The 2022 Annual Meeting of Stockholders (the “Meeting”) of BioCryst Pharmaceuticals, Inc. (“BioCryst” or the “Company”) will be held on June 7, 2022 at 10:00 a.m. Eastern Time at our Company headquarters at 4505 Emperor Blvd., Suite 200, Durham, NC 27703. As previously disclosed in our Proxy Statement, the record date for determining the Company’s stockholders entitled to vote at the Meeting has been fixed as of the close of business on April 11, 2022.

Our Proxy Statement requests that the Company’s stockholders consider and vote upon a number of proposals, including a proposal to approve an amendment and restatement to the BioCryst Pharmaceuticals, Inc. Stock Incentive Plan (as amended and restated, the “Stock Incentive Plan”), increasing the number of shares of the Company’s common stock (“Common Stock”) available for issuance under the Stock Incentive Plan by 8,000,000 shares (“Proposal 4”).

Glass Lewis & Co. Inc. has recommended a vote FOR Proposal 4. Another advisory firm, Institutional Shareholder Services (“ISS”), found that the Stock Incentive Plan’s estimated costs, the plan features, and our equity grant practices resulted in a favorable score, but recommended against Proposal 4 based on its dilution calculation. Although we respect the ISS approach, please consider the following points as you evaluate Proposal 4:

As of May 23, 2022, the Company had a total of 185,623,300 shares of Common Stock outstanding. The potential share dilution from the 8,000,000 additional shares to be reserved for issuance under the Stock Incentive Plan, for which stockholder approval is being requested, is 4.3% of the Company's outstanding shares of Common Stock as of such date. Approximately 33% of shares reserved for awards already granted under our equity plans are underwater as of May 23, 2022.

Our Board of Directors unanimously recommends that you vote FOR the approval of the amended and restated Stock Incentive Plan described in Proposal 4.

Even if voting instructions for your proxy have already been given, you can change your vote at any time before the Meeting by giving new voting instructions as described in more detail in the Proxy Statement. Should you have any questions or need any assistance in submitting your proxy to vote your shares, please contact our proxy solicitor, Georgeson LLC, toll-free at 877-278-4774.

Our Proxy Statement, including this Supplement, and our Annual Report on Form 10-K for the fiscal year ended December 31, 2021 are available free of charge at www.proxyvote.com.

This Supplement contains forward-looking statements, including statements regarding the Company’s plans and expectations for ORLADEYO. These statements involve known and unknown risks, uncertainties and other factors which may cause the Company’s actual results, performance, or achievements to be materially different from those expressed or implied by the forward-looking statements. These statements reflect our current views with respect to future events and are based on assumptions and are subject to risks and uncertainties. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Some of the factors that could affect the forward-looking statements contained herein include: the Company’s ability to successfully implement its commercialization plans for, and to commercialize, ORLADEYO, which could take longer or be more expensive than planned; the commercial viability of ORLADEYO, including its ability to achieve market acceptance; and actual financial results may not be consistent with expectations, including that revenue may not be within management's expected ranges. Please refer to the documents the Company files periodically with the Securities and Exchange Commission, specifically the Company’s most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K, all of which identify important factors that could cause actual results to differ materially from those contained in the Company’s projections and forward-looking statements.