SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13D/A

Under the Securities Exchange Act of 1934

(Amendment No. 4)*

If the filing person has previously filed a statement on Schedule 13G to report the acquisition which is the subject of this Schedule 13D, and is filing this schedule because of Rule 13d-1(e), Rule 13d-1(f) or Rule 13d-1(g), check the following box  ¨.

Note: Schedules filed in paper format shall include a signed original and five copies of the schedule, including all exhibits. See Rule 13d-7(b) for other parties to whom copies are to be sent.

The information required on the remainder of this cover page shall not be deemed to be “filed” for purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall be subject to all other provisions of the Act (however, see the Notes).

EXPLANATORY NOTE

This Amendment No. 4 (the “Amendment”) to Schedule 13D is being filed with the Securities and Exchange Commission (the “SEC”) on behalf of the Reporting Persons (as defined below) and relates to the common stock, par value $0.001 per share (the “Common Stock”), of Cocrystal Pharma, Inc. (the “Issuer”). This Amendment is being filed as a result of a change in the Issuer’s issued and outstanding Common Stock and, where so stated, amends and supplements Amendment No. 3 to the Schedule 13D filed by OPKO Health, Inc. a Delaware corporation (“OPKO”), Phillip Frost, M.D. (“Dr. Frost”), Frost Gamma Investments Trust (“FGIT”), and Steven D. Rubin (“Mr. Rubin”) (collectively, the “Reporting Persons”) filed with the SEC on November 19, 2020, Amendment No. 2 to the Schedule 13D filed with the SEC on March 10, 2020, which amended and supplemented the statement on Amendment No. 1 filed with the SEC on November 22, 2019, which amended and supplemented the statement on Schedule 13D filed with the SEC on May 9, 2019 (the “May 2019 Schedule 13D”), which amended and restated the (i) Schedule 13D originally filed on December 5, 2014 filed jointly by OPKO, Dr. Frost, FGIT, Mr. Rubin and certain other persons (the “Original 13D”), as amended with respect to Dr. Frost, FGIT, Mr. Rubin and certain other persons by Amendment No. 1 filed on June 19, 2018 and Amendment No. 2 filed on March 19, 2019, and (ii) Schedule 13G filed by OPKO on May 10, 2017, as amended on February 2, 2018 and February 14, 2019. This Amendment is being filed solely by the Reporting Persons and does not amend or supplement the Original 13D or any other amendments thereto with respect to any other persons that jointly filed the Original 13D with the Reporting Persons. Except as set forth herein, this Amendment does not modify any of the information previously reported by the Reporting Persons in the May 2019 Schedule 13D. Unless otherwise indicated, all capitalized terms used herein have the meanings ascribed to them in the May 2019 Schedule 13D.

Items 5(a)-(c), (e) are hereby amended and restated to read as follows:

(a) Dr. Frost holds 71,041 shares of Common Stock issuable upon exercise of options exercisable within 60 days. Dr. Frost, as the sole trustee of FGIT, may be deemed to beneficially own the 3,655,265 shares of Common Stock beneficially owned by FGIT. The 3,726,306 shares of Common Stock beneficially owned by Dr. Frost constitute approximately 3.8% of the Issuer’s issued and outstanding shares, based on (i) 97,468,755 shares outstanding as of May 14, 2021, as reported by the Issuer in its Form 10-Q; and (ii) 71,041 shares of Common Stock issuable upon exercise of options exercisable within 60 days. FGIT holds 3,655,265 shares of Common Stock or approximately 3.8% of the Issuer’s issued and outstanding shares, based on 97,468,755 shares outstanding as of May 14, 2021, as reported by the Issuer in its Form 10-Q.

Mr. Rubin holds (i) 24,448 shares of Common Stock; and (ii) 82,041 shares of Common Stock issuable upon exercise of options exercisable within 60 days, or approximately 0.1% of the Issuer’s issued and outstanding shares, based on (i) 97,468,755 shares outstanding as of May 14, 2021, as indicated by the Issuer in its Form 10-Q; and (ii) 82,041 shares of Common Stock owned by Mr. Rubin and issuable upon exercise of options exercisable within 60 days.

(b) Dr. Frost, as the sole trustee of FGIT, has sole voting and dispositive power over 3,655,265 shares of Common Stock beneficially owned by FGIT. Dr. Frost individually owns and has sole voting and dispositive power with respect to 71,041 shares of Common Stock issuable upon exercise of options exercisable within 60 days.

FGIT directly beneficially owns 3,655,265 shares of Common Stock. Dr. Frost is the sole trustee of FGIT and has sole voting and dispositive power with respect to 3,655,265 shares of Common Stock.

Mr. Rubin individually owns and has sole voting and dispositive power with respect to 24,448 shares of Common Stock and 82,041 shares of Common Stock issuable upon exercise of options exercisable within 60 days.

(c) There have been no transactions in the Common Stock effected by the Reporting Persons in the last 60 days

(e) As of June 9, 2021, each of the Reporting Persons ceased to be the beneficial owner of more than five percent of the Issuer’s Common Stock. This Amendment No. 4 represents the final amendment to the Schedule 13D and constitutes an exit filing for the Reporting Persons.

SIGNATURES

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.