Document:

3rd Amendment to Captisol Supply Agreement

 Exhibit 10.103 
 CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION. 
 3rd Amendment to the 

CAPTISOL® SUPPLY AGREEMENT 
 dated as of

 December 20th, 2002 and amended July 29, 2005 and March 1, 2007 

BY AND BETWEEN 
 CYDEX, INC. 
 AND 

THE HOVIONE GROUP 
 Dated as of January 28, 2008 

 3rd AMENDMENT TO THE CAPTISOL® SUPPLY AGREEMENT 
 THIS 3rd
AMENDEMENT TO THE CAPTISOL SUPPLY AGREEMENT (the “AGREEMENT”) is entered into as of January 28, 2008, by and between: 

 

	 	(1)	CYDEX, INC., a Delaware corporation with an office at 10513 W. 84th Terr, Lenexa, Kansas, 66214 (“CYDEX”); and 

 

	 	(2)	HOVIONE LLC, a New Jersey limited liability company with an office at 40 Lake Drive, East Windsor, New Jersey 08250 (“AGENT”), acting as exclusive
sales agent for the USA for the manufacturers, HOVIONE FARMACIENCIA S.A., a Portuguese corporation (“HOVIONE SA”), and HOVIONE PHARMASCIENCE LIMITED, a Macau corporation (“HOVIONE LIMITED”), and acting as exclusive
sales agent for the project manager HOVIONE INTERNATIONAL LIMITED, a Hong Kong corporation with an office at 172 Gloucester Road, Wanchai, Hong Kong (“HOVIONE INTERNATIONAL”), jointly and severally. AGENT, HOVIONE SA, HOVIONE
LIMITED and HOVIONE INTERNATIONAL are collectively referred to herein as “HOVIONE”). 

 This 3rd
Amendment to the Captisol Supply Agreement is hereafter referred to as the “Amendment No. 3”. 
 BACKGROUND

 Both parties declare that the original intent of the AGREEMENT entered into has been met and remains valid. The parties
feel that it is appropriate to clarify and update certain terms set forth in the AGREEMENT. Specifically, the parties have agreed to [***] the minimum annual purchase requirement of Captisol, to remove the obligation of HOVIONE to hold additional
inventory, to grant HOVIONE rights to practice under a certain patent, and to clarify how certain exchange rates should be determined and applied. 
 AGREEMENTS 
 NOW, THEREFORE, in consideration of the mutual promises
hereinafter made and the mutual benefits to be derived from this Amendment No. 3, and other good and valuable consideration, the receipt and sufficiency of which is acknowledged, the parties hereto, intending to be legally bound, hereby agree
as follows: 
 1. Definitions. All capitalized terms used herein shall have the meaning given to them in the AGREEMENT, unless otherwise
defined herein. 
 2. Amendment to Article I (Definitions). The following term has been amended to read in its entirety: 

 

	***	Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted
portions. 

  

			
	PAGE 2	 	 Hovione Contract Code

SA.00012.A.002

 ““INITIAL TERM” means the period commencing upon the
EFFECTIVE DATE and ending on March 31, 2014.” 
 3. Amendment to Section 3.5 (Forecasts, Purchase Orders and Minimum Orders).
Section 3.5 is hereby amended to change the minimum annual purchase requirement from a minimum of [***]to [***]. As amended, Section 3.5 shall read in its entirety: 

“3.5 FORECASTS, Purchase Orders and Minimum Quantities. Within [***]) days after the commencement of any CONTRACT YEAR, CYDEX
shall provide HOVIONE with a written [***] forecast of its anticipated purchase order for commercial quantities of CAPTISOL for the subsequent [***] (“FORECAST”), specifying quantities and delivery dates. Not later than [***] months in
advance of such CONTRACT YEAR, CYDEX shall be required to place its irrevocable purchase order for [***] % of the aggregate quantities of CAPTISOL specified in its FORECAST, provided that CYDEX shall have the right, with respect to not more than
[***] % of FORECASTED quantities, to (i) [***] such FORECASTED quantities, and/or (ii) [***] among deliveries scheduled and new delivery dates, provided in aggregate the changed amounts are not disproportionately concentrated in time
thereby causing HOVIONE to produce and deliver in that period in excess of the [***]% its obligations. CYDEX’s irrevocable purchase order shall be for at least [***]. HOVIONE shall confirm acceptance of such annual irrevocable purchase order
within [***] days of receipt. Should CYDEX desire to make additional changes in quantities and/or delivery dates, CYDEX shall notify HOVIONE and HOVIONE will use its best commercial efforts to accommodate CYDEX’s requests.” 

4. Deletion of Section 3.7 (Additional Inventory). The parties agree that HOVIONE is not required to manufacture and hold in inventory an
additional quantity of CAPTISOL equal to [***]% of the quantities specified by CYDEX in each of its purchase orders. Accordingly, Section 3.7 of the AGREEMENT is hereby deleted in its entirety. 

5. Amendment to Section 4.1 (Initial UNIT PRICES). Section 4.1 is hereby amended to read in its entirety: 

“4.1 Initial UNIT PRICES. As full compensation for the performance of HOVIONE hereunder for the manufacture
and supply of CAPTISOL from its Loures site from and after the COMMERCIAL PRODUCTION DATE, CYDEX shall pay HOVIONE the following supply prices (“UNIT PRICES”) for CAPTISOL: 

 

					
	 Quantities of CAPTISOL Supplied

in a CONTRACT YEAR
	  	UNIT PRICES
(US$)
	 [***]
	  	[***]

  

	***	Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted
portions. 

  

			
	PAGE 3	 	 Hovione Contract Code

SA.00012.A.002

 For supplies in excess of [***] CYDEX shall pay HOVIONE the following supply prices
(“UNIT PRICES”) for CAPTISOL, till a minimum price of $ [***] 
 Price = [***] 

e.g.: for a supply of [***] 

Such UNIT PRICES shall be adjusted only as provided in Section 4.2 hereof. An estimated UNIT PRICE for deliveries of CAPTISOL to be
used for all invoices in a given CONTRACT YEAR shall be based on the purchase order for such CONTRACT YEAR. Within [***] days following the end of each CONTRACT YEAR, CYDEX shall submit to HOVIONE a reconciliation of the total amount that should
have been paid by CYDEX for all quantities of CAPTISOL purchased during such CONTRACT YEAR in accordance with the actual UNIT PRICE against the total amounts actually billed by HOVIONE and paid for by CYDEX for such quantities based on the estimated
UNIT PRICE for such year. If such reconciliation shows that CYDEX has overpaid for such purchases, then HOVIONE shall, upon [***] days’ notice, at CYDEX’s election, either refund such overpayment or credit such overpayment against future
purchases of CAPTISOL. If such reconciliation shows that CYDEX has underpaid for such purchases, then CYDEX shall remit the balance so determined to be due to HOVIONE within [***] [***] days of its submission of such reconciliation. Such UNIT PRICES
include all raw materials, conversion costs and delivery costs (other than customs duties, if any, in the country where CAPTISOL is to be delivered as directed by CYDEX).” 
 6. Amendment to Section 6.11 (Relationship Management). The representatives to the Technical Committee and the Management Committee shall be amended to be as follows: 

“The Technical Committee shall be composed of one representative of each party. Initially, such representatives shall be: 

 

			
	 •    For CyDex:
	    	Dr. Vincent Antle
		
	 •    For Hovione:
	    	Mr. Pedro Duarte”

 “The
Management Committee shall be composed of one representative of each party. Initially, such representatives shall be: 
  

			
	 •    For CyDex:
	    	Mr. Allen Roberson
		
	 •    For Hovione:
	    	Mr. David Hoffman”

 7. Amendment to
Section 7.2 (Proprietary Rights). Section 7.2 is hereby amended to add a new subclause (f) that shall read in its entirety: 

 

	***	Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted
portions. 

  

			
	PAGE 4	 	 Hovione Contract Code

SA.00012.A.002

 “(f) License Under U.S. Patent No. [***]. CYDEX hereby
grants HOVIONE a limited, nonexclusive license, without the right to sublicense, under U.S. Patent No. [***] solely to manufacture CAPTISOL pursuant to this AGREEMENT. 
 For the avoidance of doubt, HOVIONE shall not have any rights under U.S. Patent No. [***] outside the scope of the license granted herein.” 
 8. Amendment to Section 8.2(v). Section 8.2(v) is hereby amended to read in its entirety: 
 “(v) In addition to the foregoing, HOVIONE warrants and represents to CYDEX that it has not, nor will it, use in any capacity the services of any person (1) debarred or suspended under 21 U.S.C.
Sections 335(a) or 335(b) or (2) debarred or suspended pursuant to any other federal, state or foreign regulatory authority which has jurisdiction over HOVIONE’s operations or products. 

9. Amendment to Exhibit D Subsection 4 (Threshold). Subsection 4 of Exhibit D is hereby amended to read in its entirety: 

“Threshold. Following the last date of release by HOVIONE to CYDEX of a commercial campaign of CAPTISOL, the parties shall
refer to the exchange rate for U.S. Dollars to Euro as reported by the Wall Street Journal, Eastern U.S. edition on the date (or the next business day if such date is on a weekend or holiday). Such exchange rate shall be referred to as the
ACTUAL EXCHANGE RATE. In the event that the ACTUAL EXCHANGE RATE for the US. Dollar to the Euro deviates by more than [***] percent ([***]%) [***] from the REFERENCE EXCHANGE RATE (as determined by subtracting the ACTUAL EXCHANGE RATE from the
REFERENCE EXCHANGE RATE and then taking the result and dividing it by the REFERENCE EXCHANGE RATE), then the UNIT PRICES for such commercial campaign batch of CAPTISOL released by HOVIONE to CYDEX shall be proportionately adjusted as described in
Subsection 5 of this Exhibit D. The parties hereby agree that they anticipate adjusting the UNIT PRICES for currency exchange rate deviations no more than [***] a CONTRACT YEAR. If currency exchange rate deviations cause the UNIT PRICES to be
adjusted more frequently than [***] in a given CONTRACT YEAR, then the parties shall negotiate in good faith whether this Subsection 4 of this Exhibit D should be further amended. 

By way of example, if the last date of release of a commercial campaign batch of CAPTISOL was released by HOVIONE to CYDEX on
January 15 of a given CONTRACT YEAR, then the parties would refer to the exchange rate for U.S. Dollars to Euro as reported by the Wall Street Journal, Eastern U.S. edition on January 15 of such CONTRACT YEAR (or the next business
day if such date was on a weekend or holiday). If such ACTUAL EXCHANGE RATE differed from the REFERENCE EXCHANGE RATE by more than [***] percent ([***]%), then the UNIT PRICES for such 

 

	***	Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted
portions. 

  

			
	PAGE 5	 	 Hovione Contract Code

SA.00012.A.002

 
commercial campaign batch would be adjusted according to Subsection 5 of this Exhibit D.” 
 10. Amendment to Exhibit D Subsection 5 (Calculations). Reference to “for the new CONTRACT YEAR” in the second line of Subsection 5 of Exhibit D is hereby deleted. For
the avoidance of doubt, but subject to the limitation of frequency described in Subsection 4 of Exhibit D, an ADJUSTMENT FACTOR shall be calculated after each release by HOVIONE to CYDEX of a commercial campaign batch of CAPTISOL. 

11. Governing Law. This Amendment No. 3 shall be construed in accordance with the laws of the State of Delaware in the United States of
America, without giving effect to the principles of conflicts of law thereof. 
 12. Continuing Effect. Nothing in this Amendment
No. 3 is meant to subvert or otherwise alter the rights and obligations of either HOVIONE or CYDEX under the AGREEMENT, except as and to the extent expressly stated herein. 
 13. Counterparts. This Amendment No. 3 may be executed in multiple counterparts, each of which shall be an original as against any party whose signature appears thereon but each of which
together shall constitute one and the same instrument. 
 Signature Page to Follow 

  

			
	PAGE 6	 	 Hovione Contract Code

SA.00012.A.002

 IN WITNESS WHEREOF, the parties, through their authorized representatives, have duly
executed this Amendment No. 3 as of the date first written above. 
  

									
	CYDEX, INC.	 	 	 	HOVIONE LLC
					
	By:	 	 /s/ Allen K. Roberson
	 		 	By:	 	 /s/ David Hoffman

	Name:	 	Allen K. Roberson	 		 	Name:	 	David Hoffman
	Title:	 	Chief Financial Officer	 		 	Title:	 	President-US Operations
	Date:	 	5 February 2008	 		 	Date:	 	4 Feb 2008
			
	HOVIONE FARMACIENCIA S.A.	 		 	HOVIONE PHARMASCIENCE LIMITED
					
	By:	 	 /s/ Noé Carreira
	 		 	By:	 	 /s/ G. Villax

	Name:	 	Noé Carreira	 		 	Name:	 	G. Villax
	Title:	 	Director	 		 	Title:	 	Chief Executive
	Date:	 	25 Jan. 2008	 		 	Date:	 	25 Jan. 2008
				
	HOVIONE INTERNATIONAL LIMITED	 		 		 	
					
	By:	 	 /s/ G. Villax
	 		 		 	
	Name:	 	G. Villax	 		 		 	
	Title:	 	Chief Executive	 		 		 	
	Date:	 	25 Jan. 2008	 		 		 	

 Signature Page to Amendment No. 3 to the Captisol Supply Agreement 

  

			
	PAGE 7	 	 Hovione Contract Code

SA.00012.A.002

 [HOVIONE LOGO]4th Amendment to Captisol Supply Agreement

 Exhibit 10.104 
 CERTAIN MATERIAL (INDICATED BY AN ASTERISK) HAS BEEN OMITTED FROM THIS DOCUMENT PURSUANT TO A REQUEST FOR CONFIDENTIAL TREATMENT. THE OMITTED MATERIAL HAS BEEN FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION. 
  

					
		 		 	Hovione FarmaCiencia SA
		 		 	Sete Casas
		 		 	2574-506 Loures
		 		 	Portugal
		 		 	
		 		 	October 04, 2009

 4th Amendment to the 
 CAPTISOL SUPPLY AGREEMENT 
 Dated as of 

December 20th, 2002 and amended July 29, 2005, 
 March 1, 2007 and January 28, 2008 
 BY AND BETWEEN 

CYDEX PHARMACEUTICALS, INC. 
 AND 
 THE HOVIONE GROUP 

Dated as of September 23, 2009 

 4th AMENDMENT TO THE CAPITSOL SUPPLY AGREEMENT 

This
4th amendment to the Captisol Supply Agreement (the
“AGREEMENT”) is entered into as of September 23, 2009, by and between: 
  

	1)	 CYDEX PHARMACEUTICALS, INC., A Delaware Corporation with an office at 10513 W. 84th Terrace, Lenexa, KS 66214 (“CYDEX”), formerly known as “CyDex, Inc.”; and

  

	2)	HOVIONE, LLC, a New Jersey limited liability company with an address at 40 Lake Drive, East Windsor, NJ 08520 (“AGENT), acting as exclusive sales agent for
the USA for the manufacturers, HOVIONE FARMACIENCIA, S.A., a Portuguese Corporation (“HOVIONE SA”), and HOVIONE PHAMASCIENCE LIMITED, a Macau Corporation (“HOVIONE LIMITED”), and acting as exclusive sales agent for
the project manager HOVIONE INTERNATIONAL LIMITED, an Hong Kong Corporation with an office at 172 Gloucester Road, Wanchai, Hong Kong (“HOVIONE INTERNATIONAL”), jointly and severally, AGENT, HOVIONE SA, HOVIONE LIMITED, and HOVIONE
INTERNATIONAL are collectively known as (“HOVIONE”). 

 This 4th Amendment to the Captisol Supply Agreement is hereafter referred to
as “Amendment No. 4”. 
 BACKGROUND 

Both parties declare that the original intent of the AGREEMENT entered into has been and remains valid. The parties feel that it is in
the best interests of both parties to clarify and update certain terms set forth in the AGREEMENT. Specifically the parties have agreed to the terms and conditions related to reimbursing to CYDEX the original Loures Engineering Services costs for
the Captisol program, clarify invoicing procedures and extending the current term of the AGREEMENT. 
 AGREEMENTS

 NOW, THEREFORE, in consideration of the mutual promises hereinafter made and the mutual benefits derived from this
Amendment No. 4, and other good and valuable consideration, the receipt and sufficiency of which is acknowledged, the parties hereto, intend to be legally bound, hereby agree to as follows: 

 

	1.	Definitions: All capitalized terms used herein shall have the meaning given to them in the AGREEMENT, unless otherwise defined herein. 

 

	2	Amendment to Article 1 (Definitions). The following term has been amended to read in its entirety: 

““INITIAL TERM” means the period commencing upon the EFFECTIVE DATE and ending on December 31, 2019.” 

	3.	Amendment to Section 4.2 h (Adjustments to UNIT PRICES for Reimbursement for Loures Engineering Services). Section 4.2 h is hereby amended to read in
its entirety: 

 “4.2 (h) Reimbursement for Loures Engineering
Services. Commencing on the 1st of January, 2010,
HOVIONE will [***] the UNIT PRICES of CAPTISOL by [***] of CAPTISOL purchased by CYDEX from HOVIONE. This [***] will apply to all CAPTISOL purchased after the 1st of January, 2010 up to [***] of CAPTISOL purchased or on March 31st, 2014 irrespective of the quantity purchased. Once the total amount
of [***] have been purchased or the period of time for the said reimbursement expires, namely: on
March 31st, 2014, the reimbursement shall expire and
the UNIT PRICES will return to the standard calculation as outlined in Amendment No. 3 executed on the
28th January, 2008.” 

 

	4.	Amendment to Section 4.3 (Payment). The following sentence shall be inserted as the third sentence of Section 4.3 of the AGREEMENT:

 “For clarity, HOVIONE shall not issue invoices for CAPTISOL prior to the date of actual
shipment of CAPTISOL by HOVIONE for deliveries to CYDEX to fulfill CYDEX’s purchase orders, even if HOVIONE has earlier released the relevant quantities of CAPTISOL for quality control purposes unless agreed to in writing by both CYDEX and
HOVIONE.” 
  

	5.	Governing Law. This Amendment No. 4 shall be construed in accordance with the laws of the State of Delaware in the United States of America, without giving
effect to the principles of conflicts to the laws thereof. 

  

	6.	Continuing Effect. Nothing in the Amendment No. 4 is meant to subvert or otherwise alter the rights and obligations of either HOVIONE or CYDEX under the
AGREEMENT, except as and to the extent expressly stated herein. 

  

	7.	Counterparts. This Amendment No. 4 may be executed in multiple counterparts, each of which shall be an original as against a party whose signature appears
thereon but each of which together shall constitute one and the same instrument. 

 Signature Page to Follow

  
  

	***	Certain information on this page has been omitted and filed separately with the Commission. Confidential treatment has been requested with respect to the omitted
portions. 

 IN WITNESS WHEREOF, the parties, through their authorized representatives, have duly
executed this Amendment No. 4 as of the date first written above. 
  

			
	CyDex Pharmaceuticals, Inc.
	By:	 	 /s/ Theron E. Odlaug

	Name: Theron E. Odlaug
	Title: Pres. & CEO
	Date: Sept. 18, 2009
	
	Hovione, LLC
	By:	 	 /s/ David Hoffman

	Name: David Hoffman
	Title: VP EX & PD Business Units
	Date: 18 Sept. 2009
	
	Hovione Farmaciencie, S.A.
	By:	 	 /s/ Noé Carreira

	Name: Noé Carreira
	Title: VP-Manufacturing
	Date: Lisbon 30/Sep/2009
	
	Hovione Pharmascience Limited
	By:	 	 /s/ Jorge Pasticha

	Name: Jorge Pasticha
	Title: General Manager — Macau Plant
	Date: Macau, 06 Oct. 2009
	
	Hovione International Limited
	By:	 	 /s/ G. Villax

	Name: G. Villax
	Title: Chief Executive
	Date: Princeton, 23 Sept. 2009

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00185-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00185-of-00352.parquet"}]]