing and commercialization experience in the pharmaceutical and biopharmaceutical industry as well as his extensive management experience at publicly-traded companies biopharmaceutical companies.

Barry E. Greene.Mr. Greene has served as a member of our board of directors since January 2013 and as our Lead Independent Director since January 2015. Mr. Greene has served as President and Chief Operating Officer of Alnylam Pharmaceuticals, Inc., a public biopharmaceutical company, since 2007, and served as its Chief Operating Officer sincefrom 2003 and from 2004 through 2005, as its Treasurer.to 2016. Mr. Greene joined Alnylam in 2003, bringing over 15 years of experience in the healthcare industry and in consulting. Prior to Alnylam, he was General Manager of Oncology at Millennium Pharmaceuticals, Inc., a biopharmaceutical company, where he led the company’s global strategy and execution for its oncology business, including strategic business direction and execution, culminating in the successful FDAFood and Drug Administration approval and launch of VELCADE^® (bortezomib) inmid-2003. Prior to joining Millennium in 2001, Mr. Greene served as Executive Vice President and Chief Business Officer for Mediconsult.com, a healthcare consulting company. Prior to Mediconsult.com, Mr. Greene’s experience included serving as Vice President of Marketing and Customer Services for AstraZeneca (formerly AstraMerck), a biopharmaceutical company; Vice President, Strategic Integration with responsibility for the AstraZeneca North American post-merger integration; and a partner of Andersen Consulting, a consulting company, where he was responsible for the pharmaceutical/biotechnology marketing and sales practice. Mr. Greene currently is a member of the board of directors of Acorda Therapeutics, Inc., a public biopharmaceutical company.company, where he

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serves as a member of its compensation committee. Mr. Greene received his B.S. in Industrial Engineering from the University of Pittsburgh and served as a Senior Scholar at Duke University, Fuqua School of Business. We believe Mr. Greene’s qualifications to serve on our board of directors and as our Lead Independent Director include his extensive experience in the healthcare and consulting industries as well his practical experience with business and product aspects of the biopharmaceutical industry, including guiding new drugs through research, development, and the commercialization process.

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Mansoor Raza Mirza,M.D. Dr. Mirza has served as a member of our board of directors since October 2010. He has also served as a clinical consultant to us since 2010. Dr. Mirza is Chief Oncologist at the Department of Oncology, Rigshopitalet—the Copenhagen University Hospital, Denmark.Denmark and Medical Director of Nordic Society of Gynaecological Oncology (NSGO). Dr. Mirza is both a medical and radiation oncologist, with a primary focus innon-surgical treatment of gynecologic cancers. His key academic goals are to promote clinical research, international trial collaboration and education, and he has broad experience in clinical protocol development, trial conduct and clinical trial regulations. Dr. Mirza is the author of several phase 1, 2 and 3 studies, several of those leading to Food and Drug Administration and European Medicines Agency registration. He serves as the chair of thein several Independent Data Safety Monitoring CommitteeCommittees of international studies. He is an invited speaker at several international conferences, such as “Meet the OUTBACK trial, which is a large international cervical cancer trial.Professor” at American Society of Clinical Oncology and “Presidential Symposium” at European Society for Medical Oncology. He is the senior author of national Danish guidelines for the management of endometrial, cervical, vulvar andnon-epithelial ovarian cancers as well as of the Nordic Society of Gynecologic Oncology (NSGO) radio therapyNSGO radiotherapy guidelines for cervical and vulvar cancers. He is author of European Guidelines in endometrial and vulvar cancers. His other current appointments include service as President-ElectESGO Council Member (European Society of the NSGO, MedicalGynaecological Oncology), Executive Director of the NSGO-Clinical Trial Unit,GCIG (Gynecologic Cancer InterGroup), Vice-Chairman of the Danish Gynecological Cancer Society, Founding Executive Member of the European Network of Gynecologic Oncology Trials Group, and membership on the faculty member of the European Society of Medical Oncology.Oncology and of the International Gynecologic Cancer Society. He also serves on the board of directors of the Gynecologic Cancer Intergroup, a private organization promoting high quality clinical trials, and Metamark GeneticsSera Prognostics, Inc., a private biopharmaceutical company. He has multiple publications in high-impact journals like the New England Journal of Medicine. He holds a M.D., Diploma in Surgery and Diploma in Clinical Oncology from the Pirogov Moscow State Medical Institute as well as post-graduate education and certification in radiation and medical oncology from the University of Southern Denmark. We believe Dr. Mirza’s qualifications to serve on our board of directors include his position as an expert in thenon-surgical treatment of cancer, and gynecologic cancers in particular, and his knowledge of our company and its business through service on our board since October 2010.

Recommendation of the Board of Directors

OUR BOARD OF DIRECTORS UNANIMOUSLY RECOMMENDS THAT THE STOCKHOLDERS VOTE FOR THE ELECTION OF DR. DEEPIKA R. PAKIANATHAN AS A CLASS II DIRECTOR.

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CORPORATE GOVERNANCE

General

We believe that good corporate governance is important to ensure that Karyopharm Therapeutics Inc. is managed for the long-term benefit of our stockholders. This section describes key corporate governance practices that we have adopted. We have adopted a Code of Business Conduct and Ethics, which applies to all of our officers, directors and employees, Corporate Governance Guidelines, and charters for our audit committee, our compensation committee and our nominating and corporate governance committee. We have posted copies of our Code of Business Conduct and Ethics and Corporate Governance Guidelines, as well as each of our committee charters, on the Corporate Governance page of the Investors section of our website, www.karyopharm.com, which you can access free of charge. Information contained on the website is not incorporated by reference in, or considered part of, this proxy statement. We intend to disclose on our website any amendments to, or waivers from, our Code of Business Conduct and Ethics that are required to be disclosed by law or Nasdaq listing standards. We will also provide copies of these documents as well as our other corporate governance documents, free of charge, to any stockholder upon written request to Karyopharm Therapeutics Inc., 85 Wells Avenue, Newton, Massachusetts 02459, Attn: Investor Relations.

Director Independence

Rule 5605 of the Nasdaq Listing Rules requires a majority of a listed company’s board of directors to be comprised of independent directors within one year of listing. In addition, the Nasdaq Listing Rules require that, subject to specified exceptions, each member of a listed company’s audit, compensation and nominating and corporate governance committees be independent and that audit committee members also satisfy independence criteria set forth in Rule10A-3 under the Exchange Act.

Under Rule 5605(a)(2) of the Nasdaq Listing Rules, a director will only qualify as an “independent director” if, in the opinion of our board of directors, that person does not have a relationship that would interfere with the exercise of independent judgment in carrying out the responsibilities of a director. In order to be considered independent for purposes of Rule10A-3 of the Exchange Act, a member of an audit committee of a listed

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company may not, other than in his or her capacity as a member of the audit committee, the board of directors, or any other board committee, accept, directly or indirectly, any consulting, advisory, or other compensatory fee from the listed company or any of its subsidiaries or otherwise be an affiliated person of the listed company or any of its subsidiaries.

In addition, in affirmatively determining the independence of any director who will serve on a company’s compensation committee, Rule10C-1 under the Exchange Act requires that a company’s board of directors consider all factors specifically relevant to determining whether a director has a relationship to such company which is material to that director’s ability to be independent from management in connection with the duties of a compensation committee member, including, but not limited to: (i) the source of compensation of the director, including any consulting, advisory or other compensatory fee paid by such company to the director; and (ii) whether the director is affiliated with the company or any of its subsidiaries or affiliates.

Our board of directors has undertaken a review of the composition of our board of directors and its committees and the independence of each director. Based upon information requested from and provided by each director concerning his background, employment and affiliations, including family relationships, our board of directors has determined that each of our directors, with the exception of Drs. Kauffman and Mirza, is an “independent director” as defined under Rule 5605(a)(2) of the Nasdaq Listing Rules. Our board of directors also determined that Messrs. Bohlin and GreeneGarland and Dr. Pakianathan, who currently comprise our audit committee, Messrs. Greene and Weg and Dr. Pakianathan, who comprise our compensation committee, and Messrs. Bohlin Garland and Weg and Dr. Dolsten, who currently comprise our nominating and corporate governance committee, satisfy the independence standards for such committees established by the SEC and the Nasdaq Listing Rules, as

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applicable. In making such determinations, our board of directors considered the relationships that each suchnon-employee director has with our company and all other facts and circumstances our board of directors deemed relevant in determining independence, including the beneficial ownership of our capital stock by eachnon-employee director.

There are no family relationships among any of our directors or executive officers, except that Dr. Kauffman, our Chief Executive Officer and a director, is married to Dr. Shacham, our President and Chief Scientific Officer.

Board Leadership Structure

Our bylaws and Corporate Governance Guidelines provide our board of directors with flexibility to combine or separate the positions of Chairman of the Board and Chief Executive Officer and/or to implement the role of Lead Independent Director in accordance with its determination that utilizing one or the other structure would be in the best interests of our company.

At this time, we do not have a Chairman of the Board, though our board of directors appointed Mr. Greene to serve as Lead Independent Director in January 2015. While our board of directors believes that oversight of our company is the responsibility of our board of directors as a whole, and this responsibility can be properly discharged without a Chairman or Lead Independent Director, our board of directors determined that appointing Mr. Greene as Lead Independent Director would facilitate interactions between Dr. Kauffman, our Chief Executive Officer, and the other independent directors and would enable the board of directors and the companyCompany to utilize Mr. Greene’s breadth of experience across many strategic and operational matters in development stage biotechnology companies.

Mr. Greene serves as a liaison between our Chief Executive Officer and our  independent directors. Mr. Greene meets regularly and communicates directly with the independent directors outside the presence of management and reports any comments and concerns of the independent directors to our Chief Executive Officer. He also meets regularly with our senior management to discuss operational and strategic matters. Mr. Greene presides over executive sessions of the board of directors and provides our Chief Executive Officer with a formal annual review, as well as regular informal feedback, based on the consensus views collected from members of our board of directors.

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While Dr. Kauffman facilitates communications between members of our board of directors and works with management in the preparation of the agenda for each meeting of the board of directors, Mr. Greene also has an important role in establishing the agenda, determining what information is provided to our board of directors and coordinating with management to ensure that sufficient meeting time is allocated to each agenda item. Additionally, all of our directors are encouraged to make suggestions for agenda items orpre-meeting materials for meetings of our board of directors.

Our board of directors has concluded that the current leadership structure described above is appropriate at this time. However, our board of directors will continue to periodically review our leadership structure and may make such changes in the future, as it deems appropriate.

The Board’s Role in Risk Oversight

Our board of directors has responsibility for the oversight of the company’sCompany’s risk management processes and, either as a whole or through its committees, regularly discusses with management our major risk exposures, the potential impact of these risks on our business and the steps we take to manage them. The risk oversight process includes receiving regular reports from board committees and members of senior management to enable our board of directors to understand the company’sCompany’s risk identification, risk management and risk mitigation strategies with respect to areas of potential material risk, including operations, finance, legal, regulatory, strategic and reputational risk.

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The audit committee reviews information regarding liquidity and operations, and oversees our management of financial risks. Periodically, the audit committee reviews our policies with respect to risk assessment, risk management, loss prevention and financial-related regulatory compliance. Oversight by the audit committee includes direct communication with our external auditors, and discussions with management regarding significant risk exposures and the actions management has taken to limit, monitor or control such exposures. The compensation committee is responsible for assessing whether any of our compensation policies or programs has the potential to encourage excessive risk-taking. The nominating and corporate governance committee manages risks associated with the independence of members of our board of directors, corporate disclosure practices, and potential conflicts of interest. The compliance committee assists our board of directors with oversight of ournon-financial compliance program by overseeing and monitoring our compliance policies, standards, procedures, systems and initiatives as well as our information technology systems dedicated to quality, regulatory and commercial compliance. While each committee is responsible for evaluating certain risks and overseeing the management of such risks, the entire board is regularly informed through committee reports about such risks. Matters of significant strategic risk are considered by our board of directors as a whole.

Board of Directors Meetings

Our board of directors met seventen times during our fiscal year 2014,2017, including telephonic meetings. During that year, each of our directors attended or participated telephonically in 75% or more of the aggregate of (i) the total number of meetings of the board of directors held during the period for which he or she served as a director and (ii) the total number of meetings of all committees on which the director served during the periods that he served.or she served, other than Mr. Weg, who attended or participated telephonically in 70% of the aggregate of such meetings.

Committees of the Board of Directors

We have threefour standing committees: the audit committee, the compensation committee, and the nominating and corporate governance committee and the compliance committee. Each of these committees has a written charter approved by our board of directors. A copy of each charter can be found under the heading “Corporate Governance” in the “Investors” section of our website at www.karyopharm.com.

Audit Committee

The members of our audit committeeAudit Committee are Messrs. Bohlin and GreeneGarland and Dr. Pakianathan. Mr. Bohlin is the chair of the audit committee. Our board of directors has determined that Mr. Bohlin qualifies as an “audit committee financial expert” within the meaning of SEC regulations and the Nasdaq Listing Rules. In making this determination, our board has considered the formal education and nature and scope of Mr. Bohlin’s previous

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experience, coupled with past and present service on various audit committees. Our audit committee assists our board of directors in its oversight of our accounting and financial reporting process and the audits of our financial statements. The audit committee met eightsix times during the fiscal year 2014,ended December 31, 2017, or fiscal year 2017, including telephonic meetings. The audit committee’s responsibilities include:

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Compensation Committee

The members of our compensation committee are Messrs. Greene and Weg and Dr. Pakianathan. Mr. Greene is the chair of the compensation committee. Our compensation committee assists our board of directors in the discharge of its responsibilities relating to the compensation of our executive officers. The compensation committee met sevensix times during fiscal year 2014.2017, including telephonic meetings. The compensation committee’s responsibilities include:

The compensation committee generally meets at least four times annually and with greater frequency if necessary. The agenda for each meeting is usually developed by the chair of the compensation committee, in consultation with our Chief Executive Officer our Chief Financial Officer and/or our General Counsel. The compensation committee meets regularly in executive session. However, from time to time, various members of management and other employees, as well as outside advisors or consultants, may be invited by the compensation committee to make presentations, to provide financial or other background information or advice,

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or to otherwise participate in compensation committee meetings. No officer may participate in, or be present during, any deliberations or determinations of the compensation committee regarding the compensation for such officer or any immediate family member of such officer. The charter of the compensation committee grants the compensation committee full access to all of our books, records, facilities, and personnel, as well as authority to obtain, at our expense, advice and assistance from internal and external legal, accounting, or other advisors and consultants, and other external resources that the compensation committee considers necessary or appropriate in the performance of its duties. In particular, the compensation committee has the sole authority to retain compensation consultants to assist in its evaluation of executive and director compensation, including the authority to approve the consultant’s reasonable fees and other retention terms.

During the fiscal year ended December 31, 2014,2017, the compensation committee engaged Arnosti Consulting, Inc., or ACI,Arnosti, an independent compensation consultant, to provide comparative data on executive and board compensation practices in our industry and to advise on our executive compensation program generally. The companyCompany pays the cost for ACI’sArnosti’s services. However, the compensation committee retains the sole authority to direct, terminate, or engage ACI’sArnosti’s services. Other than the services provided to the compensation committee, ACIArnosti provided advice to the companyCompany with respect to compensation for employees at the Vice President level. The decision to use Arnosti for advice regarding compensation for employees at the level of Vice President was made by management. Compensation for all services provided to the companyCompany by ACI did not exceed $120,000 during the fiscal year ended December 31, 2014.2017.

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Historically, the compensation committee has approved most of the significant adjustments to executives’ annual compensation, determined variable cash compensation and equity awards, and established new performance objectives at one or more meetings held during the last quarter of the year. However, the compensation committee also considers matters related to individual compensation, such as compensation for new executive hires, as well as high-level strategic issues, such as the efficacy of our compensation strategy, potential modifications to that strategy, and new trends, plans, or approaches to compensation, at various meetings throughout the year. The compensation committee is responsible for making determinations, or making recommendations to our board of directors, regarding compensation of executive officers, making changes topre-approved salary ranges, salary increases,increase budgets, equity awards,award budgets, variable cash compensation targets, incentive payments, andpre-approved equity ranges for new hires and high performers, and making material changes to benefits offered to our employees. In determining compensation of executive officers other than our chief executive officer and president and chief scientific officer, the compensation committee also considers the recommendations of our chief executive officer. In addition, the compensation committee, with input from its compensation consultant, makes recommendations to our board of directors regarding the compensation ofnon-employee directors. The compensation committee also administers our equity-based plans and determines whether to approve the maximum increases or smaller increases inpermitted to the number of shares reserved under our 2013 Stock Incentive Plan, or 2013 Plan, and 2013 Employee Stock Purchase Plan, or 2013 ESPP, that automatically occur each year pursuant to the “evergreen” provisions of such plans.

Under its charter, the compensation committee may form, and delegate authority to, subcommittees, consisting of independent directors, as it deems appropriate. In November 2014,Pursuant to our 2013 Plan, the compensation committee has delegated to our Chief Executive Officer, President, Chief Financial Officer and General Counsel the authority to determineapprove grants of stock options and to our Chief Executive Officer and the appropriate option grant for newPresident and Chief Scientific Officer the authority to approve grants of awards of restricted stock units, or RSUs, to employees based on ranges approved by the committeewho are not executive officers, subject to certain limitations for each seniority level. The delegation of authority only permits specified members of our senior management to issue options grants to new employees on their respective start dates and does not permit option grants to executive officers or employees at or above the level of vice president. Optionsemployment and an annual aggregate maximum amount of awards that can be granted pursuant to this delegation are subject to the form of stock option agreement under the 2013 Plan that our board of directors has previously approved and 25% of the shares underlying each option vest one year from the employment start date and the remainder vest monthly thereafter. The exercise price of options granted pursuant to this delegation is the closing price of our common stock on the Nasdaq Global Select Market on the date of grant. The maximum number of shares underlying options that may be granted annually under this delegation is 500,000, subject to adjustment as provided in the 2013 Plan.such delegated authority.

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Nominating and Corporate Governance Committee

The members of our nominating and corporate governance committee are Messrs. Weg, Bohlin, and Garland.Weg and Dr. Dolsten. Mr. Weg is the chair of the nominating and corporate governance committee. The committee met four times during fiscal year 2014.2017. The nominating and corporate governance committee’s responsibilities include:

We believe that the compositionCompliance Committee

Messrs. Garland and Greene and Dr. Dolsten serve as members of our nominating and corporate governancecompliance committee meets the requirements for independence under current Nasdaq listing standards and SEC rules and regulations. Ourthat our board of directors has determined that Messrs. Bohlin,established in late-2017. Mr. Garland is the chair of the compliance committee. The compliance committee’s responsibilities include:

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Compensation Committee Interlocks and Insider Participation

During 2014,2017, the members of our compensation committee were Messrs. Greene and Weg and Dr. Pakianathan. Mr. Greene is the chair of our compensation committee. None of our executive officers served as a director or a member of a compensation committee (or other committee serving an equivalent function) of any other entity, one of whose executive officers served as a director or member of our board of directors or our compensation committee during the fiscal year ended December 31, 2014.2017. During 2014,2017, no member of our compensation committee was a current or former officer or employee of Karyopharm or had any related person transaction involving Karyopharm.

Code of Business Conduct and Ethics

We have adopted a written Code of Business Conduct and Ethics that applies to our directors, officers and employees, including our principal executive officer, principal financial officer, principal accounting officer or controller, or persons performing similar functions. We have posted on our website, www.karyopharm.com, a current copy of the Code of Business Conduct and Ethics and all disclosures that are required by law or Nasdaq listing standards concerning any amendments to, or waivers from, any provision of the Code of Business Conduct and Ethics. Information contained on the website is not incorporated by reference in, or considered part of, this proxy statement.

Director Nomination Process

Director Qualifications

In evaluating director nominees, the nominating and corporate governance committee will consider, among other things, the following factors:

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The nominating and corporate governance committee’s goal is to assemble a board of directors that brings to the companyCompany a variety of perspectives and skills derived from high quality business and professional experience. Moreover, the nominating and corporate governance committee believes that the background and

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qualifications of the members of our board of directors, considered as a group, should provide a significant breadth of experience, knowledge and abilities that to assist the board of directors to fulfill its responsibilities. Nominees are not discriminated against on the basis of race, religion, national origin, sex, sexual orientation, disability, or any other basis proscribed by law.

The nominating and corporate governance committee has not adopted a formal policy with respect to a fixed set of specific minimum qualifications for its candidates for membership on the board of directors. The committee may considerconsiders such factors, including without limitation, diversity,those set forth above, as it may deem are in the best interests of our company and its stockholders. The committee further believes it is appropriate for at least one member of our board of directors to meet the criteria for an “audit committee financial expert” as that phrase is defined under the regulations promulgated by the SEC, and that a majority of the members of our board of directors be independent as required under the Nasdaq qualification standards. The committee believes it is appropriate for our Chief Executive Officer to serve as a member of our board of directors. Our directors’ performance and qualification criteria are reviewed periodically by the nominating and corporate governance committee.

Identification and Evaluation of Nominees for Directors

The nominating and corporate governance committee identifies nominees for director by first evaluating the current members of our board of directors willing to continue in service. Current members with qualifications and skills that are consistent with the nominating and corporate governance committee’s criteria for board of directors service and who are willing to continue in service are considered forre-nomination, balancing the value of continuity of service by existing members of our board of directors with that of obtaining a new perspective or expertise.

If any member of our board of directors does not wish to continue in service or if our board of directors decides not tore-nominate a member forre-election, and our board seeks to fill such vacancy, the nominating and corporate governance committee identifies a new nominee that meets the criteria above. The committee generally inquires of our board of directors and members of management for their recommendations. The committee may also review the composition and qualification of the boards of directors of our competitors and may seek input from industry experts or analysts. The nominating and corporate governance committee reviews the qualifications, experience, and background of suggested candidates. Final candidates, if other than our current directors, would be interviewed by the members of the nominating and corporate governance committee and by certain of our other independent directors and executive management. In making its determinations, the nominating and corporate governance committee evaluates each individual in the context of our board of directors as a whole, with the objective of assembling a group that can best contribute to the success of our company and represent stockholder interests through the exercise of sound judgment. After review and deliberation of all feedback and data, the nominating and corporate governance committee makes its recommendation to our board of directors. In June

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2014, theThe nominating and corporate governance committee has previously engaged Russell Reynolds Associatesa search firm to conduct a search for additional directors with extensive development or commercialization expertise to join our board of directors. The nominating and corporate governance committee may in the future engage this or otheradditional third-party search firms in those situations where particular qualifications are required or where existing contacts are not sufficient to identify an appropriate candidate.

We have not received director candidate recommendations from our stockholders and do not have a formal policy regarding consideration of such recommendations. However, any recommendations received from stockholders will be evaluated in the same manner that potential nominees suggested by board members, management, or other parties are evaluated. We do not intend to treat stockholder recommendations in any manner different from other recommendations.

Under our bylaws, stockholdersStockholders wishing to suggestrecommend a director candidate for directorconsideration by our nominating and corporate governance committee must write to our Corporate Secretary. In order to give the nominating and corporate governance committee sufficient time to evaluate a recommended candidate and/or include the candidate in our proxy statement for the 2016 annual meetingRecommendation of stockholders, the recommendationdirector candidates must be received by our Corporate Secretary at our principal executive offices in accordance with our procedures detailed in the section below entitled “Stockholder Proposals.”offices. Such submissions must state the

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nominee’s name, together with appropriate biographical information and background materials, and information with respect to the stockholder or group of stockholders making the recommendation, including the number of shares of common stock owned by such stockholder or group of stockholders, as well as other information required by our bylaws.stockholders. We may require any proposed nominee to furnish such other information as we may reasonably require to determine the eligibility of such proposed nominee to serve as an independent director or that could be material to a reasonable stockholder’s understanding of the independence, or lack thereof, of such proposed nominee.

Stockholders also have the right under our bylaws to directly nominate director candidates, without any action or recommendation on the part of the nominating and corporate governance committee or the board of directors, by following the procedures set forth under “Stockholder Proposals.” If our board of directors determines to nominate a stockholder-recommended candidate and recommends his or her election, then his or her name will be included in our proxy statement and proxy card for the next annual meeting of stockholders. Otherwise, candidates nominated by stockholders in accordance with the procedures set forth in the bylaws will not be included in our proxy statement and proxy card for the next annual meeting.

Director Attendance at Annual Meetings

Although weWe do not have a formal policy regarding attendance by members of our board of directors at our annual meeting of stockholders, we encourage all of our directors to attend. Two directors, of the sixstockholders. Three members of our board of directors serving at the time attended our 20142017 annual meeting of stockholders held on June 9, 2014.15, 2017 in person or by teleconference.

Communications with Our Board of Directors

Stockholders seeking to communicate with our board of directors must submit their written comments to our Corporate Secretary, Karyopharm Therapeutics Inc., 85 Wells Avenue, Newton, Massachusetts 02459. The Corporate Secretary will forward such communications to each member of our board of directors; provided that, if in the opinion of our Corporate Secretary it would be inappropriate to send a particular stockholder communication to a specific director, such communication will only be sent to the remaining directors (subject to the remaining directors concurring with such opinion).

Director Compensation

We compensatenon-employee members of our board of directors for their service.service using a combination of cash and equity compensation. Directors who are also employees do not receive cash or equityany compensation for service on the board of directors in addition to compensation payable for their service as our employees. Thenon-employee members of our board of directors are also reimbursed for travel, lodging, and other reasonable expenses incurred in attending board of directors or committee meetings.

Our compensation committee periodically reviews the compensation we pay ournon-employee directors, with input from its independent compensation consultants, and makes recommendations to our board of directors. In October 2013,January 2017, our board of directors, upon the recommendation of our compensation committee, establishedrevised the following compensation guidelines fornon-employee board members:

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The table below reflects the changes to compensation guidelines fornon-employee director serving as independent Chairman or Lead Independent Director of our board of directors will receive an additional cash retainer of $20,000 per year;

The following table sets forth information concerning the compensation for ournon-employee directors during the fiscal year ended December 31, 2014:2017:

Director Compensation

Limitation of Liability and Indemnification

Our certificate of incorporation limits the personal liability of directors for breach of fiduciary duty to the maximum extent permitted by the Delaware General Corporation Law and provides that no director will have personal liability to us or to our stockholders for monetary damages for any breach of fiduciary duty as a director. However, these provisions do not eliminate or limit the liability of any of our directors:

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Any amendment to or repeal of these provisions will not eliminate or reduce the effect of these provisions in respect of any act, omission or claim that occurred or arose prior to such amendment or repeal. If the Delaware General Corporation Law is amended to provide for further limitations on the personal liability of directors of corporations, then the personal liability of our directors will be further limited to the greatest extent permitted by the Delaware General Corporation Law.

In addition, our certificate of incorporation provides that we must indemnify our directors and officers, and we must advance expenses, including attorneys’ fees, to our directors and officers in connection with legal proceedings, subject to very limited exceptions.

We maintain an insurance policy that covers certain liabilities of our directors and officers arising out of claims based on acts or omissions in their capacities as directors or officers. In addition, we have entered into indemnification agreements with our directors. These indemnification agreements require us, among other things, to indemnify each such director for some expenses, including attorneys’ fees, judgments, fines, and settlement amounts incurred by him in any action or proceeding arising out of his service as one of our directors.

Certain of ournon-employee directors may, through their relationships with their employers, be insured and/or indemnified against certain liabilities incurred in their capacity as members of our board of directors.

Insofar as indemnification for liabilities arising under the Securities Act of 1933, as amended, or the Securities Act, may be permitted to directors, executive officers or persons controlling us, in the opinion of the SEC, such indemnification is against public policy as expressed in the Securities Act and is therefore unenforceable.

Report of the Audit Committee of the Board of Directors

The audit committee oversees the Company’s financial reporting process on behalf of the board of directors. We have reviewed the Company’s audited consolidated financial statements for the fiscal year ended December 31, 20142017 and discussed them with Company management and Ernst & Young LLP, the Company’s independent registered public accounting firm for the fiscal year ended December 31, 2014.2017.

We have received from, and discussed with, Ernst & Young LLP, which is responsible for expressing an opinion on the conformity of the Company’s audited consolidated financial statements with accounting principles generally accepted in the United States, its judgments as to the quality, not just the acceptability, of the Company’s accounting principles and such other matters as are required to be discussed with the audit committee under generally accepted auditing standards, including the matters to be discussed as required by Auditing Standard No. 16,AS 1301: Communications with Audit Committees, as adopted by the Public Company Accounting Oversight Board (the “PCAOB”) and all other communications required under the standards of the PCAOB. In addition, we have discussed with Ernst & Young LLP its independence from management and the Company, have received from Ernst & Young LLP the written disclosures and the letter required by applicable requirements of the PCAOB regarding its communications with us concerning independence, and have considered the compatibility ofnon-audit services with the auditors’ independence.

Based on the review and discussions referred to above, we recommended to the board of directors that the audited consolidated financial statements be included in the Company’s Annual Report on Form10-K for the year ended December 31, 2014.2017.

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This report of the audit committee is not “soliciting material,” shall not be deemed “filed” with the SEC and shall not be incorporated by reference by any general statement incorporating by reference this proxy statement into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the date hereof and irrespective of any general incorporation language in any such filing, except to the extent that we specifically incorporate this information by reference, and shall not otherwise be deemed filed under such acts.

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The foregoing report has been furnished by the audit committee.

Respectfully submitted,

The Audit Committee of the Board of Directors

Garen G. Bohlin (chair)

J. Scott Garland

Deepika R. Pakianathan

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Narrative Disclosure to Summary Compensation Table

Our compensation committee makes compensation decisions regarding our named executive officers or makes recommendations concerning executive compensation to our board of directors. In May 2013, our compensation committee engaged ACI,Arnosti Consulting, Inc., or Arnosti, an independent compensation consultant, to provide expertise-based advice, research and analytical services relating to peer group composition and trends and comparative data on executive compensation practices in our industry and in particular within companies whom we consider peers in terms of market capitalization, development stage and size and to advise on our executive compensation program generally. ACIArnosti provided these consulting services throughout 2014.2016 and 2017. Although our board of directors and compensation committee consider the advice and recommendation of any independent compensation consultants as to our executive compensation program, the board of directors and compensation committee ultimately make their own decisions about these matters.

Base Salary

Base salaries are used to recognize the experience, skills, knowledge and responsibilities required of our named executive officers. Historically, base salaries for our named executive officers typically have been established through arm’s length negotiation at the time the named executive officer is appointed, taking into account the position for which the named executive officer is being considered and the named executive officer’s qualifications, prior experience and prior salary. None of our named executive officers is currently party to an employment agreement or other service agreement that provides for automatic or scheduled increases in base salary. However, on an annual basis, our compensation committee reviews and evaluates the need foradvisability of any adjustment of the base salaries of each of our named executive officers, including our Chief Executive Officer. Our Chief Executive Officer provides input to our compensation committee with respect to the base salaries of our named executive officers other than our Chief Executive Officerhimself and our President and Chief Scientific Officer. In making decisions regarding salary increases, we may also draw upon the experience of members of our board of directors with other companies.

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In 2013, we paid base salaries to Dr. Kauffman and Dr. Shacham of $380,507 and $380,507, respectively. In 2014,2016, we paid base salaries to Dr. Kauffman, Dr. Shacham and Mr. Renz, Mr. FrenkelPrimiano of $440,000, $385,000, $129,375,$515,000, $415,000 and $64,157,$360,000, respectively. The base salaries for 20152017 for each of Dr. Kauffman, Dr. Shacham and Mr. Renz are $500,000, $412,000Primiano were $530,500, $435,000 and $355,000,$390,000, respectively. Mr. Frenkel’s base salary for 2015 is €245,000, which was the equivalent of $296,401 on January 1, 2015 based on an exchange rate of €1.00 to $1.2098.

Annual Performance-Based Cash Incentives

We have designed our annual performance-based cash incentive program to emphasizepay-for-performance, on both corporate and individual levels, and to reward our named executive officers for the preceding year’s performance. Subsequent to our initial public offering, each named executive officer has been eligible, at our compensation committee’s discretion, to receive an annual performance-based cash incentive, which we refer to as an annual cash incentive, in an amount corresponding to a percentage of his or her base salary. The target amount of the annual cash incentive is determined, prior to the applicable fiscal year, by our compensation committee, with the actual payment to be based upon the accomplishment of certain objective corporate milestones for the applicable fiscal year, and theyear. The amount of the annual cash incentive paid to our named executive officers is determined by our compensation committee, upon a consideration of the level of achievement of these milestones. The final evaluation made by our compensation committee does not involvedepend on a predetermined mathematical formula. Our compensation committee has authority to adjust the incentive payout each year in connection with its review of our company’s performance and the named executive officer’s individual performance.

performance as well as other relevant factors. For 2013, the objective factors contributing to corporate performance were based on (i) the achievement of multiple fundraising milestones, including the completion of the sale of our series B and series B-1 preferred stock and our initial public offering and (ii) the achievement of clinical milestones, including expansion of Phase 1 clinical trials of selinexor, enrollment of patients in clinical trials, initiation of investigator sponsored trials of selinexor, preparation for registration-directed trials in hematological malignancy indications and completion of a Phase 2b clinical trial of verdinexor in pet dogs with newly-diagnosed or after first relapse lymphomas. Based upon these clinical achievements and the completion of the company’s fundraising milestones, along with subjective factors related to each named executive officer’s individual performance, the compensation committee of2017, our board of directors approved target cash

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incentive compensation at 60% of Dr. Kauffman’s annual salary and 50% of Dr. Shacham’s annual salary, and the compensation committee approved target cash incentivesincentive compensation at 40% of Mr. Primiano’s annual salary. No changes were made to these targets for Drs. Kauffman and Shacham of 85% of each named executive officer’s respective target for 2013.2018.

For 2014,2016, the objective factors contributing to corporate performance were based on (i) the achievement of clinical milestones, including initiating registration-directedthose relating to the accrual of patients in clinical trials, results from later phase studies in hematologic malignancies and Phase 2 studies in solid tumors, meeting with the U.S. Foodinitiation of clinical trials and Drug Administration regarding the enddetermination of recommended phase 2 doses for several studies, (ii) advancement of our Phase 1 studies and advancingdrug candidates in our pipeline compounds in non-oncology indications and (ii) the closing of our July 2014 public offering of our common stock.(iii) year-end cash position. Based upon these clinical and development achievements and the completion of the company’s fundraisingCompany’s capital raising activities, the compensation committee and our board of directors, on the recommendation of the compensation committee, determined that it was appropriate for each of Drs. Kauffman and Shacham and Messrs. Frenkel and Renz to receive 90%80% of eachsuch named executive officer’s respective annual cash incentive target for 2014, consistent with2016, and the levelcompensation committee determined that it was appropriate for Mr. Primiano to receive 85% of his respective annual cash incentive target for 2016.

For 2017, the objective factors contributing to corporate performance were based on (i) the advancement of the clinical development of our drug candidates, particularly selinexor, (ii) the accrual of patients to our clinical trials, (iii) the achievement of corporate goals.

In 2013, we awardedclinical milestones relating to the results from clinical trials of our drug candidates in hematologic malignancies and solid tumors, (iv) the completion of clinical publications, (v) the generation of cash incentives to Dr.from our business development activities and(vi) year-end cash position. Based upon these clinical and development achievements and the entry into strategic transactions with Ono Pharmaceutical Co. Ltd. and Anivive Lifesciences as well as the completion of the Company’s capital raising activities, our board of directors, on the recommendation of the compensation committee, determined that it was appropriate for each of Drs. Kauffman and Dr. Shacham to receive 79% of such named executive officer’s respective annual cash incentive target for 2017, and the compensation committee determined that it was appropriate for Mr. Primiano to receive 86% of his respective annual cash incentive target for 2017.

Based on the determinations described above, in the amounts of $170,000 and $129,342, respectively. In 2014,2016, we awarded cash incentives to Dr. Kauffman, Dr. Shacham and Mr. RenzPrimiano in the amounts of $198,000, $138,500$247,200, $166,000 and $36,000,$122,000, respectively, and, in 2017, we awarded cash incentives to Dr. Kauffman, Dr. Shacham and Mr. Primiano in the amounts of $251,503, $171,856 and $133,770, respectively.

Special Cash Bonus Awards

From time to time, we may utilize cash bonus awards as compensation tools that provide, among other things, incentives to reward outstanding performance by executives. In November 2017, Mr. Frenkel’sPrimiano received a bonus in the amount of $1,500 approved by the compensation committee related to his efforts to complete and enter into our license agreement with Ono Pharmaceutical Co., Ltd., which we announced on October 12, 2017. In addition, in January 2018, in connection with our compensation committee’s review and approval of Mr. Primiano’s annual performance-based cash incentive awardcompensation, our compensation committee awarded Mr. Primiano a discretionary bonus of $30,000 for 2014 was €12,500, which washis efforts in 2017 related to the equivalent of $15,611 based on the average conversation rate during the fourth quarter of 2014 of €1.00 to $1.2489.transaction with Ono Pharmaceutical Co., Ltd.

Equity Incentive Awards

Our equity award program is the primary vehicle for offering long-term incentives to our named executive officers. While we do not currently have any equity ownership guidelines for our named executive officers, we

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believe that equity grants provide our named executive officers with a strong link to our long-term performance, create an ownership culture and help to align the interests of our named executive officers and our stockholders. We believe stock options and RSUs provide meaningful incentives to our named executive officers to achieve increases in the value of our stock over time. In addition, the vesting feature of our equity grants contributes to executive retention by providing an incentive to our named executive officers to remain employed by us during the vesting period.

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We have used stock options to compensate our named executive officers in the form of initial grants in connection with the named executive officer’s appointment to his or her position, generally on an annual basis thereafter, and also at various times, including, prior to our initial public offering, concurrent with our preferred stock financings in order to address dilution to existing options attributable to such financings.thereafter. Prior to our initial public offering, the award of stock options to our named executive officers has beenwas made upon the recommendation of the compensation committee and the approval of our board of directors. Subsequent to our initial public offering, such awards have been made upon the approval of our compensation committee, or in the case of Drs. Kauffman and Shacham, upon the approval of our board of directors following the recommendation of the compensation committee. None of our named executive officers is currently party to an employment or other service agreement with us that provides for automatic award of stock options. WeSince our initial public offering, we have granted stock options to our named executive officers with time-based vesting, and, prior to our initial public offering, have also granted stock options with performance-based vesting and an ability to early exercise.vesting. The options that we grant to our named executive officers with time-based vesting typically become exercisable as to 25% of the shares underlying the option on the first anniversary of the grant date, and as to an additional 1/48th of the shares underlying the option on a monthly basis thereafter. The options that we have granted to our named executive officers with performance-based vesting become exercisable upon the attainment of certain operational milestone events recommended by the compensation committee and approved by our board of directors. The options that we have granted to our named executive officers with an ability to early exercise are immediately exercisable in full, provided that any shares issued upon exercise will remain subject to the original vesting terms. In addition, in the event such named executive officer ceases service to us or our successor in the capacity of an employee, officer, director or consultant for cause, then such shares that are both vested and unvested are subject to repurchase by us. In the event such named executive officer ceases service to us or our successor, other than for cause, then only the unvested portion of such shares are subject to repurchase by us. For all options, vesting rights cease upon, and exercise rights cease shortly after, termination of employment or other service except in the case of death or disability. Prior to the exercise of an option, the holder has no rights as a stockholder with respect to the shares subject to such option, including no voting rights and no right to receive dividends or dividend equivalents.

In 2014,2017, our compensation committee granted stock options to our named executive officers, pursuant to the 2013 Plan, as follows in connection with their hiring:follows:

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20142017 Outstanding Equity Awards at FiscalYear-End

The following table sets forth information concerning outstanding equity awards for each of our named executive officers at December 31, 2014:2017:

Employment Agreements, Severance and Change in Control Arrangements

Historically, we have entered into employment agreements with each of our named executive officers pursuant to which such named executive officers are employed “at will,” meaning the executive or we may terminate the employment arrangement at any time. Such employment agreements establish the named executive officer’s title, initial compensation arrangements, eligibility for benefits made available to employees generally and also provide for certain benefits upon termination of employment under specified conditions. The following summarizes such termination benefits under our named executive officers’ existing employment agreements.

In January 2015 our compensation committee authorized us to enter into a revised employment agreement with Mr. Renz, and our board of directors, following the recommendation of our compensation committee, authorized us to enter into revised employment agreements with Drs. Kauffman and Shacham. TheShacham, and in September 2015, our compensation committee authorized us to enter into a revised

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Mr. Primiano. The revised employment agreements were intended to ensure that overall compensation for each named executive officer provides appropriate retention and performance incentives based in part on the recommendations of our compensation consultant and the review and approval of our compensation committee or board of directors, as applicable. The following summarizes such termination benefits under our named executive officers’ existing employment agreements.

Benefits Provided Upon Termination Without Cause or for Good Reason Upon a Change in Control

Under the terms of the amended employment agreements we have entered into in January 2015 with each of Dr.Drs. Kauffman Dr.and Shacham and Mr. Renz, and the original agreement that we entered intoin September 2015 with Mr. Frenkel in October 2014, subject to the execution and effectiveness of a separation agreement that includes a release of claims against us, if such executive’s employment is terminated by us without cause or by such executive for good reason, as defined in such employment agreements,Primiano, we have agreed to provide the benefits described below.

If we terminate Dr. Kauffman’s employment without cause or if Dr. Kauffman terminates his employment for good reason, in either case, prior to a change of control, we will be required to pay as severance to Dr. Kauffman his base salary for 12 months. If we terminate Dr. Kaufman’s employment without cause or if Dr. Kauffman terminates his employment for good reason, in either case, after a change of control, we will be required to pay as severance to Dr. Kauffman his base salary for 18 months. If Dr. Kauffman elects to continue his and his eligible dependents’ participation in our medical and dental benefit plans pursuant to the Consolidated Omnibus Budget Reconciliation Act of 1986, or COBRA, we will pay the monthly premium to continue such coverage during the applicable severance period.

If we terminate Dr. Shacham’s employment without cause or if Dr. Shacham terminates her employment for good reason, in either case, prior to a change of control, we will be required to pay as severance to Dr. Shacham her base salary for nine months. If we terminate Dr. Shacham’s employment without cause or if Dr. Shacham terminates her employment for good reason, in either case, after a change of control, we will be required to pay as severance to Dr. Shacham her base salary for 12 months. If Dr. Shacham elects to continue her and her eligible dependents’ participation in our medical and dental benefit plans pursuant to COBRA, we will pay the monthly premium to continue such coverage during the applicable severance period.

If we terminate Mr. Renz’sPrimiano’s employment without cause or if Mr. RenzPrimiano terminates his employment for good reason, in either case, prior to a change of control, we will be required to pay as severance to Mr. RenzPrimiano his base salary for six months. If we terminate Mr. Renz’sPrimiano’s employment without cause, or if Mr. RenzPrimiano resigns for good reason, in either case, within one year following a change of control, we will be required to pay as severance to Mr. RenzPrimiano his base compensation for 12 months. If Mr. RenzPrimiano elects to continue his and his eligible dependents’ participation in the Company’s medical and dental benefit plans pursuant to COBRA, the Company will pay the monthly premium to continue such coverage during the applicable severance period.

If we terminate Mr. Frenkel’s employment without cause or if Mr. Frenkel terminates his employment for good reason, in either case, after July 15, 2015 and prior to a change of control, we will be required to pay as severance to Mr. Frenkel his base salary for six months. If we terminate Mr. Frenkel’s employment without cause, or if Mr. Frenkel resigns for good reason, in either case, after July 15, 2015 and within one year following a change of control, we will be required to pay as severance to Mr. Frenkel his base compensation for nine months.

Non-Disclosure Agreements

We have entered intonon-disclosure and inventions assignment agreements with Dr.Drs. Kauffman Dr.and Shacham and Mr. Renz.Primiano. Under thenon-disclosure and inventions assignment agreements, Dr.Drs. Kauffman Dr.and Shacham and Mr. RenzPrimiano have agreed (i) not to compete with us during his or her employment and for a period of twelve months after the termination of his or her employment; (ii) not to solicit our employees or customers

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during his or her employment and for a period of twelve months after the termination of his or her employment; (iii) to protect our confidential and proprietary information, and (iv) to assign to us related intellectual property that is developed during the course of his or her employment. In his employment contract with Karyopharm Europe GmbH, Mr. Frenkel agreed (i) not to compete with us during his employment; (ii) to protect our confidential and proprietary information, and (iii) to assign to us related intellectual property that is developed during the course of his employment.

Equity Compensation Plans and Other Benefits

2013 Stock Incentive Plan

Our board of directors adopted, and our stockholders approved, the 2013 Stock Incentive Plan, which we refer to as the 2013 Plan, which became effective immediately prior to the closing of our initial public offering.

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The 2013 Plan provides for the grant of incentive stock options, nonstatutory stock options, stock appreciation rights, restricted stock awards, restricted stock unit awards, and other stock-based awards. As of February 28, 2015, 1,988,647March 31, 2018, 1,348,253 shares of our common stock are reserved for issuance under the 2013 Plan. Additional shares of our common stock may also become available for issuance under the 2013 Plan. The number of such additional shares is equal to the sum of (1) the number of shares of our common stock subject to outstanding awards under the2010the amended and restated 2010 stock incentive plan, which we refer to as the 2010 Plan that expire, terminate or are otherwise surrendered, cancelled, forfeited or repurchased by us at their original issuance price pursuant to a contractual repurchase right and (2) an annual increase to be added on the first day of each fiscal year, until, and including, the fiscal year ending December 31, 2023, equal to the least of (A) 1,939,393 shares of our common stock, (B) 4% of the number of shares of our common stock outstanding on the first day of the fiscal year, and (C) an amount determined by our board of directors.

Our employees, officers, directors, consultants, and advisors, and employees, officers, directors, consultants, and advisors of any of our present or future parent or subsidiary corporations and any other business venture (including, without limitation, joint venture or limited liability company) in which we have a controlling interest, as determined by our board of directors, are eligible to be granted awards under the 2013 Plan. However, incentive stock options may only be granted to employees who are eligible to receive incentive stock options under the Internal Revenue Code.

The 2013 Plan is administered by our board of directors, a committee appointed by our board of directors or one or more officers appointed by such committee or the board of directors. Pursuant to the terms of the 2013 Plan, our board of directors or such committee or officers (subject to the below) selects the recipients of awards and determines:

Our board of directors has delegated its powers under the 2013 Plan to our compensation committee. As described above in the section “Corporate Governance—Committees of the Board of Directors—Compensation

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Committee,” our compensation committee has delegated the authority to members of our senior management to grant options and awards of RSUs to new employees below the level of vice president, subject to specified limitations.

In the event of any stock split, reverse stock split, stock dividend, recapitalization, combination of shares, reclassification of shares,spin-off or other similar change in capitalization or event, or any dividend or distribution to holders of our common stock other than an ordinary cash dividend, our board of directors is required by the 2013 Plan to make equitable adjustments, in a manner determined by our board of directors, to:

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In connection with a merger or other reorganization event (as defined in the 2013 Plan), our board of directors may take any one or more of the following actions as to all or any portion of any outstanding awards other than restricted stock, on such terms as it determines:

Our board of directors is not obligated under the 2013 Plan to treat all awards, all awards held by a participant, or all awards of the same type, identically in connection with a reorganization event.

In the case of restricted stock unitRSU awards that are subject to Section 409(a) of the Internal Revenue Code, no assumption or substitution will be permitted and the restricted stock unitRSU awards will instead be settled in accordance with the terms of the applicable restricted stock unitRSU agreement, and in certain circumstances, any unvested restricted stock unitRSU awards will be terminated immediately prior to the consummation of the reorganization event without any payment in exchange therefor.

Upon the occurrence of a reorganization event other than our liquidation or dissolution, the repurchase and other rights with respect to outstanding awards of restricted stock will continue for the benefit of the successor

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company and will, unless our board of directors otherwise determines, apply to the cash, securities or other property into which our common stock was converted into or exchanged for pursuant to the reorganization event in the same manner and to the same extent as they applied to such restricted stock. Upon the occurrence of a reorganization event involving our liquidation or dissolution, all restrictions and conditions on all restricted stock then outstanding will automatically be deemed terminated or satisfied, unless otherwise provided in the instrument evidencing the award of restricted stock or any other agreement between a participant and us.

At any time, our board of directors may provide that any award under the 2013 Plan shall become immediately exercisable in whole or in part, free of some or all restrictions or conditions, or otherwise realizable in whole or in part, as the case may be.

In addition, the 2013 Plan provides that, notwithstanding the provisions of the plan that may apply upon a reorganization event and except as otherwise provided for in the instrument evidencing an option or award of

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restricted stock or any other agreement between us and the participant, upon the occurrence of a change in control event (as defined in the 2013 Plan) each option shall become immediately exercisable and each award of restricted stock shall become immediately free from all conditions and restrictions, if, in either case, the employment of the participant holding such award is terminated by us (or our acquiring or succeeding corporation) without cause (as defined in the 2013 Plan) or by the participant for good reason (as defined in the 2013 Plan), on or prior to the first anniversary of the date of the change in control event. Our board of directors may specify in an award at the time of grant the effect of a change in control event on any stock appreciation right, restricted stock unitRSU or other stock-based award.

Except with respect to certain actions requiring stockholder approval under the Internal Revenue Code or the rules of the Nasdaq Stock Market, our board of directors may amend, modify or terminate any outstanding award under the 2013 Plan, including but not limited to, substituting therefor another award of the same or a different type, changing the date of exercise or realization, and converting an incentive stock option into anon-qualified stock option, subject to certain participant consent requirements. Unless our stockholders approve such action, the 2013 Plan provides that we may not (except as otherwise permitted in connection with a change in capitalization or reorganization event):

No award may be granted under the 2013 Plan after October 21, 2023, but awards previously granted may extend beyond that date. Our board of directors may amend, suspend or terminate the 2013 Plan or any portion thereof at any time, subject to certain stockholder approval requirements and limitations under the Internal Revenue Code.

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2013 Employee Stock Purchase Plan

Our board of directors adopted, and our stockholders approved, the 2013 Employee Stock Purchase Plan, or the 2013 ESPP. The 2013 ESPP is administered by our board of directors or by a committee appointed by our board of directors. The board of directors has delegated authority for administering the 2013 ESPP to our compensation committee. The 2013 ESPP provides participating employees with the opportunity to purchase shares of our common stock. As of February 28, 2015, 563,329March 31, 2018, 433,511 shares of our common stock are reserved for issuance under the 2013 Plan.ESPP. Additional shares of our common stock may also become available for issuance under the 2013 Plan.ESPP. The number of shares of our common stock reserved for issuance under the 2013 ESPP will automatically increase on the first day of each fiscal year through December 31, 2023, in an amount equal to the least of (1) 484,848 shares of our common stock, (2) 1% of the total number of shares of our common stock outstanding on the first day of the applicable year, and (3) an amount determined by our board of directors.

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All of our employees and employees of any of our designated subsidiaries, as defined in the 2013 ESPP, are eligible to participate in the 2013 ESPP, provided that:

No employee may purchase shares of our common stock under the 2013 ESPP and any of our other employee stock purchase plans in excess of $25,000 of the fair market value of our common stock (as of the date of the option grant) in any calendar year. In addition, no employee may purchase shares of our common stock under the 2013 ESPP that would result in the employee owning 5% or more of the total combined voting power or value of our stock.

Each offering to our eligible employees to purchase stock under the 2013 ESPP will consist of asix-month offering period during which payroll deductions will be made and held for the purchase of our common stock at the end of the offering period. Our board of directors may, at its discretion, choose a different period of not more than 12 months for offerings. The firstsix-month offering period under the 2013 ESPP began on May 1, 2014 and subsequent offering periods occur over each successivesix-month period thereafter until the board of directors determines otherwise.

On the commencement date of each offering period, each eligible employee may authorize up to a maximum of 15% of his or her compensation to be deducted by us during the offering period. Each employee who continues to be a participant in the 2013 ESPP on the last business day of the offering period will be deemed to have exercised an option to purchase from us the number of whole shares of our common stock that his or her accumulated payroll deductions on such date will pay for, not in excess of the maximum numbers set forth above. Under the terms of the 2013 ESPP, the purchase price shall be determined by our board of directors for each offering period and will be at least 85% of the applicable closing price of our common stock. If our board of directors does not make a determination of the purchase price, the purchase price will be 85% of the lesser of the closing price of our common stock on the first business day of the offering period or on the last business day of the offering period.

An employee may for any reason withdraw from participation in an offering prior to the end of an offering period and permanently draw out the balance accumulated in the employee’s account. If an employee elects to discontinue his or her payroll deductions during an offering period but does not elect to withdraw his or her funds, funds previously deducted will be applied to the purchase of common stock at the end of the offering period. If a participating employee’s employment ends before the last business day of an offering period, no additional payroll deductions will be made and the balance in the employee’s account will be paid to the employee.

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We will be required to make equitable adjustments to the number and class of securities available under the 2013 ESPP, the share limitations under the 2013 ESPP, and the purchase price for an offering period under the 2013 ESPP to reflect stock splits, reverse stock splits, stock dividends, recapitalizations, combinations of shares, reclassifications of shares, spin-offs and other similar changes in capitalization or events or any dividends or distributions to holders of our common stock other than ordinary cash dividends.

In connection with a merger or other reorganization event (as defined in the 2013 ESPP), our board of directors or a committee of our board of directors may take any one or more of the following actions as to

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outstanding options to purchase shares of our common stock under the 2013 ESPP on such terms as our board or committee determines:

Our board of directors may at any time, and from time to time, amend or suspend the 2013 ESPP or any portion thereof. We will obtain stockholder approval for any amendment if such approval is required by Section 423 of the Internal Revenue Code. Further, our board of directors may not make any amendment that would cause the 2013 ESPP to fail to comply with Section 423 of the Internal Revenue Code. The 2013 ESPP may be terminated at any time by our board of directors. Upon termination, we will refund all amounts in the accounts of participating employees.

2010 Stock Incentive Plan

In July 2013, our board of directors adopted and our stockholders approved the amended and restated 2010 stock incentive plan, which we refer to as the 2010 Plan. The 2010 Plan provides for the grant of incentive stock options, nonstatutory stock options, restricted stock awards, restricted stock unit awards, and other stock-based awards. We no longer grant awards under the 2010 Plan, but awards remain outstanding under the 2010 Plan in accordance with their terms.

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The 2010 Plan is administered by our board of directors. Pursuant to the terms of the 2010 Plan, our board of directors selected the recipients of awards and determined:

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To the extent permitted by applicable law, our board of directors may delegate its powers under the 2010 Plan to one or more committees or subcommittees of our board or to one or more of our executive officers.

In the event of any stock split, reverse stock split, stock dividend, recapitalization, combination or reclassification of shares,spin-off or other similar change in capitalization or event, we are required by the 2010 Plan to make appropriate adjustments, in a manner determined by our board, to:

Upon the consummation of a merger or other event constituting an acquisition (as defined in the 2010 Plan), our board of directors or the board of directors of the surviving or acquiring entity shall, as to outstanding awards under the 2010 Plan (on the same basis or on different bases), either:

Unless otherwise determined by the applicable board of directors, any repurchase rights or other rights that relate to an award shall continue to apply to consideration, including cash that has been substituted, assumed or

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amended for an award in connection with an acquisition. We may require that all or any portion of such consideration payable in respect of an award in connection with an acquisition shall be held in escrow (including in an escrow pursuant to the agreement effecting such acquisition) in order to effectuate any continuing restrictions.

At any time, our board of directors may provide that any award under the 2010 Plan shall become immediately exercisable in full or in part or free of some or all restrictions or conditions, or otherwise realizable in full or in part, as the case may be.

Our board of directors may amend, modify or terminate any outstanding award under the 2010 Plan, including, but not limited to, substituting therefor another award of the same or a different type, changing the

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date of exercise or realization, and converting an incentive stock option to a nonstatutory stock option, subject to certain participant consent requirements. In addition, our board of directors may, without stockholder approval, amend any outstanding option to reduce the exercise price of such option or cancel any outstanding option and grant in substitution therefor new options covering the same or a different number of shares of our common stock and having a lower exercise price than the cancelled options. Our board of directors may amend, suspend or terminate the 2010 Plan or any portion thereof at any time.

401(k) Retirement Plan

We maintain a 401(k) retirement plan that is intended to be atax-qualified defined contribution plan under Section 401(k) of the Internal Revenue Code. In general, all of our U.S.-based employees are eligible to participate in the 401(k) plan beginning on the first day of the month followingupon commencement of their employment. The 401(k) plan includes a salary deferral arrangement pursuant to which participants may elect to reduce their current compensation by up to the statutorily prescribed limit, equal to $17,500$18,000 (an additional $6,000 in 2014,contributions is allowed for participants age 50 and over) in 2017, and have the amount of the reduction contributed to the 401(k) plan. We also match employee contributions to 401(k) plans up to a maximum of 4% of an employee’s cash compensation during each pay period.

Health and Welfare Benefits

Our named executive officers other than Mr. Frenkel who is employed by Karyopharm Europe GmbH, our wholly-owned subsidiary, are eligible to participate in all of our employee benefit plans, including our medical, dental, vision, group life and disability insurance plans, in each case on the same basis as other employees. We believe that these health and welfare benefits help ensure that we have a productive and focused workforce through reliable and competitive health and other benefits.

CERTAIN RELATIONSHIPS AND RELATED PARTYPERSON TRANSACTIONS

Related Person Transactions

Since January 1, 2014,2017, we have engaged in the following transactions with our directors and executive officers and holders of more than 5% of our voting securities and affiliates of our directors, executive officers and such 5% stockholders. We believe that all of the transactions described below were made on terms no less favorable to us than could have been obtained from unaffiliated third parties.

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Participation in Public Offering

In July 2014, we conducted a public offering of our common stock in which certain of our 5% stockholders and their affiliates purchased an aggregate of 950,000 shares. Each of those purchases was made through the underwriters at the public offering price. The following table sets forth the aggregate number of shares of our common stock that these 5% stockholders and their affiliates purchased in our public offering:

Registration Rights

We are a party to a third amended and restated investors’ rights agreement, last amended in July 2013, with the former holders of our preferred stock, including certain of our directors, executive officers and 5% stockholders and their affiliates. The investor rights agreement provides these holders the right to demand that we file a registration statement or request that their shares be covered by a registration statement that we are otherwise filing.

Severance and Change in Control Agreements

See the “Executive Compensation—Employment Agreements, Severance and Change in Control Arrangements” section of this proxy statement for a further discussion of these arrangements.

Indemnification of Directors

Our certificate of incorporation limits the personal liability of directors for breach of fiduciary duty to the maximum extent permitted by the Delaware General Corporation Law and provides that no director will have

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personal liability to us or to our stockholders for monetary damages for any breach of fiduciary duty as a director. In addition, we have entered into indemnification agreements with each of our directors that that require us, among other things, to indemnify each director for certain expenses, including attorneys’ fees, judgments, fines and settlement amounts incurred by him or her in any action or proceeding arising out of his or her service as one of our directors. See the “Corporate Governance—Limitation of Liability and Indemnification” section of this proxy statement for a further discussion of these arrangements.

Consulting Arrangements

We are party to a consulting agreement with Mirza Consulting, an entity that is wholly owned by Dr. Mirza, a member of our board of directors. Pursuant to this agreement, we paid Dr. Mirza (through such entity) a consulting fee of $22,500$11,250 per month during the fiscal year endedfrom January 1, 2017 through December 31, 2014. We have agreed to pay Dr. Mirza a consulting fee of $22,500 per month beginning2017. Effective January 1, 2015.

During 2014, we were also a party to a2018, the consulting agreement with Dr. Tami Rashal,Mirza Consulting was amended to extend the sisterterm of Dr. Shacham, our President and Chief Scientific Officer, and the sister-in-law of Dr. Kauffman, our Chief Executive Officer and member of our board of directors. Pursuant to this agreement we paid Dr. Rashaluntil December 31, 2018 with a consultingmonthly fee of $12,083 per month, effective January 1, 2014. Effective June 1, 2014, we agreed to pay Dr. Rashal a$9,500.

The consulting fee of $20,167 per month as well as a one-time retroactive consulting payment of $12,688 for the period January 2014 to May 2014. In February 2015, we paid Dr. Rashal an additional year-end consulting fee of $27,500 related to work performed in 2014. In January 2014, we granted Dr. Rashal an option to purchase 5,500 shares of our common stock at an exercise price of $26.65 per share. Dr. Rashal became a full-time employee on March 1, 2015 and we agreed to pay her an annual base salary of $206,000 and a $15,000 reimbursement for her relocation to our headquarters in Newton, Massachusetts.

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The compensationfees described above for Drs.Dr. Mirza and Rashal has been reviewedwas approved by our compensation committee and approved by our audit committee pursuant to the policies and procedures for the review of related party transactions, which are described below.

Policies and Procedures for Related Person Transactions

On October 8, 2013, our board of directors adopted written policies and procedures for the review of any transaction, arrangement or relationship in which we are a participant, the amount involved exceeds $120,000, and one of our executive officers, directors, director nominees or 5% stockholders (or their immediate family members), each of whom we refer to as a “related person,” has a direct or indirect material interest.

If a related person proposes to enter into such a transaction, arrangement or relationship, which we refer to as a “related person transaction,” the related person must report the proposed related person transaction to our principal financial officer. The policy calls for the proposed related person transaction to be reviewed and, if deemed appropriate, approved by the audit committee of our board of directors. Whenever practicable, the reporting, review, and approval will occur prior to effectiveness or consummation of the related person transaction. If advance review and approval is not practicable, the committee will review, and, in its discretion, may ratify the related person transaction. The policy also permits the chairman of the audit committee to review and, if deemed appropriate, approve proposed related person transactions that arise between audit committee meetings, subject to ratification by the audit committee at its next meeting. Any related person transactions that are ongoing in nature will be reviewed annually.

A related person transaction reviewed under the policy will be considered approved or ratified if it is authorized by the committee after full disclosure of the related person’s interest in the transaction. As appropriate for the circumstances, the committee will review and consider:

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The audit committee may approve or ratify the related person transaction only if the committee determines that, under all of the circumstances, the transaction is in, or is not inconsistent with, our best interests. The audit committee may impose any conditions on the related person transaction that it deems appropriate.

In addition to the transactions that are excluded by the instructions to the SEC’s related person transaction disclosure rule, our board of directors has determined that the following transactions do not create a material direct or indirect interest on behalf of related persons and, therefore, are not related person transactions for purposes of this policy:

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The policy provides that transactions involving compensation of executive officers shall be reviewed and approved by the compensation committee in the manner specified in its charter.

PROPOSAL 2:

RATIFICATION OF SELECTION OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

The audit committee has selected Ernst & Young LLP as the company’sCompany’s independent registered public accounting firm for the fiscal year ending December 31, 20152018, and the board of directors has directed that management submit the selection of the company’sCompany’s independent registered public accounting firm for ratification by the stockholders at the annual meeting.Annual Meeting. Representatives of Ernst & Young LLP are expected to be present at the annual meeting,Annual Meeting, will have an opportunity to make a statement if they so desire, and be available to respond to appropriate questions. Ernst & Young LLP was appointed to serve as our independent registered public accounting firm for the fiscal year ending December 31, 2014 on April 11, 2014. McGladrey LLP served as our independent registered public accounting firm for the fiscal year ended December 31, 2013. See “—Change in Independent Registered Public Accounting Firm” below.

Stockholder ratification of the selection of Ernst & Young LLP as the company’sCompany’s independent registered public accounting firm is not required by Delaware law or ourthe Company’s certificate of incorporation or our bylaws. However, the board is submitting the audit committee’s selection of Ernst & Young LLP to the stockholders for ratification as a matter of good corporate practice. If the stockholders fail to ratify the selection, the audit committee will reconsider whether to retain that firm. Even if the selection is ratified, the audit committee in its discretion may direct the selection of a different independent registered public accounting firm at any time during the year if the audit committee determines that such a change would be in the best interests of the companyCompany and its stockholders.

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Independent Registered Public Accountants’Accountant Fees

The following tables set forth aggregate fees billed to us (i) by McGladrey LLP, our independent registered public accounting firm for the fiscal year ended December 31, 2013 and from January 1, 2014 through April 11, 2014 for services related to the fiscal years ended December 31, 2013 and December 31, 2014 and (ii) by Ernst & Young LLP, our independent registered public accounting firm beginning April 17, 2014 for services related to the fiscal year ended December 31, 2014.

McGladrey LLP

The audit committee has considered the services listed above to be compatible with maintaining McGladrey LLP’s independence.

Ernst & Young LLP

The audit committee has considered the services listed above to be compatible with maintaining Ernst & Young LLP’s independence.

Change in Independent Registered Public Accounting Firm

On April 11, 2014, the audit committee selected Ernst & Young LLP as our independent registered public accounting firm for the fiscal year ending December 31, 2014, and dismissed McGladrey LLP from service as our independent registered public accounting firm. We formally engaged Ernst & Young LLP on April 17, 2014.

McGladrey LLP’s reports on our financial statements as of and for the fiscal years ended December 31, 2013 and 2012 did not contain any adverse opinion or disclaimer of opinion, nor were they qualified or modified as to uncertainty, audit scope, or accounting principles.

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During the fiscal years ended December 31, 2013 and 2012 and the subsequent interim period through April 11, 2014, there were (i) no “disagreements” (as that term is defined in Item 304(a)(1)(iv) of Regulation S-K and the related instructions) between us and McGladrey LLP on any matter of accounting principles or practices, financial statement disclosure, or auditing scope or procedure, which disagreements, if not resolved to the satisfaction of McGladrey LLP, would have caused McGladrey LLP to make reference to the subject matter of the disagreement in its reports on our consolidated financial statements and (ii) no “reportable events” (as that term is defined in Item 304(a)(1)(v) of Regulation S-K).

During the fiscal years ended December 31, 2013 and 2012 and the subsequent interim period through April 16, 2014, neither we, nor anyone on our behalf, consulted Ernst & Young LLP regarding (i) the application of accounting principles to a specified transaction, either completed or proposed, or the type of audit opinion that might be rendered on our consolidated financial statements, and no written report or oral advice was provided to us by Ernst & Young LLP that Ernst & Young LLP concluded was an important factor considered by us in reaching a decision as to any accounting, auditing or financial reporting issue or (ii) any matter that was the subject of a “disagreement” (as that term is defined in Item 304(a)(1)(iv) of Regulation S-K and the related instructions) or a “reportable event” (as that term is defined in Item 304(a)(1)(v) of Regulation S-K).

Pre-Approval Policies and Procedures

Our audit committee has established a policy that all audit and permissiblenon-audit services provided by our independent registered public accounting firm will bepre-approved by the audit committee, and all such services werepre-approved in accordance with this policy during the fiscal years ended December 31, 20132016 and 2014.2017. These services may include audit services, audit-related services, tax services and other services. The audit committee considers whether the provision of eachnon-audit service is compatible with maintaining the independence of our auditors.Pre-approval is detailed as to the particular service or category of services and is generally subject to a specific budget. Our independent registered public accounting firm and management are required to periodically report to the audit committee regarding the extent of services provided by the independent registered public accounting firm in accordance with thispre-approval, and the fees for the services performed to date.

Recommendation of the Board of Directors

THE BOARD OF DIRECTORS UNANIMOUSLY RECOMMENDS THAT THE STOCKHOLDERS VOTE TO RATIFY THE SELECTION OF ERNST & YOUNG LLP AS OUR INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM FOR THE FISCAL YEAR ENDING DECEMBER 31, 2015.2018.

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SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT

The following table sets forth information relating to the beneficial ownership of our common stock as of February 28, 2015,March 31, 2018, by:

The percentage of shares beneficially owned is computed on the basis of 35,682,76049,670,328 shares of our common stock outstanding as of February 28, 2015.March 31, 2018. The number of shares beneficially owned by each stockholder is

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determined under rules issued by the Securities and Exchange Commission and includes voting or investment power with respect to securities. Under these rules, beneficial ownership includes any shares as to which the individual or entity has sole or shared voting power or investment power. In computing the number of shares beneficially owned by an individual or entity and the percentage ownership of that person, shares of common stock subject to options or other rights held by such person that are currently exercisable or will become exercisable within 60 days of February 28, 2015March 31, 2018 are considered outstanding, although these shares are not considered outstanding for purposes of computing the percentage ownership of any other person. Unless otherwise indicated, the address of all listed stockholders is c/o Karyopharm Therapeutics Inc., 85 Wells Avenue, Newton, Massachusetts 02459. Each of the stockholders listed has sole voting and investment power with respect to the shares beneficially owned by the stockholder unless noted otherwise, subject to community property laws where applicable.

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Ltd. and as to which each of such directors may be deemed to share voting and investment power and beneficial ownership. Each of such directors disclaims such voting and investment power and beneficial ownership with respect to shares held by Plio Limited. The address for Chione Ltd. is Simou Menardou 8Kifisia Court, 2nd Floor, Flat/Office 225, 6015 Larnaca, Cyprus. The address for Mr. Smolokowski is Chalet Lenotchka, Chemin des Marais 1, Chesieres, Switzerland. For information regarding Chione Ltd. and its affiliates, we have relied on Amendment No. 3 to Schedule 13G filed by Chione Ltd. with the SEC on February 14, 2018.

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SECTION 16(a) BENEFICIAL OWNERSHIP REPORTING COMPLIANCE

Under Section 16(a) of the Exchange Act, directors, executive officers and beneficial owners of 10% or more of our common stock, or reporting persons, are required to report to the SEC on a timely basis the initiation of their status as a reporting person and any changes with respect to their beneficial ownership of our common stock. Based solely on our review of copies of forms that we have received, or written representations from

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reporting persons, we believe that during the fiscal year ended December 31, 2014,2017, all executive officers, directors and greater than 10% stockholders timely complied with all applicable filing requirements, except as follows: Ran Frenkel filed a Form 3 on October 27, 2014 setting forth his shareholdings (due ten days following the commencement of his service as one of our officers) that was filed one business day late; Chione Ltd., Marcin Czernik, Andreas Hadjimichael, Amalia Hadjimichael and Wiaczeslaw Smolokowsi filed a Form 4 on December 1, 2014 setting forth shareholdings of Chione Ltd. and reflecting the sale of common stock on dates including November 26, 2014, November 28, 2014 and December 1, 2014 (in each case, due within two business days following the date of sale) that was filed one business day late with respect to the sales on November 26, 2014; Marcin Czernik, Andreas Hadjimichael and Amalia Hadjimichael filed a Form 4 on August 21, 2014 setting forth certain indirect shareholdings and reflecting the sale of common stock on August 18, 2014 (due within two business days following the date of sale) that was filed one business day late; and Scott Garland filed a Form 4 on November 12, 2014 reflecting the grant of an option to purchase 20,000 shares of common stock on November 3, 2014 (due within two business days following the date of grant) that was filed seven business days late.requirements.

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SECURITIES AUTHORIZED FOR ISSUANCE UNDER EQUITY COMPENSATION PLANS

The following table contains information about our equity compensation plans as of December 31, 2014.2017. As of December 31, 2014,2017, we had three equity compensation plans, each of which was approved by our stockholders: the 2010 Plan, the 2013 Plan and the 2013 ESPP.

Equity Compensation Plan Information

STOCKHOLDER PROPOSALS

Proposals of stockholders intended to be presented at our annual meeting of stockholders to be held in 20162019 must be received by us no later than December 9, 2015,28, 2018, which is 120 calendar days prior to theone-year anniversary of the date on which our proxy statement was released to stockholders in connection with this year’s annual meeting of stockholders, in order to be included in our proxy statement and form of proxy relating to the 20162019 annual meeting of stockholders, unless the date of the 20162019 annual meeting of stockholders is changed by more than 30 days from the anniversary of our 20152018 Annual Meeting, in which case the deadline for such proposals will be a reasonable time before we begin to print and send our proxy materials. These proposals must comply with the requirements as to form and substance established by the SEC for such proposals in order to be included in the proxy statement.

In addition, our bylaws establish an advance notice procedure for nominations for election to our board of directors and other matters that shareholdersstockholders wish to present for action at an annual meeting other than those to be included in our proxy statement. In general, notice must be received at our principal executive offices not less than 90 calendar days before nor more than 120 calendar days before theone-year anniversary of the previous year’s annual meeting of stockholders. Therefore, to be presented at our 20162019 annual meeting of stockholders, such a proposal must be received by us no earlier than January 23, 2016February 19, 2019 and no later than February 22, 2016. March 21, 2019.

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However, if the date of the 20162019 annual meeting of stockholders is more than 20 days earlier or more than 60 days later than such anniversary date, notice must be received no earlier than the close of business 120 calendar days prior to such annual meeting and no later than the close of business on the later of (i) 90 days prior to such annual meeting and (ii) 10 days following the day on which notice of the date of such annual meeting was mailed or public announcement of the date of such annual meeting was first made.made, whichever first occurs. Any proposals we do not receive in accordance with the above standards will not be voted on at the 20162019 annual meeting of stockholders. Stockholders are advised to review our bylaws which also specify requirements as to the form and content of a stockholder’s notice.

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Any proposals, notices or information about proposed director candidates should be sent to:

Karyopharm Therapeutics Inc.

85 Wells Avenue

Newton, Massachusetts 02459

Attention: Corporate Secretary

STOCKHOLDERS SHARING THE SAME ADDRESS

The rules promulgated by the SEC permit companies, banks, brokerage firms or other intermediaries to deliver a single copy of a proxy statement and annual report to households at which two or more stockholders reside. This practice, known as “householding,” is designed to reduce duplicate mailings and save significant printing and postage costs as well as natural resources. Stockholders sharing an address who have been previously notified by their bank, brokerage firm or other intermediary and have consented to householding will receive only one copy of our proxy statement and annual report. If you would like to opt out of this practice for future mailings and receive separate proxy statements and annual reports for each stockholder sharing the same address, please contact your bank, brokerage firm or other intermediary from whom you received such mailing. We will promptly deliver a separate copy of the proxy statement and/or annual report to you if you contact us at the following address or telephone number: Karyopharm Therapeutics Inc., 85 Wells Avenue, Newton, Massachusetts 02459, Attention: Corporate Secretary, (617)-658-0600.658-0600. We will promptly send additional copies of the proxy statement or annual report upon receipt of such request. Stockholders sharing an address that are receiving multiple copies of the proxy statement or annual report can request delivery of a single copy of the proxy statement or annual report by contacting their bank, brokerage firm or other intermediary or by contacting us at the address or telephone number above.

OTHER MATTERS

We do not know of any business that will be presented for consideration or action by the stockholders at the annual meetingAnnual Meeting other than that described in this proxy statement. If, however, any other business is properly brought before the meeting, shares represented by proxies will be voted in accordance with the best judgment of the persons named in the proxies or their substitutes. All stockholders are urged to complete, sign and return the accompanying proxy card in the enclosed envelope.

DIRECTIONS TO ANNUAL MEETING

Directions to the 20152018 Annual Meeting of Stockholders, to be held at our headquarters, 85 Wells Avenue, Newton, Massachusetts 02459, are set forth below.

From the North, West and East

Route 95 South to Exit 19B, Highland Avenue.19A, Turn left onto Hunting Avenue. Take 3rd left onto Kendrick Street. Kendrick Street becomes Nahanton Street. Turn right onto Wells Avenue. 85 Wells Avenue is on the right.

From the South

Route 95 North to Exit 19A, Highland Avenue. Take the second right onto 2nd Avenue.19A. Turn right on 4th Avenue. Turn left onto Kendrick Street. Kendrick Street becomes Nahanton Street. Turn right onto Wells Avenue. 85 Wells Avenue is on the right.

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