Document:

Amendment No. 1

 Exhibit 10.218 
  
 Portions of this exhibit marked [*] are omitted and are requested to be treated confidentially. 
  
 AMENDMENT NO. 1 TO THE AGREEMENT 
  
 This Amendment No. 1 (the “Amendment”), is effective as of the
10th day of October, 2005, by and among Takeda San Diego, Inc., a Delaware corporation having a place of business at 10410 Science Center Drive, San Diego, CA 92121 (“TSD”), Takeda Pharmaceutical Company Limited, a
corporation organized under the laws of Japan, having its principal place of business at 1-1 Doshomachi 4-chome, Chuo-ku, Osaka, Japan ( “TPC”), Development Partners, LLC, a Delaware limited liability company having its
principal place of business at 3151 South 17th Street, Wilmington, NC 28412 (“PPD”), and Pharmaceutical Product Development, Inc., a North Carolina corporation having its principal place of business at 3151 South 17th Street,
Wilmington, NC 28412 (“PPD, Inc.”). 
  
 WHEREAS,
TSD, TPC, PPD and PPD, Inc. are parties to that certain Agreement dated July 13, 2005 (the “Agreement”); and 
  
 WHEREAS, TSD, TPC, PPD and PPD, Inc. wish to amend the Agreement in order to modify the timing and transfer of the IND for 322 and 619, modify milestone
payments associated with Phase III development and clarify the contract assignment and indemnification obligations of the Parties. 
  
 NOW, THEREFORE, that for and in consideration of the foregoing premises, the mutual covenants herein contained, and other good and valuable consideration,
the receipt and sufficiency of which is hereby acknowledged, the parties agree as follows: 
  
 1. All capitalized terms used but not otherwise defined herein will have the meanings ascribed to them in the Agreement. 

 2. Schedule 2.1(a)(i)(2) (Third Party Contracts Assumed by TSD) is replaced in its entirety with the
attached new Schedule 2.1(a)(i)(2) in which subsection I (Renal Impairment Site Agreements) has been deleted. 
  
 3. Section 3.3 is replaced in its entirety with the following new Section 3.3: 
  
 3.3. Delivery of Documents and Materials. Promptly following the Effective Date, PPD shall deliver to TSD any and all
data and documentation in PPD’s Control related to the development of a Compound or Product, and not in the possession of TSD, on the Effective Date. Following the Effective Date, PPD shall promptly notify TSD if it later discovers any data or
documentation in PPD’s Control related to the development of a Compound or Product that was not previously delivered to TSD and shall promptly deliver such to TSD. PPD transferred to Takeda Global Research & Development Center, Inc.
(“TGRD”) the legal title to the associated INDs presently on file and any comparable filings in other countries of the Territory for SYR110322 and SYR110619 on September 1, 2005. PPD shall transfer to TSD ownership of all Drug
Substance, CTM and Finished Product of SYR110322 and SYR110619 and any other Material in its possession as of the Effective Date of this Agreement, the amounts of which are listed on Schedule 3.3. 
  
 4. The table in Section 5.2(a) is replaced in its entirety with the
following new table for Section 5.2(a): 
  

			
	 Milestone Event

	 	 Milestone Payment

		
	 Dosing of any Product to the twentieth (20th) subject in a Phase III Trial
	 	 Fifteen million dollars ($15,000,000)

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million dollars ($[*])

		
	 [*]
	 	 [*] million [*] hundred thousand dollars ($[*])

  
 5. Section 7.1 is
deleted in its entirety and replaced with the following: 
  
 7.1
TSD Indemnification of PPD. TSD hereby agrees to indemnify, defend and hold harmless PPD and its Affiliates and their directors, officers, agents and employees (the “PPD Indemnitees”) from and against any and all
damages, 

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 liabilities, expenses and/or loss, including reasonable legal expenses and reasonable attorneys’
fees (“Losses”) resulting from suits, claims, proceedings, or causes of action (“Claims”) brought by a Third Party against such PPD Indemnitee arising from: (i) any allegation of infringement or
misappropriation of a Third Party’s intellectual property relating to the subject matter of this Agreement; (ii) any breach by TSD or its Affiliates of a representation or warranty contained in this Agreement; (iii) any breach of this
Agreement or applicable law by TSD or its Affiliates; (iv) the handling, possession, development, manufacturing, marketing, distribution, promotion, sale or use of Product; (v) any allegation of injury or death caused by any person’s
use of Product; (vi) any liability or other claim (including without limitation, injury or death) for the use of any Drug Substance, CTM, or Product; (vii) the breach or other violation of any underlying license to the Intellectual
Property licensed to TSD by PPD in Section 3.2, by TSD and its Permitted Sellers and other licensees or subcontractors; (viii) the exercise of any right(s) under the Intellectual Property, by TSD and its Permitted Sellers and other
licensees or subcontractors; (ix) any failure by TSD or its Affiliates to comply in all material respects with applicable laws in connection with the performance of their respective obligations or the exercise of their respective rights under
this Agreement; (x) the negligence or willful misconduct of TSD or its Affiliates in the performance of this Agreement; (xi) the contracts listed in Schedule 2.1(a)(i)(l) that are assigned to TSD pursuant to Section 2.1(a)(i), but
only to the extent such Claim arises from activities under such contracts that occur after the Effective Date; and/or (xii) the Letters of Indemnification, Phase II Clinical Research Agreements and Renal Impairment Site Agreements identified on
Schedule 7.1 attached hereto, but only to the extent a Claim arises from activities under such agreements that occur after the Effective Date. 
  
 The foregoing indemnification obligations shall not apply to the extent such PPD Losses result from (1) breach by PPD or its Affiliates of a
representation or warranty contained in this Agreement or, with respect to Section 7.1(xii) only, the Global Master Agreement, Clinical Research Management Services (Phases II-IV) dated July 13, 2005 executed by PPD, Takeda Global
Research & Development Center, Inc. and Takeda Europe Research & Development Centre Ltd. (“Clinical Agreement”); and/or (2) breach of this Agreement, applicable law or, with respect to Section 7.1(xii)
only, the Clinical Agreement by the PPD Indemnitee; and/or (3) the negligence or willful misconduct of the PPD Indemnitee in the performance of this Agreement or, with respect to Section 7.1(xii) only, the Clinical Agreement. TSD and TPC
agree to indemnify, defend and hold the PPD Indemnitees harmless from any Claim against the PPD Indemnitees as a result of [*]. 
  
 6. Attached hereto is a new Schedule 7.1 to the Agreement containing a list of Phase II Clinical Research Agreements and Letters of Indemnification and a
list of Renal Impairment Site Agreements for which TSD or an Affiliate of TSD will assume the role of sponsor as defined in 21 CFR §312.3(b) after the Effective Date. 

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 7. Section 7.3 is deleted in its entirety and replaced with the following: 
  
 7.3 Indemnification Procedure. 
  

	 	(a)	If any action is brought against a party entitled to indemnification under Section 7.1 or 7.2, as applicable, (each, an “Indemnified Party”), such Indemnified Party
or Parties shall promptly notify the party obligated to provide indemnification (an “Indemnifying Party”) in writing of the institution of such action. 

  

	 	(b)	Promptly upon receipt of notice pursuant to subparagraph (a) above, the Indemnifying Party shall promptly assume the defense of such action, including, without limitation, the
employment of counsel reasonably satisfactory to such Indemnified Party or Parties, and payment of expenses. An Indemnified Party or Parties shall have the right to employ its or their own counsel in any such case, but the fees and expenses of such
counsel shall be at the expense of such Indemnified Party or Parties, unless: 

  

	 	(i)	the employment of such counsel shall have been authorized in writing by the Indemnifying Party in connection with the defense of such action; or 

  

	 	(ii)	the named parties to such action include both the Indemnified Party or Parties and the Indemnifying Party and such Indemnified Party or Parties shall have reasonably concluded that
there may be one or more legal defenses available to it or them or to other Indemnified Parties which are different from, or in addition to, those available to the Indemnifying Party. 

  
 In either of the foregoing events, such fees and expenses shall be borne by
the Indemnifying Party and the Indemnifying Party shall not have the right to direct the defense of such action on behalf of the Indemnified Party or Parties. Notwithstanding anything to the contrary set forth herein, under no circumstances shall
the Indemnifying Party be obligated to assume responsibility for the expenses for more than one counsel for all the Indemnified Parties. 
  
 (c) Notwithstanding anything contained in this Section 7.3 to the contrary, the Indemnifying Party shall not be liable for any settlement of any such
claim or action effected without its written consent, which consent shall not be unreasonably withheld. The Indemnifying Party shall have the right to settle or compromise any action, or permit a default or consent to the entry of judgment in, or
otherwise seek to terminate, any pending or threatened action, in respect of which indemnity may be sought hereunder (whether or not any Indemnified Party is a party thereto), provided such settlement, compromise, consent, or termination
includes an unconditional release of each Indemnified Party from all liability in respect of such action. In the event such an unconditional release is not obtainable for each Indemnified Party, then the Indemnifying Party must obtain the prior
written consent of any Indemnified Party not so released before the Indemnifying Party may enter into such settlement, compromise, consent or termination. 

 8. PPD represents and warrants that the Sites listed under “Phase II Clinical Research Agreements
and Letters of Indemnification” on Schedule 7.1 have not executed contracts with third party providers for services performed under the respective Clinical Research Agreements for Protocol [*] entitled, “[*]”. 
  
 9. Except as expressly provided herein, in the event of a conflict between
the terms of this Amendment and the Agreement, the terms of this Amendment shall control. 
  
 10. Except as otherwise amended herein, the Agreement shall remain in full force and effect. 
  
 IN WITNESS WHEREOF, the Parties have executed this Amendment No. 1 through duly authorized representatives as of the date first set forth herein.

  

							
	Takeda San Diego, Inc.	 	Takeda Pharmaceutical Company Limited
				
	By:	 	 /s/ Stephen W. Kaldor

	 	By:	 	 /s/ Yasuhiko Yamanaka

	Name:	 	 Stephen W. Kaldor

	 	Name:	 	 Yasuhiko Yamanaka

	Title:	 	 President and Chief Scientific Officer

	 	Title:	 	 General Manager, Corporate Strategy and Planning

		
	Development Partners, LLC	 	Pharmaceutical Product Development, Inc.
				
	By:	 	 /s/ Fred N. Eshelman

	 	By:	 	 /s/ Fred N. Eshelman

	Name:	 	 Fred N. Eshelman

	 	Name:	 	 Fred N. Eshelman

	Title:	 	 President

	 	Title:	 	 Chief Executive Officer

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 2.1(a)(i)(2) 
  
 THIRD PARTY CONTRACT TO BE ASSUMED BY TSD 
  
 [*] 
  

  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC. 

 Schedule 7.1 
  
 CLINICAL RESEARCH AGREEMENTS AND 
 LETTERS OF INDEMNIFICATION 
  
 [*] 
  

	[*]	Confidential treatment requested; certain information omitted and filed separately with the SEC.Third Amendment to Loan and Security Agreement

 EXHIBIT 10.1 
 THIRD AMENDMENT 
 TO LOAN AND SECURITY AGREEMENT 
  
 THIS THIRD AMENDMENT TO LOAN AND SECURITY AGREEMENT (this
“Amendment”) is made and entered into as of the 11th day of October, 2005 among Bank of America,
N.A. (“Bank”), Omega Protein Corporation, a Nevada corporation (“Parent”), Omega Protein, Inc., a Virginia corporation (“OPI”; Parent and OPI are sometimes referred to individually as a
“Borrower” and collectively as “Borrowers”), Omega Shipyard, Inc., a Delaware corporation (“OSI”), Omega International Distribution Company, formerly known as Omega Net, Inc., a Delaware corporation
(“OIDC”), and Protein Finance Company, a Delaware corporation (“PFC”; OSI, OIDC, and PFC referred to individually as a “Guarantor” and collectively as “Guarantors”; Borrowers and Guarantors are
sometimes referred to herein individually as an “Obligor” and collectively as “Obligors”). 
  
 W I T N E S S E T H : 
  
 WHEREAS, Bank and Borrowers have entered into that certain Loan and Security Agreement dated as of December 20, 2000 (as amended, restated, modified or supplemented from time to time, the “Loan
Agreement”); and 
  
 WHEREAS, the Guarantors, together with
Protein Operating Company, a Delaware corporation (“POC”), Protein Securities Company, a Delaware corporation (“PSC”), and Protein (U.S.A.) Company, a Delaware corporation (“Protein USA”; POC, PSC and Protein USA are
herein after collectively referred to as the “Former Protein Subsidiaries”); entered into that certain Unconditional Guaranty in favor of Bank dated as of December 20, 2000 (as amended, restated, modified or supplemented from time to
time, the “Guaranty”), pursuant to which the Guarantors and the Former Protein Subsidiaries guaranteed to Bank the payment of all obligations of Borrowers to Bank however arising, including, without limitation, amounts due under the Loan
Agreement; and 
  
 WHEREAS, the Guarantors and the Former Protein
Subsidiaries entered into that certain Security Agreement in favor of Bank dated as of December 20, 2000 (as amended, restated, modified or supplemented from time to time, the “Security Agreement”), pursuant to which the Guarantors
and the Former Protein Subsidiaries granted to Bank a security interest in all assets of each Guarantor and each Former Protein Subsidiary in order to secure their respective obligations under the Guaranty and Borrowers’ obligations under the
Loan Agreement; and 
  
 WHEREAS, on or about December 17,
2003, each of the Former Protein Subsidiaries merged with and into POI, with POI being the surviving entity of such mergers; and 
  
 WHEREAS, the Borrowers have requested that the Bank agree to amend Section 8(b)(ii) of the Loan Agreement to permit the Borrowers to increase the
amount of “Title XI Loans” (as such term is defined in the Loan Agreement) outstanding at any time; and 

 WHEREAS, the Bank has agreed to so amend the Loan Agreement, subject to the terms and conditions
contained herein; 
  
 NOW, THEREFORE, in consideration of the
foregoing premises, and other good and valuable consideration, the receipt and legal sufficiency of which are hereby acknowledged, the parties hereto hereby agree as follows: 
  
 1. All capitalized terms used herein and not otherwise expressly defined herein shall have the respective meanings given to
such terms in the Loan Agreement. 
  
 2. The Loan Agreement is
amended by deleting the dollar amount of “$25,000,000” contained in Section 8(b)(ii) and substituting a dollar amount of “$31,000,000” in lieu thereof. 
  
 3. The effectiveness of the amendment contained in this Amendment is expressly conditioned Bank’s receipt of a fully
executed original of this Amendment, in form and substance acceptable to Bank in its discretion. 
  
 4. Each Borrower hereby restates, ratifies, and reaffirms each and every term, condition representation and warranty heretofore made by it under or in
connection with the execution and delivery of the Loan Agreement, as amended hereby, and the other Loan Documents, as fully as though such representations and warranties had been made on the date hereof and with specific reference to this Amendment
and the Loan Documents. Each Guarantor hereby restates, ratifies, and reaffirms each and every term, condition representation and warranty heretofore made by it under or in connection with the execution and delivery of the Security Agreement and the
Guaranty, in each case as amended hereby, and the other Loan Documents, as fully as though such representations and warranties had been made on the date hereof and with specific reference to this Amendment and the Loan Documents. 
  
 5. Except as expressly set forth herein, the Loan Agreement, the Security
Agreement and the Guaranty shall be and remain in full force and effect as originally written, and shall constitute the legal, valid, binding and enforceable obligations of the Obligors party thereto to Bank. This Amendment shall not be effective to
waive any Event of Default or to consent to any failure by the Borrowers or any other Obligor to strictly comply with the provisions of the Loan Agreement and the other Loan Documents. 
  
 6. In addition to any other fees described in this Amendment, each Borrower jointly and severally agrees to pay on demand
all costs and expenses of Bank in connection with the preparation, execution, delivery and enforcement of this Amendment and all other Loan Documents and any other transactions contemplated hereby, including, without limitation, the fees and
out-of-pocket expenses of legal counsel to Bank. 
  
 7. To induce
Bank to enter into this Amendment, each Obligor hereby (a) represents and warrants that, as of the date hereof, both before and after giving effect to the terms hereof, there exists no Default (or any event which with the giving of notice or
passage of time would constitute a Default) under the Loan Agreement, the Security Agreement, the Guaranty or any of the other Loan Documents, and (b) acknowledges and agrees that no right of offset, defense, 
  

 2 

 counterclaim, claim or objection in favor of any Obligor against Bank exists arising out of or with respect to the Loan
Agreement, the Security Agreement, the Guaranty or any other Loan Document, or any of the Secured Obligations. Without limiting the generality of the foregoing any other provision of this Amendment, each Guarantor acknowledges that, notwithstanding
the amendment to the Loan Agreement set forth herein, and after giving effect hereto, the Guaranty remains in full force and effect, as amended hereby. 
  
 8. Each Obligor agrees to take such further action as Bank shall reasonably request in connection herewith to evidence the amendment herein contained to
the Loan Agreement. 
  
 9. This Amendment may be executed in any
number of counterparts and by different parties hereto in separate counterparts, each of which, when so executed and delivered, shall be deemed to be an original and all of which counterparts, taken together, shall constitute but one and the same
instrument. 
  
 10. This Amendment shall be binding upon and inure
to the benefit of the successors and permitted assigns of the parties hereto. 
  
 11. This Amendment shall be governed by, and construed in accordance with, the laws of the State of Georgia, other than its laws respecting choice of law. 
  

 3 

 IN WITNESS WHEREOF, Obligors and Bank have caused this Amendment to be duly executed as of the date first
above written. 
  

			
	OMEGA PROTEIN CORPORATION
		
	By:	 	 /s/ Robert W. Stockton

	 	 	 Robert W. Stockton
 Executive Vice
President

	
	OMEGA PROTEIN, INC.
		
	By:	 	 /s/ Robert W. Stockton

	 	 	 Robert W. Stockton
 Vice President

	
	OMEGA SHIPYARD, INC.
		
	By:	 	 /s/ Robert W. Stockton

	 	 	Robert W. Stockton
	 	 	Vice President
	
	OMEGA INTERNATIONAL DISTRIBUTION COMPANY
		
	By:	 	 /s/ Robert W. Stockton

	 	 	 Robert W. Stockton
 Vice President

	
	PROTEIN FINANCE COMPANY
		
	By:	 	 /s/ Robert W. Stockton

	 	 	 Robert W. Stockton
 Vice President

  

 4 

			
	BANK OF AMERICA, N.A.
		
	By:	 	 /s/ Wes Manus

	 	 	Wes Manus
	 	 	Vice President

  

 5

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