PolyPid Ltd美股招股说明书(2025-11-26版)

PROSPECTUS SUPPLEMENT NO. 2(to Prospectus dated July 12, 2024) Up to $15,000,000 This prospectus supplement amends and supplements the information in the prospectus, dated July 12, 2024, filed with theSecurities and Exchange Commission as a part of our registration statement on Form F-3 (File No. 333-280658), or the RegistrationStatement, as previously supplemented by our prospectus supplement dated November 8, 2024, or collectively the Prior Prospectus,relating to the offer and sale of up to $8,250,000 of our ordinary shares, no par value, or Ordinary Shares, pursuant to the salesagreement, or the Sales Agreement, with Oppenheimer & Co. Inc., or Oppenheimer, dated November 8, 2024. This prospectussupplement should be read in conjunction with the Prior Prospectus, and is qualified by reference thereto, except to the extent that the We are filing this prospectus supplement to supplement and amend, as of November 26, 2025, the Prior Prospectus toincrease the maximum aggregate offering price of our Ordinary Shares that may be offered, issued and sold under the Sales Agreementfrom $8,250,000 to $15,000,000. Accordingly, under the Prior Prospectus, as amended by this prospectus supplement, we may now Sales of our Ordinary Shares, if any, under the Prior Prospectus and this prospectus supplement, may be made in salesdeemed to be “at the market offering” as defined in Rule 415 promulgated under the Securities Act of 1933, as amended, or theSecurities Act. Oppenheimer is not required to sell any specific number or dollar amount of securities but will act as a sales agent on abest efforts basis and will use commercially reasonable efforts consistent with its normal trading and sales practices, on mutually Oppenheimer will be entitled to compensation at a commission rate of 3.0% of the gross sales price per share sold pursuant tothe terms of the Sales Agreement. We have also agreed to reimburse Oppenheimer for certain specified expenses, including the feesand disbursements of its legal counsel, in an amount not to exceed $40,000.See “Plan of Distribution” beginning on page S-10 of thePrior Prospectus for additional information regarding the compensation to be paid to Oppenheimer. In connection with the sale of ourOrdinary Shares on our behalf, Oppenheimer will be deemed to be an “underwriter” within the meaning of the Securities Act, and the Our Ordinary Shares are listed on The Nasdaq Capital Market, or Nasdaq, under the symbol “PYPD”. On November 25,2025, the last reported sale price of our Ordinary Shares on Nasdaq was $3.68 per Ordinary Share. The aggregate market value of our Ordinary Shares held by non-affiliates as of November 25, 2025, pursuant to GeneralInstruction I.B.5 of Form F-3 is $65,953,832 which was calculated based on 17,175,477 Ordinary Shares outstanding held by non-affiliates and at a price of $3.84 per Ordinary Share, the closing price of our Ordinary Shares on October 30, 2025. We have sold an Investing in our Ordinary Shares involves risk. See “Risk Factors” beginning on page S-3 of the Prior Prospectus andin the documents incorporated by reference into the Prior Prospectus for a discussion of information that should be considered Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved ofthese securities or passed upon the adequacy or accuracy of the Prior Prospectus, this prospectus supplement or the Oppenheimer & Co. The date of this prospectus supplement is November 26, 2025.