Document:

rare-ex102_413.htm

Exhibit 10.2

AMENDMENT NO. 1 TO COLLABORATION AND LICENSE AGREEMENT

 

This Amendment No. 1 to the Collaboration and License Agreement (“Amendment”) is made and entered into by and between Kyowa Hakko Kirin Co., Ltd., a company organized and existing under the laws of Japan, with an address at 1-6-1 Ohtemachi, Chiyoda-ku, Tokyo, 100-8185, Japan (“KHK”) and Ultragenyx Pharmaceutical Inc., a company organized and existing under the laws of the State of Delaware, with an address at 60 Leveroni Court, Novato, CA 94949 (“Ultragenyx”). 

RECITALS

 

	
 
	
A.
	
WHEREAS, KHK and Ultragenyx entered into a Collaboration and License Agreement effective as of August 29, 2013 (the “Agreement”).

 

	
 
	
B.
	
WHEREAS, both Parties wish to amend the Agreement as set forth below.

 

	
 
	
C.
	
NOW, THEREFORE, in consideration of the mutual covenants and premises herein contained, the Parties agree as follows:

 

	
 
	
1.
	
This Amendment shall be effective as of August 24, 2015 (the “Amendment Effective Date”).

 

	
 
	
2.
	
A new Section 2.1.4 shall be added that provides as follows:

 

“2.1.4.  Licenses for Japan and Korea.  Subject to the terms and conditions of this Agreement, KHK hereby grants to UGNX a non-exclusive, royalty-free license under the Licensed Technology to Develop the Licensed Products in the Field in Japan and the Republic of Korea  (“Korea”) until the completion of UGNX Core Development Activities in Japan and Korea, respectively; provided, however, that any activities in Japan or Korea other than activities incorporated in the Core Development Plan pursuant to Section 4.2.1 remain within KHK Non-Core Development Activities as stipulated in Section 4.11.1(a) and out of the scope of this license in this Section 2.1.4. For the avoidance of doubt, any and all regulatory activities related to applications or filing for Marketing Approvals and Pricing and/or Reimbursement Approvals in Japan and Korea remain within KHK Non-Core Development Activities.”

 

	
 
	
3.
	
The existing Section 2.1.4 in the Agreement shall be renamed Section 2.1.5.

 

	
 
	
4.
	
Section 4.2.1 shall be deleted in its entirety and replaced with the following:

 

“The Parties shall prepare in writing an overall Development plan and budget (as such plan and budget may be amended from time to time in accordance with this Agreement, the “Core Development Plan”) covering the entire Development period and the Development activities and costs required in order to obtain and 

maintain the Marketing Approvals and (if applicable) the Pricing and/or Reimbursement Approvals for the Licensed Products (including Phase 4 Clinical Trials, if applicable) for the First Indication and Additional Indications, if any, in the Profit Share Territory, the European Territory, Japan and Korea (such activities, the “Core Development Activities”), provided that the Core Development Plan related to Japan and/or Korea shall be limited to Clinical Trials mutually agreed by the Parties. The Parties acknowledge and agree that, in the Profit Share Territory and the European Territory, it is their intent to seek Marketing Approval in the First Indication for a label that is as broad as reasonably possible (including, for clarity, broad use by age), taking into account, among other things, the requirements of Applicable Laws and the interest in making Licensed Products in the Field commercially available in a timely manner.  In the Profit Share Territory and the European Territory, in addition to Clinical Trial(s) designed to obtain Marketing Approval for pediatric patients from the age of five (5) through the age of eighteen (18), unless otherwise agreed upon in writing by the Parties, the Core Development Plan shall include a Clinical Trial for pediatric patients below the age of 5.  For clarity, the Core Development Plan and Core Development Activities shall cover the 001 and 002 Studies.  The initial Core Development Plan has been mutually agreed in writing by the Parties as of the date of signing this Agreement, and shall be the operative Core Development Plan until amended with the approval of the JSC.”

 

	
 
	
5.
	
Section 4.3.1(a) shall be deleted in its entirety and replaced with the following:

 

“UGNX shall be the lead Party for the Development of Licensed Products in the Field in the Profit Share Territory, the European Territory, Japan and Korea (“Lead Development Party”) for the following activities beginning on the Effective Date (collectively, “UGNX Core Development Activities”): (i) all of the Core Development Activities (except for the 001 and 002 studies) conducted in the Profit Share Territory through the day immediately preceding the Profit Share Territory Transition Date; (ii) all of the Core Development Activities conducted in the European Territory through the day immediately preceding the applicable European Transition Date; and (iii) all of the Core Development Activities conducted in Japan and Korea; provided, however, that UGNX shall in each case under (i) and (ii) continue to be the Lead Development Party for any Phase 4 Clinical Trials and/or Clinical Trials for additional indications in the Field (but excluding for clarity Phase 5 Clinical Trials), if any, commenced (Initiation) by UGNX in the Profit Share Territory or the European Territory prior to the Profit Share Territory Transition Date or the Applicable European Transition Date, as applicable, until completion of such respective Clinical Trial (“On-Going Clinical Trials”).”

	
 
	
6.
	
A new Section 4.9.1(d) shall be added that provides as follows: 

 

“KHK shall be solely responsible for one hundred percent (100%) of the Development Costs for all of the Core Development Activities in Japan and Korea.”  

 

	
 
	
7.
	
A new Section 4.13 shall be added that provides as follows: 

 

“4.13Subcontractors in Japan and Korea.  

4.13.1In Japan and Korea respectively, in addition to complying with Sections 2.2 and 17.10, UGNX shall have CROs and /or any other subcontractors which UGNX employs to carry out the Development of the Licensed Products maintain complete and accurate scientific records of the Development of the Licensed Products and shall store such records in accordance with the conditions and terms under the provisions of Good Clinical Practice of Japan and that of Korea, including their future amendments.

 

In Japan and Korea, respectively, UGNX shall have the CROs and/or any other subcontractors employed to carry out the Development of the Licensed Products accept any inspection by relevant Regulatory Authorities and allow such Regulatory Authorities to access any scientific records of the Development of the Licensed Products. UGNX shall advise KHK promptly, but in no event later than thirty (30) days after UGNX’s receipt of notice thereof, of any planned Regulatory Authority visit to the CROs and/or subcontractors or any written inquiries by a Regulatory Authority concerning such CROs and/or subcontractors in the relevant country.  If the Regulatory Authority makes an unannounced or unplanned visit, or if UGNX does not have at least thirty (30) days’ notice of the visit, UGNX shall inform KHK of the visit within one (1) Business Day after UGNX obtains actual knowledge of the visit.  UGNX shall inform KHK as soon as practicable regarding the purpose and result of such visit or inquiry, and shall provide to KHK copies of any minutes of the inspection generated by UGNX or the CROs and/or subcontractors following such inspection and any report or correspondence provided by UGNX or the CROs and/or subcontractors to the Regulatory Authority or issued by or provided by the Regulatory Authority to UGNX or the CROs and/or subcontractors, in connection with such visit or inquiry.  UGNX shall advise KHK of the material aspects of such minutes and correspondence at the next JSC meeting.

 

4.13.2Not more than once per year, if KHK has any reasonable concerns regarding the CROs and/or any other subcontractors as set forth in Section 4.13.1, UGNX shall have such CROs and/or subcontractors accept inspection or audit by KHK or its designee, at KHK’s expense and on not less than thirty (30) days’ 

prior notice, and allow KHK or its designee to access, during normal business hours, any record set forth in Section 4.13.1.

 

4.13.3Before entering into an agreement with a CRO which carries out monitoring service related to the Clinical Trials in Japan or Korea, respectively, or any amendment thereof, UGNX shall allow KHK to review the draft of such agreement or amendment and UGNX shall take into consideration KHK’s opinion or advice in good faith. UGNX shall promptly provide KHK with a copy of each executed agreement or amendment.”

 

	
 
	
8.
	
A new Section 5.1.5 shall be added that provides as follows:

 

“5.1.5 UGNX Assistance In Japan and Korea (a) Though any and all regulatory activities related to applications or filing for Marketing Approvals and Pricing and/or Reimbursement Approvals in Japan and Korea remain within KHK Non-Core Development Activities as stipulated in section 2.1.4, UGNX shall provide all assistance reasonably requested by KHK at KHK’s sole expense.  (b) UGNX shall take all steps reasonably necessary, at KHK’s sole expense, to transfer and assign the UGNX Regulatory Data for the Licensed Products in Japan and Korea to KHK.  (c) At KHK’s sole expense, UGNX shall provide KHK with copies of all material correspondence between UGNX and any Regulatory Authorities with respect to the Development of the Licensed Products in Japan and Korea.  (d) Upon request of KHK, UGNX shall use Commercially Reasonable Efforts to assist KHK at KHK’s cost in connection with any meetings with, or requests from, Regulatory Authorities with respect to Licensed Products in Japan and Korea.”

 

	
 
	
9.
	
Except as expressly provided in this Amendment, all other terms, conditions and provisions of the Agreement shall continue in full force and effect as provided therein. Capitalized terms used in this Amendment that are not otherwise defined herein shall have the same meanings as such terms are defined in the Agreement.

 

	
 
	
10.
	
This Amendment may be executed in identical duplicate copies exchanged by facsimile or e-mail (PDF form) transmission.  The Parties agree to execute two identical original copies of this Amendment after exchanging signed facsimile versions.  Each identical counterpart will be deemed an original, but all of which together will constitute one and the same instrument.

 

 

[Remainder of page intentionally left blank]

IN WITNESS WHEREOF, the Parties have executed this Amendment No. 1 to Collaboration and License Agreement to be effective as of the Amendment Effective Date. 

 

	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 
	
 

	
KYOWA HAKKO KIRIN CO., LTD.
	
 
	
 
	
 
	
ULTRAGENYX PHARMACEUTICAL INC.

	
 
	
 
	
 
	
 
	
 

	
By:
	
 
	
/s/ Tamao Watanabe
	
 
	
 
	
 
	
By:
	
 
	
/s/ Tom Kassberg

	
Name:
	
 
	
Tamao Watanabe
	
 
	
 
	
 
	
Name:
	
 
	
Tom Kassberg

	
Title:
	
 
	
Director, Business Development Department
	
 
	
 
	
 
	
Title:
	
 
	
CBOrare-ex103_414.htm

Exhibit 10.3

 

AMENDMENT NO. 3 TO LICENSE AND SERVICES AGREEMENT

This AMENDMENT NO. 3 TO LICENSE AND SERVICES AGREEMENT (herein referred to as “Amendment No. 3”) is made effective September 21, 2015 (the “Amendment No. 3 Effective Date”), by and between Ultragenyx Pharmaceutical Inc. (“Ultragenyx”), a Delaware corporation, and The Buck Institute for Research on Aging (“Buck Institute”), each herein referred to as “Party” and collectively as “Parties.”

RECITALS

WHEREAS, the above named parties desire to amend the Agreement (as defined below) as set forth below;

WHEREAS, the Parties now desire to amend the Agreement to provide for Ultragenyx’s use of an expanded laboratory and office space and for the exercise of Ultragenyx’s right of first refusal to certain office space;

NOW, THEREFORE, in consideration of the mutual covenants and agreements contained in this Amendment No. 3, the sufficiency of which is hereby acknowledged, the parties agree as follows:

	
 
	
1.
	
This Amendment No. 3 shall serve as an amendment to that certain License and Services Agreement, dated September 24, 2010, by and between Ultragenyx and Buck Institute, as amended by Amendment No. 1 to License and Services Agreement, dated as of September 4, 2012 and by Amendment No. 2 to License and Services Agreement (“Amendment No. 2”), effective as of September 15, 2014 (as so amended, the “Agreement”). Except as expressly modified hereby, the Agreement shall continue in full force according to its terms. Capitalized terms not otherwise defined in this Amendment No. 3 shall have the meanings ascribed to them in the Agreement.

	
 
	
2.
	
Section 2 of Amendment No. 2 shall be deleted in its entirety and replaced with the following:

C. Ultragenyx wishes to procure access at the Facility to certain laboratory space in Building G of the Facility, Fourth Floor, as shown on the attached Exhibit “A” as “Licensed Lab Space” in order to conduct research and facilitate its therapeutic development programs;

	
 
	
3.
	
In Section 8 of Amendment No. 2, $305,000.00 and $25,416.67 will be replaced by $378,872.00 and $31,573.00, respectively.

	
 
	
4.
	
Attachment No. 1 of Amendment No. 2 is hereby deleted and replaced in its entirety with Attachment No. 1 hereto.

	
 
	
5.
	
In addition to the laboratory and office space mentioned in this Amendment No. 3 and shown in Attachment No. 1 hereto, Ultragenyx also wishes to procure certain laboratory space inside the Mass Spectrometry Core (“Core”) at the Facility. Said space (the “MS Space”) will include 80sf of exclusive space for the placement of a Mass Spectrometry machine (“MS”), the location of which initial space shall be as designated in Attachment No. 2 and may be changed as necessary by mutual agreement between Ultragenyx and the director of the Core. Buck shall provide a constant and reliable supply of high purity, high pressure N2 gas suitable for use in operation of MS instrumentation. Room temperature, humidity and exhaust services will be controlled to a range meeting specifications for MS instrument operation, which specifications will be the same as for all Buck owned instruments. Ultragenyx will also be able to coordinate with the Core director for the use of the two chemical fume hoods, the clean room with laminar flow, tissue culture hood for sample preparation and of the appropriate solvent cabinets for disposal and storage of HPLC solvents. It will be possible to interact with lab members of both the Gibson and Ramanathan groups and principal investigators for discussion of new protocols and data analysis.   If necessary, the sporadic use of other MS instruments in the Core can be made available at a 15% discounted fee-for service basis.

	
 
	
6.
	
For the use of the MS Space, Ultragenyx will pay an annual fee of $55,000, payable in equal monthly installments of $6,600 on the first day of each month during the Term. This sum shall be prorated for any partial months of the Term or until the MS is removed from the Core, whichever is later.

	
 
	
7.
	
This Amendment No. 3 shall inure to the benefit of and be binding upon the Parties and their respective heirs, successors, trustees, transferees and assigns.

	
 
	
8.
	
In the event of a conflict between the provisions of this Amendment No. 3 and the provisions of the Agreement, the provisions of this Amendment No. 3 shall control.

	
 
	
9.
	
This Amendment No. 3 may be executed in any number of counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

 

[Signature page follows]

IN WITNESS WHEREOF, the Parties, intending to be legally bound hereby, have caused this Amendment No. 3 to be executed and delivered by their proper and duly authorized officers effective as of the Amendment No. 3 Effective Date.

The Buck Institute for Research on AgingUltragenyx Pharmaceutical Inc.

__/s/ Remy Gross III_____________/s/ Emil Kakkis_____________

By:   Remy Gross III                   By: Emil Kakkis

Title: VP Business DevelopmentTitle: CEO

Date: 21 September 2015Date: 29 September 2015

Attachment No. 1

 

Attachment No. 2

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