Document:

exv10w4

Exhibit 10.4

NISOURCE INC.

FORM OF

CHANGE IN CONTROL AND TERMINATION AGREEMENT

     NiSource Inc., a Delaware corporation (“Employer”), which as used herein shall mean NiSource
Inc. and all of its Affiliates, and Jon Veurink (“Executive”) hereby enter into a Change in Control
and Termination Agreement as of February 1, 2010, (the “Effective Date”), which Agreement is
hereinafter set forth (“Agreement”).

WITNESSETH

     WHEREAS, Employer considers the ability to attract and retain talented management to be part
of its corporate strategy and necessary in protecting and enhancing the interests of the Employer
and its shareholders. As part of this strategy, Employer desires to retain Executive in its
employment notwithstanding any actual or threatened Change in Control; and

     WHEREAS, Executive and Employer desire to enter into this Agreement pertaining to the terms of
Executive’s employment in the event of any actual or threatened Change in Control;

     NOW, THEREFORE, in consideration of the mutual covenants and promises contained herein, and
other good and valuable consideration, the receipt of which is hereby acknowledged, the parties
agree as follows:

     1. Term. This Agreement shall begin on the Effective Date and shall continue in
effect until the date which is 24 months after the date on which either Employer or Executive has
given written notice to the other party of its or his election to have this Agreement terminate
(“Term”).

     2. Definitions. For purposes of this Agreement:

          (a) “Affiliate” or “Associate” shall have the meaning set forth in Rule 12b-2 under the
Securities Exchange Act of 1934.

          (b) “Base Salary” shall mean Executive’s monthly base salary at the rate in effect on the date
of a reduction for purposes of paragraph (g) of this Section, or on the date of a termination of
employment under circumstances described in subsections 3(a) or (b) below, whichever is higher;
provided, however, that such rate shall in no event be less than the highest rate in effect for
Executive at any time during the Term.

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          (c) “Beneficiary” shall mean the person or entity designated by Executive, by written
instrument delivered to Employer, to receive the benefits payable under this Agreement in the event
of his death. If Executive fails to designate a Beneficiary, or if no Beneficiary survives
Executive, such death benefits shall be paid:

               (i) to his surviving spouse; or

               (ii) if there is no surviving spouse, to his living descendants per stirpes; or

               (iii) if there is neither a surviving spouse nor descendants, to his duly appointed and
qualified executor or personal representative.

          (d) “Bonus” shall mean Executive’s target annual incentive bonus compensation for the calendar
year in which the date of a termination of employment under circumstances described in subsection
3(a) below occurs, under the NiSource Inc. Corporate Incentive Plan or such other incentive bonus
compensation plan then maintained by Employer (“Annual Incentive Plan”); provided, however, that
such target annual incentive bonus compensation shall in no event be less than the highest target
annual incentive bonus compensation of Executive under any such Annual Incentive Plan for any
calendar year commencing during the Term.

          (e) A “Change in Control” shall be deemed to take place on the occurrence of any of the
following events:

       (1) The acquisition by an entity, person or group (including all Affiliates or
Associates of such entity, person or group) of beneficial ownership, as that term is
defined in Rule 13d-3 under the Securities Exchange Act of 1934, of capital stock of
NiSource Inc. entitled to exercise more than 30% of the outstanding voting power of all
capital stock of NiSource Inc. entitled to vote in elections of directors (“Voting
Power”);

       (2) The effective time of (i) a merger or consolidation of NiSource Inc. with one
or more other corporations unless the holders of the outstanding Voting Power of
NiSource Inc. immediately prior to such merger or consolidation (other than the
surviving or resulting corporation or any Affiliate or Associate thereof) hold at least
50% of the Voting Power of the surviving or resulting corporation (in substantially the
same proportion as the Voting Power of NiSource Inc. immediately prior to such merger or
consolidation), or (ii) a transfer of a

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Substantial Portion of the Property, of NiSource Inc. other than to an entity of which
NiSource Inc. owns at least 50% of the Voting Power; or

     (3) The election to the Board of Directors of NiSource Inc. (the “Board”) of
candidates who were not recommended for election by the Board, if such candidates
constitute a majority of those elected in that particular election (for this purpose,
recommended directors will not include any candidate who becomes a member of the Board
as a result of an actual or threatened election contest or proxy or consent solicitation
on behalf of anyone other than the Board or as a result of any appointment, nomination,
or other agreement intended to avoid or settle a contest or solicitation).
Notwithstanding the foregoing, a Change in Control shall not be deemed to take place by
virtue of any transaction in which Executive is a participant in a group effecting an
acquisition of NiSource Inc. and, after such acquisition, Executive holds an equity
interest in the entity that has acquired NiSource Inc.

        (f) “Good Cause” shall be deemed to exist if, and only if Employer notifies Executive, in
writing, within 60 days of its knowledge that one of the following events occurred:

             (1) Executive engages in acts or omissions constituting dishonesty, intentional
breach of fiduciary obligation or intentional wrongdoing or malfeasance, in each case
that results in substantial harm to Employer; or

             (2) Executive is convicted of a criminal violation involving fraud or dishonesty.

        (g) “Good Reason” shall be deemed to exist if, and only if:

             (1) there is a significant diminution in the nature or the scope of Executive’s
authorities or duties;

             (2) there is a significant reduction in Executive’s monthly rate of Base Salary and
his opportunity to earn a bonus under an incentive bonus compensation plan maintained by
Employer or his benefits; or

             (3) Employer changes by 50 miles or more the principal location at which Executive
is required to perform services as of the date of a Change in Control.

          (h) “Pension Plan” shall mean any Retirement Plan that is a defined benefit plan as defined in
Section 3(35) of the Employee Retirement Income Security Act of 1974, as amended (“ERISA”).

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          (i) “Retirement Plan” shall mean any qualified or nonqualified supplemental employee pension
benefit plan, as defined in Section 3(2) of ERISA, currently or hereinafter made available by
Employer in which Executive is eligible to participate.

          (j) “Severance Period” shall mean the period beginning on the date Executive’s employment with
Employer terminates under circumstances described in subsection 3(a) and ending on the date 24
months thereafter.

          (k) “Substantial Portion of the Property of NiSource Inc.” shall mean 50% of the aggregate
book value of the assets of NiSource Inc. and its Affiliates and Associates as set forth on the
most recent balance sheet of NiSource Inc., prepared on a consolidated basis, by its regularly
employed, independent, certified public accountants.

          (l) “Welfare Plan” shall mean any health and dental plan, disability plan, survivor income
plan or life insurance plan, as defined in Section 3(1) of ERISA, currently or hereafter made
available by Employer in which Executive is eligible to participate.

     3. Benefits Upon Termination of Employment.

          (a) The following provisions will apply if a Change in Control occurs during the Term, and at
any time during the 24 months after the Change in Control occurs (whether during or after the
expiration of the Term), the employment of Executive with Employer is terminated by Employer for
any reason other than Good Cause, or Executive terminates his employment with Employer for Good
Reason. In addition, the following provisions also will apply if (i) a Change in Control occurs
during the Term, (ii) Employer has terminated Executive’s employment other than for Good Cause
during the year prior to the Change in Control but after a third party and/or Employer had taken
steps reasonably calculated to effect a Change in Control and (iii) it is reasonably demonstrated
by Executive that such termination of employment was in connection with or in anticipation of a
Change in Control.

     (1) Employer shall pay Executive an amount equal to 24 times the sum of (a)
Executive’s Base Salary plus (b) one-twelfth of his Bonus. Such amount shall be paid to
Executive in a lump sum within 60 days following Executive’s termination of employment.

     (2) Employer shall pay Executive an amount equal to the pro rata portion of
Executive’s target annual incentive bonus compensation for the

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calendar year under the Annual Incentive Plan then maintained by Employer, that is
applicable to the period commencing on the first day of such calendar year and ending on
the date of termination. Such bonus amount shall be paid to Executive in a lump sum
within 30 days after his date of termination of employment.

     (3) Executive shall receive any and all benefits accrued through the date of
termination of employment under any Retirement Plan, Welfare Plan or other plan or
program in which he participates at the date of termination of employment. The amount,
form and time of payment of such benefits will be determined by the terms of such
Retirement Plan, Welfare Plan and other plan or program. Further, Executive’s
employment shall be deemed to have terminated by reason of retirement without regard to
vesting limitations in all such plans and other plans or programs not subject to the
qualification requirements of Section 401(a) of the Internal Revenue Code of 1986 as
amended (“Code”), under circumstances that have the most favorable result for Executive
thereunder for all purposes of such Plans and other plans or programs. Payment shall be
made at the earliest date permitted under any such Plan or other plan or program that is
not funded with a trust agreement.

     (4) If upon the date of termination of Executive’s employment Executive holds any
options with respect to stock of Employer, all such options will immediately become
exercisable upon such date and will be exercisable for 200 days thereafter (but not
longer than the regularly scheduled term of such options). Any restrictions on stock of
Employer owned by Executive on the date of termination of his employment will lapse on
such date.

     (5) In lieu of a contribution by Employer to, or a reimbursement to Executive for,
any coverage premiums and any other expenses payable by Executive during the Severance
Period under all Welfare Plans maintained by Employer in which he and his spouse and
other dependents were participating immediately prior to the date of his termination,
Employer will pay to Executive an amount equal to 130% of such coverage premiums and
expenses otherwise payable during the Severance Period. Such amount shall be paid to
Executive in a lump sum within 60 days following Executive’s termination

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of employment.

     (6) Executive shall receive outplacement services for a period commencing on the
date of termination of employment and continuing until the earlier to occur of the
Executive accepting other employment or 12 months after the date of termination, in an
amount not to exceed $25,000.

     (7) During the Severance Period, Executive shall not be entitled to reimbursement
for fringe benefits, including without limitation, dues and expenses related to club
memberships, automobile expenses, expenses for professional services and other similar
perquisites.

        (b) If the employment of Executive with Employer is terminated by Employer or Executive other
than under circumstances set forth in subsection 3(a), Executive’s Base Salary shall be paid
through the date of his termination, and Employer shall have no further obligation to Executive or
any other person under this Agreement. Such termination shall have no effect upon Executive’s
other rights, including but not limited to, rights under the Retirement Plans and the Welfare
Plans.

        (c) Notwithstanding anything herein to the contrary, (1) in the event Employer shall terminate
the employment of Executive for Good Cause hereunder, Employer shall give Executive at least thirty
(30) days prior written notice specifying in detail the reason or reasons for Executive’s
termination, and (2) in the event Executive terminates his employment for Good Reason hereunder,
Executive shall give Employer at least 30 days prior written notice specifying in detail the Good
Reason conditions. If Employer cures such conditions, any subsequent termination of employment by
Executive will not be considered to be made for Good Reason.

        (d) This Agreement shall have no effect, and Employer shall have no obligations hereunder, if
Executive’s employment terminates for any reason at any time other than (i) during the 24 months
following a Change in Control; or (ii) as otherwise specifically set forth in Subsection 3(a).

     4. Setoff. No payments or benefits payable to or with respect to Executive pursuant
to this Agreement shall be reduced by any amount Executive or his spouse or Beneficiary, or any
other beneficiary under the Pension Plans, may earn or receive from employment with another
employer or from any other source, except as expressly provided in subsection 3(a)(6).

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     5. Death. If Executive’s employment with Employer terminates under circumstances
described in subsections 3(a) or (b), then upon Executive’s subsequent death, all unpaid amounts
payable to Executive under subsections 3(a)(1), (2) or (3) or 3(b), or Section 4, if any, shall be
paid to his Beneficiary.

     6. No Solicitation of Representatives and Employees. Executive agrees that he shall
not, during the Term or the Severance Period, directly or indirectly, in his individual capacity or
otherwise, induce, cause, persuade, or attempt to do any of the foregoing in order to cause, any
representative, agent or employee of Employer to terminate such person’s employment relationship
with Employer, or to violate the terms of any agreement between said representative, agent or
employee and Employer.

     7. Confidentiality. Executive acknowledges that preservation of a continuing business
relationship between Employer and their respective customers, representatives, and employees is of
critical importance to the continued business success of Employer and that it is the active policy
of Employer to guard as confidential certain information not available to the public and relating
to the business affairs of Employer. In view of the foregoing, Executive agrees that he shall not
during the Term and at any time thereafter, without the prior written consent of Employer, disclose
to any person or entity any such confidential information that was obtained by Executive in the
course of his employment by Employer. This section shall not be applicable if and to the extent
Executive is required to testify in a legislative, judicial or regulatory proceeding pursuant to an
order of Congress, any state or local legislature, a judge, or an administrative law judge or is
otherwise required by law to disclose such information.

     8. Forfeiture. If Executive shall at any time violate any obligation of his under
Sections 7 or 8 in a manner that results in significant damage to the Employer or its business, he
shall immediately forfeit his right to any benefits under this Agreement, and Employer shall
thereafter have no further obligation hereunder to Executive or his spouse, Beneficiary or any
other person.

     9. Executive Assignment. No interest of Executive, his spouse or any Beneficiary, or
any other beneficiary under the Pension Plans, under this Agreement, or any right to receive any
payment or distribution hereunder, shall be subject in any manner to sale, transfer, assignment,
pledge, attachment, garnishment, or other alienation or

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encumbrance of any kind, nor may such interest or right to receive a payment or distribution be
taken, voluntarily or involuntarily, for the satisfaction of the obligations or debts of, or other
claims against, Executive or his spouse, Beneficiary or other beneficiary, including claims for
alimony, support, separate maintenance, and claims in bankruptcy proceedings.

     10. Benefits Unfunded. All rights under this Agreement of Executive and his spouse,
Beneficiary or other beneficiary under the Pension Plans, shall at all times be entirely unfunded,
and no provision shall at any time be made with respect to segregating any assets of Employer for
payment of any amounts due hereunder. None of Executive, his spouse, Beneficiary or any other
beneficiary under the Pension Plans shall have any interest in or rights against any specific
assets of Employer, and Executive and his spouse, Beneficiary or other beneficiary shall have only
the rights of a general unsecured creditor of Employer.

     11. Waiver. No waiver by any party at any time of any breach by the other party of,
or compliance with, any condition or provision of this Agreement to be performed by such other
party shall be deemed a waiver of any other provisions or conditions at the same time or at any
prior or subsequent time.

     12. Litigation Expenses. Following the occurrence of Change in Control, Employer
shall pay Executive’s reasonable attorneys’ fees and legal expenses in connection with any judicial
proceeding to enforce this Agreement, or to construe or determine the validity of this Agreement or
otherwise in the event Executive is successful in one material claim in such litigation. Such
reimbursement shall occur by March 15 of the calendar year after the calendar year in which such
reimbursement obligation was finally determined.

     13. Continuing Indemnification and Advancement of Expenses. Following the occurrence
of a Change in Control, to the full extent permitted by law, Employer shall indemnify Executive
against any actual or threatened action, suit or proceeding, whether civil, criminal,
administrative or investigative, arising by reason of Executive’s status as a director, officer,
employee and/or agent of Employer. In addition, to the extent permitted by law, Employer shall
advance or reimburse any expenses, including reasonable attorney’s fees, Executive incurs in
investigating and defending any actual or threatened action, suit or proceeding for which Executive
may be entitled to indemnification under this Section 14. Executive agrees to repay any expenses
paid or reimbursed by Employer if it is ultimately determined that Executive is not

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legally entitled to be indemnified by Employer.

     14. Applicable Law. This Agreement shall be construed and interpreted pursuant to the
laws of Indiana.

     15. Entire Agreement. This Agreement contains the entire Agreement between the
Employer and Executive and supersedes any and all previous agreements; written or oral; between the
parties relating to the subject matter hereof. For the avoidance of doubt, if Executive becomes
entitled to the benefits under this Agreement, Executive shall not be eligible for any duplicative
benefits under any other agreement, offer letter, plan, program or policy. No amendment or
modification of the terms of this Agreement shall be binding upon the parties hereto unless reduced
to writing and signed by Employer and Executive.

     16. No Employment Contract. Nothing contained in this Agreement shall be construed to
be an employment contract between Executive and Employer or provide Executive with the right to
continued Employment with Employer.

     17. Counterparts. This Agreement may be executed in counterparts, each of which shall
be deemed an original.

     18. Severability. In the event any provision of this Agreement is held illegal or
invalid, the remaining provisions of this Agreement shall not be affected thereby.

     19. Successors. This Agreement shall be binding upon and inure to the benefit of the
parties hereto and their respective heirs, representatives and successors.

     20. Employment with an Affiliate. For purposes of this Agreement, (A) employment or
termination of employment of Executive shall mean employment or termination of employment with
Employer and all Affiliates, (B) Base Salary and Bonus shall include remuneration received by
Executive from Employer and all Affiliates, and (C) the terms Pension Plan, Retirement Plan and
Welfare Plan maintained or made available by Employer shall include any such plans of any Affiliate
of Employer.

     21. Notice. Notices required under this Agreement shall be in writing and sent by
registered mail, return receipt requested, to the following addresses or to such other address as
the party being notified may have previously furnished to the other party by written notice:

			
	If to Employer:	 	NiSource Inc.
 801 E. 86th Avenue

Merrillville, Indiana 46410

Attention: Robert D. Campbell

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	If to Executive:	 	Jon Veurink

1621 Tuckaway Trail

West Chester, PA 19380

     22. 409A Savings Clause. Employer and Executive intend that this Agreement be
interpreted in a manner that is compliant with Code Section 409A so that Executive does not incur
additional taxes or penalties under Code Section 409A. If and to the extent that any payment or
benefit under this Agreement is determined by Employer to constitute “non-qualified deferred
compensation” subject to Code Section 409A and is payable to Executive by reason of Executive’s
termination of employment, then (a) such payment or benefit shall be made or provided to Executive
only upon a “separation from service” as defined for purposes of Code Section 409A under applicable
regulations and (b) if Executive is a “specified employee” (within the meaning of Code Section 409A
and as determined by Employer), such payment or benefit shall not be made or provided before the
date that is six months after the date of Executive’s separation from service (or Executive’s
earlier death). Any amount not paid in respect of the six month period specified in the preceding
sentence will be paid to Executive in a lump sum after the expiration of such six month period.
Any such payment or benefit shall be treated as a separate payment for purposes of Section Code
409A to the extent Code Section 409A applies to such payments.

     IN WITNESS WHEREOF, Executive has hereunto set his hand, and Employer has caused these
presents to be executed in its name on its behalf, all on the 2 day of February,
2010.

	 	 	 	 	 
	 	NISOURCE INC.

 	 
	 	By:  	/s/ Robert C. Skaggs Jr.
 	 
	 	 	 	 
	 	Title:    	      President & CEO 	 
	 	 	 	 
	 
	 	EXECUTIVE

 	 
	 	                                                     /s/ Jon D. Veurink
 	 
	 	Jon Veurink 	 
	 	 	 
	 

- 10 -Exhibit 10.56

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

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