EX-4.4



 Exhibit 4.4 

SECOND AMENDMENT TO WARRANT AGENCY AGREEMENT 

THIS SECOND AMENDMENT TO WARRANT AGENCY AGREEMENT made as of May 10, 2016 (this “Second Amendment”), amends that
certain Warrant Agency Agreement, dated June 19, 2015 (the “Original Agreement”), as amended by the First Amendment to Warrant Agency Agreement dated as of December 31, 2015 (together with the Original Agreement, the
“Warrant Agency Agreement”), between Provectus Biopharmaceuticals, Inc., a Delaware corporation, with offices at 7327 Oak Ridge Highway, Suite A, Knoxville, Tennessee 37931 (the “Company”), and Broadridge Corporate
Issuer Solutions, Inc., with offices at 1717 Arch Street, Suite 1300, Philadelphia, Pennsylvania 19103 (the “Warrant Agent”). Capitalized terms that are used and not defined in this Second Amendment shall have the meanings assigned
to them in the Warrant Agency Agreement. 
 WHEREAS, the Company is engaged in a tender offer (the “Second Tender
Offer”) to promote the early exercise of certain of the Company’s outstanding warrants that were issued to investors in connection with various private placement transactions between November 2011 and December 2015 with exercise prices
between $1.00 and $3.00 per share (the “Existing Warrants”); 
 WHEREAS, the Second Tender Offer, which, as defined
by the documents relating to the Second Tender Offer, is the period from May 13, 2016, until June 28, 2016 at 4:00 P.M. Eastern Time, unless earlier withdrawn or otherwise extended by the Company (the “Offer Period”), so
that each Existing Warrant holder who tenders an Existing Warrant for early exercise may exercise such Existing Warrant at a discount to the applicable strike price of $0.75, and will receive, in addition to the shares of the Company’s common
stock, par value $0.001 per share (the “Common Stock”), purchased upon exercise of such Existing Warrant, a new warrant expiring June 19, 2020 to purchase the same number of shares of Common Stock at an exercise price of $0.85
per share (the “Second Replacement Warrants”); 
 WHEREAS, on June 19, 2015, the Company engaged the Warrant
Agent to act on behalf of the Company in connection with the issuance, registration, transfer, exchange, redemption and exercise of 17,500,000 warrants issued to investors in connection with the Company’s public offering pursuant to that
certain Registration Statement, No. 333-182476 on Form S-3 (the “2015 Registration Statement”), filed with the U.S. Securities and Exchange Commission (the “Commission”), which warrants were the subject of the
Original Agreement (the “Public Warrants”); 
 WHEREAS, on December 31, 2015, the Company engaged in a prior
tender offer (the “Tender Offer”) to promote the early exercise of the Existing Warrants and in connection therewith, issued to each Existing Warrant holder who tendered an Existing Warrant for early exercise, Common Stock purchased
upon exercise of such Existing Warrant and a new warrant expiring June 19, 2020 to purchase the same number of shares of Common Stock at an exercise price of $0.85 per share (the “Replacement Warrants” and together with the
Public Warrants and the Second Replacement Warrants, the “Warrants”) pursuant to that certain Registration Statement on Form S-4, No. 333-208816; 

WHEREAS, as a result of the Second Tender Offer, the Company may issue and deliver the Second Replacement Warrants to purchase up
to 51,149,594 shares of Common Stock to those Existing Warrant holders who tender their Existing Warrants for early exercise during the Offer Period (the “2016 Warrant Shares”), pursuant to a certain Registration Statement on
Form S-4 (the “2016 Registration Statement”), to be filed with the Commission; 
 WHEREAS, the Company desires
the Warrant Agent to act on behalf of the Company, and the Warrant Agent is willing to so act, in connection with the issuance, registration, transfer, exchange, redemption and exercise of the Second Replacement Warrants in addition to the Public
Warrants and the Replacement Warrants; 
 WHEREAS, Section 9.8 of the Warrant Agency Agreement provides that the Warrant Agency
Agreement may be amended by the parties thereto without the consent of any registered Warrant holder for the purpose of adding or changing any provisions with respect to matters arising under the Warrant Agency Agreement as the parties may deem
necessary or desirable and that the parties deem shall not adversely affect the interest of the holders of the Public Warrants and the Replacement Warrants; and 

  
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 WHEREAS, the parties desire to amend the Warrant Agency Agreement to expand the scope
of the Warrant Agent’s appointment to include the Second Replacement Warrants, in addition to the Public Warrants and the Replacement Warrants, and the parties deem that such amendment does not adversely affect the interest holders of the
Public Warrants and the Replacement Warrants. 
 NOW, THEREFORE, in consideration of the foregoing and the mutual agreements
herein contained, and intending to be legally bound hereby, the Company and the Warrant Agent hereby agree as follows: 
 1. Definition of
“Warrants” to Include the Second Replacement Warrants. The term “Warrants” as used in the Warrant Agency Agreement shall be deemed to include the Public Warrants, the Replacement Warrants and the Second Replacement
Warrants. 
 2. Definition of “Warrant Shares” to Include the Second 2016 Warrant Shares. The term “Warrant Shares” as
used in the Warrant Agency Agreement shall be deemed to include the Warrant Shares (as defined in the Warrant Agency Agreement), registered with the Commission pursuant to the 2015 Registration Statement, the 2016 Warrant Shares, registered with the
Commission pursuant to the 2016 Registration Statement and the Second 2016 Warrant Shares, registered with the Commission pursuant to the Second 2016 Registration Statement. 

3. Amendment to Section 3.2. Section 3.2 of the Warrant Agency Agreement shall be deleted in its entirety and replaced with the following:

 3.2 Duration of Warrants. A Public Warrant may be exercised only during the period commencing on June 19, 2015, and
terminating at 5:00 P.M., Philadelphia, Pennsylvania time on June 19, 2020 (the “Public Warrant Expiration Date”). A Replacement Warrant or Second Replacement Warrant, as applicable, may be exercised only during the period
commencing on the date of issuance of the Replacement Warrant or Second Replacement Warrant, as applicable, and terminating at 4:00 p.m., Philadelphia, Pennsylvania time on June 19, 2020 (the “Replacement Warrant Expiration
Date” and together with the Public Warrant Expiration Date, the “Expiration Date”). Each Warrant not exercised on or before the Expiration Date shall become void, and all rights thereunder and all rights in respect
thereof under this Warrant Agency Agreement shall cease at the close of business on the Expiration Date. “Issuance Date” shall mean, with respect to the Public Warrants, June 19, 2015, and with respect to the Replacement Warrants
or Second Replacement Warrants, the date such Replacement Warrant or Second Replacement Warrant, as applicable, was issued. “Exercise Period” shall mean, with respect to the Public Warrants, the period commencing on June 19,
2015, and terminating on the Public Warrant Expiration Date, and with respect to the Replacement Warrants or Second Replacement Warrants, the period commencing on the date such Replacement Warrant or Second Replacement Warrant, as applicable, was
issued, and terminating on the Replacement Warrant Expiration Date. 
 4. Binding Effect. Except to the extent expressly provided herein, the
Warrant Agency Agreement shall remain in full force and effect in accordance with its terms. This Second Amendment shall be governed by and construed as one with the Warrant Agency Agreement, and the Warrant Agency Agreement shall be read and
construed so as to incorporate this Second Amendment. 
 5. Governing Law. The validity, interpretation, and performance of this Second Amendment
shall be governed in all respects by the laws of the State of New York, without giving effect to conflicts of law principles that would result in the application of the substantive laws of another jurisdiction. The Company hereby agrees that any
action, proceeding or claim against it arising out of or relating in any way to this Second Amendment shall be brought and enforced in the courts of the State of New York or the United States District Court for the Southern District of New York, and
irrevocably submits to such jurisdiction, which jurisdiction shall be exclusive. The Company hereby waives any objection to such exclusive jurisdiction and that such courts represent an inconvenience forum. Any such process or summons to be served
upon the Company may be served by transmitting a copy thereof by registered or certified mail, return receipt requested, postage prepaid, addressed to it at the address set forth in Section 9.2 of the Warrant Agency Agreement. Such mailing
shall be deemed personal service and shall be legal and binding upon the Company in any action, proceeding or claim. 

  
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 6. Counterparts; Effectiveness. This Second Amendment may be executed in any number of counterparts
and each of such counterparts shall for all purposes be deemed to be an original, and all such counterparts shall together constitute but one and the same instrument. 

[Signature Page Follows.] 

  
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 IN WITNESS WHEREOF, this Second Amendment to Warrant Agency Agreement has been duly
executed by the parties hereto as of the day and year first above written. 
  

			
	PROVECTUS BIOPHARMACEUTICALS, INC.
		
	By:	 	 /s/ John R. Glass

	Name:	 	John R. Glass
	Its:	 	Interim Chief Financial Officer
	
	 BROADRIDGE CORPORATE ISSUER

SOLUTIONS, INC.

		
	By:	 	 /s/ John P. Dunn

	Name:	 	 John P. Dunn

	Its:	 	 Vice President



 Signature Page to Second Amendment to Warrant Agency Agreement