Document:

FOURTH
AMENDMENT TO AMENDED AND RESTATED CREDIT AGREEMENT

This FOURTH AMENDMENT
TO AMENDED AND RESTATED CREDIT AGREEMENT (this “Amendment”) is made and entered into as of July 29, 2016
(the “Amendment Closing Date”) by and among Bacterin
International, Inc., a Nevada corporation (the “Borrower”), ROS
acquisition offshore lp, a Cayman Islands Exempted Limited Partnership (“ROS”) and OrbiMed Royalty
Opportunities II, LP, a Delaware limited partnership (“Royalty Opportunities”).

WHEREAS, the
Borrower, ROS and Royalty Opportunities are party to that certain Amended and Restated Credit Agreement, dated as of July 27, 2015,
as amended by that certain First Amendment to Amended and Restated Credit Agreement, dated as of March 31, 2016, that certain Second
Amendment to Amended and Restated Credit Agreement, dated as of May 25, 2016 and that certain Third Amendment to Amended and Restated
Credit Agreement, dated as of June 30, 2016 (the “Credit Agreement”), pursuant to which (i) ROS and Royalty
Opportunities, as Lenders under the Credit Agreement, have extended credit to the Borrower on the terms set forth therein and (ii)
each Lender has appointed ROS as the administrative agent (the “Administrative Agent”) for the Lenders;

WHEREAS, pursuant
to Section 11.1 of the Credit Agreement, the Credit Agreement may be amended by an instrument in writing signed by each of the
Borrower and the Administrative Agent (acting on behalf of the Lenders);

WHEREAS, the
Borrower and the Lenders desire to amend certain provisions of the Credit Agreement as provided in this Amendment.

NOW, THEREFORE,
in consideration of the mutual agreements herein contained, and for other good and valuable consideration, the receipt and sufficiency
of which are hereby acknowledged, the parties hereto agree as follows:

1.                 
Definitions; Loan Document. Capitalized terms used herein without definition shall have the meanings assigned
to such terms in the Credit Agreement. This Amendment shall constitute a Loan Document for all purposes of the Credit Agreement
and the other Loan Documents.

2.                       
Amendments to Section 1.1.

(a)              
Section 1.1 of the Credit Agreement is hereby amended by inserting the following new defined terms therein in the proper
alphabetical order:

“Initial
Commitment” means, with respect to each Lender, its obligations (if any) to make New Loans hereunder on the Restatement
Date.

“Tranche
A Closing Date” means July 29, 2016.

     

     

    

“Tranche
A Commitment” means, with respect to the Tranche A Lender, its obligations (if any) to make the Tranche A Loan hereunder
on the Tranche A Closing Date.

“Tranche
A Commitment Amount” means $1,000,000 in the aggregate. The Tranche A Commitment Amount of ROS is $638,333 and the Tranche
A Commitment Amount of Royalty Opportunities is $361,667.

“Tranche
A Commitment Termination Date” means the earliest to occur of (i) the Tranche A Closing Date (immediately after the making
of the Tranche A Loan on such date) and (ii) July 30, 2016, if the Tranche A Loan shall not have been made hereunder prior to such
date.

“Tranche
A Loan” is defined in Section 2.1.

(b)              
The definition of “Commitment” in Section 1.1 of the Credit Agreement is hereby amended by restating it in its
entirety as follows:

“Commitment”
means (i) the Initial Commitment and (ii) the Tranche A Commitment.

(c)              
The definition of “Loans” in Section 1.1 of the Credit Agreement is hereby amended by restating it in its entirety
as follows:

“Loans”
means (i) the Continuing Loans, (ii) the New Loans and (iii) the Tranche A Loan.

3.                 
Amendment to Section 2.1. Section 2.1 of the Credit Agreement is hereby amended and restated in its entirety
to read as follows:

“SECTION
2.1 Restatement Date and Tranche A Closing Date Transactions. Subject to the terms and conditions set forth herein, (a)
the Continuing Lender will continue as a Lender under this Agreement holding on the Restatement Date, after giving effect to the
transactions provided for herein, a Loan in the amount set forth as a Continuing Loan opposite the name of such Lender on Schedule
2.1, (b) each Lender having an Initial Commitment as set forth in Schedule 2.1 agrees to make a New Loan to the Borrower
on the Restatement Date in a principal amount equal to its Initial Commitment, with the result that each Lender will hold on the
Restatement Date, after giving effect to the transactions provided for herein, Loans in the amount set forth opposite its name
on Schedule 2.1 and (c) each agrees to make a term loan (the “Tranche A Loan”) to the Borrower on the
Tranche A Closing Date in an amount equal to (but not less than) the Tranche A Commitment Amount of such Lender. Amounts paid or
prepaid in respect of Loans may not be reborrowed. The Initial Commitment of the Lenders shall expire at 5:00 p.m., New York City
time, on the Restatement Date. The Tranche A Commitment of each Lender shall expire at 5:00 p.m., New York City time, on the Tranche
A Closing Date.”

    	 	 -2-	 

     

    

4.                 
Amendment to Section 2.2. Section 2.2 of the Credit Agreement is hereby amended and restated in its entirety
to read as follows:

“SECTION
2.2 Loans and Borrowing. Each Loan outstanding on the Restatement Date or the Tranche A Closing Date, after giving effect
to the transactions provided for in Section 2.1, shall be part of a borrowing consisting of Loans held ratably by the Lenders
in accordance with the percentages that their respective Loans bear to the aggregate principal amount of the outstanding Loans.
The failure of any Lender having a Commitment to make any New Loan or Tranche A Loan required to be made by it on the Restatement
Date or Tranche A Closing Date (as applicable) shall not relieve any other Lender of its obligations hereunder; provided that the
Commitments of the Lenders are several and no Lender shall be responsible for any other Lender’s failure to make New Loans
or Tranche A Loans as required.”

5.                 
Amendment to Section 2.3. Section 2.3 of the Credit Agreement is hereby amended and restated in its entirety
to read as follows:

“SECTION
2.3 Borrowing Procedure. The Borrower may irrevocably request that the New Loans be made by delivering to the Administrative
Agent a Loan Request on or before 10:00 a.m. on the Restatement Date. The Borrower may irrevocably request that the Tranche A Loan
by made by delivering to the Administrative Agent a Loan Request on or before 10:00 a.m. on the Tranche A Closing Date.”

6.                 
Amendment to Section 2.4. Section 2.4 of the Credit Agreement is hereby amended and restated in its entirety
to read as follows:

“SECTION
2.4 Funding. After receipt of the Loan Request for the New Loans or the Tranche A Loans, the Lenders shall, on the Restatement
Date or on the Tranche A Closing Date (as applicable) and subject to the terms and conditions hereof, make the requested proceeds
of the New Loans or the Tranche A Loans (as applicable) available to the Borrower by wire transfer to the account the Borrower
shall have specified in its Loan Request.”

7.                 
Amendment to Section 2.5. Section 2.5 of the Credit Agreement is hereby amended and restated in its entirety
to read as follows:

“SECTION
2.5 Reduction of the Commitment Amounts. The Commitment Amount shall automatically and permanently be reduced to zero on
the Commitment Termination Date. The Tranche A Commitment Amount shall automatically and permanently be reduced to zero on the
Tranche A Commitment Amount Termination Date.”

    	 	 -3-	 

     

    

8.                 
Conditions to Effectiveness of Amendment. This Amendment shall become effective upon:

(a)              
receipt by the Borrower and the Administrative Agent of a counterpart signature of the other to this Amendment duly executed
and delivered by each of the Borrower and the Administrative Agent; and

(b)              
the receipt by the Administrative Agent, from Holdings, the Borrower and each Subsidiary party to a Loan Document, of a
certificate, dated as of the Amendment Closing Date, duly executed and delivered by such Person’s Secretary or Assistant
Secretary, managing member or general partner, as applicable, as to (i) resolutions of each such Person’s Board of Directors
(or other managing body, in the case of other than a corporation) then in full force and effect authorizing the execution, delivery
and performance of each Loan Document to be executed by such Person and the transactions contemplated hereby and thereby; (ii)
the incumbency and signatures of those of its officers, managing member or general partner, as applicable, authorized to act with
respect to each Loan Document to be executed by such Person; and (iii) the full force and validity of each Organic Document of
such Person and copies thereof; upon which certificates the Administrative Agent may conclusively rely until it shall have received
a further certificate of the Secretary, Assistant Secretary, managing member or general partner, as applicable, of any such Person
canceling or amending the prior certificate of such Person.

9.                 
Expenses. The Borrower agrees to pay on demand all expenses of the Administrative Agent (including, without
limitation, the fees and out-of-pocket expenses of Covington & Burling LLP, counsel to the Administrative Agent) incurred in
connection with the Administrative Agent’s review, consideration and evaluation of this Amendment, including the rights and
remedies available to it in connection therewith, and the negotiation, preparation, execution and delivery of this Amendment.

10.             
Representations and Warranties. The Borrower represents and warrants to each Lender as follows:

(a)              
After giving effect to this Amendment, the representations and warranties of the Borrower and the Guarantors contained in
the Credit Agreement or any other Loan Document shall, (i) with respect to representations and warranties that contain a materiality
qualification, be true and correct in all respects on and as of the date hereof, and (ii) with respect to representations and warranties
that do not contain a materiality qualification, be true and correct in all material respects on and as of the date hereof, and
except that the representations and warranties limited by their terms to a specific date shall be true and correct as of such date.

(b)              
After giving effect to this Amendment, no Default or Event of Default under the Credit Agreement will occur or be continuing.

11.             
No Implied Amendment or Waiver. Except as expressly set forth in this
Amendment, this Amendment
shall not, by
implication or otherwise,
limit, impair, constitute
a waiver of or otherwise affect any rights or remedies of the Administrative Agent or the
Lenders under the Credit Agreement or the other Loan Documents, or alter, modify, amend or in any
way affect any of the terms, obligations or covenants contained in the Credit
Agreement or the other Loan Documents, all of which shall continue in full force and
effect. Nothing in this Amendment shall be construed to imply any willingness on the part of the Administrative
Agent or the Lenders to agree to or grant any similar or future amendment, consent or waiver of any
of the terms and conditions of the Credit Agreement or the other Loan Documents.

    	 	 -4-	 

     

    

12.             
Waiver and Release. TO INDUCE THE ADMINISTRATIVE AGENT, ACTING ON BEHALF OF THE LENDERS, TO AGREE TO THE TERMS
OF THIS AMENDMENT, THE BORROWER REPRESENTS AND WARRANTS THAT AS OF THE DATE HEREOF THERE ARE NO CLAIMS OR OFFSETS AGAINST OR RIGHTS
OF RECOUPMENT WITH RESPECT TO OR DEFENSES OR COUNTERCLAIMS TO ITS OBLIGATIONS UNDER THE LOAN DOCUMENTS AND IN ACCORDANCE THEREWITH
IT:

(a)              
WAIVES ANY AND ALL SUCH CLAIMS, OFFSETS, RIGHTS OF RECOUPMENT, DEFENSES OR COUNTERCLAIMS, WHETHER KNOWN OR UNKNOWN, ARISING
PRIOR TO THE DATE HEREOF; AND

(a)              
RELEASES AND DISCHARGES THE ADMINISTRATIVE AGENT,
THE LENDERS, THEIR AFFILIATES AND THEIR OFFICERS, DIRECTORS, EMPLOYEES, AGENTS, SHAREHOLDERS
AND ATTORNEYS (COLLECTIVELY THE "RELEASED PARTIES") FROM ANY AND ALL
OBLIGATIONS, INDEBTEDNESS, LIABILITIES, CLAIMS, RIGHTS, CAUSES OF ACTION OR DEMANDS
WHATSOEVER, WHETHER KNOWN OR UNKNOWN, SUSPECTED OR UNSUSPECTED, IN LAW OR EQUITY,
WHICH THE BORROWER
EVER HAD, NOW
HAS, CLAIMS TO
HAVE OR

 

(b)              
MAY HAVE AGAINST ANY RELEASED PARTY ARISING PRIOR TO THE DATE HEREOF
AND FROM OR
IN CONNECTION WITH
THE LOAN DOCUMENTS
OR THE TRANSACTIONS CONTEMPLATED
THEREBY.

13.             
Counterparts; Governing Law. This Amendment may be executed in any number of counterparts and by different
parties hereto on separate counterparts, each of such when so executed and delivered shall be an original, but all of such counterparts
shall together constitute but one and the same agreement. Delivery of an executed counterpart of a signature page of this Amendment
by fax transmission or other electronic mail transmission (e.g., “pdf” or “tif”) shall be effective as
delivery of a manually executed counterpart of this Amendment. THIS AMENDMENT SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE
WITH, THE INTERNAL LAWS OF THE STATE OF NEW YORK (INCLUDING FOR SUCH PURPOSE SECTIONS 5-1401 AND 5-1402 OF THE GENERAL OBLIGATIONS
LAW OF THE STATE OF NEW YORK).

[Remainder
of Page Intentionally Left Blank]

    	 	 -5-	 

     

    

IN WITNESS WHEREOF, the parties
hereto have caused this Amendment to be executed by their respective officers thereunto duly authorized as of the day and year
first above written.

 

	 	
        BACTERIN INTERNATIONAL, INC.,

        as the Borrower

	 	 
	 	By:  John P. Gandolfo
	 	Name:  John P. Gandolfo
	 	Title:    Chief Financial Officer
	 	 
	 	ROS Acquisition Offshore LP,

as a Lender and as the Administrative Agent
	 	By ROS Acquisition Offshore GP Ltd.,
	 	its General Partner
	 	By OrbiMed Advisors LLC,
	 	its investment manager
	 	 
	 	By:  W. Carter Neild
	 	Name:  W. Carter Neild
	 	
        Title: Member

         

         

	 	 
	 	ORBIMED ROYALTY OPPORTUNITIES II, LP,

as a Lender 
	 	By OrbiMed ROF II LLC,
	 	its General Partner
	 	By OrbiMed Advisors LLC,
	 	its Managing Member
	 	 
	 	By:  W. Carter Neild
	 	Name:  W. Carter Neild
	 	Title:    Member

 

 

Signature Page to Fourth Amendment to A&R Credit AgreementExhibit 10.4

 

AMENDMENT TO INCENTIVE STOCK OPTION
AGREEMENT

 

This AMENDMENT TO INCENTIVE STOCK
OPTION AGREEMENT (this “Amendment”), dated as of                ,
2016, is made and entered into by and between PhaseRx, Inc., a Delaware corporation (the “Company”),
and                 (the “Participant”).
Terms used in this Amendment with initial capital letters that are not otherwise defined herein shall have the meanings ascribed
to such terms in the Incentive Stock Option Agreement by and between the Company and the Participant, dated                ,
2016 (the “Option Agreement”), and in the PhaseRx 2016 Long-Term Incentive Plan.

 

WHEREAS, pursuant to the Option
Agreement, the Company granted an option (the “Option”) to the Participant to purchase a total of                
(               ) full shares of Common
Stock of the Company at an Option Price equal to $               
per share; and

 

WHEREAS,
Section 24 of the Option Agreement provides that the Option Agreement can be amended by a writing signed by the parties thereto,
and the Company and the Participant now desire to amend the Option Agreement to revise the vesting provisions that would apply
in connection with a Change in Control.

 

NOW, THEREFORE,
in accordance with the terms of the Option Agreement, and for good and valuable consideration, the sufficiency of which is hereby
acknowledged, the Company and the Participant agree as follows:

 

		1.	Section 3 of the Option Agreement is
                                         amended by deleting the last paragraph of said Section and replacing it with the following
                                         new paragraph as follows:

 

In the event that a Change in
Control occurs, (i) fifty percent (50%) of the total Optioned Shares not previously vested shall become vested and exercisable
upon the effective date of the Change in Control and (ii) any remaining Optioned Shares not previously vested shall become fully
vested and exercisable on the date of the Participant’s Termination of Service by the Company without Cause (as defined
herein) if such Termination of Service occurs on or before the first anniversary of the Change in Control’s effective date.

 

		2.	Section 4(b) of the Option Agreement
                                         is amended by deleting said Section in its entirety and replacing it with the following
                                         new Section 4(b) as follows:

 

b.      
For purposes of this Agreement, “Cause” means the Participant’s Termination of Service by the
Company because of: (i) the Participant’s conviction of, or plea of nolo contendere to, a felony or crime involving moral
turpitude or (ii) the Participant’s breach of fiduciary duty which involves personal profit. Notwithstanding the foregoing,
in the case of any Participant who has entered into an employment agreement with the Company or any Subsidiary that contains the
definition of “cause” (or any similar definition), then during the term of such employment agreement the definition
contained in such employment agreement shall be the applicable definition of “cause” under the Agreement as to such
Participant if such employment agreement expressly so provides.

 

		3.	The Option Agreement, except as modified
                                         by this Amendment, shall remain in full force and effect.

 

     

     

    

 

IN WITNESS WHEREOF,
the Company and the Participant have executed, or caused to be executed, this Amendment effective as of the day and year first
written above.

 

	 	PhaseRx,
    Inc.
	 	 	 
	 	By:	 
	 	 	Name:
	 	 	Title:
	 	 	 
	 	THE PARTICIPANT
	 	 
	 	[Name]	 

 

    2

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