UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

SCHEDULE 13G

Under the Securities Exchange Act of 1934

(Amendment No. 2)*

ELEVEN BIOTHERAPEUTICS, INC.

(Name of Issuer)

Common Stock, par value $0.001 per share

(Title of Class of Securities)

28622106

(CUSIP Number)

June 13, 2016

(Date of Event which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule if filed:

¨ Rule 13d-1(b)

x Rule 13d-1(c)

¨ Rule 13d-1(d)

The information required in the remainder of this cover page shall not be deemed to be “filed” for the 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).

This Amendment No. 2 (“Amendment No. 2”) amends and supplements the statement on Schedule 13G filed on May 25, 2016, as amended by Amendment No. 1 filed on June 6, 2016 (the “Original Filing”) by Boxer Capital, LLC (“Boxer Capital”), Boxer Asset Management Inc. (“Boxer Management”), MVA Investors, LLC (“MVA Investors”) and Joe Lewis. Boxer Capital, Boxer Management, MVA Investors and Joe Lewis are collectively referred to herein as the “Reporting Persons.” The Original Filing remains in effect except to the extent that it is amended, restated or superseded by information contained in this Amendment No. 2. Capitalized terms used and not defined in this Amendment No. 2 have the meanings set forth in the Original Filing.

Item 4. Ownership.

Boxer Capital, Boxer Management and Joe Lewis beneficially own 1,255,412* shares of Common Stock. MVA Investors beneficially owns 268,160* shares of Common Stock.

The shares of Common Stock beneficially owned by Boxer Capital, Boxer Management and Joe Lewis represent 6.3%* of the Issuer’s outstanding shares of Common Stock. The shares of Common Stock beneficially owned by MVA Investors represent 1.3%* of the Issuer’s outstanding shares of Common Stock.

MVA Investors has the sole power to vote or direct the vote of the 268,160* shares of Common Stock it beneficially owns. Boxer Capital, Boxer Management and Joe Lewis do not have the sole power to vote or direct the vote of any shares of Common Stock.

Boxer Capital, Boxer Management and Joe Lewis have shared power to vote or to direct the vote of the 1,255,412* shares of Common Stock they beneficially own. MVA Investors does not have power to vote or to direct the vote of any shares of Common Stock.

MVA Investors has the sole power to dispose or direct the disposition of the 268,160* shares of Common Stock it beneficially owns. Boxer Capital, Boxer Management and Joe Lewis do not have the sole power to dispose or direct the disposition of any shares of Common Stock.

Boxer Capital, Boxer Management and Joe Lewis have shared power to dispose or direct the disposition of the 1,255,412* shares of Common Stock they beneficially own. MVA Investors does not have shared power to dispose of or direct the disposition of any shares of Common Stock.

Item 10. Certification.

(c) By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect, other than activities solely in connection with a nomination under §240.14a-11.

Exhibits

1 Joint Filing Agreement, dated May 25, 2016, among the Reporting Persons (incorporated by reference to Exhibit 1 to the Schedule 13G dated May 25, 2016).

SIGNATURE

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.

June 14, 2016