EXPLANATORY NOTE

This registration statement is being filed to register the issuance of an additional 1,787,500 shares of common stock, par value $0.001 per share (the “Common Stock”) of Windtree Therapeutics, Inc. (the “Company”) that may be issued pursuant to the Company’s 2011 Long-Term Incentive Plan (the “2011 Plan”) and 10,243 shares of Common Stock that may be issued under an option awarded to Craig Fraser in connection with his employment by the Company as its President and CEO (“Inducement Grant”), plus any additional securities that become issuable under either the 2011 Plan or the terms of the Inducement Grant by reason of any stock splits, stock dividends or recapitalizations or other similar transactions.

The 2011 Plan was approved by a requisite vote of the stockholders of the Company on October 3, 2011, and the Company previously registered the issuance of the 13,214 shares then underlying such plan on a registration statement on Form S-8 (File No. 333-180497) on March 30, 2012. On September 13, 2012, the stockholders of the Company voted to amend the 2011 Plan to increase the number of shares available for issuance under such plan by 8,929 shares, and the Company registered the issuance of the 8,929 additional shares on a registration statement on Form S-8 (File No. 333-184277) on October 3, 2012. On June 11, 2013, the stockholders of the Company voted to amend the 2011 Plan to increase the number of shares available for issuance under such plan by 5,357 shares, and the Company registered the issuance of the 5,357 additional shares on a registration statement on Form S-8 (File No. 333-189966) on July 15, 2013. On June 10, 2014, the stockholders of the Company voted to amend the 2011 Plan to increase the number of shares available for issuance under such plan by 17,857 shares, and the Company registered the issuance of the 17,857 additional shares on a registration statement on Form S-8 (File No. 333-197139) on June 30, 2014. On January 21, 2016, the stockholders of the Company voted to amend the 2011 Plan to increase the number of shares available for issuance under such plan by 53,571 shares and the Company registered the issuance of the 53,571 additional shares on a registration statement on Form S-8 (File No. 333-209141) on January 27, 2016. On June 30, 2017, the stockholders of the Company voted to amend the 2011 Plan to increase the number of shares available for issuance under such plan by 37,500 shares and, on October 25, 2017 the Company’s Board of Directors voted to amend the 2011 plan to increase the number of shares available for issuance under such plan by 1,750,000 shares of Common Stock, which action was approved and ratified by the majority stockholder of the Company by written consent on November 13, 2017. Pursuant to General Instruction E to Form S-8 and with respect to the additional shares of Common Stock registered hereunder for issuance under the 2011 Plan, the contents of such registration statements, including all exhibits thereto as applicable, are incorporated herein by reference.

All documents subsequently filed by the Company pursuant to Sections 13(a), 13(c), 14 and 15(d) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), prior to the filing of a post-effective amendment which indicates that all securities offered have been sold or which deregisters all securities then remaining unsold, shall be deemed to be incorporated by reference herein and to be part hereof from the date of filing of such documents. Any statement contained herein or in a document incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for purposes of this registration statement to the extent that a statement contained herein or in any other subsequently filed document which also is incorporated or deemed to be incorporated by reference herein modifies or supersedes such statement. Any such statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this registration statement.