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Common Stock We have entered into an At the Market Offering Agreement (the “Sales Agreement”), with H.C. Wainwright & Co., LLC(“Wainwright” or the “sales agent”) relating to the sale of shares of our common stock, par value $0.001 per share (the “commonstock”), offered by this prospectus supplement and the accompanying prospectus. In accordance with the terms of such SalesAgreement, we may offer and sell shares of our common stock having an aggregate offering price of up to $15,000,000 from time totime through or to Wainwright acting as our agent or principal. Sales of our common stock, if any, under this prospectus supplement and the accompanying prospectus will be made by any methodpermitted that is deemed an “at the market” offering as defined in Rule415(a)(4) under the Securities Act of 1933, as amended, or theSecurities Act, including sales made directly on or through the Nasdaq Capital Market (“Nasdaq”), or any other existing tradingmarket in the United States for our common stock, sales made to or through a market maker other than on an exchange or otherwise,directly to Wainwright as principal, in negotiated transactions at market prices prevailing at the time of sale or at prices related to suchprevailing market prices and/or in any other method permitted by law. If we and Wainwright agree on any method of distribution otherthan sales of shares of our common stock on or through the Nasdaq or another existing trading market in the United States at marketprices, we will file a further prospectus supplement providing all information about such offering as required by Rule424(b) under theSecurities Act. Under the Sales Agreement, Wainwright is not required to sell any specific number or dollar amount of securities, butWainwright will act as our sales agent using commercially reasonable efforts consistent with its normal trading and sales practices.There is no arrangement for funds to be received in any escrow, trust or similar arrangement. Wainwright will be entitled to compensation at a commission rate of 3.0% of the gross sales price per share sold under the SalesAgreement. See “Plan of Distribution” beginning on page S-14 for additional information regarding the compensation to be paid toWainwright. In connection with the sale of the shares of common stock on our behalf, Wainwright will be deemed to be an“underwriter” within the meaning of the Securities Act, and the compensation of Wainwright will be deemed to be underwritingcommissions or discounts. We have also agreed to provide indemnification and contribution to Wainwright with respect to certainliabilities, including liabilities under the Securities Act. This offering pursuant to this prospectus supplement and the accompanyingprospectus will terminate upon termination by us or Wainwright of the Sales Agreement pursuant to its terms. Our common stock is listed on Nasdaq under the symbol “KALA.” On January7, 2026, the last reported sale price of the commonstock on Nasdaq was $0.665 per share. Investing in our securities involves risks that are described in the “Risk Factors” beginning on page S-8 of this prospectussupplement, page 6 of the accompanying prospectus and under similar headings in the documents incorporated by referenceherein and therein. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of thesesecurities or determined if this prospectus supplement or the accompanying prospectus is truthful or complete. Anyrepresentation to the contrary is a criminal offense. H.C. Wainwright & Co. The date of this prospectus supplement is January8, 2026. TABLE OF CONTENTS Prospectus Supplement PageABOUT THIS PROSPECTUS SUPPLEMENTS-1CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTSS-2PROSPECTUS SUPPLEMENT SUMMARYS-4RISK FACTORSS-8USE OF PROCEEDSS-12DIVIDEND POLICYS-13PLAN OF DISTRIBUTIONS-14LEGAL MATTERSS-15EXPERTSS-15WHERE YOU CAN FIND ADDITIONAL INFORMATIONS-15INCORPORATION OF DOCUMENTS BY REFERENCES-16 Prospectus ABOUT THIS PROSPECTUS1WHERE YOU CAN FIND MORE INFORMATION2INCORPORATION OF CERTAIN DOCUMENTS BY REFERENCE2CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS AND INDUSTRY DATA3ABOUT KALA PHARMACEUTICALS, INC.5RISK FACTORS6USE OF PROCEEDS7DESCRIPTION OF DEBT SECURITIES8DESCRIPTION OF CAPITAL STOCK17DESCRIPTION OF DEPOSITARY SHARES24DESCRIPTION OF SUBSCRIPTION RIGHTS27DESCRIPTION OF UNITS28DESCRIPTION OF WARRANTS29FORMS OF SECURITIES30PLAN OF DISTRIBUTION32LEGAL MATTERS34EXPERTS34 ABOUT THIS PROSPECTUS SUPPLEMENT This document contains two parts. The first part is the prospectus supplement, which describes the specific terms of this offering andalso updates information contained in the accompanying prospectus and the documents incorporated by reference into this prospectussupplement and the accompanying prospectus. The second part is the accompanying prospectus, which provides more generalinformation, some of which may not apply to this offering. This prospectus