Exhibit 10.56

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

FIRST AMENDMENT TO THE
COLLABORATION AND LICENSE AGREEMENT OF 7 SEPTEMBER 2006
This First Amendment to the Collaboration and License Agreement of 7
September 2006 (the “First Amendment”) is entered into and is effective as of 22
March, 2010 by and between Ipsen Biopharm Limited, a company organized and
existing under the laws of England and Wales, with registered offices located at
Ash Road, Wrexham Industrial Estate, Wrexham LL13 9UF, United Kingdom (“Ipsen”)1
and GTx, Inc., a Delaware corporation having its principal place of business at
175 Toyota Plaza, 7th Floor, Memphis, Tennessee 38103 (“GTx”), each on behalf of
itself and its Affiliates (Ipsen and GTx, collectively, the “Parties” and
individually a “Party”).
WHEREAS, Ipsen and GTx entered into the Collaboration and License Agreement on 7
September 2006 (the “License Agreement”) which, among other things, provides for
certain terms and conditions relating to the conduct of certain development
activities for the purpose of obtaining Regulatory Approvals in the United
States of America and its territories and possessions (“US”) and in the European
Territory for the Initial Products in certain indications, including the ADT
Indication and the PIN Indication, for Commercialization Activities by Ipsen of
the Licensed Product in the European Territory (as such capitalized terms are as
defined either in the License Agreement or in this First Amendment).
WHEREAS, GTx is currently the sponsor of an NDA for toremifene 80 mg for the
prevention of bone fractures and serious side effects in men with prostate
cancer on androgen deprivation therapy, identified in the License Agreement as
being within the scope of the ADT Indication.
WHEREAS, the FDA has requested that an additional Phase III Clinical Study of
toremifene 80mg for the ADT Indication be conducted by GTx for the obtaining of
Regulatory Approval in the ADT Indication in the US (the “Additional Phase III
Study”).
WHEREAS, Ipsen desires that GTx continue development of, obtain Regulatory
Approval for, and market the Licensed Product in the US and Ipsen desires to
continue development of, obtain Regulatory Approval for, and market the Licensed
Product in the European Territory and in certain other territories identified
herein.
WHEREAS, Ipsen and GTx have agreed to collaborate in the design of the
Additional Phase III Study to gain Regulatory Approvals by the FDA and the EMEA,
and to get input from the FDA on the protocol for the Additional Phase III Study
to better ascertain the FDA’s commitment that the Additional Phase III Study
will be sufficient to support Regulatory Approval in the US, assuming the study
achieves the agreed upon efficacy endpoints and the product candidate is
determined to be safe. The Additional Phase III study design and expected
timelines as estimated as of the Signature Date are described at Appendix C
attached hereto.
 

      1  
On 1st January 2010, Ipsen Biopharm Limited acquired the business and assets of
Ipsen Developments Limited (formerly known as Ipsen Limited), the entity that
entered into the Collaboration and License Agreement dated 7 September 2006 with
GTx. With effect as from 1st January 2010, Ipsen Biopharm Limited became
entitled to the benefits and assumes all obligations of Ipsen Developments
Limited (formerly known as Ipsen Limited) under the Collaboration and License
Agreement.

 

 

--------------------------------------------------------------------------------

 

WHEREAS, GTx has sought from Ipsen an Additional Milestone Payment in
consideration of additional rights granted hereunder, including but not limited
to expanding Ipsen’s territory and co-promoting the Licensed Product in the ADT
Indication in the US; and Ipsen desires to effect payment in respect thereof.
WHEREAS, the Parties considered the necessity of amending their rights and
obligations under the License Agreement subject to the terms and conditions of
this First Amendment.
WHEREAS, the License Agreement and this First Amendment shall be considered as
the Parties’ whole agreement (the “Agreement”) as of the Signature Date of this
First Amendment.
NOW THEREFORE IN CONSIDERATION OF THE PREMISES SET FORTH ABOVE AND INTENDING TO
BE LEGALLY BOUND, THE PARTIES HAVE AGREED AS FOLLOWS:
SECTION 1: DEFINITION
1. The following term used in this First Amendment have the meaning indicated
below :

  1.1  
“Additional Milestone Payment” shall have the meaning ascribed to it in Section
2 of this First Amendment.

  1.2  
“Additional Phase III Study” shall have the meaning ascribed to it in the
Preamble of this First Amendment.

  1.3  
“Calendar Year” shall begin on January 1st of the calendar year of the Signature
Date and “Calendar Quarter” shall mean each of the three consecutive calendar
month periods ending March 31, June 30, September 30 and December 31 of such
year.

  1.4  
“€” shall mean European Euro currency.

  1.5  
“Field” shall have the meaning ascribed to it in Article 5.8(a) of the License
Agreement. For the sake of clarity, the side effects of ADT in men with prostate
cancer include among others bone fractures.

  1.6  
“GTx Patent” shall have the meaning prescribed to it in Section 4.1 of this
First Amendment. For the avoidance of doubt, “GTx Patent”, as defined herein,
shall supersede the definition of GTx Patent defined in the License Agreement. A
list of the GTx Patent identified as of the Signature Date is attached hereto as
Appendix A to this First Amendment.

  1.7  
“GTx Territory” shall mean the US and all other parts of the world, except the
Ipsen Territory.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

2//22

--------------------------------------------------------------------------------

 

  1.8  
“Ipsen Territory” shall mean the European Territory, Algeria, Tunisia, Morocco,
Lebanon, Iran, Saudi Arabia, Egypt, Jordan, Kuwait, UAE, Australia, China,
Vietnam, Korea, Taiwan, Thailand, the Philippines and Indonesia. For the
avoidance of doubt, “Ipsen Territory”, as defined herein, shall supersede the
territory granted under license from GTx to Ipsen as defined as the “European
Territory” under the License Agreement.
    1.9  
“Signature Date” shall mean the last signature date of this First Amendment.

  1.10  
“US Net Sales” shall have the meaning ascribed to it in Section 4.7(ii) of this
First Amendment.

  1.10  
“US Royalty Payment” shall have the meaning ascribed to it in Section 4.7(i) of
this First Amendment.

SECTION 2: ADDITIONAL MILESTONE PAYMENT

2.1.  
In consideration of the additional and amended license rights granted to Ipsen
by GTx under this First Amendment, Ipsen agrees to pay to GTx an Additional
Milestone Payment in the total amount which shall not exceed €42 million (VAT
excluded).

2.2.  
Such Additional Milestone Payment shall be paid in six installments upon written
notification by GTx that the milestone event has occurred, as follows:

  (i)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following notification to
Ipsen by GTx of [ * ];

  (ii)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following notification to
Ipsen by GTx of [ * ];

  (iii)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following notification to
Ipsen by GTx of [ * ];

  (iv)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following notification to
Ipsen by GTx of [ * ];

  (v)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following [ * ] and

  (vi)  
Ipsen shall pay GTx €[ * ] within [ * ] calendar days following [ * ], subject
to the following payment adjustment mechanisms:

  (a)  
In the event the total and final external third party costs for the Additional
Phase III Study are known to GTx at the time [ * ], and (a) if such amount (€ X)
is [ * ] but [ * ], then [ * ] (i.e., [ * ]); (b) if such amount (€ X) is [ * ]
and also [ * ], then [ * ] and [ * ] (i.e., [ * ]).

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

3//22

--------------------------------------------------------------------------------

 

  (b)  
In the event the total actual amount of the external third party costs for the
Additional Phase III Study is unknown to GTx at the time [ * ], GTx shall
furnish to Ipsen the final actual external third party costs for the Additional
Phase III Study within [ * ] days of the FSR, and [ * ] if the actual total
external costs for the Additional Phase III Study are [ * ].

  (c)  
For the purposes of calculating the total amount of external third party costs
that GTx has paid in US dollars for the Additional Phase III Study and whether [
* ] or whether [ * ], all as set forth above in Section 2.2(vi)(a) and (b), the
Parties agree that at the end of each Calendar Quarter as the Additional Phase
III Study proceeds, GTx shall aggregate that quarter’s actual external third
party costs in US dollars and convert such costs into euros € using the middle
market spot exchange rate on the last business day of the relevant quarter as
published in the New York edition of the Wall Street Journal. GTx shall inform
Ipsen of such US dollar and euro equivalent costs within [ * ] days of the end
of each quarter. The cumulative total of such quarterly euro amounts paid in
respect of the Additional Phase III Study shall be included in the quarterly
reports from GTx. At the time that [ * ], as set forth above, GTx will determine
the aggregate euro equivalent costs of the Additional Phase III Study [ * ].
This calculation shall be used to determine if [ * ] or whether [ * ] as
provided in this Section 2.2 (vi)(a) and (b) above. If [ * ] or if [ * ], the
amount of the [ * ] or [ * ], will be the euro [ * ] or [ * ] and will be
settled between Ipsen and GTx in euros.

SECTION 3: GTX’S OBLIGATION

3.1.  
Additional Phase III Protocol:

GTx commits to conduct the Additional Phase III Study in accordance with the
protocol approved by GTx and Ipsen (the “Additional Phase III Protocol”) to
ensure that the Additional Phase III Protocol would meet the requirements of the
FDA and the EMEA (and other Regulatory Agencies within the Ipsen Territory),
unless major safety concerns develop during the Additional Phase III Study or
the FDA or other equivalent Regulatory Agency requires that the Study be
stopped. GTx acknowledges and agrees that such Additional Phase III Protocol and
any and all amendments thereto must be approved by the CMO of Ipsen or any
medical appointee designated by the CMO prior to its submission to the FDA for
FDA input, which approval by Ipsen shall not be unreasonably delayed or
withheld. Upon Ipsen and GTx agreeing on the Additional Phase III Protocol, GTx
shall get input from the FDA on such Additional Phase III Protocol to determine
FDA’s concurrence that the Additional Phase III Study should be sufficient to
support GTx’s NDA for Regulatory Approval in the US. Sufficiency for the purpose
of allowing GTx and Ipsen to seek Regulatory Approvals from the FDA and the EMEA
(and other Regulatory Agencies within the Ipsen Territory) respectively for the
ADT Indication assumes the study achieves the agreed upon efficacy endpoints and
the product candidate is found to be safe.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

4//22

--------------------------------------------------------------------------------

 

      3.2.  
Study Budget:

  (i)  
GTx acknowledges and agrees that upon receiving FDA’s comments on the Additional
Phase III Protocol, it shall then finalize the Protocol and the associated
clinical study budget for all third party external costs for the Additional
Phase III Clinical Study (the “Study Budget”) and submit it to the CMO of Ipsen
or any medical appointee designated by the CMO for review and approval, which
Ipsen agrees to accomplish within [ * ] of its receipt of the Study Budget. The
total amount set forth in the Study Budget shall be deemed to be the actual
total third party external costs for the Additional Phase III Clinical Study.

  (ii)  
GTx acknowledges and agrees that upon finalizing the Study Budget with Ipsen, it
shall then have the obligation and responsibility to carry out the Additional
Phase III Clinical Study of the 80mg toremifene Initial Product to allow GTX and
Ipsen to obtain Regulatory Approvals of the product candidate for the ADT
Indication from the FDA and the EMEA (and other Regulatory Agencies in the Ipsen
territory) respectively.

  (iii)  
In the event the total third party external costs in the Study Budget approved
by GTx and Ipsen exceed the amount of €42 million (VAT excluded) by an amount up
to, but not exceeding, [ * ]% of Ipsen’s €42 million Additional Milestone
Payment, GTx agrees that it will pay such excess costs. In the event the total
third party external costs of the Study Budget approved by GTx and Ipsen are
expected to exceed the [ * ]% threshold, GTx shall promptly notify Ipsen of such
excess amount accompanied with all relevant supporting documents, copies of all
correspondence and responses received by GTx from the relevant Regulatory Agency
within sufficient time to allow Ipsen to review and consider the same. The
Parties shall then agree to discuss as to whether to initiate the Additional
Phase III Study and/or to renegotiate the terms of this First Amendment.

  (iv)  
For the sake of clarity, once the Study Budget is finalized and approved by GTx
and Ipsen and the Additional Phase III Study is initiated, and should the total
actual third party external costs exceed the finalized Study Budget, any such
excess amount shall be borne by GTx’s only and shall be upon GTx’s sole
responsibility unless the Parties shall otherwise agree in writing.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

5//22

--------------------------------------------------------------------------------

 

      3.3.  
CRO selection & audit

GTx acknowledges and agrees that the execution of the contract with a global
clinical research organization (CRO) to conduct the data management for the
Additional Phase III Study [ * ] shall only occur once the Study Budget is
finalized with Ipsen. Any CROs to conduct the data management for the Additional
Phase III Study and the monitoring of investigations shall be selected by GTx
among CROs identified by GTx and acceptable to Ipsen as of the Signature Date. A
list of CROs acceptable to both Parties as of the Signature Date is attached
hereto at Appendix D and incorporated herein by reference. The Parties agree
that such list may be amended by GTx after the Signature Date upon Ipsen’s
consultation and approval, which approval shall not be unreasonably withheld of
delayed.
Upon Ipsen’s request filed [ * ] days in advance (which shall be not more than
once annually and at Ipsen’s own and sole costs), GTx shall permit an
independent expert selected by Ipsen and reasonably acceptable to GTx to grant
access to, and audit and inspect, during normal business hours any of the CROs
conducting the data management and/or the monitoring of investigation to assess
compliance with GCP standards and applicable regulatory requirements.

      3.4.  
Statistical Analytical Plan and the Final Study Report:

GTx acknowledges and agrees that the Statistical Analytical Plan (SAP) and any
and all amendments thereto must be approved in advance of the submission to the
FDA by the CMO of Ipsen or any medical appointee designated by such CMO, each
review and each approval process of which shall be concluded within [ * ] days
of the receipt thereof. GTx further acknowledges and agrees that the Final Study
Report (FSR) shall be provided to the CMO of Ipsen or any medical appointee
designated by the CMO for his/her review and approval prior to GTx’s submission
of such documents to FDA as a part of its NDA. Ipsen agrees that each review and
each approval of the FSR shall be concluded within [ * ] days of its receipt
thereof.

      3.5.  
Integrated Summary of Safety and Integrated Summary of Efficacy:

Additionally, the NDA Integrated Summary of Safety (ISS) and Integrated Summary
of Efficacy (ISE) will be both submitted to the CMO of Ipsen or any medical
appointee designated by such CMO for his/her comments. GTx shall make its best
efforts to include Ipsen’s comments in the final ISS and ISE. Ipsen agrees that
its comments on the ISS and ISE shall be concluded, within [ * ] days of their
receipt thereof.

3.6.  
All notices and communication under Sections 3.1, 3.2, 3.3, 3.4 and 3.5 shall be
made in writing and delivered by hand, facsimile, registered mail or email (with
the sending party keeping the mechanical print-out registering the sending) as
follows:

Ipsen Pharma SAS
65, Quai George Gorse
92100 Boulogne Billancourt
France
Tel: +33.(0)1.58.33.50.00
Fax: +33.(0)1.58.33.50.15
Attn: Corporate Legal Affairs, General Counsel

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

6//22

--------------------------------------------------------------------------------

 

      3.7.  
Records and Audit Right:

During the term of the Additional Phase III Study and until the completion of
the Phase III Final Study Report, GTx shall be responsible for maintaining a
complete, accurate and detailed account of all third party external costs
expended for the Additional Phase III Study. For the sake of clarity, the costs
expended for such Additional Phase III Study shall [ * ] and shall [ * ]. GTx
shall furnish to Ipsen a detailed written report of such expended external costs
within [ * ] days of the end of each Calendar Quarter period. Upon Ipsen’s
request, which shall be sent with at least [ * ] day prior written notice, Ipsen
will have the right not more than once per calendar year to have an inspection
during ordinary business hours conducted at Ipsen’s sole cost and expense by an
independent certified accounting firm of an internationally recognized standing
selected by Ipsen and to which GTx has no reasonable objection, of such GTx’s
records, books and accounts as may be necessary to verify the accuracy of
information submitted in respect of the costs incurred by GTx in connection with
the Additional Phase III Study [ * ]. In case any discrepancy is found by the
independent accountant in the total actual external Third Party costs incurred
by GTx for the Additional Phase III Study, which findings shall be made in
writing and communicated to the Parties as a final and binding investigation
report, the Parties agree to [ * ] so that [ * ]. The amount of [ * ] as
determined by the independent accountant shall be [ * ] within [ * ] calendar
days after [ * ] the final investigation report of the independent accountant.
SECTION 4: IPSEN’S RIGHTS

      4.1.  
Ipsen Territory:

The Parties agree that Ipsen’s rights granted by GTx pursuant to the License
Agreement and this First Amendment shall be extended to the Ipsen Territory. For
the sake of clarity, Ipsen shall have, and GTx agrees to grant, pursuant to
Article 5 of the License Agreement: (i) a non-exclusive royalty-free license to
develop the Licensed Product for any Indication under the GTx Know-how and GTx
Patent as well as (ii) an exclusive, royalty-bearing license to conduct
Commercialization Activities, including the right to sublicense, within the
Ipsen Territory for any Indication under the GTx Patent, GTx Know-how and the
Licensed Trademark. In accordance with the Parties’ agreement to extend the
licensed territory, the Parties agree that Exhibit A to the License Agreement
related to all Patents and Patent Applications Controlled by GTx in the European
Territory which Cover the Licensed Products shall be amended in the form as
attached hereto at Appendix A as a new Exhibit A and incorporated herein by
reference, to include all Patents and Patent Applications Controlled by GTx in
the Ipsen Territory (the “GTx Patent”).

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

7//22

--------------------------------------------------------------------------------

 

      4.2.  
Ipsen’s Release of ADT Milestone Payments:

GTx acknowledges and agrees that Ipsen shall be irrevocably, perpetually and
fully released from the milestone payment obligations set forth in
Article 3.2(4) and (6) of the License Agreement related to the ADT Indication
that are pending as of the Signature Date:

              Released   Released Milestone Payment   Payment  
4. Filing with the EMEA or with the relevant Regulatory Agency [ * ] for
Regulatory Approval of [ * ]
  € [ * ]
6. Obtaining a Regulatory Approval by the EMEA/European Commission or by the
Regulatory Agency [ * ] of [ * ]
  € [ * ]

For the sake of clarity, the above-listed milestone payments shall no longer be
due by Ipsen and owed to GTx under Article 3.2 of the License Agreement for the
ADT Indication.

      4.3.  
Ipsen’s Release of Pricing Milestone Payments:

GTx acknowledges and agrees that Ipsen shall be irrevocably, perpetually and
fully released from its milestone payment obligation as set forth in
Article 3.2(7) of the License Agreement related to the pricing of toremifene in
the ADT Indication or in the PIN Indication that is pending as of the Signature
Date:

              Released   Released Milestone Payment   Payment  
7. On a [ * ] basis, the determination by the relevant Regulatory Agency of a
List Price for [ * ]
  € [ * ]

      4.4.  
Reduction of Royalty Payment:

From and after the date hereof, GTx and Ipsen acknowledge and agree that Ipsen’s
obligation to make quarterly Royalty Payments on Net Sales of the Licensed
Product in the Ipsen Territory in the ADT Indication (i.e., including the
prevention of bone fractures in men with prostate cancer on ADT), will be
reduced to a fixed Base Royalty Rate of 12%. In accordance with the agreements
contained herein, the Parties hereto agree that Article 3.4 of the License
Agreement shall be amended by deleting the article in its entirety and
substituting in lieu thereof a new Article 3.4 set forth in Appendix B attached
hereto and made a part hereof.

      4.5.  
Use of Additional Phase III Data:

GTx acknowledges and agrees that Ipsen shall be authorized and have the right to
use, without payment of any additional costs, all data generated during the
Additional Phase III Study in the Ipsen Territory for purposes of, but not
limited to, obtaining and maintaining Regulatory Approvals in the ADT Indication
and PIN Indication within the Ipsen Territory.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

8//22

--------------------------------------------------------------------------------

 

      4.6.  
Co-promotion Rights:

  (i)  
GTx agrees to grant to Ipsen an exclusive right, unless otherwise agreed by the
Parties, to co-promote with GTx the Licensed Product in the US in the ADT
Indication, which co-promotion right shall be [ * ] in accordance with the terms
and conditions of a co-promotion agreement that shall be negotiated in good
faith between the Parties. The Parties agree that the negotiation to enter into
a definitive co-promotion agreement shall not be initiated prior to the earlier
to occur of either of the following two events: (i) [ * ] or [ * ] of [ * ] of
the [ * ] for the [ * ], or (ii) [ * ] days following [ * ] of the [ * ] the [ *
] for the [ * ]. The Parties shall, among others, agree that in the framework of
the co-promotion agreement between the Parties in the US, Ipsen shall [ * ] in
the [ * ] for the [ * ]. Additionally, the Parties shall, among others, agree
that Ipsen may [ * ] through [ * ] but [ * ] for [ * ] or [ * ] of [ * ] with a
[ * ], which [ * ] or [ * ].

  (ii)  
In the event the Parties are unable to enter into a final and binding
co-promotion agreement upon mutually acceptable terms, or should Ipsen decide to
opt-out of its right to co-promote with GTx the Licensed Product in the US in
the ADT Indication, which right to opt-out shall be exercised (a) within [ * ]
days following the [ * ] or [ * ] of [ * ] of the [ * ] for the [ * ], or
(b) within [ * ] days following the [ * ] of the [ * ] the [ * ] as [ * ] for
the [ * ] for the [ * ] in the event the [ * ] shall [ * ] or [ * ] of [ * ] of
the [ * ] for the [ * ] (the “Opt-Out Election”), GTx shall pay to Ipsen running
royalty payments on Net Sales in the US (the “US Net Sales”) for Licensed
Product in the ADT Indication in accordance with Sections 4.7 and 4.8(ii)(e)
hereof.

      4.7.  
GTx’s Payment of Running Royalties to Ipsen on US Net Sales:

  (i)  
In the event the Parties fail to enter into a final and binding co-promotion
agreement upon mutually acceptable terms, or should Ipsen exercise its Opt-Out
Election, GTx acknowledges and agrees that GTx shall pay to Ipsen running
royalty payments in US dollars on US Net Sales of the Licensed Product for the
ADT Indication (“US Royalty Payment”), until the later to occur of, but in no
event earlier than [ * ]: (a) the last to expire of a Valid Patent Claim in the
US or (b) marketing exclusivity for the ADT Indication in the US as follows:

          Annual US Net Sales   Royalty  
< $ [ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
> $[ * ]
    [ * ]%

The US Royalty Payment due to Ipsen on account of US Net Sales shall be payable
by GTx within [ * ] days of the end of each Calendar Quarter for which royalty
payments are owed, accompanied by a quarterly report providing in reasonable
detail in quantity and value an accounting of the US Net Sales made during such
Calendar Quarter. Furthermore, Article 11.4 of the License Agreement (i.e.,
records and audit rights) shall apply mutatis mutandis to Ipsen’s right to
verify the accuracy of GTx’s reports for the calculation of US Net Sales of the
Licensed Product for the ADT Indication.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

9//22

--------------------------------------------------------------------------------

 

  (ii)  
US Net Sales means, consistently applied across the GTx pharmaceutical product
line, the gross sales received by GTx, its Affiliates, sub-licensees (including
GTx’s co-promotion and/or co-marketing partners) to Third Parties for the
Licensed Product in the ADT Indication in the US, less:

  (a)  
credits and allowances or adjustments granted to customers on account of
rejections, recalls or returns of Licensed Product in the ADT Indication
previously sold;

  (b)  
any customary and reasonable trade and cash discounts, any customary service
fees paid to Third Party wholesalers (which are not Affiliates of GTx), and any
credits, rebates and charge backs paid to managed care and government agencies,
granted in connection with the distribution or sale of Licensed Product in the
ADT Indication;

  (c)  
sales, tariff duties and/or use taxes directly imposed and with reference to
particular sales; and

  (d)  
outbound transportation prepaid or allowed, amounts allowed or credited on
returns, export licenses, import duties, value added tax, and prepaid freight.

For the sake of clarity, Sales of Licensed Product in the ADT Indication by and
between GTx and its Affiliates, sublicensees are not sales to Third Parties and
shall be excluded from the US Net Sales calculations for all purposes. Sales of
Licensed Product in the ADT Indication for use in conducting clinical trials of
Licensed Product candidates in order to obtain applicable Regulatory Approval of
the Licensed Product shall be excluded from the US Net Sales calculations for
all purposes.

      4.8.  
Ipsen’s Release of PIN Milestone Payments:

  (i)  
Within the time-period of Article 4.2(e)(i) of the License Agreement, Ipsen
shall retain the right to elect license rights to the Licensed Products for the
PIN Indication against payment of the Election Fee and Past Initial Development
Expenses set forth in Article 4.2(e)(iii) of the License Agreement and against
payment of Milestone Payments provided in Article 3.2 of the License Agreement
that are applicable to the PIN Indication.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

10//22

--------------------------------------------------------------------------------

 

  (ii)  
In the event Ipsen intends to exercise its PIN Election, it shall notify GTx of
its intent to do so within the time period prescribed in the License Agreement.
If Ipsen shall exercise its Opt-Out Election or the Parties shall then fail to
enter into a final and binding co-promotion agreement upon mutually acceptable
terms, then Ipsen shall have right to elect either (i) to make the payments to
GTx on account of the PIN Election calculated in accordance with
Article 4.2(e)(iii) of the License Agreement (the “PIN Election Payments”) or
(ii) to have the terms and provisions of Article 4.2(e)(iii) of the License
Agreement amended in the following particulars (the “PIN Amendment Right”), as
follows:

  (a)  
Ipsen shall be fully, irrevocably and perpetually released by GTx from paying
the Election Fee set forth in Article 4.2(e)(iii) of the License Agreement,

  (b)  
Ipsen shall be fully, irrevocably and perpetually released by GTx from paying
the Past Initial Development Expenses set forth in Article 4.2(e)(iii) of the
License Agreement,

  (c)  
Ipsen shall be fully, irrevocably and perpetually released by GTx from paying
the Joint Initial Development Expenses set forth in Article 4.2(f)(iii)(2) of
the License Agreement,

  (d)  
Ipsen shall be fully, irrevocably and perpetually released by GTx from all
milestone payments set forth in Article 3.2(2), (3), (5) and (8) of the License
Agreement related to the PIN Indication that are pending as of the Signature
Date:

          Released Milestone Payment   Released Payment  
2. Achievement of [ * ]
  € [ * ]
3. Filing with the EMEA or with the relevant Regulatory Agency [ * ] for
Regulatory Approval of [ * ]
  € [ * ]
5. Obtaining a Regulatory Approval by the EMEA/European Commission or by the
Regulatory Agency [ * ] of [ * ]
  € [ * ]
8. Obtaining a Regulatory Approval [ * ] for a diagnostic test for [ * ]
  € [ * ]

For the sake of clarity, the pricing milestone payment related to the pricing of
toremifene in the PIN Indication listed as payment #7 in Article 3.2 of the
License Agreement shall no longer be due by Ipsen and owed to GTx pursuant to
Section 4.3 above.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

11//22

--------------------------------------------------------------------------------

 

  (e)  
If Ipsen shall exercise the PIN Election and Ipsen shall have exercised its
Opt-Out Election as set forth in Section 4.6 above or the Parties shall have
failed to enter into a final and binding co-promotion agreement upon mutually
acceptable terms, and Ipsen shall have elected the PIN Amendment Right described
in Section 4.8(ii) above, the US Royalty Payment by GTx to Ipsen on US Net
Sales, as set forth in Section 4.7 above for the ADT Indication, shall be
reduced as follows:

          Annual US Net Sales   Royalty  
< $[ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
Between $[ * ] and $[ * ]
    [ * ]%
> $[ * ]
    [ * ]%

  (f)  
For the sake of clarity, at the time of the PIN Election, in lieu of paying the
PIN Election Payments to GTx, Ipsen can elect to have the US Royalty Payment
reduced as set forth in subsection (e) above. If the Parties shall also enter
into a final and binding co-promotion agreement, Ipsen agrees that it shall then
not be entitled to receive any of the US Royalty Payment set forth in
Section 4.7 hereof from GTx. If Ipsen shall not exercise the PIN Election, the
Parties shall determine [ * ] the amount of the [ * ] US Royalty Payment that
would be appropriate to support a co-promotion agreement that the Parties may
then negotiate.

      4.9.  
Ipsen’s Right of First Negotiation to GTx-758:

  (i)  
GTx shall have the sole responsibility to develop GTx-758, a ER alpha agonist.
GTx aims at developing GTx-758 as an alternative treatment to LHRH-a (e.g.,
leuprolide, triptoreline) in the treatment of prostate cancer with a better
safety profile. The Parties acknowledge and agree that GTx shall consider Ipsen
as its preferential partner for the development, marketing, sale and
distribution of GTx-758 in the Ipsen Territory, and in this regard, GTx hereby
grants to Ipsen a right of first negotiation to enter into good faith
negotiations with GTx for the period hereinafter stated for an exclusive
royalty-bearing license to conduct Commercialization Activities for GTx-758 in
the Ipsen Territory upon such terms and conditions as the Parties may reasonably
agree in a definitive agreement.

  (ii)  
GTx shall not, either by itself or by or through any of its directors, officers,
subsidiary, representative, agent, or otherwise, directly or indirectly, engage
in negotiations with any third party relating to the development, marketing,
sale and distribution of GTx-758 in the Ipsen Territory until Ipsen shall have
failed to meet any of the time periods set forth in this Section 4.9(iv),
including the Parties failing to enter into a definitive and binding agreement
for an exclusive royalty-bearing license to conduct Commercialization Activities
for GTx-758 in the Ipsen Territory or Ipsen shall have waived its right to
pursue its first right of negotiation. Notwithstanding the foregoing, nothing
herein shall prevent GTx from entering into discussions with a Third Party
interested in a transaction for GTx-758 in the GTx Territory.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

12//22

--------------------------------------------------------------------------------

 

  (iii)  
GTx acknowledges that it is its intent to complete a Phase IIb clinical study
for GTx-758 assessing efficacy (including [ * ]) and treatment safety profile
(including [ * ]), with a current estimated completion date for the clinical
study in [ * ]. Upon completion of such Phase IIb clinical study, GTx shall
furnish to Ipsen the TFL, the draft study report and such additional information
and data as Ipsen shall reasonably request at the time of its receipt of the TFL
and draft study report for Ipsen to assess GTx-758 and make a decision to
exercise its right of first negotiation. Such additional information and data
available to GTx shall include all information developed at that time, including
CMC, preclinical pharmacology, toxicology, IND, clinical data, regulatory agency
correspondence and market research information, if available.

  (iv)  
Within [ * ] days of receipt by Ipsen of the last of the information and data
described in Section 4.9(ii) above, Ipsen shall notify GTx in writing of its
desire to negotiate a definitive agreement for an exclusive royalty-bearing
license to conduct Commercialization Activities for GTx-758 in the Ipsen
Territory and it will also then furnish GTx with a non binding term sheet
setting forth the material financial terms of its proposal. If Ipsen so notifies
GTx, the Parties agree to enter into good faith negotiations with the aim to
finalize and execute a definitive agreement for the exclusive royalty-bearing
license rights to GTx -758 within an additional period that shall in no event
exceed [ * ] days from GTx’s receipt of such notice unless the time-period is
extended by mutual agreement of the Parties. [ * ], if either [ * ] shall [ * ]
to [ * ] of [ * ] to [ * ] for a [ * ] within the [ * ] and [ * ] the [ * ] for
[ * ] or if [ * ] shall [ * ] to [ * ] and [ * ] a [ * ] within the [ * ], [ * ]
shall [ * ] or [ * ] to [ * ] hereunder.

  (v)  
[ * ], in the event of a [ * ] of [ * ] prior to [ * ], [ * ] acknowledges and
agrees that [ * ], as set forth in [ * ], shall [ * ] if [ * ] or the [ * ] a [
* ] in [ * ] in [ * ] within [ * ] days of the [ * ] of the [ * ] event that [ *
] to [ * ] described in [ * ] in the [ * ] of the [ * ]:

  (a)  
in the [ * ] (as [ * ] defined in the License Agreement), if the [ * ] and [ * ]
that [ * ] that [ * ] in [ * ];

  (b)  
in [ * ], if the [ * ] and [ * ] that [ * ] that [ * ] in [ * ];

  (c)  
in [ * ], if the [ * ] and [ * ] that [ * ] that [ * ] in [ * ].

  (d)  
In the event the [ * ] and [ * ] that [ * ] that [ * ] in [ * ] of the [ * ] in
[ * ], then [ * ] described in [ * ] shall [ * ] in the [ * ]. For the sake of
clarity, [ * ] under this Section 4.9(v) shall mean [ * ] of the [ * ] in [ * ]
listed in [ * ] which [ * ] or [ * ] the [ * ].

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

13//22

--------------------------------------------------------------------------------

 

SECTION 5: BANKRUPTCY

5.1  
In the event of occurrence during the Additional Phase III Study of GTx’s
bankruptcy or a petition against GTx under any bankruptcy, insolvency or similar
laws not being dismissed within the applicable period of time, Ipsen shall have
the right to elect to conduct or continue the development of the Additional
Phase III Study for purposes of, but not limited to, obtaining and maintaining
Regulatory Approvals in the ADT Indication within the Ipsen Territory.

5.2  
In the event Ipsen exercises its right to terminate the Agreement pursuant to
Article 12.4 of the License Agreement due to GTx’s bankruptcy or due to a
petition against GTx under any bankruptcy, insolvency or similar laws not being
dismissed within the applicable period of time, whether during the Pre-Clinical,
Clinical Study, or Post-Marketing Phases, Ipsen will [ * ], to the extent
permitted under relevant applicable law:

  (a)  
[ * ] and [ * ] (whether or not [ * ]); and

  (b)  
[ * ] and [ * ].

Such [ * ] shall [ * ] as of the effective termination date, or if [ * ], from
the [ * ] on a country by country basis or on an Indication by Indication basis.
SECTION 6: MISCELLANEOUS

6.1  
GTx expressly represents and warrants that no consent is required to be obtained
from UTRF and Orion under the GTx Licenses relating to the execution of this
First Amendment, including the extension of the Territory to be granted to
Ipsen. After execution of this First Agreement, GTx agrees to assist Ipsen in
entering into negotiations with Orion to finalize and execute an amendment to
the Partial Assignment of Amended and Restated License & Supply Agreement that
shall be executed among GTx, Ipsen and Orion pertaining to the manufacture and
the supply of Licensed Product for the extended licensed territory.

6.2  
Except as modified herein, the terms and conditions of the License Agreement
shall remain in full force and effect. In the event of conflict between the
terms of the First Amendment and the License Agreement, the terms of the First
Amendment shall govern.

6.3  
In the event of termination of this First Amendment, the terms of the License
Agreement shall be enforceable as originally executed unless otherwise agreed to
by the Parties in writing.

6.4  
Unless earlier terminated, this First Amendment shall expire or terminate upon
the expiration or termination date of the License Agreement.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

14//22

--------------------------------------------------------------------------------

 

This First Amendment may be executed in one or more counterparts, each of which
is an original but all of which together constitute one and same instrument.

         
Ipsen Biopharm Ltd.
  GTx, Inc.    
 
       
/s/ Christian de la Tour
 
Christian de la Tour
  /s/ Mitchell S. Steiner, M.D.
 
Name: Mitchell S. Steiner, M.D.    
Chairman
  Title: CEO    
Date: 22 March 2010
  Date: 03/22/2010    

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

15//22

--------------------------------------------------------------------------------

 

APPENDIX A
AMENDED EXHIBIT A
Patents & Patent Applications Controlled by GTx, Inc.
in the Ipsen Territory which cover the Licensed Products
[ * ]

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

16//22

--------------------------------------------------------------------------------

 

APPENDIX B
New Article 3.4 of the Collaboration and License Agreement
3.4 Royalty Payments.
(a) In consideration for the rights granted to Ipsen under this Agreement, Ipsen
shall pay to GTx running royalty payments, determined as follows (the “Royalty
Payment”):
(i) ADT Royalty Payment. For the first calendar year as from the first Launch
Date of the toremifene 80mg Licensed Product in the Ipsen Territory for the ADT
Indication, Ipsen shall pay, on a country-by-country basis, a Royalty Payment
equal to 12% of Net Sales.
(ii) PIN Royalty Payment. For the first calendar year as from the first Launch
Date of the Licensed Product in the Ipsen Territory (“Y1”) for the PIN
Indication, Ipsen shall pay, on a country-by-country basis, a Royalty Payment
equal to the applicable royalty rates set forth in this Section 3.4(a)(ii) (the
“Base Royalty Rate”), multiplied by the Net Sales of Licensed Product for the
PIN Indication (the “PIN Base Royalty rate”).
(A) the PIN Base Royalty shall be equal to the greater of [ * ]% and F, where F
is the result of the following calculation:
F = [ * ],
Where [ * ] is equal to [ * ] of [ * ] forecasted by Ipsen for Y1, [ * ] the
corresponding number of [ * ] that [ * ].
For the purposes of calculating [ * ] for the PIN Indications for the initial
calculation of the PIN Base Royalty, Ipsen shall update its forecast based upon
the actual [ * ] received from each of the appropriate agencies within the Ipsen
Territory upon receiving [ * ] for products that have launched in the first
quarter when the Royalty Payment is due.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

17//22

--------------------------------------------------------------------------------

 

(iii) Within [ * ] days as from the end of the Y1, Ipsen shall determine the
following amounts:

  •  
“A” which is equal to the aggregate annual Net Sales of the Licensed Product for
the PIN Indication of Y1, multiplied by the following royalty rates:

     
For annual aggregate Net Sales of Licensed Products for the PIN Indication in
the Ipsen Territory, up to and including [ * ] Euros
  [ * ]%
 
   
For annual aggregate Net Sales of Licensed Products for the PIN Indication in
the Ipsen Territory greater than [ * ] Euros and equal to or less than [ * ]
Euros
  [ * ]%
 
   
For annual aggregate Net Sales of Licensed Products for the PIN Indication in
the Ipsen Territory greater than [ * ] Euros and equal to or less than [ * ]
Euros
  [ * ]%
 
   
For annual aggregate Net Sales of Licensed Products for the PIN Indication in
the Ipsen Territory greater than [ * ] Euros
  [ * ]%

  •  
“B” which is equal to [ * ]

  •  
“PIN Supply Price” for the European Territory being equal to (a) [ * ] in [ * ],
(b) [ * ] in the rest of the European Territory outside of [ * ]. Such PIN
Supply Prices shall be [ * ] for the [ * ] in any instances in accordance with [
* ] and [ * ] only as direct application of Section [ * ] of the [ * ] with
respect to the [ * ] and [ * ] of the [ * ], as [ * ] pursuant to the [ * ];
provided however, for purposes hereof, nothing herein shall be construed to
require [ * ] if Ipsen shall [ * ] to [ * ] the [ * ] for the [ * ] pursuant to
Section [ * ] of [ * ] to the [ * ] of the [ * ] as of the [ * ] and (c) [ * ]
in the Ipsen Territory, excluding the European Territory.

  •  
“C” which is equal to [ * ]. For clarity, C includes [ * ]. If [ * ] in the
Ipsen Territory (excluding the European Territory), the PIN Supply Price in the
Ipsen Territory (excluding the European Territory), for calculation of the PIN
Royalty Payment shall be the amount as defined at (c) above [ * ].

(A) In the event B is superior to C, then:
(i) Ipsen shall [ * ];
(ii) For the following year (Y2), the Base Royalty Rates shall be [ * ] in order
to [ * ]. Ipsen shall calculate an amount for the new PIN Base Royalty Rate so
that [ * ]. In other words, the new PIN Base Royalty would be determined so
that: [ * ]. In determining the new Base Royalty Rates for Y2, Ipsen shall use
all of the data available to it at the end of Y1, including actual pricing and
sales information.
(B) In the event B is inferior to C, then:
(i) Ipsen may [ * ] and [ * ] as appropriate, [ * ].

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

18//22

--------------------------------------------------------------------------------

 

(ii) For the following year (Y2), the Base Royalty Rates shall be [ * ] in order
to [ * ]. Ipsen shall calculate an amount for the new PIN Base Royalty Rate so
that [ * ]. In other words, the new PIN Base Royalty would be determined so
that: [ * ]. In no event can the new PIN Base Royalty Rate be [ * ]. In
determining the new Base Royalty Rates for Y2, Ipsen shall use all of the data
available to it at the end of Y1, including actual pricing and sales
information.
For the following calendar years (“Y”) (notwithstanding the Offset set forth
above):
(A) quarterly Royalty Payments are determined using the new Base Royalty Rates
applicable for that year;
(B) within [ * ] as from the end of year Y, A, B and C shall be calculated with
respect to the concerned year Y using the Base Royalty Rates and Net Sales
applicable for year Y;
(C) Ipsen shall [ * ] if [ * ];
(D) Ipsen may [ * ] and [ * ] as appropriate, [ * ] if [ * ];
(E) the Base Royalty Rates applicable to Y+1 shall be [ * ] in accordance with
sections (A) (ii) or (B) (ii) above, where in each subsequent year the Base
Royalty Rates shall be [ * ] in order to [ * ] by changing the Base Royalty
Rates so that [ * ]. In other words, the new PIN Base Royalty Rate would be
determined so that: [ * ]. In no event can the new PIN Base Royalty Rate be [ *
].
Examples Rates are attached hereto as Exhibit A1 for purposes of further
clarification for the calculations described in this Section 3.4.
(b) Generic Competition. If a Generic is sold in any Major Country of the
European Territory and for two (2) succeeding calendar quarters the sales of
such Generic in that country equal or exceed [ * ] of the Net Sales of Licensed
Products (calculated on a unit basis) in that country by Ipsen, its Affiliates
or sublicensees, then the Royalty Payments shall be reduced to [ * ] of the
amount of the Royalty Payment otherwise due to GTx on account of Net Sales of
such Licensed Product for the ADT Indication or [ * ] of the amount of the
Royalty Payment otherwise due to GTx on account of Net Sales of such Licensed
Product for the PIN Indication in such country, with such reduction to be
applicable to the immediately succeeding calendar quarters only.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

19//22

--------------------------------------------------------------------------------

 

(c) Dominating Patents. If (i) Ipsen would be prevented from developing, using,
selling, or importing the Licensed Products in any country of the European
Territory on the grounds that by doing so they would infringe one (or more)
Dominating Patent held by a Third Party in said country and (ii) Ipsen licenses
rights to such Dominating Patent in said country, then [ * ] of any royalties on
Licensed Products sales paid by Ipsen to such Third Party in any calendar year
in such country with respect to such Dominating Patent shall be deducted from
any Royalty Payments payable to GTx by Ipsen in such calendar year (the “Royalty
Reduction”), provided, however, that (i) such Dominating Patent relates solely
to [ * ] and (ii) GTx has been informed of the Dominating Patent and has had an
opportunity to provide input on any related discussion of whether to license
such Dominating Patent and negotiation of royalty rates; and (iii) subject to
the warranties and representations made by GTx under Section 10.1 (b) of the
License Agreement, the amount of the Royalty Reduction in any calendar year
shall not exceed [ * ] of the Royalty Payments (the “Royalty Reduction Cap”)
that would have otherwise been payable by Ipsen to GTx for such calendar year
and for such country. Any amount of the Royalty Reduction which is not offset
against Royalty Payments due to GTx from Ipsen (because it exceeds the Royalty
Reduction Cap) shall be carried forward to and deducted in subsequent calendar
years until the expiration of the Royalty Term.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

20//22

--------------------------------------------------------------------------------

 

APPENDIX C
Additional Phase III top-line study design and expected timelines
(as estimated as of the Signature Date)

•  
[ * ], randomized, double-blind, placebo-controlled, multi-centre study, in
patients [ * ]

  •  
[ * ]

•  
Population

  •  
[ * ]

•  
Drop-out rate assumed at [ * ]
  •  
Primary end point

  •  
[ * ]

•  
Secondary end point Efficacy

  •  
[ * ]

•  
Secondary end points Safety

  •  
[ * ]

•  
Estimated Timelines

  •  
First Patient First Visit — [ * ]

  •  
Last Patient First Visit — [ * ]

  •  
Last Patient Last Visit — [ * ]

  •  
Tables, Listings, Figures — [ * ]

  •  
Final Study Report — [ * ]

  •  
Regulatory Filing — [ * ]

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

21//22

--------------------------------------------------------------------------------

 

APPENDIX D
List of Clinical Research Organizations
The CROs in charge of data management and/or of monitoring of investigations
shall be selected among the following list below:
[ * ]
The CRO in charge of medical publications and writings shall deliver eCRF that
meets specifications and requirements of the FDA and the EMEA.

      [ * ] =  
Certain confidential information contained in this document, marked by brackets,
has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

 

22//22