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BIOCRYST PHARMACEUTICALS, INC. 4505 Emperor Blvd., Suite 200 Durham, North Carolina 27703

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BIOCRYST PHARMACEUTICALS, INC. 4505 Emperor Blvd., Suite 200 Durham, North Carolina 27703 BIOCRYST PHARMACEUTICALS, INC. 4505 Emperor Blvd., Suite 200 Durham, North Carolina 27703 NOTICE OF ANNUAL MEETING OF STOCKHOLDERS To Be Held May 25, 2021 To the Stockholders of BioCryst Pharmaceuticals, Inc.: Notice is hereby given that the Annual Meeting of Stockholders of BioCryst Pharmaceuticals, Inc., a Delaware corporation (the “Company”), will be held at our corporate offices at 4505 Emperor Blvd., Suite 200, Durham, NC 27703 on Tuesday, May 25, 2021 at 10:00 a.m., Eastern Daylight Time (the “Meeting”), for the following purposes: 1. To elect the two directors nominated in this Proxy Statement to serve for a term ending at the 2024 annual meeting of stockholders and until a successor is duly elected and qualified; 2. To ratify the selection of Ernst & Young LLP as our independent registered public accountants for 2021; 3. To hold an advisory vote regarding executive compensation; 4. To approve an amendment to the Stock Incentive Plan to increase the number of shares available for issuance under the Stock Incentive Plan by 7,500,000 shares; 5. To approve an amendment to the Employee Stock Purchase Plan to increase the number of shares available for issuance under the Employee Stock Purchase Plan by 3,500,000 shares; and 6. To transact such other business as may properly come before the Meeting or any adjournment thereof. THE BOARD OF DIRECTORS UNANIMOUSLY RECOMMENDS THAT YOU VOTE IN FAVOR OF PROPOSALS 1, 2, 3, 4, AND 5. The proposals are further described in the accompanying Proxy Statement. The Board of Directors has fixed the close of business on March 30, 2021 as the record date for the determination of stockholders entitled to receive notice of and to vote at the Meeting or any adjournment thereof. The Meeting may be adjourned from time to time without notice other than announcement at the Meeting, and any business for which notice of the Meeting is hereby given may be transacted at any such adjournment. A list of the stockholders entitled to vote at the Meeting will be open to examination by any stockholder, for any purpose germane to the Meeting, during ordinary business hours, for a period of at least ten days prior to the Meeting at the principal executive offices of the Company in Durham, North Carolina. In the event that the Company’s principal executive offices are closed during such period due to the ongoing COVID-19 pandemic, stockholders wishing to examine the list may make arrangements to do so by contacting our Corporate Secretary at 4505 Emperor Blvd., Suite 200, Durham, North Carolina 27703 or (919) 859-1302. Due to the COVID-19 pandemic, we are implementing safety protocols for the Meeting. All attendees will be required to wear masks and follow social distancing protocols. We reserve the right to implement other safety measures as we deem prudent or as required by any applicable laws or government orders. If we determine that it is not possible or advisable to hold the Meeting in person at our corporate offices on the meeting date, we may make alternative arrangements to hold the Meeting at a different date or time, in a different location, and/or by means of remote communication. In the event we determine it is necessary or appropriate to make alternative arrangements for the Meeting, we will announce the decision to do so in advance, and details on how to participate will be issued by press release, posted on our website, and filed with the SEC as additional proxy soliciting material. Please review carefully the Proxy Card and Proxy Statement. BY ORDER OF THE BOARD OF DIRECTORS Alane P. Barnes, Corporate Secretary Durham, North Carolina April 13, 2020 ALL STOCKHOLDERS ARE INVITED TO ATTEND THE ANNUAL MEETING IN PERSON. WHETHER OR NOT YOU PLAN TO ATTEND THE MEETING, PLEASE VOTE PROMPTLY. A PERSON GIVING A PROXY HAS THE POWER TO REVOKE IT. IF YOU ATTEND THE MEETING, YOUR PROXY WILL NOT BE COUNTED WITH RESPECT TO ANY MATTER UPON WHICH YOU VOTE IN PERSON. TABLE OF CONTENTS Page PROXY STATEMENT ................................................................................................................................................................... 1 ITEMS TO BE VOTED UPON ...................................................................................................................................................... 4 1. ELECTION OF DIRECTORS .................................................................................................................................................... 4 2. RATIFICATION OF APPOINTMENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTANTS FOR 2021 ........... 7 3. ADVISORY VOTE TO APPROVE EXECUTIVE COMPENSATION .................................................................................... 8 4. APPROVAL OF AN AMENDMENT TO THE STOCK INCENTIVE PLAN TO INCREASE THE NUMBER OF SHARES AVAILABLE FOR ISSUANCE UNDER THE STOCK INCENTIVE PLAN BY 7,500,000 SHARES .................. 9 5. APPROVAL OF AN AMENDMENT TO THE EMPLOYEE STOCK PURCHASE PLAN TO INCREASE THE NUMBER OF SHARES AVAILABLE FOR ISSUANCE UNDER THE EMPLOYEE STOCK PURCHASE PLAN BY 3,500,000 SHARES ..................................................................................................................................................................................... 17 CORPORATE GOVERNANCE ..................................................................................................................................................... 20 EXECUTIVE OFFICERS ............................................................................................................................................................... 24 COMPENSATION DISCUSSION AND ANALYSIS ................................................................................................................... 26 COMPENSATION COMMITTEE REPORT ................................................................................................................................. 34 EXECUTIVE COMPENSATION .................................................................................................................................................. 35 2020 SUMMARY COMPENSATION TABLE ......................................................................................................................... 35 GRANTS OF PLAN-BASED AWARDS IN 2020 ..................................................................................................................... 36 OUTSTANDING EQUITY AWARDS AT DECEMBER 31, 2020........................................................................................... 37 2020 OPTION EXERCISES AND STOCK VESTED ............................................................................................................... 38 POTENTIAL PAYMENTS UPON TERMINATION OR CHANGE IN CONTROL ............................................................... 38 CEO PAY RATIO ...................................................................................................................................................................... 42 2020 DIRECTOR COMPENSATION ............................................................................................................................................ 43 AUDIT COMMITTEE REPORT.................................................................................................................................................... 45 SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT .................................................... 46 DELINQUENT SECTION 16(a) REPORTS .................................................................................................................................. 48 STOCKHOLDER PROPOSALS .................................................................................................................................................... 48 NO INCORPORATION BY REFERENCE ................................................................................................................................... 48 OTHER MATTERS ........................................................................................................................................................................ 48 GENERAL INFORMATION ......................................................................................................................................................... 49 ANNEX A ....................................................................................................................................................................................... A-1 ANNEX B ....................................................................................................................................................................................... B-1 This page intentionally left blank BIOCRYST PHARMACEUTICALS, INC. 4505 Emperor Blvd., Suite 200 Durham, North Carolina 27703 PROXY STATEMENT General This Proxy Statement is furnished in connection with the solicitation of proxies by the Board of Directors (the “Board” or the “Board of Directors”) of BioCryst Pharmaceuticals, Inc. (“BioCryst” or the “Company”) for the Annual Meeting of Stockholders of the Company to be held at our corporate offices at 4505 Emperor Blvd., Suite 200, Durham, NC 27703 on Tuesday, May 25, 2021 at 10:00 a.m., Eastern Daylight Time, and at any adjournment thereof (the “Meeting”), and for the purposes set forth in the accompanying Notice of Annual Meeting of Stockholders. In this document, the words “BioCryst,” “the Company,” “we,” “our,” “ours,” and “us” refer only to BioCryst Pharmaceuticals,
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