Document:

reta-ex101_29.htm

Exhibit 10.1

THIRD SUPPLEMENT TO EXCLUSIVE LICENSE AND SUPPLY AGREEMENT

Regarding Phase 3 Clinical Study (Alport Syndrome) in Japan

This Third Supplement (herein so called), effective as of December 6, 2017 (the “Supplement Effective Date”), to the Exclusive License and Supply Agreement, effective as of December 24, 2009 (the “Original Agreement”), is by and between Reata Pharmaceuticals, Inc., a corporation organized and existing under the laws of Delaware, USA, with an address at 2801 Gateway Drive, Suite 150, Irving, Texas 75063 (“Reata”), and Kyowa Hakko Kirin Co., Ltd., a company organized and existing under the laws of Japan, with an address at 1-9-2 Ohtemachi, Chiyoda-ku, Tokyo, 100-0004, Japan (“Kyowa Kirin”). Reata and Kyowa Kirin are sometimes hereinafter referred to each as a “Party” and collectively as the “Parties”.

WHEREAS, pursuant to the Original Agreement, Reata has granted to Kyowa Kirin an exclusive, royalty-bearing license under the Licensed Technology to research, develop, use, sell, offer for sale, import, and export Licensed Compound and Licensed Product in the Field in the Territory.

WHEREAS, Reata wishes to perform portions of a Phase 3 clinical study of RTA 402 (which is included in the Licensed Compound) in the field of Alport Syndrome (which is included in the Field) (“AS”) in Japan (where is included in the Territory) (“Study”).

WHEREAS, in order to permit Reata to perform in Japan all activities necessary to complete the Study without violating the terms and provisions of the Original Agreement, the Parties wish to supplement the terms of the Original Agreement as set forth herein.

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

1. License

Kyowa Kirin grants to Reata a non-exclusive, royalty-free license to perform the Study under the Licensed Technology, which is exclusively granted to KHK in the Territory, to the extent necessary to support Reata’s efforts to develop, use, sell, offer for sale, import and export RTA 402 in the Field outside the Territory. Reata shall be entitled to undertake all activities necessary to complete the Study in accordance with the protocol of the Study and Applicable Laws.

2. Obligation and Responsibility of Reata

2.1The IND holder and site responsibility of the Study shall be Reata. For clarity, Reata shall designate an in-country (Japan) caretaker of the Study at Reata’s sole discretion and responsibility. Kyowa Kirin shall reimburse actual Study costs incurred by or on behalf of Reata, whether incurred before or after the Supplement Effective Date (the “Costs”) up to three million United States dollars (US$3,000,000) (the “Reimbursement Amount”). Costs shall not include 

 

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission.

 

 

the salary or other overhead costs of any Reata employee. Reata shall invoice Kyowa Kirin each quarter for the Costs, and Kyowa Kirin shall pay each invoice within 30 days after receipt until Kyowa Kirin has paid the Reimbursement Amount. Reata shall bear any and all Costs above the Reimbursement Amount.

2.2Reata shall provide Kyowa Kirin with a protocol of the Study. Reata shall report and discuss the current status and the progress of the Study at the JSC as reasonably required or upon Kyowa Kirin’s reasonable request. In addition, Reata, at any time, shall discuss the current status of the Study with Kyowa Kirin as reasonably required or upon Kyowa Kirin’s reasonable request, and Reata shall report the progress of the Study to Kyowa Kirin in written manner at least quarterly. The discussion and the update by report shall include but not be limited to the topics such as interaction with Regulatory Authorities, Study sites, key opinion leaders and/or CROs.

2.3Reata shall be responsible for undertaking all communications and obligations that derive from this Third Supplement with or toward Regulatory Authorities under Applicable Laws regarding the enforcement of the Study (“Regulatory Activities For Study”) and all activities under this Third Supplement (collectively “Activities”). Such Activities include but are not limited to the supply of RTA 402 to Third Parties. For clarity, Reata confirms that Reata shall not obligate Kyowa Kirin to supply RTA 402 to patients or doctors as part of “compassionate use” programs or other similar regulations or orders in Japan. All such Activities shall be conducted in a manner consistent with the protocol of the Study. Kyowa Kirin will use Commercially Reasonable Efforts to assist Reata in connection with Regulatory Activities For Study. For Kyowa Kirin’s review and comments, Reata shall provide Kyowa Kirin with a draft of the Japanese regulatory filing for the Study (“Study Regulatory Filing”), which includes a description of the development of RTA 402 for the treatment of chronic kidney disease, one (1) month prior to the filing of such draft of the Study Regulatory Filing. Reata shall discuss with Kyowa Kirin any comments to the draft of the Study Regulatory Filing that Kyowa Kirin provides to Reata prior to the filing. Reata shall provide Kyowa Kirin with the copy of all correspondence with Regulatory Authorities and Study Regulatory Filings that Reata files with Japanese Regulatory Authorities. Reata shall keep Kyowa Kirin informed of all material events and developments occurring in the course of Regulatory Activities For Study. Reata shall provide Kyowa Kirin with advance notice of any formal, scheduled meetings with Japanese Regulatory Authorities and provide a brief description of the topics to be presented or discussed at the meeting. Reata shall allow Kyowa Kirin to participate in preparation and /or attendance of any such meeting if applicable.

2.3Upon the request from Kyowa Kirin and/or completion of the Study, Reata shall provide Kyowa Kirin with all data generated from the Study (“Study Data”), including but not limited to any Japanese regulatory filings for RTA 402, under no obligation and at no cost to Kyowa Kirin above the Reimbursement Amount. Kyowa Kirin shall have a right to access, a right of reference, and a right to use and incorporate all Study Data in any regulatory filings, including all Study Regulatory Filings, or for other uses with respect to Licensed Products in the Territory under no obligation and at no cost to Kyowa Kirin. Reata will hold title to all Study Data, including all Study Regulatory Filings.

 

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission.

 

 

3. Regulatory Activities

In accordance with Section 5.1 of the Original Agreement, [***].

4. Original Agreement

4.1Notwithstanding Section 8.3.1 of the Original Agreement, the term of negotiation and execution of Commercial Supply Agreement shall be postponed and a new term shall be discussed and determined promptly after the Supplement Effective Date by both Parties.

4.2Except as supplemented and amended by this Third Supplement, the Original Agreement, the Supplement to Exclusive License and Supply Agreement dated January 1, 2016, between the Parties (the “First Supplement”), and the Second Supplement to Exclusive License and Supply Agreement dated March 21, 2017, between the Parties, shall remain in full force and effect pursuant to their terms. For the avoidance of doubt, the initiation of the Study shall not require Kyowa Kirin to make any Regulatory Milestone Payment related to the “Initiation of Phase 2b Clinical Trial for a Licensed Product in Japan” or “Initiation of Phase 3 Clinical Trial for a Licensed Product in Japan” as set forth in Section 7.2 of the Original Agreement; provided, however, any payments required to be made pursuant to Section 7.2 of the Original Agreement as a result of future milestone events, including unpaid Regulatory Milestone Payments related to the “Initiation of Phase 2b Clinical Trial for a Licensed Product in Japan” or “Initiation of Phase 3 Clinical Trial for a Licensed Product in Japan”, shall continue to be due and payable pursuant to the terms of Section 7.2 of the Original Agreement.

5. Other Provisions

5.1This Third Supplement shall become effective on the Supplement Effective Date and shall continue until the termination of the Original Agreement.

5.2Kyowa Kirin will have the right to terminate this Third Supplement upon breach of any obligations of Reata if Reata has not cured such breach within ninety (90) days after receipt of written Notice thereof (describing such breach in reasonable detail) by Kyowa Kirin.

5.3Except where specifically defined herein, capitalized terms used herein shall have the same meanings ascribed to them in the Original Agreement.

5.4The headings to the several Articles hereof are not part of this Third Supplement, but are merely guides or labels to assist the locating and reading the several Articles hereof.

IN WITNESS WHEREOF, the Parties have executed this Third Supplement to be effective as of the Supplement Effective Date.

 

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission.

 

 

KYOWA HAKKO KIRIN CO., LTD.

			
	
By: 
	
/s/ Tamao Watanabe
	
 

	
 
	
 
	
 

	
Name:
	
Tamao Watanabe
	
 

	
 
	
 
	
 

	
Title:
	
Executive Officer, Director, 
	
 

	
 
	
 
	
 

	
 
	
Business Development Department
	
 

	
 
	
 
	
 

	
Date:
	
December 6, 2017
	
 

 

REATA PHARMACEUTICALS, INC.

			
	
By: 
	
/s/ J. Warren Huff
	
 

	
 
	
 
	
 

	
Name:
	
J. Warren Huff
	
 

	
 
	
 
	
 

	
Title:
	
President and Chief Executive Officer
	
 

	
 
	
 
	
 

	
Date:
	
December 7, 2017reta-ex102_28.htm

Exhibit 10.2

FOURTH SUPPLEMENT TO EXCLUSIVE LICENSE AND SUPPLY AGREEMENT 

Regarding Milestone payments, Supply price and Products manufacturing

This Fourth Supplement (herein so called), effective as of December 6, 2017 (the “Supplement Effective Date”), to the Exclusive License and Supply Agreement, effective as of December 24, 2009 (the “Original Agreement”), is by and between Reata Pharmaceuticals, Inc., a corporation organized and existing under the laws of Delaware, USA, with an address at 2801 Gateway Drive, Suite 150, Irving, Texas 75063 (“Reata”), and Kyowa Hakko Kirin Co., Ltd., a company organized and existing under the laws of Japan, with an address at 1-9-2 Ohtemachi, Chiyoda-ku, Tokyo, 100-0004, Japan (“Kyowa Kirin”). Reata and Kyowa Kirin are sometimes hereinafter referred to each as a “Party” and collectively as the “Parties”. 

WHEREAS, pursuant to the Original Agreement, Reata has granted to Kyowa Kirin an exclusive, royalty-bearing license under the Licensed Technology to research, develop, use, sell, offer for sale, import, and export Licensed Compound and Licensed Product in the Field in the Territory.

WHEREAS, the Parties executed the Supplement to the Original Agreement dated January 1, 2016 (“First Supplement”), under which Kyowa Kirin agreed to allow Reata to perform a Phase 3 clinical study of RTA 402 (which is included in the Licensed Compound) in the field of connective tissue disease associated pulmonary arterial hypertension (which is included in the Field) (“CTD-PAH”) in Japan (which is included in the Territory) (“CTD-PAH Study”).

WHEREAS, the Parties executed the Second Supplement to the Original Agreement dated March 21, 2017 (“Second Supplement”), under which Kyowa Kirin agreed to allow Reata to perform portions of CTD-PAH studies in the Philippines (which is included in the Territory).

WHEREAS, the Parties executed the Third Supplement to the Original Agreement dated December 6, 2017 (“Third Supplement”), under which Kyowa Kirin agreed to allow Reata to perform a Phase 3 clinical study of RTA 402 in the field of Alport Syndrome (“AS”) in Japan (“AS Study”) and agreed to bear Reata’s actual development costs incurred in the AS Study up to three million United States dollars (US $3,000,000).

WHEREAS, the Parties wish to amend the terms of the Original Agreement as set forth herein.

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

 

1. Milestone payments

1.1   Section 7.2.1 (Regulatory Milestones) of the Original Agreement is hereby amended by adding the following to the end of the section:

“Notwithstanding the foregoing, if the milestone event of [***] shall be as follows:

	
i)
	
[***] 

	
ii)
	
[***]

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission. 

 

	
iii)
	
[***]

	
iv)
	
[***]

For the avoidance of doubt, [***]. [***].

Additionally, notwithstanding anything in this Agreement to the contrary, a Regulatory Milestone Payment of [***]. 

The Parties agree that an amount of Regulatory Milestone Payments [***] shall be discussed in good faith and determined by the Parties in writing prior to the achievement of such Regulatory Milestone Events.

1.2   Section 7.2.2 (Sales Milestones) of the Original Agreement is hereby amended by adding the following to the end of the section:

“The Parties agree that the maximum amount of Regulatory Milestone Payments for Licensed Product in Japan and Sales Milestone Payments shall be US $[***]. Notwithstanding the foregoing, [***] shall be added to the Sales Milestone Payments in order of the sales milestone events set forth in the Sales Milestone Payment table in this Section 7.2.2; provided, however, that the addition of any Unpaid Regulatory Milestone Payment for [***] to a Sales Milestone Payment shall not cause the amount of a Sales Milestone Payment to exceed the amount set forth in the following table.  If a Submission Milestone Payment is paid to Reata after the Unpaid Regulatory Milestone Payment for [***] has been added to the Sales Milestone Payments, then the amount of such Submission Milestone Payment shall be deducted, in reverse order of the sales milestone events set forth in the Sales Milestone Payment table, with the amount deducted from a Sales Milestone Payment not to exceed the amount of the Unpaid Regulatory Milestone Payment for [***] previously added to such Sales Milestone Payment.

 

		
	
Sales Milestone Event 
	
Sales Milestone Payment (US$)

	
[***]
	
$[***]

	
[***]
	
$[***]

	
[***]
	
$[***]

	
[***]
	
$[***]

 

[***]:

				
	
Sales Milestone Event 
	
Sales Milestone Payment (US$) set forth in this Section 7.2.2
	
Unpaid Regulatory Milestone Payment for DKD in total: $[***]
	
Sales Milestone Payment (US$) for AS

	
[***]
	
$[***]
	
$[***]
	
$[***]

2

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission. 

 

 

 

				
	
[***]
	
$[***]
	
$[***]
	
$[***]

	
[***]
	
$[***]
	
$[***]
	
$[***]

	
[***]
	
$[***]
	
$[***]
	
$[***]

 

[***].

2.  Product manufacturing

   Section 8.1 (Reata Obligation to Supply Licensed Product) of the Original Agreement is hereby  eliminated and substituted with the following:

“8.1  Reata Obligation to Supply of the Licensed Product.    Kyowa Kirin will obtain [***] percent ([***]%) of its and its Affiliates’ requirements of the finished formulation of the Licensed Product (“Finished Product”) for Commercialization in the Territory from Reata, and Reata agrees to manufacture or have manufactured and supply to Kyowa Kirin [***] of Kyowa Kirin’s and its Affiliates’ requirements of the Finished Product for Commercialization in the Territory, in all such cases except to the extent otherwise provided in, and in any event subject to and in accordance with the terms of, this ARTICLE VIII. Reata also agrees to grant Kyowa Kirin an option (“KHK Option”) to (i) request Reata to supply to Kyowa Kirin and [***] of Kyowa Kirin’s and its CMOs’ their requirements of the intermediate, Spray-Dried Dispersion (“SDD”) for manufacture of the Finished Product, and (ii) obtain a license from Reata to manufacture or have its CMOs (including Reata’s designated CMOs) manufacture the Finished Product using SDD supplied by Reata. Upon Kyowa Kirin’s such exercise of KHK Option, Reata shall supply the SDD to Kyowa Kirin or its CMOs and, consistent with the provisions of Section 8.4.6(b) with respect to the manufacturing technology transfer from Reata to Kyowa Kirin, , provided that Kyowa Kirin shall bear the expense for such transfer , shall grant Kyowa Kirin or its CMOs a non-exclusive royalty-free license to manufacture the Finished Product in and outside the Territory using all Reata’s necessary technologies, patents or know-how and shall provide all necessary technical support to such parties set forth above. For clarity, in this Agreement, the word “Licensed Product” includes both the Finished Product and the SDD.”

 

3.  Supply Agreement

3.1  The first sentence of Section 8.3.1 (Commercial Supply Agreement) of the Original Agreement shall be eliminated and substituted with the following:

“8.3.1 Commercial Supply Agreement.  [***], the Parties shall negotiate and execute definitive commercial supply agreements for the supply of both the Finished Product (“Commercial Supply Agreement for Finished Product”) and the  SDD  (“Commercial Supply Agreement for SDD ”) to Kyowa Kirin and its Affiliates for marketing and sales (including post-approval studies) of such Licensed Products in the Territory (collectively, “Commercial Supply Agreements”). ”

 Accordingly, the word “Commercial Supply Agreement” in the Original Agreement shall be substituted with the word “Commercial Supply Agreements”.

3

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission. 

 

 

 

          3.2  The words “[***]” in the third sentence of Section 8.3.1 of the Original Agreement shall be eliminated and substituted with the following:  “[***]”.

4. Supply price

The first sentence of the Section 8.3.2 (Commercial Supply Price) of the Original Agreement shall be eliminated and substituted with the following:

“ 8.3.2 Commercial Supply Price for The Finished Product and SDD.  During the Term of this Agreement, Reata shall supply the Finished Product to Kyowa Kirin and its Affiliates for use in marketing and sales (including post-marketing studies) in the Territory at [***], consistent with the provisions of Section 8.4 and 8.5 of this  Agreement. 

5.  Other Provisions

5.1   This Fourth Supplement shall become effective on the Supplement Effective Date and shall continue until the termination of the Original Agreement.

5.2 Except where specifically defined herein, capitalized terms used herein shall have the same meanings ascribed to them in the Original Agreement.

5.3  The headings to the several Articles hereof are not part of this Fourth Supplement, but are merely guides or labels to assist the locating and reading the several Articles hereof.

5.4  Except as stated herein, all terms and conditions of the Original Agreement, the First Supplement, the Second Supplement, and the Third Supplement shall remain in full force and effect during the effective period of the Original Agreement.

 

IN WITNESS WHEREOF, the Parties have executed this Fourth Supplement to be effective as of the Supplement Effective Date.

 

 

KYOWA HAKKO KIRIN CO., LTD.

By:/s/ Tamao Watanabe ________________

Name:Tamao Watanabe

Title: Executive Officer, Director, 

Business Development Department

Date:_December 6, 2017_________________

REATA PHARMACEUTCALS, INC.

By:/s/ J. Warren Huff__________________

Name:J. Warren Huff

Title:President and Chief Executive Officer

 

Date:_December 7, 2017_________________ 

4

Specific terms in this Annex have been redacted because confidential treatment for those terms has been requested. These redacted terms have been marked in this Annex with three asterisks [***]. An unredacted version of this Annex has been separately filed with the Securities and Exchange Commission.

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