Document:

Amendment, among EndoResearch Inc. and each of Schering Corporation

 Exhibit 10.8 
 AMENDMENT AGREEMENT 
 This AMENDMENT AGREEMENT (“Amendment”), effective as of the last date
on the signature page hereof (the “Amendment Date”), by and among ENDORECHERCHE, INC. (“ENDORECHERCHE”), SCHERING CORPORATION and SCHERING-PLOUGH LTD. amends and supplements that certain agreement by and between ENDORECHERCHE and
SCHERING CORPORATION effective January 1, 1992, as extended pursuant to that certain Letter of Understanding dated December 19, 1995 (collectively the “Agreement”). The Agreement is amended with reference to the following facts:

 WHEREAS, ENDORECHERCHE and SCHERING CORPORATION each desire to further extend the term of the Agreement; and 
 WHEREAS. ENDORECHERCHE, SCHERING CORPORATION AND SCHERING-PLOUGH LTD. each desire to add SCHERING-PLOUGH LTD. as a party to the Agreement; and 
 WHEREAS. ENDORECHERCHE, SCHERING CORPORATION and SCHERING-PLOUGH LTD. each desire to expand the scope of the Agreement to encompass the discovery, development and
commercialization of compounds in the field of human and animal health arising from research using the “Type-5 Gene Technology” (as defined below. 
  

 1 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 NOW, THEREFORE, ENDORECHERCHE, SCHERING CORPORATION and SCHERING-PLOUGH LTD. agree that the terms and conditions of the
Agreement shall be amended as follows: 
 All references in the Agreement and this Amendment to “SCHERING” shall mean SCHERING
CORPORATION and SCHERING-PLOUGH LTD. 
 ARTICLE 1 - DEFINITIONS 
 Article 1, Paragraph (h) shall be amended to read in its entirety as follows: 
 (b) ( 1
) “Earned Royalty” means the following percentages of Net Sales of each Licensed Product, including Net Sales of Licensed Combinations thereof calculated in accordance with Paragraph (b) (2) below: 
 (A) [***]% of Net Sales up to and including U.S. $[***] per calendar year. 
 (B) [***]% of Net Sales in excess of US $[***] per calendar year. 
 (C) [***] of the royalty rates described in (A) and (B) above will be applied with respect to Net Sales in any country in
the Territory where sales of Licensed Product are not covered by a Valid Claim during the period that a product containing, as an active ingredient, compound identical to a Licensed Compound is being sold in such country. 
 (D) Notwithstanding the foregoing, and subject to Paragraph (b) (2) below, with respect to Licensed Product(s) 

  

 2 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
containing a Licensed Compound discovered by or on behalf of SCHERING through use of the Type-5 Gene Technology (e.g. a Licensed Compound which is a SCHERING
Invention) the percentage of Net Sales used to calculate Earned Royalties shall be: 
 (i) [***]% of Net Sales up to
and including U.S. $[***] per calendar year. 
 (ii) [***]% of Net Sales in excess of U.S.$[***] and up
to and including U.S.$[***] per calendar year. 
 (iv) [***]% of Net Sales in excess of U.S.$[***] and
up to and including U.S.$[***] per calendar year. 
 (iv) [***]% of Net Sales in excess of U.S.$[***]
per calendar year. [***] For purposes of clarity, the parties acknowledge and agree that a Licensed Compound shall be deemed discovered by or on behalf of SCHERING if it is discovered by or on behalf of SCHERING through screening using the
Type-5 Gene Technology and/or through a program of medicinal chemical research conducted by or on behalf of SCHERING based upon a Licensed Compound previously discovered by or on behalf of either SCHERING or ENDORECHERCHE, provided,
however, 

  

 3 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
that if such previously discovered Licensed Compound was discovered by or on behalf of ENDORECHERCHE, then any subsequently discovered Licensed Compound
which is [***] on the previously discovered Licensed Compound, [***] shall be deemed to be discovered by or on behalf of ENDORECHERCHE. 
 (2) With respect to Licensed Combinations, “Earned Royalty” means the foregoing percentages of the sums ca1culated by multiplying Net Sales of Licensed Combinations by a fraction whose numerator is the cost
of Licensed Compound:-; contained therein and whose denominator is the sum of the numerator and the cost (calculated on the same basis if manufactured; otherwise on the basis of purchase price) of all other active ingredients contained therein. In
each case cost is to be determined in accordance with SCHERING’s standard accounting procedures. 
 Article l, Paragraph (f) shall be amended to
read in its entirety as follows: 
 (f) “Know-How” means all data, instructions, processes, formulae, expert opinion
and information relating to the development, manufacture, use or sale of Licensed Compounds, intermediates thereof, and Licensed Products including, without limitation, all 

  

 4 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
biological, chemical, pharmacological, toxicological, pharmaceutical, physical and analytical, clinical, safety, manufacturing and quality control data and
information. “ENDORECHERCHE Know-How” means that Know-How which is developed by or on behalf of ENDORECHERCHE during the term of this Agreement, including as it may be extended. “SCHERING Know-How” means that Know-How which is
developed by or on behalf of SCHERING during the term of this Agreement, including as it may be extended, and using ENDORECHERCHE Know-How, ENDORECHERCHE Patents and/or Licensed Compounds. 
 Article l, Paragraph (h) shall be amended to read in its entirety as follows: 
 (g) “Licensed Compounds” means (i) any compounds existing on the effective date of this Agreement which were conceived of
as antiestrogen or antiandrogen compounds by or on behalf of ENDORECHERCHE; (ii) any additional novel or existing compounds which are conceived of as compounds in the Field by or on behalf of ENDORECHERCHE while carrying out research in the
Program as that term is defined in Paragraph (a) of Article 4 of this Agreement during the four (4) year period commencing on the effective date of this Agreement, as such period may be extended; and (iii) any novel or existing
compounds which are conceived of as compounds in the Field by or on behalf of ENDORECHERCHE and arising from research using the Type-5 Gene Technology, including, without limitation, through use of the Type-5 Gene Technology for compound
screening, conducted during the Program (as defined above) or during the two 

  

 5 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
year drug discovery and development period set forth in Article 4a, Paragraph (b), including as it may be extended. The parties acknowledge and agree that
for purposes of determining Net Sales and Earned Royalties under Article 1, Paragraph (b)(l)(D). Licensed Compounds shall also include compounds discovered by or on behalf of SCHERING and arising from research using the Type-5 Gene Technology.

 Article 1, Paragraph (1) shall be amended to read in its entirety as follows: 
 (1) “Patent Rights” means: (i) all pending United States patent applications and issued patents relating to Licensed
Compounds described in Paragraph (h)(i) of Article 1, including without limitation, the pending United States patent applications and issued patents listed, as of the effective date of this Agreement, in Exhibit A attached hereto and made a part
hereof; (ii) all claims of any patent applications or issued patents filed or issued during or after the term of this Agreement to which Fernand Labrie, M.D. and/or ENDORECHERCHE have rights covering any compositions for, processes for, or
methods of use of any Licensed Compounds in the Field; (iii) all existing or future United States patent applications and issued patents relating to Type-5 Gene Technology or the use of Type-5 Gene Technology to screen for or otherwise identify
Licensed Compounds; (iv) all claims of any foreign counterpart patent applications and/or issued patents of (i), (ii) or (iii); (v) any reissues, extensions, substitutions, confirmations, registrations, revalidations, additions,
continuations, continuations-in-part, divisions 

  

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 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
or supplementary protection certificates, of or to any of the foregoing which are hereafter granted in the Territory. Exhibit A shall be updated periodically
to reflect the current status of the Patent Rights. “ENDORECHERCHE Patent Rights” means Patent Rights as defined above in which Fernand Labrie. M.D. and/or ENDORECHERCHE hold all rights, title and interest, or otherwise hold rights by
virtue of their status as inventor, co-inventor, assignee or licensee. “SCHERING Patent Rights” means Patent Rights as defined above in which SCHERING, or its Affiliate, holds all rights, title and interest. 
 In Article 1, new Paragraphs (s) and (t) shall be added to read in their entirety as follows: 
 (s) “Type-5 Gene Technology” means the enzyme known as 17ß-HSD-5. DNA expressing 17ß-HSD-5 (including, without
limitation, the wildtype gene and any mutant genes prepared by or on behalf of ENDORECHERCHE), plasmids or other vectors comprising such DNA, transformed or transfected cell lines, assays or screening methods for identifying and/or evaluating the
efficacy of compounds which are inhibitors of 17 ß -HSD-5 and any other materials or methods developed by or on behalf of ENDORECHERCHE for use in such assays or screening methods. 
 (t) “ENDORECHERCHE Inventions” means any discoveries, developments, innovations or inventions relating to Licensed Compounds or
the Type-5 Gene Technology (collectively, “Inventions”) made at least in part, by Dr. Fernand Labrie or other employees of ENDORECHERCHE, or otherwise owned or controlled by 

  

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 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
ENDORECHERCHE by virtue of an assignment of rights to such Inventions. “SCHERING Inventions” means any Inventions made solely by employees or
agents of SCHERING. Inventorship of all Patent Rights relating to Licensed Compounds will be determined in accordance with United States patent law. 
 ARTICLE 2 - LICENSE GRANT 
 Article 2 shall be amended to read in its entirety as follows: 
 (a) ENDORECHERCHE hereby grants to SCHERING, and SCHERING hereby accepts from ENDORECHERCHE, exclusive, worldwide licenses under the
ENDORECHERCHE Patent Rights and to use ENDORECHERCHE Know-How, with a right to sublicense, to make, have made, use and sell Licensed Compounds and Licensed Products in the Field in the Territory. The foregoing licenses shall be exclusive, even as to
ENDORECHERCHE, except as necessary for ENDORECHERCHE to make and use Licensed Compounds for the express purposes stated in this Agreement. As between SCHERING CORPORATION and SCHERING-PLOUGH LTD., SCHERING CORPORATION shall own and control the
rights granted under this Paragraph (a) in the United States and SCHERING-PLOUGH LTD. shall own and control such rights in all other countries in the Territory. 
 (b) ENDORECHERCHE and SCHERING each acknowledge that ENDORECHERCHE is conducting research in the Field using the [***] and all
materials and/or Know-How related thereto or derived therefrom). 
  

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 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 ENDORECHERCHE and SCHERING further acknowledge that ENDORECHERCHE will utilize a portion of the payments
received from SCHERING under this Agreement to support continuation of its research using the [***], which research shall be conducted concurrently with its drug discovery and development obligations under the terms of this Agreement. In
consideration for SCHERING’s support ENDORECHERCHE agrees to keep SCHERING informed regarding its research using the [***] and hereby grants to SCHERING, and SCHERING hereby accepts from ENDORECHERCHE, a first option to obtain exclusive,
worldwide rights to develop and commercialize any development candidate compounds discovered and developed by ENDORECHERCHE using [***] during the drug discovery and development periods set forth in Article 4A. Such rights shall include an
exclusive, worldwide licence under all existing and future patent applications and issued patents in the Territory owned or controlled by ENDORECHERCHE and relating to compounds discovered and developed using the [***], and the use of all
related ENDORECHERCHE Know-How. The parties will commence negotiations to enter into such a license agreement following completion by ENDORECHERCHE of all development work required to identity a development candidate compound and upon
SCHERING’s agreement that a suitable development candidate has been identified. The terms of the license will be determined by good faith negotiations between the parties, provided, however, that ENDORECHERCHE and SCHERING agree that in any
such license to be negotiated by the parties SCHERING shall have no obligation to reimburse or otherwise compensate ENDORECHERCHE for any drug discovery and development costs leading up to the identification of said development candidate compounds.

  

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 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 ARTICLE 3 - PAYMENTS AND ROYALTIES 
 New Paragraph (j) shall be added to Article 3 to read in its entirety as follows: 
 (j)
It is understood that as of the Amendment Date, SCHERING’s obligation to pay Earned Royalties shall be apportioned between SCHERING CORPORATION and SCHERING-PLOUGH LTD. in accordance with this Paragraph (j). SCHERING CORPORATION shall be
responsible for payment of Earned Royalties on Net Sales in the United States and SCHERING-PLOUGH LTD. shall be responsible for payment of Earned Royalties on Net Sales in an other countries in the Territory. Notwithstanding the foregoing. SCHERING
CORPORATION and SCHERING-PLOUGH LTD. shall remain jointly and severally liable for all Earned Royalties payable to ENDORECHERCHE under this Article 3. 
 New
Article 3A shall be added after Article 3 to read in its entirety as follows: 
 ARTICLE 3A - ADDITIONAL PAYMENTS 
 In consideration for the rights relating to Type-5 Gene Technology granted to SCHERING pursuant to this Amendment, and subject to the
other terms in this Agreement, SCHERING agrees to make the following payments in U.S. dollars to ENDORECHERCHE, 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
which payments shall be in addition to any other payments set forth in this Agreement and which shall be non-refundable and non-creditable against future
royalties: 
 (i) [***] ($ [***] upon transfer to SCHERING of all materials and Know-How relating to Type-5 Gene
Technology to enable SCHERING to establish an operational high-throughput screening program for inhibitors of 17ß-HSD-5, inc1uding, but not limited to 17ß-HSD-5 overexpressing 293 cells and other reagents and antibodies, as necessary.

 (ii) [***] ($ [***] upon the successful development by ENDORECHERCHE [***].  
 (iii) [***] ($ [***] upon the identification of an inhibitor of 17ß-HSD-5 which is
a suitable “lead candidate”, i.e., an inhibitor which meets at least the following criteria: (a) potency of less than 5nM;(b) selective inhibition of human 17ß-HSD-5, but no inhibition of 17ß-HSD-3a or other related
enzymes; (c) lack of intrinsic steroidal activity; (d) reduces testosterone and DHT levels using the prostate cell-based assay at IC50 £ 100 nM, with comparison to PROSCAR.]. 
 (iv) [***] ($ [***] upon identification of a “development candidate” for clinical study, i.e., a compound which
meets criteria inc1uding the following: (a) [***];  
  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 (b) establishment of in vivo predictive animal models; (c) demonstrated in vivo efficacy at
acceptable clinical doses; (d) completed drug metabolism studies (ADME); (e) medicinal chemistry modification (as necessary based upon ADME, etc.); (f) repeated efficacy / ADME studies (as necessary); (g) demonstrated lack of
enzyme induction potential; (h) completion of three (3) month toxicology studies in two animal species; (i) negative in genotoxicity testing; (j) all such studies being performed in compliance with current standards of good
laboratory practice (GLP) acceptable for worldwide regulatory submissions, including any applicable U.S. Food and Drug Administration (FDA) standards. 
 (v) [***] ($ [***] upon [***]. 
 (vi) [***] ($ [***]upon
completion of [***] and SCHERING’s notification to ENDORECHERCHE of its decision [***].  
 (vii)
[***] ($ [***] when [***] and SCHERING has notified ENDORECHERCHE of its decision to [***]. Completion for purposes of this Paragraph means [***].  
  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 (viii) [***] ($ [***] upon completion [***]  
 [***] 
 Notwithstanding any provision
in this Agreement to the contrary, SCHERING’s obligation to pay the milestone payments set forth in this Article 3A shall be limited solely to those Licensed Compounds which meet the definition set forth in Article 1, Paragraph h(iii) (i.e.,
only those Licensed Compounds which are conceived of as compounds in the Field by or on behalf of ENDORECHERCHE and which arise from research using the Type-5 Gene Technology). The parties each acknowledge and agree that the milestone
payments set forth in this Article 3A are in addition to the milestone payment obligations set forth in Article 3, provided, however, that any Licensed Compound which is subject to the milestone payment obligations of this Article 3A
(i.e., one which arises from research using the Type-5 Gene Technology shall not also be deemed the first Licensed Compound for purposes of triggering the milestone payment obligations set forth in Article 3. 
 SCHERING shall have no obligation to make milestone payments under this Article 3A with respect to Licensed Compounds which meet the definition set forth
in Article l, Paragraphs (h)(i) and (h)(ii) hereof, provided, however, that SCHERING shall remain obligated to 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
pay milestone payments for such compounds under the provisions set forth in Article 3 hereof. The parties acknowledge and agree that, notwithstanding any
statement in Article 3 to the contrary, the total aggregate sum of the milestone payments set forth in Article 3 is twelve million dollars ($12,000,000.00). 
 It is understood that as of the Amendment Date, SCHERING’s obligation to make milestone payments under Article 3 of the Agreement and under this Article 3A shall be apportioned between SCHERING CORPORATION and
SCHERING-PLOUGH LTD. SCHERING CORPORATION shall be responsible for paying [***] %) of such amounts and SCHERING-PLOUGH LTD. shall be responsible for paying [***] %) of such amounts. Notwithstanding the foregoing, SCHERING CORPORATION
and SCHER1NG-PLOUGH LTD. shall remain jointly and severally liable for all milestone payments payable to ENDORECHERCHE under Article 3 of the Agreement or this Article 3A. 
 ARTICLE 4 - DEVELOPMENT EFFORTS 
 The first two complete sentences of Article 4, Paragraph (a) shall be amended
to read in their entirety as follows: 
  

	 	(a)	 ENDORECHERCHE will continue its drug discovery efforts in the Field using its best efforts during the initial four (4) year period commencing on the effective
date of this Agreement, including as it may be extended, and will continue its development efforts as 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

	 	 
necessary during the thirty (30) year term of this Agreement using its best efforts to meet the milestones described in paragraph (a) of Article 3
(such discovery and development efforts hereinafter referred to as the “Program”). Except as set forth in Article 4A of this Amendment, ENDORECHERCHE shall in no event be obligated hereunder to undertake any new drug discovery, efforts
after the initial four(4) year term of the Program or any extension thereof pursuant to the operation of this Paragraph (a). 

 The
remainder of Article 4, Paragraph (a) as set forth in the Agreement shall remain in full force and effect. 
 Article 4, Paragraphs (i) and
(j) shall be amended to read in their entirety as follows: 
 (i) For the second or any subsequent Licensed Compound
designated by SCHERING for development. SCHERING shall at its option either reimburse ENDORECHERCHE, on [***], for its properly documented actual out-of-pocket expenses for any development work through completion of Phase 1 clinical
trials, [***] or perform such work itself. Notwithstanding any provisions of this Agreement to the contrary, SCHERING shall, at its option, have the right to conduct all further development work on any second or subsequent Licensed Compounds
designated by SCHERING for development (including, without limitation, phase II clinical trials, phase III clinical trials and NDA toxicology). 
  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 (j) Except for the proper exercise of any licenses granted and rights reserved under the
provisions of this Agreement, each party agrees that it and its Affiliates (and sublicensees in the case of SCHERING) will not publish or otherwise divulge or use for its or their own benefit confidential information furnished to it by the other
party including, without limitation, confidential SCHERING Know-How, and in addition in the case of ENDORECHERCHE Program results, without the prior written approval of such other party in each instance. The foregoing obligation shall not be imposed
on a party with respect to any information which it can demonstrate: (i) was at the time of disclosure to it (or shall thereafter, but prior to its publication, divulgence or use for the benefit of a party or any of its Affiliates, become,
through no fault of such party or its Affiliates) a part of the public domain by publication or otherwise; or (ii) was already properly and lawfully in its possession at the time it was received from the other party; or (iii) was lawfully
received from a third party who was under no obligation of confidentiality to the disclosing party with respect thereto; or (iv) is required by law to be disclosed (but only to the extent of such required disclosure). This obligation shall
extend until the last to occur of (i) the expiration of this Agreement, or (ii) [***] years following the Amendment Date, or (iii) [***] years following any termination of this Agreement prior to expiration thereof.

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 New Articles 4A and 4B shall be added after Article 4 to read in their entirety as follows: 
 ARTICLE 4A - ADDITIONAL DEVELOPMENT EFFORTS 
 (a) ENDORECHERCHE and SCHERING each acknowledge and agree: (i) that ENDORECHERCHE has conducted drug discovery and development efforts in the Field (as set forth in Article 4) during the four (4) year period
commencing on the effective date of the Agreement (i.e., from January 1, 1992 through December 31, 1995); and (ii) that ENDORECHERCHE’s obligation to conduct such drug discovery and development efforts in the Field using its best
efforts has been extended for an additional two (2) year period (i.e.,. from January 1, 1996 through December 31, 1997), pursuant to Article 4 of the Agreement, and as set forth in the Letter of Understanding dated December 19,
1995. 
 (b) Notwithstanding any provisions to the contrary in the Agreement, ENDORECHERCHE and SCHERING each further
acknowledge and agree that in addition to the foregoing drug discovery and development obligations. ENDORECHERCHE shall conduct drug discovery and development efforts (as set forth in Article 4 of the Agreement) in the Field using the Type-5 Gene
Technology, [***], and using its best efforts during the Program and for the two (2) year period commencing on the Amendment Date. SCHERING shall have the option, but not the Obligation, to extend the two (2) year period set forth
in this Paragraph (b) for an additional period of one (1) year upon giving at least ninety (90) days notice prior to the end of said two (2) year period. In the event that SCHERING elects to exercise its aforementioned option to
extend the period for an additional one (1)

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
year, SCHERING will pay to ENDORECHERCHE an additional payment of $2 million dollars. SCHERING’s decision to exercise, or its failure to exercise, its
extension option shall have no effect on ENDORECHERCHE’s continuing obligation to conduct development efforts using its best efforts to me et the milestones described in Article 3A, and in Paragraph (a) of Article 3, during the term of
this Agreement (which remains thirty (30) years from the effective date). 
 (c) During the duration of the drug
discovery and development period set forth in Paragraph (b) above, including as it may be extended, while this Agreement remains in effect, neither ENDORECHERCHE nor Dr. Fernand Labrie will participate in, alone or with others, any other
research and/or development: (i) using the Type-5 Gene Technology [***] to identify, develop or commercialize compounds for the prophylactic or therapeutic treatment of cancer in animals or man; or (ii) of antiestrogen and/or
antiandrogen compounds for the prophylactic or therapeutic treatment of cancer in animals or man. 
 ARTICLE 4B - PROJECT COORDINATING
COMMITTEE 
 The parties hereto agree to establish a Project Coordinating Committee (hereinafter the “PCC”) to oversee all drug
discovery and development research efforts to be conducted by ENDORECHERCHE pursuant to this Agreement and to coordinate such efforts with the drug discovery and development research efforts to be conducted by or on behalf of SCHERING. The PCC shall
also serve 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
as a decision making body for the mutual resolution of problems and issues relating to such research efforts that may arise from time to time during the
conduct of such research by the parties. The PCC shall be comprised of senior representatives from each of SCHERING and ENDORECHERCHE, with each party appointing two such representatives to serve on the PCC. The PCC shall meet as necessary, but at
least twice each year, during the drug discovery and development period set forth in Article 4A. Paragraph (b), including as it may be extended, for the purposes set forth above. All decisions of the PCC shall be based upon unanimous agreement of
the parties. In the event that the PCC is unable to reach agreement on an issue, then the parties agree to refer such issues to the most senior executive managers at ENDORECHERCHE and SCHERING responsible for the development and commercialization of
Licensed Compounds, i.e., the Chief Executive Officer of ENDORECHERCHE and a similarly responsible officer of SCHERING (who may be an officer of the SCHERING Affiliate responsible for Licensed Compounds in the Territory), for resolution.
Notwithstanding the foregoing, the parties acknowledge and agree that Schering shall retain all final decision making authority and control with regard to selection of Licensed Compounds and/or Licensed Products for development and/or
commercialization, and all aspects of the development, manufacturing, distribution, marketing, promotion and sales activities for such Licensed Compounds and/or Licensed Products. 
  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 Article 6 shall be amended to read in its entirety as follows: 
 ARTICLE 6 - PATENT RIGHTS AND UNLICENSED SALES 
 As long as SCHERING has rights
to Licensed Compounds hereunder. ENDORECHERCHE shall, or shall permit SCHERING, as hereinafter provided, to prepare, file, prosecute and maintain ENDORECHERCHE Patent Rights with respect to such Licensed Compounds which remain potential candidates
for development and marketing, including any such Patent Rights claiming compositions of matter, methods of use thereof or processes therefor in accordance with the terms of this Article, as follows: 
 (a) After the effective date of this Agreement, if SCHERING wishes patent protection in any country or countries in the Territory for any
ENDORECHERCHE Inventions, ENDORECHERCHE shall prepare, file, prosecute and maintain ENDORECHERCHE Patent Rights covering such Inventions and SCHERING shall reimburse ENDORECHERCHE [***] related thereto. [***] received by ENDORECHERCHE
to reimburse it for patent expenses shall not be counted as an off-set against [***] for purposes of the aforementioned calculation. SCHERING shall be provided reasonable opportunity to participate in the selection of patent counsel and to
review and comment upon the contents of any proposed patent application and on the contents of any document relating to the prosecution and maintenance of ENDORECHERCHE Patent Rights, and at its option, in lieu of the foregoing, SCHERING may
prepare, prosecute and maintain any 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 
ENDORECHERCHE Patent Rights itself solely at its expense, in which event ENDORECHERCHE agrees to provide reasonable assistance to SCHERING, at no
out-of-pocket expense, including causing the execution of any necessary patent documents, to facilitate SCHERING’s efforts to prepare, prosecute and maintain such ENDORECHERCHE Patent Rights. For Patent Rights prepared, prosecuted and
maintained by ENDORECHERCHE, SCHERING shall reimburse ENDORECHERCHE [***] with respect to those issued patents claiming [***] to the extent not reimbursed through [***]. It is the intention of the parties that any patent
application, as filed and prosecuted, shall be of the same quality, scope and coverage as would be sought by the party filing for its own valuable proprietary property which it did not intend to license. SCHERING shall at its sole discretion and at
its expense, prepare, file, prosecute and maintain, SCHERING Patent Rights covering any SCHERING Inventions relating to Licensed Compounds, which SCHERING Patent Rights shall remain the sole property of SCHERING, and will provide ENDORECHERCHE an
opportunity to review and comment upon the contents of any proposed patent application and on the contents of any document relating to the prosecution and maintenance of SCHERING Patent Rights, provided, however, that SCHERING shall have final
control over the contents of any such patent applications or documents. 
  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 (b) With respect to any issued patent within the Patent Rights, ENDORECHERCHE will
designate SCHERING as its agent for obtaining an extension of such patent where available in any country in the Territory or, if not feasible, at SCHERING’s option, will permit SCHERING to file in ENDORECHERCHE’s name or diligently obtain
such extension for SCHERING at SCHERING’s expense. Furthermore, ENDORECHERCHE agrees to provide reasonable assistance, at no out-of-pocket expense, to facilitate SCHERING’s efforts to obtain any extension. 
 (c) SCHERING agrees to promptly take all reasonable legal action necessary to protect the SCHERING Patent Rights against infringements by
third parties. ENDORECHERCHE agrees to promptly take all reasonable legal action necessary to protect the ENDORECHERCHE Patent Rights against infringements by third parties. If within three (3) months following the receipt of written notice
from SCHERING, ENDORECHERCHE fails to file suit or take such other action as appropriate to halt the alleged infringement, SCHERING shall, in its sole discretion, have the right to take such action as it deems warranted in its own name or in the
name of ENDORECHERCHE. The foregoing notwithstanding, in the event that an alleged infringer certifies pursuant to 21 U.S.C. §355(b)(2)(A)(iv) against an issued patent covering a Licensed Product and within the ENDORECHERCHE Patent Rights,
ENDORECHERCHE shall immediately notify SCHERING upon receipt of notice of such certification, and if fourteen (14) days prior to expiration of the forty-five (45) day period set forth in 21 U.S.C. §355(c)(3)((C), ENDORECHERCHE fails
to file suit, SCHERING shall, in its sole 

  

 22 

 
discretion, have the right to take such action as it deems warranted in its own name or in the name of ENDORECHERCHE. ENDORECHERCHE agrees to render such
reasonable assistance (which assistance does not place unduly burdensome demands on ENDORECHERCHE’s time or finances) as SCHERING may request in the event such action is taken by SCHERING. Costs of maintaining any such action and damages
recovered therefrom shall be paid by and belong to the party bringing the action. If SCHERING consents in the exercise of its sole discretion to a license to any third party infringer hereunder, then after deduction by SCHERING of any costs and
expenses of prosecuting any claims against the third party which are incurred by SCHERING prior to licensing such party, the parties shall split any advance or running royalty payments received from any third party, [***] %) to SCHERING and
[***] %) to ENDORECHERCHE. 
 Article 7 shall be amended to read in its entirety as follows: 
 ARTICLE 7 - TERM AND TERMINATION 
 (a) Unless sooner terminated
under the provisions hereof, this Agreement shall expire thirty (30) years after its effective date. To the extent not previously granted, SCHERING shall thereafter be free to use and commercialize at no cost any remaining proprietary rights
granted pursuant to Article 2 herein as it sees fit in the Territory. 
  

 23 
 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 (b) Either party may, at its option, terminate this Agreement by giving the other party
prior notice in writing to that effect of not less than ninety (90) days in the event the other party shall commit a material breach of this Agreement, and shall fail to cure such breach during the ninety (90) day period following receipt
of said notice from the non-breaching party or such longer period as may be agreed upon by the parties, provided the breaching party continues its diligent efforts to cure; provided, however, that any such termination shall not release the breaching
party from any obligations hereunder incurred prior thereto and provided further that if a breach by SCHERING occurs after the conclusion of the four (4) year drug discovery and development period described in Article 4A, Paragraph (a) as
extended by the Letter Of Understanding dated December 19, 1995, and after the conclusion of the two (2) year drug discovery and development period described in Article 4A, Paragraph (b) or any extension thereto, the Agreement shall
be terminable by ENDORECHERCHE only with respect to Licensed Compound(s) or Licensed Product(s) to which the breach specifically relates. 
 (c) Deleted in its entirety. 
 (d) The parties may at any time terminate this Agreement in
part or in its entirety by mutual written agreement, provided, however, that the termination date shall be set by mutual agreement of the parties such that both SCHERING and ENDORECHERCHE are provided adequate notice to cease work being performed
under the Agreement. 
 (e) Deleted in its entirety. 
  

 24 

 (f) Upon any partial or complete Agreement termination, all Earned royalties due for Net
Sales of Licensed Products to the Effective date of said termination shall accrue and become due and payable on the sixtieth (60th) day thereafter. 
 (g) In the event of the termination of any license rights with respect to a Licensed Product prior to the expiration of this Agreement, inventory of Licensed Products may be sold after date of termination provided
Earned Royalties are paid thereon. 
 (h) In the event this Agreement is terminated by the parties pursuant to Paragraph
(d) of this Article, then ENDORECHERCHE shall have the following rights and obligations: 
 (i) At the written request of
ENDORECHERCHE given within ninety (90) days of the termination, SCHERING will transfer or cause to be transferred to ENDORECHERCHE or its designee, to the extent reasonably feasible and with any out-of-pocket expenses associated with the
transfer(s) paid by ENDORECHERCHE, any government health registration and pricing approvals of SCHERING and its Affiliates for any Licensed Products (excluding Licensed Combinations) which contain as the sole active pharmaceutical ingredient(s)
Licensed Compounds covered by the ENDORECHERCHE Patent Rights, and shall also promptly provide or cause to be provided SCHERING Know-How essential (as determined by SCHERING) for the commercialization of such Licensed Products and developed during
the drug discovery and development periods set forth in Article 4A, Paragraphs (a) and (b), provided, however, that any SCHERING Know-How made available to 

  

 25 

 
ENDORECHERCHE pursuant to this Article 7, Section h(l) shall be used by ENDORECHERCHE solely for the purpose of commercializing such Licensed Products. The
parties acknowledge and agree that, with respect to SCHERING Know-How related to manufacturing, SCHERING’s obligation to provide such SCHERING Know-How to ENDORECHERCHE shall be limited to Know-How developed by SCHERING exclusively for the
manufacture of Licensed Products, and that such obligation shall be subject to the parties reaching mutual agreement upon commercial terms to reasonably reimburse SCHERING for the use of such Know-How; 
 (ii) Deleted in its entirety. 
 (iii) ENDORECHERCHE and any designee or sublicensee shall indemnify and hold SCHERING, its Affiliates and their respective employees, officers, directors, shareholders and agents harmless, to the maximum extent
permitted by law, from and against any claims, liability, loss, damages, costs or expenses (including reasonable attorney’s fees) which the indemnified party may incur, suffer or be required to pay resulting from or arising in connection with
the use of or sale of any Licensed Products, Licensed Compounds, Patent Rights or Know-How described in this Paragraph. Furthermore, to the extent permitted by law. SCHERING makes no warranties, express or implied, with respect to any rights.
Licensed Compounds or Licensed Products described in this Paragraph and shall not be liable to ENDORECHERCHE or any third party with respect to the manufacture, use or sale of any Licensed Compounds or Licensed Products describe in this Paragraph;
and 
  

 26 

 (iv) SCHERING shall return to ENDORECHERCHE or dispose of any ENDORECHERCHE Know-How, to
the extent reasonably feasible, as requested by ENDORECHERCHE, within a reasonable time after the termination. 
 ARTICLE 9 - MISCELLANEOUS

 In Article 9, paragraph (b), amend the address for notice to SCHERING by adding the following addition al address for SCHERING-PLOUGH LTD.:

 Schering-Plough Ltd. 
 Topferstrasse 5 
 6004 Lucerne, Switzerland 
 Except as expressly amended and supplemented hereby, all other terms of the Agreement shall remain in full force and effect. 
 [The remainder of this page is intentionally left blank.] 
  

 27 

 IN WITNESS WHEREOF, the parties hereto have caused this Amendment Agreement to be executed in duplicate
by their duly authorized representatives. 
  

							
	ENDORECHERCHE INC.	 	SCHERING CORPORATION
				
	BY:	 	 /s/ Fernand Labrie
	 	BY:	 	 /s/ David Poorvin

	NAME:	 	Fernand Labrie	 	NAME:	 	David Poorvin
	TITLE:	 	President	 	TITLE:	 	Vice President
	DATE:	 	November 14, 1996	 	DATE:	 	November 18, 1996
			
		 		 	SCHERING-PLOUGH LTD.
				
		 		 	BY:	 	 /s/ David Poorvin

		 		 	NAME:	 	David Poorvin
		 		 	TITLE:	 	Prokurist
		 		 	DATE:	 	November 18, 1996

  

 28Addendum, among EndoResearch Inc. and each of Schering Corporation

 Exhibit 10.9 
 Addendum Agreement 
 This Addendum Agreement (the “Addendum”), entered into and made effective as of
the latest date of signature appearing below (the “Addendum Date”) by and among Endorecherche, Inc. (“Endorecherche”) and Schering Corporation and Schering-Plough Ltd. (together, “Schering”), amends and supplements that
certain agreement by and between Endorecherche and Schering, dated January 1, 1992, as previously amended (the “Agreement”). 
 WHEREAS,
Endorecherche and Schering have been collaborating in the development of a certain antiestrogen compound as a Licensed Compound under the terms of the Agreement; and 
 WHEREAS, Endorecherche now desires to assume sole responsibility for the continued development of such antiestrogen compound; and 
 WHEREAS, Schering is willing to grant such responsibility to Endorecherche on the terms and conditions set forth in this Addendum, 
 NOW,
THEREFORE, Endorecherche and Schering agree that the terms and conditions of the Agreement shall be amended as follows: 
 Article I.
Definitions 
 Except as otherwise expressly set forth in this Addendum, all capitalized terms used herein, whether in the singular or plural, shall have
the respective meanings set forth in the Agreement. 
 1.01 “Acolbifene” shall mean the specific antiestrogen compound known as acolbifene (also
referred to by the parties as EM-652 or SCH 57068) and having the chemical structure set forth in Exhibit 1 (attached hereto). 
 1.02 “Canadian
Development Costs” shall have the meaning set forth in Section 3.05(c) of this Addendum. 
 1.03 “Commercial Rights in Canada” shall have
the meaning set forth in Section 3.05 of this Addendum. 
 1.04 “Development Costs” shall mean any and all internal and external costs
actually incurred by EndoRecherche or its Affiliates on or after the Addendum Date in connection with the development of Acolbifene. 
 1.05 “Diligence
Period” shall mean the period of sixty (60) days beginning on the date on which Schering receives all of the Phase III Results. 
  

 [***] Represents information redacted and filed separately with the Commission pursuant to a request for
confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 1.06 “Earned Royalty”, solely as such term is used in this Addendum with respect to Licensed Products
containing Acolbifene, shall have the meaning set forth in Section 3.03(f) of this Addendum. 
 1.07 “Existing Patent Rights” shall mean
(i) any Patent Rights existing on the Addendum Date, and (ii) any continuations, divisions, extensions, renewals, reissues, reexaminations or supplementary protection certificates arising after the Addendum Date based upon any such Patent
Rights. 
 1.08 “Option” shall have the meaning set forth in Section 3.01 of this Addendum. 
 1.09 “Option Date” shall have the meaning set forth in Section 3.03(a) of this Addendum. 
 1.10 “Option Period” shall mean the period beginning on the Addendum Date and expiring on the earlier of (i) ninety (90) days after the date on which Schering receives all of the Phase III Results,
including as such ninety (90) day period may be extended pursuant to Section 3.01(b), or (ii) Endorecherche’s receipt of written notice from Schering in accordance with Section 3.01. 
 1.11 “Phase III Results” shall have the meaning set forth in Section 2.02(c) of this Addendum. 
 1.12 “Regulatory Approval” shall mean any and all approvals (including NDA approvals), licenses, registrations, or authorizations of any federal, national,
multinational, state, provincial or local regulatory agency, department, bureau or other governmental entity necessary for the manufacture, use, storage, import, export, transport, promotion, marketing or sale of a prescription pharmaceutical
product for use in humans in a country in the Territory (including without limitation, any pricing or pricing reimbursement approvals). 
 1.13 “Reverse
Royalty” shall have the meaning set forth in Section 3.04 (d) of this Addendum. 
 Article II. Development Program

 2.01 Continuation of the Development Program. Effective as of the Addendum Date, and notwithstanding anything in the Agreement to the contrary,
Endorecherche shall be solely responsible for the continued development of Acolbifene in the Territory. This will include the planning, design and performance of all Phase III clinical studies, toxicology studies, and any other research and
development activities necessary or desirable, in the opinion of Endorecherche, to support any NDAs or other Regulatory Approvals for Acolbifene in the Territory. For purposes of clarity and avoidance of doubt, the parties hereto acknowledge and
agree that Endorecherche shall have the obligation to use diligent efforts in connection with the continued development of 

  

 2 

 
Acolbifene. However, Endorecherche shall have the right to terminate its continued development efforts for Acolbifene at any time. In the event that
Endorcherche determines (in its sole discretion) to terminate such efforts, it shall promptly notify Schering in writing to that effect. Effective upon Schering’s receipt of such notice, the terms of Section 6.06 of this Addendum shall
govern. 
  

	 	(a)	Use of Contractors. Endorecherche shall have the right to use third party contractors in connection with the development of Acolbifene during the Option Period. Endorecherche
shall ensure that each such third party contractor is obligated to appropriate confidentiality and non-use restrictions with respect to all proprietary data and information related to Acolbifene to which they are provided access. Endorecherche shall
also ensure that any such third party contractors are contractually obligated to assign, or exclusively license with the right to grant sublicenses, to Endorecherche (or its designee) any and all data, information, developments, inventions or
discoveries (whether patentable or not) generated by such third parties related to Acolbifene, formulations containing Acolbifene, and/or the manufacture or use thereof. 

  

	 	(b)	Obligation to cooperate. Schering shall, upon request, cooperate with Endorecherche by providing Endorecherche with a copy of and/or reasonable access to any data,
information or know-how related to Acolbifene in Schering’s or its Affiliates’ possession or control that is necessary or useful to Endorecherche in connection with the further development of Acolbifene, including without limitation
know-how related to the manufacture of Acolbifene. In addition Schering shall provide Endorecherche with appropriate documentation to grant Endorecherche rights to cross reference and to access the contents of any NDAs, INDs or other similar
regulatory submissions for Acolbifene that are held by Schering or its Affiliates in the Territory, to enable Endorecherche to carry out the further development of Acolbifene as contemplated hereunder. 

  

	 	(c)	Supplies of Acolbifene. To the extent that Schering or its Affiliates have available any supplies of Acolbifene (including supplies of bulk active drug substance and supplies
of finished product), Schering shall provide Endorecherche with a listing of such materials. Endorecherche shall have the right to request Schering to deliver such materials to Endorecherche (or its designated contractor) for use by Endorecherche in
the further development of Acolbifene in the Territory. Upon receipt of such a request in writing Schering shall, to the extent permitted under applicable law, provide the requested materials to Endorecherche. The materials will be shipped FCA
(Incoterms 2000) to a facility designated in writing by Endorecherche. To the extent available, Schering shall provide a certificate of analysis or other appropriate documentation together with such materials; provided that Schering shall not
have any obligation to complete any additional testing, re-certification or other analyses of such materials. Endorecherche shall be solely responsible for the proper storage, handling, distribution and use of all materials delivered by Schering
under this Section 2.02(c) and shall comply with all applicable laws, rules and regulations in connection therewith. 

  

 3 

	 	(d).	Warranty Disclaimer Regarding Materials. ANY SUPPLIES OF ACOLBIFENE (INCLUDING BULK ACTIVE AND FINISHED PRODUCT) REFERENCE SAMPLES OR OTHER MATERIALS DELIVERED TO
ENDORECHERCHE (OR ITS DESIGNEES) BY SCHERING PURSUANT TO SECTION 2.02(c) ARE PROVIDED “AS IS”, WITHOUT ANY REPRESENTATION OR WARRANTY OF ANY KIND, INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF NONINFRINGEMENT, ANY IMPLIED
WARRANTIES OF MERCHANTABILITY OR ANY IMPLIED WARRANTIES OF FITNESS FOR A PARTICULAR PURPOSE, ALL OF WHICH ARE HEREBY SPECIFICALLY EXCLUDED AND DISCLAIMED. 

 2.02 Development Program Results. During the Option Period, Endorecherche shall keep Schering reasonably informed as to the status and results of all development work for Acolbifene performed by or on behalf of
Endorecherche. This shall include providing Schering with semi-annual written reports describing the research and development activities related to Acolbifene being conducted by or on behalf of Endorecherche and summarizing the data and results of
work completed during the relevant calendar quarter. Any such reports, as well as any proposed protocols to be reviewed by Schering under Section 2.02(a), shall be forwarded to the attention of Schering’s Executive Vice President, Global
Clinical Development at the address for notice set forth in Section 7.05. 
  

	 	(a)	Study Protocols. Endorecherche shall be responsible (at its own expense) for the design of all preclinical and clinical studies involving Acolbifene to be undertaken during
the Option Period. Endorecherche shall provide Schering with advance copies of all protocols for proposed studies involving Acolbifene in order to provide Schering a reasonable opportunity to review and comment on the protocol and study design.
Schering shall provide any comments to the protocol within thirty (30) days of receipt and Endorecherche shall consider in good faith any comments made by Schering with respect to the protocols and/or study design. 

  

	 	(b)	Review Meetings. During the Option Period, the parties shall meet from time to time (and in any event at least once per calendar year) to review and discuss the progress and
results of development work related to Acolbifene and plans for additional development work to be undertaken by or on behalf of Endorecherche. These review meetings shall take place at times and places to be agreed upon by the parties, and may be
conducted in person, via teleconference or videoconference. Each party shall be solely responsible for its own costs and expenses incurred in connection with such meetings. 

  

	 	(c)	Phase III Results. Following the successful completion of the Phase III clinical studies necessary to support the filing of an NDA for Acolbifene in the United States (i.e.,
completion of appropriately powered Phase III clinical trials meeting the established clinical endpoints for safety and efficacy of Acolbifene, as set forth in the protocol for such study), Endorecherche shall deliver to Schering a detailed report
of all final data and results of such Phase III clinical studies (the “Phase III Results”). The report of Phase III Results shall include an electronic copy of all Phase III study data in a format reasonably acceptable to Schering.

  

 4 

	 	(d)	Due Diligence. During the Diligence Period, Endorecherche shall (upon request and at Schering’s expense) provide Schering and its representatives with reasonable access
to any and all data and information related to the development of Acolbifene in Endorecherche’s possession or control to enable Schering to complete a due diligence review of such data and information. Such due diligence review shall include
access to all preclinical data (including without limitation toxicology and pharmacokinetic data), clinical data, formulation data, and data and information related to the manufacture of Acolbifene, as well as all communications with regulatory
authorities in the Territory with respect to Acolbifene. 

 2.03 Development Costs. Except as expressly set forth in this Addendum, and
notwithstanding anything in the Agreement to the contrary, Endorecherche shall be solely responsible for any and all Development Costs incurred by Endorecherche in connection with the development of Acolbifene during the Option Period. Within thirty
(30) days after providing the Phase III Results to Schering, Endorecherche shall provide Schering with an itemized statement of the aggregate total of all Development Costs actually incurred by Endorecherche during the Option Period up to
completion of the Phase III study, as well as an estimate of any additional Development Costs anticipated to be incurred during the remainder of the Option Period. 
 2.04 Unpaid Milestone Payments and Unpaid Invoices. To the extent that any amounts properly due and payable by Schering to Endorecherche under the terms of the Agreement as a result of: 
  

	 	(i)	costs of development activities for Acolbifene approved by the PCC (or otherwise agreed to by the parties) that were performed by Endorecherche prior to the Addendum Date in
accordance with the terms of the Agreement (as documented by detailed invoices with supporting documentation provided to Schering); or 

  

	 	(ii)	the achievement of any milestones set forth in Article 3, Paragraph (a) of the Agreement, 

 remain unpaid on the Addendum Date, Schering shall pay all such amounts to Endorecherche within thirty (30) days after the Addendum Date. Schering shall have the right to conduct an audit of Endorcherche’s
records in accordance with the terms of Section 3.03(g) of this Addendum in order to verify any amounts claimed by Endorecherche under Section 2.04(i). To the extent that any amounts that are claimed by Endorecherche under Sections 2.04(i)
and/or 2.04(ii) are disputed by Schering, the parties shall use good faith efforts to resolve such disputes within thirty (30) days after the Addendum Date, and any such disputes which cannot be resolved during that period shall be resolved in
accordance with the terms of Article 9, Paragraph (d) of the Agreement. 
  

 5 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 Article III. Option Rights 
 3.01 Schering Option Rights. Schering shall, except as expressly set forth in Section 3.05 with respect to rights in Canada, have the option (the “Option”) to either (i) retain its exclusive
licenses to Acolbifene in the entire Territory under the terms and conditions of the Agreement, as modified by this Addendum, or (ii) terminate its exclusive licenses to Acolbifene in the entire Territory. The Option shall be exercisable by
Schering (in its sole discretion) at any time during the Option Period by providing written notice to Endorecherche clearly identifying whether Schering is retaining or terminating its licenses to Acolbifene. 
  

	 	(a)	Effect of Failure to Provide Notice. In the event that Schering fails to provide any such notice to Endorecherche prior to the expiration of the Option Period, then
Schering’s licenses to Acolbifene shall terminate effective upon expiration of the Option Period in the same manner as if Schering had provided notice of such termination to Endorecherche. 

  

	 	(b)	Extension of Option Period. The Option Period shall be extended in the event that Schering is not able to complete a reasonable due diligence review of Acolbifene (as
contemplated under Section 2.02(d)) during the Diligence Period due to delays or failure by Endorecherche to provide access to data and information related to Acolbifene. Schering shall notify Endorecherche in writing on or before the
expiration of the Diligence Period of any such delays or failures which notice shall clearly identify the relevant data and information required to complete the due diligence review. Endorecherche shall provide Schering with access to such data and
information as soon as practicable thereafter, and the length of any such extension of the Option Period shall be such that the Option Period will expire thirty (30) days after Schering is provided access to such data and information.

 3.02 No Licenses. Except as expressly set forth in Section 3.05 with respect to Canada, during the Option Period Endorecherche
and its Affiliates shall not grant or convey (expressly, by implication or otherwise) to any third party any licenses, options or other rights, title or interests in or to Acolbifene or any Patent Rights or Know-How related thereto. 
 3.03 Effects of Retaining the Licenses. In the event that Schering exercises the Option under Section 3.01 and retains the licenses to Acolbifene, then the
provisions set forth in this Section 3.03 shall become effective and the provisions of Section 3.04 shall become null and void as of the date on which Endorecherche receives such notice. 
  

	 	(a)	 Control of Development and Commercialization. Effective upon the date on which Schering exercises the Option (the “Option Date”), and subject to
payment by Schering of the amounts provided for in this Section 3.03, Schering shall take over responsibility for the continued development and commercialization of Acolbifene within the Territory, except as expressly set forth in
Section 3.05 with regard to development and commercialization in Canada. The PCC shall continue 

  

 6 

	 	 
to be responsible for overseeing such continued development of Acolbifene throughout the entire Territory in accordance with the terms of Article 4B of the
Agreement; provided that decision making with regard to the commercialization of Acolbifene in Canada shall be governed by the provisions of Section 3.05. 

  

	 	(b)	Diligence. Schering’s diligence obligations set forth in Article 4, Paragraph (g) of the Agreement shall apply with respect to the commercialization of Acolbifene
in the Territory (excluding Canada). In particular, Schering (or its designated Affiliates or sublicensees) shall use such diligent efforts to seek to obtain and thereafter maintain marketing authorizations (including pricing and pricing
reimbursement approvals) for Acolbifene in the United States, the European Union and such other countries in the Territory (excluding Canada) where Schering determines it is commercially reasonable to do so. For purposes of clarity and avoidance of
doubt, the parties agree that factors to be considered in evaluating “diligent efforts” as used in this Section 3.03(b), shall include without limitation the commercial value and potential of the products in the relevant country, the
approved product labeling in the country, the scope and duration of patent protection and other forms of marketing exclusivity available for the product in the relevant country, and the available pricing/reimbursement approvals for the product in
the relevant country. 

  

	 	(c)	Reimbursement of Development Costs. Within thirty (30) days after Schering exercises the Option, Endorecherche shall provide Schering with a detailed itemized invoice
(including supporting documentation) of any and all Development Costs actually incurred by Endorecherche for development activities performed by or on behalf of Endorecherche on or after the Addendum Date but prior to the Option Date. Within thirty
(30) days after receipt of that invoice, Schering shall pay to Endorecherche an amount equal to one hundred and percent (100%) of the aggregate total of the documented Development Costs (excluding any Canadian Development Costs) actually
incurred by Endorecherche. 

  

	 	(d)	Additional Compensation to Endorecherche. Within thirty (30) days after Schering’s receipt of the invoice of Development Costs pursuant to Section 3.03(c),
Schering shall pay to Endorecherche the lesser of (i) an additional amount equal to fifty percent (50%) of the aggregate total of the amount properly due under Section 3.03(c) based upon documented Development Costs (excluding any
Canadian Development Costs) actually incurred by Endorecherche, or (ii) fifteen million US dollars ($15,000,000). Such payment shall be in lieu of the Phase III milestone payment provided for in Article 3, Paragraph (a)(v) of the Agreement and
Schering shall have no further obligations or liability to Endorecherche with respect thereto. 

  

	 	(e)	Change in Milestone Payments for Regulatory Approval. The milestone payment obligations provided for in Article 3, Paragraphs (a)(vi) and (a)(vii) of the Agreement are hereby
deleted and replaced in their entirety with the following revised milestone payment obligations: 

  

	 	(vi)	($ [***] upon [***]. 

  

	 	(vii)	($ [***] upon [***]. 

  

 7 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 For purposes of clarity, the parties acknowledge and agree that each of the revised milestone payments
provided for in this Section 3.03(e) shall become due and payable upon the first occurrence of the applicable milestone event, notwithstanding the cap on the aggregate total of milestone payments provided for in Article 3, Paragraph (a) of
the Agreement. The parties further acknowledge and agree that Schering’s diligence obligations set forth in Section 3.03(b) shall (without limitation) apply with respect to Schering’s efforts to achieve the foregoing milestones for
[***]. 
  

	 	(f)	Change in Earned Royalty Rate. The definition of Earned Royalty set forth in Article 1, Paragraph (b)(1) of the Agreement shall not apply solely with respect to Licensed
Products containing Acolbifene, which shall instead be governed by the following new provisions: 

 With respect to Licensed
Products containing Acolbifene (including Net Sales of Licensed Combinations containing Acolbifene as calculated in accordance with Article 1, Paragraph (b)(2) of the Agreement), the term “Earned Royalty” means an amount equal to either:

  

	 	(i)	[***]%) of such Licensed Products in those countries in the Territory (excluding Canada) where the Licensed Product are covered by a Valid Claim, and

  

	 	(ii)	[***]%)of such Licensed Products in those countries in the Territory (excluding Canada) where the Licensed Product is not covered by a Valid Claim in such country.

 For purposes of clarity, the parties acknowledge that Schering shall pay the royalties provided for in (i) or
(ii) above, as applicable, on sales of Licensed Products in each country in the Territory (excluding Canada) until (1) the date on which the Agreement expires pursuant to Article 7, Paragraph (a), or (2) solely with respect to those
countries in the Territory (excluding Canada) where the Licensed Product is covered by a Valid Claim of a Patent Right that will expire after the date the Agreement expires under Article 7, Paragraph (a), until the date of expiration of the last to
expire Patent Rights (including any extensions thereof) in such country containing a Valid Claim covering the Licensed Product. 
  

 8 
 [***]
Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

	 	(g)	Audit of Development Costs. Endorecherche shall, and will cause its Affiliates to, keep and maintain complete and accurate books and records as are required accurately to
determine all Development Costs incurred by Endorecherche during the Option Period. Schering shall have the right, at its own expense and through a certified public accountant reasonably acceptable to Endorecherche, to examine and audit such books
and records during regular business hours during the six (6) month period following the exercise of the Option by Schering. The accountant shall report to Schering only as to the accuracy of the Development Costs reported to Schering and the
related payments made pursuant to Sections 3.03(c) and 3.03(d). If such examination reveals an overpayment by Schering, then Endorecherche shall promptly reimburse Schering for such overpayment, and if the overpayment exceeds [***] of the total
amount properly due, Endorecherche shall bear the cost of the audit. 

  

	 	(h)	Effect of Diligence Failure by Schering. In the event that Schering fails to use diligent efforts (in accordance with Section 3.03(b) of this Addendum) to commercialize
at least one Licensed Product containing Acolbifene in the United States, the European Union or such other countries in the Territory where Schering determines it is commercially reasonable to do so, and fails to cure such breach in accordance with
the terms of Section 6.02 of this Addendum, then Endorecherche shall have the right to terminate this Addendum and Schering’s licenses and other rights to Licensed Products containing Acolbifene in accordance with the terms of
Section 6.02(a)(i) or 6.02(a)(ii), as applicable. The parties rights and obligations following any such termination shall be goverened by the terms of Section 6.04(a). 

 3.04 Effects of Terminating the Licenses. In the event that Schering notifies Endorecherche pursuant to Section 3.01 that it is terminating the licenses to
Acolbifene, or in the event that such licenses are terminated pursuant to Section 3.01(a) of this Addendum, then the provisions of Section 3.03 shall become null and void and the provisions set forth in this Section 3.04 shall become
effective as of the effective date of such termination. 
  

	 	(a)	 Termination of Licenses. All of Schering licenses and other rights set forth in the Agreement with respect to the development and commercialization of
Acolbifene and Licensed Products containing Acolbifene within the Territory (including Canada) shall terminate and revert to Endorecherche. Endorecherche shall, subject to the terms of Section 3.04(f), thereafter have the exclusive right (at
its own expense) to develop and commercialize within the Territory any and all Licensed Products containing Acolbifene. Endorecherche shall assume sole responsibility and control (at its own cost and expense) for the filing, prosecution,
maintenance, enforcement and defense of the ENDORECHERCHE Patent Rights covering Licensed Products containing Acolbifene in the Territory. Schering 

  

 9 

	 	 
shall reasonably cooperate with Endorecherche to complete a timely transfer to Endorecherche of full responsibility for any such ENDORECHERCHE Patent Rights
that are under Schering’s control as soon as practicable after the termination of Schering’s licenses to Acolbifene. 

  

	 	(b)	License Grant by Schering. Effective as of the date on which Schering’s licenses to Acolbifene are terminated pursuant to Section 3.04(a), Schering and its
Affiliates hereby grant to Endorecherche an exclusive, worldwide royalty-bearing license, with the right to grant sublicenses, under any SCHERING Patent Rights and to use any SCHERING Know-How to make, have made, use and sell Licensed Products
containing Acolbifene in the Field in the Territory (including Canada). The foregoing licenses shall be exclusive even as to Schering. Schering shall remain solely responsible (at its own expense) for the filing, prosecution, maintenance,
enforcement and defense of the SCHERING Patent Rights covering Licensed Products containing Acolbifene in the Territory which activities shall be governed by the terms of Article 6 of the Agreement. 

  

	 	(c)	Responsibility for maintaining Licensed SCHERING Patent Rights. In the event that Schering intends to discontinue efforts to prosecute and/or maintain one or more of the
SCHERING Patent Rights licensed to Endorecherche under this Section 3.04(b) in a given country or countries in the Territory, Schering shall promptly notify Endorecherche in writing to that effect. Upon receipt of such notice, Endorecherche
shall have the right to assume responsibility (at Endorecherche’s sole expense) for all further prosecution, maintenance, enforcement and defense of such SCHERING Patent Rights in such country(ies) by providing Schering with written notice to
that effect within thirty (30) days. If Endorecherche exercises this right to assume responsibility for such Patent Rights, Schering and Endorecherche shall cooperate to complete a timely transfer of such responsibility to Endorecherche (or its
designated outside patent counsel). 

  

	 	(d)	 Enforcement of Licensed SCHERING Patent Rights. Schering agrees to promptly take all commercially reasonable legal action to protect the SCHERING Patent
Rights licensed to Endorecherche under Section 3.04(b) against infringements by third parties. If within three (3) months following receipt of written notice from Endorecherche, Schering fails to file suit or take such other action as
appropriate to halt the alleged infringement, Endorecherche shall, in its sole discretion and at its own expense, have the right to take such action as it deems warranted in its own name or in the name of Schering. In the event of any third party
certification filed pursuant to 21 U.S.C. §355(b)(2)(A)(iv) and 355(j)(2)(A)(vii) (or any amendment or successor statute thereto) with respect to a SCHERING Patent Right licensed to Endorecherche under Section 3.04(b), if Schering fails to
file suit at least fourteen (14) days prior to the expiration of the forty-five (45) day period set forth in 21 U.S.C. §355(c)(3)(C) (or any amendment or successor statute thereto), then Endorecherche shall have the right to bring
such an infringement action, in its sole discretion and at its own expense, in its own name and/or in the name of Schering. If Endorecherche consents in the exercise of its sole discretion to grant a license under the SCHERING Patent Rights to any

  

 10 

 
third party infringer, then after deduction by Endorecherche of any out-of-pocket costs and expenses of enforcing and defending the SCHERING Patent Rights
against such third party infringer incurred by Endorecherche, the parties shall split any license fees, milestone payments, pre-paid royalties, or running royalty payments received from such third party as follows: [***] %) to Endorecherche
and [***] %) to Schering. 
  

	 	(e)	Know-How Transfer. Schering shall, upon request, reasonably cooperate with Endorecherche to transfer to Endorecherche (or its designated sublicensee) any SCHERING Know-How in
its possession or control that is reasonably necessary to enable Endorecherche to obtain Regulatory Approval for Licensed Products containing Acolbifene in the Territory (including without limitation, copies of any pre-clinical or clinical research
data for Acolbifene). The parties shall use commercially reasonable efforts to complete this transfer as soon as practicable after the termination of Schering’s licenses to Acolbifene. 

  

	 	(f)	Reverse Royalty Obligations. In consideration for the rights and licenses being conveyed to Endorecherche under this Section 3.04, Endorecherche shall pay to Schering a
Reverse Royalty equal to [***] %) of any and all Net Sales of Licensed Products containing Acolbifene. For purposes of this Section 3.04(f), the term “Net Sales” shall mean the gross amounts invoiced for sales of Licensed
Products containing Acolbifene by Endorecherche, its Affiliates or sublicensees to independent third parties (whether an end-user, a distributor or otherwise), and exclusive of intercompany transfers or sales among Endorecherche, its Affiliates
and/or Sublicensees in the Territory, less the reasonable and customary deductions from such gross amounts for (1) cash, trade and/or quantity discounts, (2) amounts repaid or credited by reason of rejections or returns of goods, rebates
or because of retroactive price reductions, and (3) freight, postage and duties (when included in billing). 

  

	 	(g)	Quarterly Sales Reports and Royalty Payments. Commencing upon the first commercial sale of a Licensed Product containing Acolbifene in the Territory, Endorecherche shall
provide to Schering within sixty (60) days after the end of each calendar quarter a full and true accounting of all Net Sales of Licensed Products containing Acolbifene in the Territory during such calendar quarter. Endorecherche shall
simultaneously pay to Schering a sum equal to the Reverse Royalty due on such Net Sales. 

  

	 	(h)	 Record Keeping and Audits. Endorecherche shall, and will cause its Affiliates and sublicensees to, keep and maintain complete and accurate books and records
as are required accurately to determine Net Sales and Reverse Royalties payable to Schering for three (3) years following the date on which such royalties were paid or reported. Schering shall have the right, at its own expense and through a
certified public accountant reasonably acceptable to Endorecherche, to examine and audit such books and records during regular business hours during the life of this Addendum and for two (2) years after its termination. The accountant shall
report to Schering only as to the amount of Net Sales and the accuracy of the 

  

 11 
 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

	 	 
Reverse Royalty statements and payments. If such examination reveals an underpayment, then Endorecherche shall promptly make up such underpayment and, for
any period in which the underpayment exceeds five percent (5%) of the total amount properly due, shall bear the cost of the audit. 

  

	 	(i)	Payment from Affiliates. Any Affiliate of Endorecherche may pay directly to Schering the Reverse Royalty due on such Affiliate’s Net Sales hereunder. Whenever
Endorecherche shall reasonably demonstrate to Schering that, in order to facilitate direct Reverse Royalty payments by an Affiliate, it is desirable that a separate license agreement be entered into between Schering and such Affiliate, Schering will
grant such license directly to such Affiliate by means of an agreement which shall be consistent with the terms and conditions of this Addendum. 

  

	 	(j)	Taxes/Withholding. All payments to Schering hereunder shall be made by bank transfer in immediately available funds into a bank account to be indicated by Schering. Where
required to do so by applicable law or treaty, Endorecherche shall withhold taxes required to be paid to a taxing authority on account of such income to Schering, and Endorecherche shall furnish Schering with satisfactory evidence of such
withholding and payment in order to permit Schering to obtain a tax credit or other relief as may be available under the applicable law or treaty. Endorecherche shall cooperate with Schering in obtaining exemption from withholding taxes where
available under applicable laws or treaties. 

  

	 	(k)	Manner of Payment. Reverse Royalties shall be payable from the country in which earned in local currency and subject to foreign exchange regulations then prevailing. All
Reverse Royalty payments shall be in US dollars (US$) to the extent that conversion to United States dollars is permitted by law, and shall be made on the dates set forth herein. The Net Sales amount calculated hereunder shall first be determined in
the currency in which the Licensed Products were sold and then converted into its equivalent US$ at the average monthly conversion rate for such foreign currency based on the conversion rates as published in The Wall Street Journal for the last
month of the applicable calendar quarter. If, due to restrictions or prohibitions imposed by national or international authority, payments cannot be made as aforesaid, the parties shall consult to find a prompt and mutually acceptable solution, and
Endorecherche shall deal with such monies as Schering may lawfully direct at no additional expense to Schering. Notwithstanding the foregoing, if Reverse Royalties in any country cannot be remitted to Schering for any reason within six
(6) months after the end of the calendar quarter during which they are earned, then Endorecherche shall be obligated to deposit the Reverse Royalties in a bank account in such country in the name of Schering (or its designated Affiliate).

  

	 	(l)	Duration of Reverse Royalty Obligations. Endorecherche’s obligation to pay Reverse Royalties to Schering under Section 3.04(f) shall expire on a country by country
basis on the first to occur of (1) the twelve year anniversary of the first commercial sale of a Licensed Product containing Acolbifene in such country, or (2) the expiration of the last to expire Existing Patent Rights having a Valid Claim
covering the Licensed Product in such country. 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

 3.05 Provisions Regarding Canada. The parties acknowledge and agree that effective as of the Addendum Date and
notwithstanding anything in the Agreement or this Addendum to the contrary, Endorecherche shall have (i) the exclusive right to distribute, market, promote, offer for sale and sell Licensed Products containing Acolbifene in Canada on the terms
and conditions set forth in this Section 3.05 (the “Commercial Rights in Canada”), and (ii) the non-exclusive right to make, have made, import and use Acolbifene and Licensed Products containing Acolbifene in Canada for the sole
purpose of distribution, marketing, promotion, offering for sale and selling Licensed Products containing Acolbifene in the Field in Canada. Endorecherche shall have the right to grant sublicenses to third parties under the foregoing rights in
Canada, if and only to the extent necessary to enable Endorecherche to exercise the Commercial Rights in Canada; provided that Endorecherche shall promptly notify Schering in writing upon granting any such sublicenses, and shall ensure that
the terms and conditions of any such sublicense are consistent with and subject to the applicable terms of this Addendum. Schering’s Option rights set forth in Section 3.01 shall not be construed (expressly or by implication) as including
the Commercial Rights in Canada. The licenses granted to Schering under Article 2, Paragraph (a) of the Agreement are hereby amended to expressly exclude the Commercial Rights in Canada, which Commercial Rights in Canada shall revert to
Endorecherche effective as of the Addendum Date. 
  

	 	(a)	License in Canada. Effective as of the Addendum Date, Schering and its Affiliates hereby grant to Endorecherche (i) an exclusive (even as to Schering), royalty-bearing
license, with the right to grant sublicenses, under any SCHERING Patent Rights and to use any SCHERING Know-How to distribute, market, promote, offer for sale and sell Licensed Products containing Acolbifene in the Field in Canada, and (ii) a
non-exclusive royalty-bearing license, with the right to grant sublicenses, under any SCHERING Patent Rights and to use any SCHERING Know-How to make, have made, import, and use Acolbifene and Licensed Products containing Acolbifene for the sole
purpose of distribution, marketing, promotion, offering for sale and selling Licensed Products containing Acolbifene in the Field in Canada. In the event that all of Schering’s licenses to Acolbifene in the Territory are terminated pursuant to
Section 3.04(a), then effective upon the date of such termination the licenses set forth in this Section 3.05(a) shall be superseded and replaced in their entirety by the licenses granted pursuant to Section 3.04(b). In addition,
during the Option Period Schering and its Affiliates shall not grant or convey to any third party any other licenses or other rights under their retained rights in Canada to the SCHERING Patent Rights or to use the SCHERING Know-How.

  

	 	(b)	 Development and Regulatory Approval of Acolbifene in Canada. Except as expressly set forth in this Section 3.05(b), all aspects of the development of
Acolbifene in Canada shall be performed by Endorecherche in accordance with and subject to the terms and conditions of Article II of this Addendum. In the 

  

 13 

	 	 
event that the provisions of Section 3.03 become effective, Endorecherche shall remain primarily responsible for the further development of Acolbifene
in Canada. Effective as of the date on which Section 3.03 becomes effective, the PCC shall again be responsible for overseeing and coordinating all aspects of development of Acolbifene throughout the Territory (including Canada);
provided, however, that Endorecherche shall have final decision making authority in accordance with Section 2.02 of this Addendum with respect to development matters that are specific to Canada alone. Endorecherche’s decision
making authority with respect to development in Canada shall include without limitation decisions regarding regulatory strategy and product labeling in Canada. In exercising its decision making authority with respect to Canada, Endorecherche shall
act in good faith to ensure that it does not undertake actions with respect to development of Acolbifene in Canada that may have a material adverse impact on development and commercialization of Acolbifene in the United States, the European Union or
other countries outside of Canada. 

  

	 	(c)	Canadian Development Costs. To the extent that Endorecherche incurs any Development Costs in connection with the development of Acolbifene that are solely due to [***]
(“Canadian Development Costs”), and notwithstanding anything in this Addendum or the Agreement to the contrary, Endorecherche shall at all times be solely responsible for any and all such Canadian Development Costs. The Canadian
Development Costs shall not be included as Development Costs in the itemized statement to be provided to Schering pursuant to Section 2.03. In the event that Schering exercises the Option to retain its licenses to Acolbifene under
Section 3.01, the Canadian Development Costs shall be expressly excluded from any determination of payments to be made by Schering pursuant to Sections 3.03(c) and 3.03(d). 

  

	 	(d)	Manufacturing in Canada. Endorecherche shall be responsible for manufacturing and/or procuring its requirement of Acolbifene and Licensed Products containing Acolbifene for
development and commercialization in Canada. The parties acknowledge and agree that Schering and its Affiliates shall have the right to manufacture, and/or to contract with third parties to manufacture on their behalf, Acolbifene and/or Licensed
Products containing Acolbifene in Canada for distribution, use and commercialization in the Territory; provided that Schering and its Affiliates shall not market, promote, offer for sale, sell or otherwise commercialize any such materials in Canada.
In the event that Endorecherche desires to arrange to purchase supplies of Acolbifene and/or Licensed Products containing Acolbifene from Schering or its Affiliates, it shall notify Schering to that effect and the parties shall promptly meet for the
purpose of negotiating in good faith the terms of a manufacturing and supply agreement for Canada on terms and conditions mutually acceptable to both parties. 

  

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 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended 

	 	(e)	Distribution and Sales in Canada. The parties acknowledge and agree that the Commercial Rights in Canada held by Endorecherche give Endorecherche, its Affiliates and
sublicensees the sole and exclusive right to distribute, market, promote, offer for sale and sell Acolbifene and Licensed Products containing Acolbifene in the Field in Canada; provided that Schering and its Affiliates shall have the limited
right to distribute Acolbifene in Canada if and to the extent necessary for the conduct of any PCC approved clinical studies being conducted by the parties which include study sites in Canada. Endorecherche shall use diligent efforts to ensure, and
shall procure that any of its sublicensees or other third party contractors use diligent efforts to ensure, that any supplies of Acolbifene and Licensed Products containing Acolbifene manufactured by or on behalf of Endorecherche (or its
sublicensees) for commercialization in Canada are not distributed, marketed, promoted, offered for sale or sold in the United States, the European Union, or any other countries or territories in the Territory. 

  

	 	(f)	Other Matters Related to Commercialization in Canada. The terms and conditions of Sections 3.04(c), 3.04(d), 3.04(e), 3.04(f), 3.04(g), 3.04(h), 3.04(i), 3.04(j), 3.04(k) and
3.04(l) shall, effective as of the Addendum Date, apply and be in full force and effect solely with respect to Canada. In the event that Schering exercises the Option under Section 3.01 and retains the licenses to Acolbifene, and
notwithstanding anything in this Addendum to the contrary, such provisions (including without limitation the obligation to pay Reverse Royalties on sales in Canada) will remain in full force and effect and continue to apply solely with respect to
Canada. 

 Article IV. Representations and Warranties 
 4.01 Representations and Warranties of Both Parties. Each of Endorecherche and Schering hereby represents, warrants and covenants to the other party as of the Addendum Date as follows: 
  

	 	(i)	it is a corporation duly organized and validly existing under the laws of the state or other jurisdiction of its incorporation or formation; 

  

	 	(ii)	it has the power and authority to execute and deliver this Addendum and to perform its obligations hereunder; 

  

	 	(iii)	the execution, delivery and performance by such party of this Addendum and its compliance with the terms and provisions hereof does not conflict with or result in a breach of any of
the terms and provisions of, or constitute a default under: (1) a loan agreement, guaranty, financing agreement, agreement affecting a product, or other agreement or instrument binding or affecting it or its property; (2) the provisions of
its charter documents or bylaws (as applicable); or (3) any order, writ, injunction or decree of any court or governmental authority entered against it or by which any of its property is bound; 

  

 15 

	 	(iv)	it does not have in effect, and during the term of this Addendum shall not enter into, any oral or written agreement or arrangement that would be inconsistent with its obligations
under this Addendum; 

  

	 	(v)	the execution, delivery and performance of this Addendum by such party does not require the consent, approval, or authorization of, or notice, declaration, filing or registration
with, any governmental or regulatory authority, and the execution, delivery or performance of this Addendum will not violate any law, rule or regulation applicable to such party; 

  

	 	(vi)	the execution, delivery and performance of this Addendum by it has been duly authorized by all requisite corporate action and constitutes such party’s legal, valid and binding
obligation enforceable against it in accordance with its terms subject, as to enforcement, to bankruptcy, insolvency, reorganization and other laws of general applicability relating to or affecting creditors’ rights and to the availability of
particular remedies under general equity principles; and 

  

	 	(vii)	it shall comply with all applicable material laws, rules and regulations relating to its activities under this Addendum. 

 4.02 Representations and Warranties by Endorecherche. Endorecherche hereby represent, warrants and covenants to Schering as follows: 
  

	 	(i)	it will use diligent efforts not to diminish the Option and other rights under the Patent Rights and Know-How granted to Schering hereunder, including, without limitation, by not
committing or permitting any acts or omissions which would cause the breach of any agreements between itself and any third party which provide for intellectual property rights applicable to the development, manufacture, use or sale of Licensed
Products containing Acolbifene in the Field in the Territory; 

  

	 	(ii)	it shall not use in any capacity, in connection with the development, manufacture or commercialization of Acolbifene or any Licensed Products containing Acolbifene, the services of
any individuals or entities that have been debarred pursuant to the United States Food, Drug and Cosmetic Act, or excluded from participation in a federal healthcare program, including, without limitation, the Medicare, Medicaid or CHAMPUS programs.

 4.03 No Warranty As to Patent Rights. Nothing in this Addendum shall be construed as a warranty or representation by either party as
to the validity, scope or enforceability of any Patent Rights. 
  

 16 

 4.04 Representation by Legal Counsel. Each party hereto represents that it has been represented by legal counsel
in connection with this Addendum and acknowledges that it has participated in the drafting hereof. In interpreting and applying the terms and provisions of this Addendum, the parties agree that no presumption shall exist or be implied against the
party which drafted such terms and provisions. 
 4.05 Warranty Disclaimer. THE REPRESENTATIONS, WARRANTIES AND COVENANTS OF EACH PARTY IN THIS
ARTICLE 4 ARE IN LIEU OF ANY OTHER WARRANTIES, EXPRESS OR IMPLIED, INCLUDING, WITHOUT LIMITATION, ANY IMPLIED WARRANTIES OF NONINFRINGEMENT, ANY IMPLIED WARRANTIES OF MERCHANTABILITY OR ANY IMPLIED WARRANTIES OF FITNESS FOR A PARTICULAR PURPOSE, ALL
OF WHICH ARE HEREBY SPECIFICALLY EXCLUDED AND DISCLAIMED. 
 Article V. Indemnification 
 The indemnification rights and obligations set forth in this Article V are in addition to and separate from any applicable indemnification provisions contained in the
Agreement, which (to the extent applicable) shall remain in full force and effect. In the event of any inconsistency between the provisions of this Article V and the provisions of the Agreement, the parties agree that the provisions of this Article
V shall control. 
 5.01 Indemnification by Endorecherche. Endorecherche shall indemnify, defend and hold harmless Schering, its Affiliates, and its
and their respective officers, directors, employees and agents from and against any and all claims, suits, liability, damages, losses, costs or expenses (including reasonable attorneys’ fees) which directly or indirectly result from or arise
out of: (i) the development, manufacture, storage, distribution, marketing, promotion, use or sale of Acolbifene and/or Licensed Products containing Acolbifene by or on behalf of Endorecherche or any of its Affiliates or contractors during the
Option Period; (ii) the development, manufacture, storage, distribution, marketing, promotion, use or sale of Acolbifene and/or Licensed Products containing Acolbifene by or on behalf of Endorecherche or any of its Affiliates or sublicensees in
Canada at any time on or after the Addendum Date; (iii) solely in the event that Schering’s licenses to Acolbifene are terminated pursuant to the terms of 3.01, the development, manufacture, storage, distribution, marketing, promotion, use
or sale of Acolbifene and/or Licensed Products containing Acolbifene by or on behalf of Endorecherche or any of its Affiliates or sublicensees on or after the effective date of such termination; (iv) the breach by Endorecherche of one or more
of its material obligations under this Addendum, or (v) the breach by Endorecherche of one or more of its representations, warranties or covenants under this Addendum, except, with respect to each of (i), (ii), (iii), (iv) and
(v) above, to the extent caused by Schering’s or its Affiliate’s gross negligence or willful misconduct. 
 5.02 Indemnification by
Schering. Schering shall indemnify, defend and hold harmless Endorecherche, its Affiliates, and its and their respective officers, directors, employees and agents from and against any and all claims, suits, liability, damages, 

  

 17 

 
losses, costs or expenses (including reasonable attorneys’ fees) which directly or indirectly result from or arise out of (i) the breach by
Schering of one or more of its material obligations under this Addendum, or (ii) the breach by Schering of one or more of its representations or warranties under this Addendum, except, with respect to each of (i) and (ii) above, to
the extent caused by Endorecherche’s or its Affiliate’s gross negligence or willful misconduct. 
 5.03 Conditions to Indemnification. Each
Party agrees to promptly give the other party notice of any claim for which indemnification may be sought. Failure of an indemnified party to provide notice of a claim to the indemnifying party shall only affect the indemnified party’s right to
indemnification hereunder if and to the extent that such failure has a material adverse effect on the indemnifying party’s ability to defend the claim and/or the nature or the amount of the liabilities under the claim. The indemnifying party
shall have the right to assume the defense of any suit or claim for which its is indemnifying the other party if it has assumed responsibility for the suit or claim in writing; provided, however, that if in the reasonable judgment of
the indemnified party, such suit or claim involves an issue or matter which could have a materially adverse effect on the business operations or assets of the indemnified party, the indemnified party may waive its rights to indemnity under this
Addendum and control the defense or settlement thereof, but in no event shall any such waiver be construed as a waiver of any indemnification rights such Party may have at law or in equity. If the indemnifying Party defends the suit or claim, the
indemnified Party may participate in (but not control) the defense thereof at its sole cost and expense. 
 5.04 Settlements. Neither party may settle
any claim or action related to a liability arising under or in connection with this Addendum or the parties’ performance hereunder without the consent of the other party if such settlement would impose any monetary obligation on the other party
or require the other party to submit to an injunction or otherwise limit the other party’s rights under this Addendum; provided that such consent shall not be unreasonably withheld or delayed. Any payment made by a party to settle any
such claim or action shall be at its own cost and expense. 
 5.05 Limitation of Liability. With respect to any claim by one party against the other
party arising out of the performance or failure of performance of the other party under this Addendum, the parties expressly agree that the liability of such party to the other party for such breach shall be limited under this Addendum or otherwise
at law or equity to direct damages only and in no event shall a party be liable to the other party for any indirect, punitive, exemplary or consequential damages suffered or incurred by the other party. 
 5.06 Insurance. Each party acknowledges and agrees that during the term of this Addendum it shall maintain adequate insurance and/or a self-insurance program for
contractual liability insurance to cover such party’s obligations under this Addendum. Each party shall provide the other party with evidence of such insurance and/or self-insurance program, upon request. 
  

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 Article VI. Term and Termination 
 6.01 Term of Agreement. This Addendum shall become effective as of the Addendum Date and, unless terminated earlier by mutual written agreement of the parties or by one party pursuant to Sections 6.02 or 6.04
below, this Addendum shall continue in effect: (1) solely in the event that Schering exercises the Option and retains rights to Acolbifene, on a country-by-country basis until the later of expiration of Schering’s Earned Royalty
obligations under Section 3.03(f), or expiration of Endorecherche’s obligation to pay Reverse Royalties in sales of Acolbifene in Canada under Sections 3.05(f); or (2) solely in the event that Schering’s licenses to Acolbifene
are terminated pursuant to Section 3.01, on a country-by-country basis until the expiration of Endorecherche’s obligation to pay Reverse Royalties to Schering in such country. 
 6.02 Termination for Breach. Each party shall have the right to unilaterally terminate this Addendum upon sixty (60) days written notice to the other party (or on ten (10) business days notice with
respect to failure to make payments when properly due) if such other party commits a material breach of one or more of its obligations under this Addendum and/or the Agreement, and thereafter fails to either (1) cure such breach within such
notice period, or (2) if the breach (excluding any failure to make payments when properly due) is not reasonably capable of being cured within sixty (60) days, to promptly undertake and thereafter use continuing diligent efforts to
complete actions reasonably expected to cure the breach within a reasonable time period to be agreed upon by the parties (not to exceed one hundred and eighty (180) days). 
  

	 	(a)	Country Specific Breach. The foregoing notwithstanding, in the event such breach occurs after Schering has exercised the Option under Section 3.01 and retained the
licenses to Acolbifene in the Territory: 

  

	 	(i)	to the extent that Endorecherche terminates this Addendum pursuant to this Section 6.02(a) due to an uncured material breach by Schering of its obligations with respect to
development and/or commercialization of Licensed Products containing Acolbifene in the United States and/or the European Union, such termination shall be effective with respect to the entire Territory; or 

  

	 	(ii)	to the extent that Endorecherche terminates this Addendum pursuant to this Section 6.02(a) due to an uncured material breach by Schering of its obligations with respect to
development and/or commercialization of Licensed Products containing Acolbifene in one or more countries in the Territory (except for the United States and the European Union), such termination shall be effective only with respect to the country or
countries in the Territory where such breach occurred. 

  

	 	(b)	Breach by Endorecherche in Canada. In the event that Schering terminates this Addendum pursuant to this Section 6.02 due to an uncured material breach by Endorecherche
of its obligations with respect to development and/or commercialization of Licensed Products containing Acolbifene in Canada, such termination shall be specific to rights in Canada and the terms of Section 6.04(b) shall apply.

  

 19 

 6.03 Termination for Insolvency. This Addendum may be immediately terminated by a party by written notice to the
other party upon the filing or institution of bankruptcy, reorganization (in connection with any insolvency), liquidation or receivership proceedings, or upon an assignment of a substantial portion of the assets for the benefit of creditors by such
other party, or in the event a receiver or custodian is appointed for such other party’s business, or if a substantial portion of such other party’s business is subject to attachment or similar process; provided, however,
that in the case of any involuntary bankruptcy proceeding such right to terminate shall only become effective if the proceeding is not dismissed within sixty (60) days after the filing thereof. 
 6.04 Effect of Termination for Breach. The expiration or earlier termination of this Addendum (in whole or in part) shall not relieve either party of any
obligation accruing under this Addendum prior to such expiration or termination. Any expiration or early termination of this Addendum shall be without prejudice to the rights of either party against the other accrued or accruing under this Addendum
prior to such expiration or termination, including the obligation to pay Earned Royalties or Reverse Royalties (as applicable) for Licensed Products sold prior to such termination. 
  

	 	(a)	Termination for Breach by Schering After Retaining the Licenses to Acolbifene. The provisions of this Section 6.04(a) shall apply solely in the event that Schering
exercises the Option under Section 3.01 and retains the licenses to Acolbifene in the Territory. In the event that this Addendum is terminated by Endorecherche pursuant to Section 6.02(a)(ii) in one or more countries in the Territory, then
the following provisions will become effective as of the date of such termination: 

  

	 	(i)	Schering’s licenses with respect to Acolbifene under this Addendum and the Agreement in such country(ies) shall terminate and revert to Endorecherche; and

  

	 	(ii)	Schering shall (at Schering’s expense) promptly transfer to Endorecherche (or its designee) any and all Regulatory Approvals for Licensed Products containing Acolbifene in such
country(ies). 

 In the event that this Addendum is terminated by Endorecherche pursuant to Section 6.02(a)(i), then the
effects of termination set forth in (i) and (ii) (above) shall apply with respect to all countries in the Territory. 
  

	 	(b)	Termination for Breach by Endorecherche with respect to Canada. In the event that this Addendum is terminated by Schering at any time after the end of the Option Period due
to a material breach of this Addendum and/or the Agreement by Endorecherche or its Affiliates in connection with the development or commercialization of Licensed Products containing Acolbifene in Canada, such termination shall be limited to rights
in Canada, and the following provisions shall govern: 

  

	 	(i)	All of Endorecherche’s licenses and other rights with respect to Acolbifene under this Addendum and the Agreement in Canada shall terminate and Schering shall thereafter hold
an exclusive (even as to Endorecherche), paid-up, royalty-free license, under all ENDORECHERCHE Patent Rights and Know-How to develop and commercialize Acolbifene and Licensed Products containing Acolbifene in Canada; and 

 

	 	(ii)	Endorecherche shall (at Endorecherche’s expense any and all) promptly transfer to Schering (or its designated Affiliate) any Regulatory Approvals for Licensed Products
containing Acolbifene in Canada. 

  

 20 

 6.05 Surviving Terms. The terms and conditions of Articles IV, V and VII, and of Sections 2.04, 3.03(g), 3.04(h),
3.04(j), 6.04, 6.05 and 6.06 of this Addendum shall survive any expiration or termination of this Addendum for any reason and remain in full force and effect. 
 6.06 Termination Upon Discontinuing Development. Solely in the event that Endorcherche notifies Schering pursuant to Section 2.01 that it has determined (in its sole discretion) to terminate development efforts under this
Addendum, then effective as of the date on which Schering receives such notice this Addendum shall immediately terminate in its entirety. Effective upon such termination the rights and obligations of the parties with respect to Licensed Products
containing Acolbifene shall revert to and be governed by the terms and conditions of the Agreement in the same manner as if this Addendum had never existed; provided that following such termination Schering’s obligations under the
Agreement to reimburse Endorecherche for development costs shall not apply to any development costs incurred by Endorecherche during the term of this Addendum. 
 Article VII. Miscellaneous Provisions 
 7.01 Assignment. This Addendum and the Option, licenses and other
rights granted herein or in the Agreement shall not be assignable by either party (except as expressly provided in Article 9, Paragraph (g) of the Agreement), either in whole or in part, whether by operation of law or otherwise, without the
prior written consent of the other party, such consent not to be unreasonably withheld. Notwithstanding the foregoing, each party may assign this Addendum to an Affiliate without the prior consent of the other party; provided that the
assigning party shall remain liable for the performance by its assignees under this Addendum. 
 7.02 Waiver. Any delay or failure by a party in
enforcing its rights under this Addendum or any waiver as to a particular default or other matter shall not constitute a 

  

 21 

 
waiver of such party’s rights to the future enforcement of such rights under this Addendum, nor operate to bar the exercise or enforcement thereof at
any time or times thereafter, excepting only as to an express written and signed waiver by such party as to a particular matter for a particular period of time. 
 7.03 Independent Relationship. Nothing in this Addendum shall be deemed to create an employment, agency, joint venture or partnership relationship between the parties hereto (or any of their respective Affiliates, agents or
employees) or any other legal arrangement that would impose liability upon one party for the act or failure to act of the other party. Neither party shall have any power to enter into any contracts or commitments or to incur any liabilities in the
name of, or on behalf of, the other party, or to bind the other party in any respect whatsoever. 
 7.04 Export Control. This Addendum is made subject
to any restrictions concerning the export of products or technical information from the United States of America which may be imposed upon or related to Endorecherche or Schering from time to time by the government of the United States of America.
Furthermore, Endorecherche agrees that it will not export, directly or indirectly, any technical information acquired from Schering under this Agreement or any products using such technical information to any country for which the United States
government or any agency thereof at the time of export requires an export license or other governmental approval, without first obtaining the written consent to do so from the Department of Commerce or other agency of the United States government
when required by an applicable statute or regulation. 
 7.05 Notice. Any notice or other communication required or permitted to be given by one party
to the other party pursuant to this Addendum shall be sent to such party (i) by certified or registered mail, return receipt and postage prepaid, (ii) by facsimile, with confirmation sent by first class mail, postage prepaid, or
(iii) by overnight delivery service, in each case addressed to: 
  

			
	 i)       for notices to Schering:
	 	
		
		 	 Schering-Plough Ltd.
 Weystrasse 20, P.O.
Box
 CH-6000, Lucerne 6
 Switzerland
 Attention: President
 Fax: 41 41 418 1626

		
		 	 Schering Corporation
 2000 Galloping Hill
Road
 Kenilworth, New Jersey 07033
 Attention: Senior Vice
President, Global Licensing
 Fax: 908-298-7366

		
	 with copies to:
	 	Attention: Senior Legal Director, Licensing
		 	Fax: 908-298-2739

  

 22 

			
	 ii)     for notices to Endorecherche:
	 	
		
		 	 Endorecherche Inc.
 2989 de la Promenade
 Sainte-Foy (Quebec) Canada
 G1W 2J5

		
		 	Attention: Dr Fernand Labrie, President
		 	Fax: (418) 651-1856

 or to such other address as a party shall designate by written notice given to the other party. 
 7.06 Entire Agreement. This Addendum together with the Agreement and all the covenants, promises, agreements, warranties, representations, conditions and
understandings contained herein or therein sets forth the complete, final and exclusive agreement between the parties with respect to the subject matter hereof. There are no covenants, promises, agreements, warranties, representations, conditions or
understandings, either oral or written, between the parties other than as are set forth in the above-mentioned documents. No subsequent alteration, amendment, change, waiver or addition to this Addendum or the Agreement shall be binding upon the
parties unless reduced to writing and signed by an authorized officer of each party. Each party in deciding to execute this Addendum has not relied on any understanding, agreement, representation or promise by the other party which is not explicitly
set forth herein. 
 7.07 Force Majeure. Failure of a party to perform its obligations under this Addendum (except the obligation to make payments
when properly due) shall not subject such party to any liability or place them in breach of any term or condition of this Addendum to the other party if such failure is due to any cause beyond the reasonable control of such non-performing party
(“force majeure”), unless conclusive evidence to the contrary is provided. Causes of non-performance constituting force majeure shall include, without limitation, acts of God, fire, explosion, flood, drought, war, riot, sabotage,
terrorism, embargo, strikes or other labor trouble, failure in whole or in part of suppliers to deliver on schedule materials, equipment or machinery, interruption of or delay in transportation, a national health emergency or compliance with any
order or regulation of any government entity acting with color of right. The party affected shall promptly notify the other party of the condition constituting force majeure as defined herein and shall exert reasonable efforts to eliminate, cure and
overcome any such causes and to resume performance of its obligations with all possible speed; provided, however, that nothing contained herein shall require any party to settle on terms unsatisfactory to such party any strike,
lock-out or other labor difficulty, any investigation or proceeding by any public authority, or any litigation by any third party. If a condition constituting force majeure as defined herein exists for more than ninety (90) consecutive days,
the parties shall meet to negotiate a mutually satisfactory resolution to the problem, if practicable. 
  

 23 

 7.08 Governing Law. This Addendum shall be construed and the legal relations between the parties hereto determined
in accordance with the laws of the State of New Jersey, without regard for the conflicts of law provisions thereof. 
 7.09 Severability. If any
provision of this Addendum is declared illegal, invalid or unenforceable by a court having competent jurisdiction, it is mutually agreed that this Addendum shall endure except for the part declared invalid or unenforceable by order of such court;
provided, however, that in the event that the terms and conditions of this Addendum are materially altered, the parties will, in good faith, renegotiate the terms and conditions of this Addendum to reasonably substitute such invalid or
unenforceable provisions in light of the intent of this Addendum. 
 7.10 Counterparts. This Addendum shall become binding when any one or more
counterparts hereof, individually or taken together, shall bear the signatures (including by facsimile) of each of the parties hereto. This Addendum may be executed in two or more counterparts, each of which shall be deemed an original, but all of
which together shall constitute one and the same instrument. 
 7.11 Further Acts. Each party agrees to execute, acknowledge and deliver such further
instruments, and to do all other acts, as may be necessary or appropriate in order to carry out the purposes and intent of this Addendum including, without limitation, any filings with any antitrust agency which may be required. 
  

 24 

 IN WITNESS WHEREOF, this Agreement has been executed by the duly authorized representatives of the
Parties as of the date set forth below. 
  

									
	ENDORECHERCHE INC.	 		 	SCHERING CORPORATION
					
	By:	 	 Fernand Labrie
	 		 	By:	 	 /s/ illegible

	Title:	 	President	 		 	Title:	 	Direktor
	Date:	 	June 9, 2005	 		 	Date:	 	June 20, 2005
				
		 		 		 	SCHERING-PLOUGH LTD.
					
		 		 		 	By:	 	 /s/ illegible

		 		 		 	Title:	 	Direktor
		 		 		 	Date:	 	June 20, 2005

  

 25 

 EXHIBIT 1 
 Chemical Structure of Acolbifene 
 Acolbifene is the chemical compound known as acolbifene hydrochloride,
which has the following chemical structure: 
 [***] 
 and may be alternatively described as: 
 [***] 
 and as used in this Agreement all references to Acolbifene shall also include any other salts, hydrates or solvates. 
  

 26 
 [***] Represents information redacted and filed separately with the Commission pursuant to a request for confidential treatment under Rule 406 of the Securities Act of 1933, as amended

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