PROSPECTUS SUPPLEMENT |
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Filed pursuant to Rule 424(b)(5) |
(To Prospectus dated August 5, 2024) |
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Registration No. 333-281262 |

CRISPR Therapeutics AG
Up to $600,000,000
Common Shares
We previously entered into an Open Market Sale AgreementSM with Jefferies LLC, or Jefferies, on August 30, 2019, or the Sales Agreement, relating to our common shares offered by this prospectus supplement and the accompanying prospectus. In accordance with the terms of the Sales Agreement, under this prospectus supplement we may offer and sell our common shares, CHF 0.03 nominal value, having an aggregate offering price of up to $600,000,000 from time to time through Jefferies, acting as our agent.
Our common shares are listed on The Nasdaq Global Market under the symbol “CRSP.” On October 13, 2025, the closing sale price of our common shares on The Nasdaq Global Market was $68.29 per share.
Sales of our common shares, if any, under this prospectus supplement and the accompanying prospectus may be made in sales deemed to be an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended, or the Securities Act. Jefferies is not required to sell any specific number or dollar amount of securities, but will act as a sales agent using commercially reasonable efforts consistent with its normal trading and sales practices, on mutually agreed terms between Jefferies and us. There is no arrangement for funds to be received in any escrow, trust or similar arrangement.
Jefferies will be entitled to compensation at a commission rate of up to 3.0% of the gross sales price per common share sold under the Sales Agreement. See “Plan of Distribution” beginning on page S-10 for additional information regarding the compensation to be paid to Jefferies. In connection with the sale of the common shares on our behalf, Jefferies will be deemed to be an “underwriter” within the meaning of the Securities Act and the compensation of Jefferies will be deemed to be underwriting commissions or discounts. We have also agreed to provide indemnification and contribution to Jefferies with respect to certain liabilities, including liabilities under the Securities Act or the Securities Exchange Act of 1934, as amended, or the Exchange Act.
Investing in our securities involves risks. See the “Risk Factors” on page S-4 of this prospectus supplement, as well as in the documents incorporated or deemed to be incorporated by reference into this prospectus supplement and the accompanying prospectus, concerning factors you should consider before buying the common shares.
Neither the Securities and Exchange Commission nor any other regulatory body has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus supplement or the accompanying prospectus. Any representation to the contrary is a criminal offense.
Jefferies
The date of this prospectus supplement is October 15, 2025.

