Document:

Exhibit
10.25

 

 

SECURITIES AMENDMENT AGREEMENT

 

 

AMONG

 

 

ELAN CORPORATION, PLC,

 

 

ELAN INTERNATIONAL SERVICES, LTD.

 

and

 

 

ACORDA THERAPEUTICS, Inc.

 

 

THIS
SECURITIES AMENDMENT AGREEMENT made this 26th day of September, 2003 (this “Agreement”)

 

AMONG:-

 

(1)                                 ELAN CORPORATION, PLC, a public limited company incorporated under
the laws of Ireland and having its registered office at Lincoln House, Lincoln
Place, Dublin 2, Ireland (“Elan Corp”);

 

(2)                                 ELAN INTERNATIONAL SERVICES,
LTD., an exempted limited
liability company incorporated under the laws of Bermuda, and having its
registered office at Clarendon House, 2 Church St., Hamilton, Bermuda, a
wholly-owned subsidiary of Elan Corp (“EIS”);
and

 

(3)                                 ACORDA
THERAPEUTICS, Inc., a
Delaware corporation having its principal place of business at 15 Skyline
Drive, Hawthorne, NY 10532, United States of America (“Acorda”).

 

RECITALS

 

A.                                   Acorda and EIS have entered into agreements
whereby Acorda sold and EIS purchased certain securities of Acorda and such
parties agreed to certain matters related to the ownership of such
securities.  Specifically:

 

(i)                                     EIS and Acorda entered into a Preferred
Stock, Convertible Note and Warrant Purchase Agreement dated as of January 22,
1997 (the “1997 Securities Purchase Agreement”);

 

(ii)                                  EIS and Acorda entered into a Securities
Purchase Agreement dated April 21, 1998 (the “1998
Securities Purchase Agreement”);

 

(iii)                               EIS and Acorda entered into a Subscription
Agreement dated as of August 6, 1999 (the “1999
Securities Purchase Agreement”);

 

(iv)                              Acorda and certain stockholders of Acorda
including EIS entered into an Amended and Restated Registration Rights
Agreement with respect to the capital stock of Acorda dated January 22, 1997,
as amended and restated July 7, 1998, August 6, 1999, December 20, 2000 and May
8, 2003, as a result of which, inter alia,
additional purchasers were added as parties to such agreement (as amended and
restated, the “Acorda Registration Rights
Agreement”); and

 

(v)                                 Elan Corp, Acorda and certain other
stockholders entered into an Amended and Restated Stockholders Agreement dated
December 20,

 

 

2000,
as amended and restated as of May 8, 2003 (the “Stockholders Agreement”).

 

B.                                     The Parties have entered into a Termination
Agreement of even date herewith (the “Termination
Agreement”).

 

C.                                     Simultaneously with the execution of the
Termination Agreement, Elan Corp and Acorda are entering into a Amended and
Restated License and Supply Agreement, pursuant to which, among other things,
certain of the parties thereto are amending and restating that certain License
Agreement (the “Restated Elan License
Agreement”) by and among Acorda, Elan Corp and MS Research and
Development Corporation (“MS R&D”).

 

D.                                    The Parties desire to enter into this
Agreement to set forth their agreements relating to certain matters relating
to: (i) the securities of Acorda held by Elan, (ii) amendments to the 1997
Securities Purchase Agreement, the Limited Recourse Note (as defined below),
the Full Recourse Note (as defined below), the Acorda Registration Rights
Agreement, the Second Closing Warrant and the SSDA (collectively, the “Amended Finance Documents”); and (iii)
Board observation rights in favor of EIS.

 

IN CONSIDERATION OF THE MUTUAL COVENANTS CONTAINED HEREIN,
AND OTHER GOOD AND VALUABLE CONSIDERATION, THE RECEIPT AND ADEQUACY OF WHICH
ARE HEREBY ACKNOWLEDGED, IT IS HEREBY AGREED AS FOLLOWS:

 

1.                                     DEFINITIONS

 

Capitalized
terms used in this Agreement shall have the same meanings assigned to them in
the Termination Agreement, unless such
terms are expressly defined to the contrary in this Agreement.

 

“Affiliate” shall mean any corporation or
entity controlling, controlled or under the common control of any other
corporation or entity.  For the purpose
of this definition, (i) “control” shall mean direct or indirect ownership of
fifty  (50%) percent or more of the
stock or shares entitled to vote for the election of directors and (ii) MS
R&D shall not be an Affiliate of Elan Corp, EPIL II or EIS.

 

“Effective Date” shall mean the date of this
Agreement.

 

“Elan”  shall
mean Elan Corp and its Affiliates.

 

“EPIL II” shall mean Elan Pharmaceuticals Investment II, Ltd.
an exempted limited liability company incorporated under the laws of Bermuda.

 

2

 

“Force Majeure” shall mean causes beyond a Party’s reasonable
control, including, without limitation, acts of God, fires, strikes, acts or
war or terrorism, or intervention of a governmental authority.

 

“Full Recourse Note” shall mean the Full Recourse Convertible
Promissory Note dated January 22, 1997 in the principal amount of $2,500,000
issued by Acorda to EIS.

 

“Limited Recourse Note” shall mean the Limited Recourse
Convertible Promissory Note dated January 22, 1997 in the principal amount of
$5,000,000 issued by Acorda to EIS.

 

“Party” shall mean Elan Corp, EIS, Acorda or MS R&D, as the
case may be, and “Parties” shall
mean all such parties together.

 

 “Second
Closing Warrant” shall mean the Second Closing Warrant to up to
100,000 Shares of the Series B Preferred Stock of Acorda
dated February 4, 2007 having an exercise price of $2.00 per share issued to
EIS.

 

2.                                       Milestone Purchases.  The Parties
hereto acknowledge and agree that none of Elan Corp, EIS, EPIL II or their
respective affiliates, subsidiaries, successors or assigns are obligated to
purchase additional securities of or from Acorda, or their respective
affiliates or subsidiaries, successors or assigns.

 

3.                                       Transfer Restrictions.  The Parties
hereby agreed to amend the Amended Finance Agreements as set forth hereinbelow:

 

3.1                                 1997 Securities Purchase
Agreement

 

(a)                                  Section 8.1 of the 1997 Securities Purchase
Agreement is hereby amended by changing all references to “50,000 of the
Shares” to “2,200,000 of the Shares.” 
The references to 2,200,000 shares shall be subject to adjustment for
stock splits, combinations, reclassifications, and other similar events.

 

(b)                                 Section 8.2 of the 1997 Securities Purchase
Agreement is hereby deleted and replaced with the following:

 

“Assignment of Rights to
Financial Information.  The rights
granted pursuant to Section 8.1 may not be assigned or conveyed by the
Purchaser or by any subsequent transferee of such rights without the prior
written consent of the Company; provided, however, that the
Purchaser and any transferee, after giving notice to the Company, may assign
such rights to any transferee that acquires no fewer than 2,200,000 shares of
Common Stock (subject to adjustment for stock splits, combinations,
reclassifications, and other similar events) (including for purposes of
determining the number of shares of Common Stock, any shares of

 

3

 

Common Stock issued or
issuable upon conversion or exercise of other securities), other than a
transferee that is a Competitor. For purposes of this Agreement, “Competitor”
shall mean any party engaged, directly or indirectly, in drug development for
therapies for spinal cord injuries or multiple sclerosis.”

 

(c)                                  Section 10 of the 1997 Securities Purchase
Agreement is hereby deleted in its entirety and replaced with the following:

 

“The Purchaser shall not
sell, assign or otherwise transfer any of the Securities to a Competitor
without the prior written consent of the Company.  In addition and in any event, the Purchaser shall be obligated to
comply with all applicable restrictions on transfer under applicable federal
and state securities laws.”

 

3.2                                 Limited Recourse Note

 

(a)                                  The first proviso of Section 1 of the Limited
Recourse Note shall be amended and restated in its entirety to read as follows:

 

“; provided, however, that
if the Board of Directors of the Company reasonably determines that such
Regulatory Approval is unlikely to be obtained or shall not be obtained in a
timely manner and provides written notice (the “Notice”) thereof to the Holder
(a “Board Termination”), then, on the thirtieth day following receipt of the
Notice by the Holder (the “Board Termination Date”), the outstanding principal
sum remaining on this Promissory Note, together with all accrued and unpaid interest
thereon, shall be automatically converted into shares of the Series D Preferred
Stock of the Company (the “Series D Preferred”) in accordance with Section 3.2
below effective as of the Board Termination Date, unless the Holder shall have
delivered a written notice to the Company prior to the Board Termination Date
of its desire to have such amount canceled (the “Cancellation Right”), in which
event, such amount shall be canceled as of the Board Termination Date;”

 

(b)                                 Section 3.1 of the Limited Recourse Note
shall be amended to:

 

(i)                                     replace the reference to “the Series D
Preferred Stock of the Company (the “Series D Preferred”)” with “Series D
Preferred”;

(ii)                                  insert the following parenthetical after
reference to $12.50: “(subject to adjustment for stock splits, combinations,
reclassifications, and other similar events)”; and

(iii)                               amend and restate the first line of the
second paragraph of Section 3.1 of the Limited Recourse Note to read in its
entirety as follows: “The right and option of the Holder to convert the unpaid
principal amount of this Promissory Note into Series D Preferred shall
terminate upon the first to occur of: (i) the automatic conversion thereof on
the Board Termination Date; and (ii) the payment (or repayment) by the Company
of all amounts owing under this

 

4

 

Promissory Note (subject to
the notice requirements of Section 2 hereof).”

 

(c)                                  Section 3.2 shall be renumbered Section 3.3,
and all references in the Limited Recourse Note to Section 3.2 (other than as
set forth in this Agreement) shall become references to Section 3.3.

 

(d)                                 A new Section 3.2 shall be inserted into the
Limited Recourse Note to read in its entirety as follows:

 

“Automatic Conversion
into Series D Preferred Sock. 
Subject to the Holder exercising the Cancellation Right in accordance
with Section 1 above, immediately prior to the Board Termination Date, the full
unpaid principal balance and accrued interest outstanding under this Promissory
Note at such time shall be automatically converted into fully paid and
nonassessable shares of Series D Preferred at a rate which shall be equal to
the quotient obtained by dividing:

 

(x)
the principal amount of this Promissory Note plus all accrued and unpaid
interest thereon, by

 

(y)
$12.50 (subject to adjustment for stock splits, combinations,
reclassifications, and other similar events).”

 

(e)                                  Section 5.7 of the Limited Recourse Note is
hereby deleted and replaced in its entirety to read as follows:

 

“Transfer Restrictions.
The Holder shall not sell, assign or otherwise transfer all or any portion of
this Promissory Note to a Competitor (as defined below) without the prior
written consent of the Company.  In
addition and in any event, the Holder shall be obligated to comply with all
applicable restrictions on transfer under applicable federal and state
securities laws. For purposes of this Note, “Competitor” shall mean any party
engaged, directly or indirectly, in drug development for therapies for spinal
cord injuries or multiple sclerosis.

 

(f)                                    All references to “Committee Termination” and
“Committee Termination Date” shall become references to “Board Termination” and
“Board Termination Date.”

 

3.3                                 Full Recourse Note

 

(a)                                  The first clause of Section 1 of the Full
Recourse Note shall be amended and restated in its entirety to read as follows:

 

“If the Holder has not
converted the outstanding principal hereunder into Preferred Stock in
accordance with Section 3 hereof by the date which is the earlier of (i) the
first anniversary after the first Regulatory Approval (as defined below) and
(ii) September 30, 2008 (the “Maturity Date”),”

 

5

 

(b)                                 The first proviso of Section 1 of the Full
Recourse Note shall be amended to replace the reference to “the Committee (as
defined in the License Agreement)” with “the Board of Directors of the
Company”.

 

(c)                                  The following proviso shall be inserted at
the end of the first sentence of Section 1 of the Full Promissory Note,
immediately prior to the definition of “Regulatory Approval”:

 

“; provided further,
however, if no Regulatory Approval has been received on or prior to the
Maturity Date, the Company shall have the right to extend the Maturity Date by
six month periods (each, an “Extension Period”) by delivery of a written notice
to the Holder certifying that it is the reasonable, good faith belief, after
due diligence and inquiry by the Company’s Board of Directors, of the Company
that such Regulatory Approval is likely to be obtained in a timely manner
(each, an “Extension Notice”), at least 30 days prior to the Maturity Date or
the then current Extension Period, as the case may be.”

 

(d)                                 Section 5.6 of the Full Recourse Note is
hereby deleted and replaced in its entirety to read as follows:

 

“Transfer Restrictions.
The Holder shall not sell, assign or otherwise transfer all or any portion of
this Promissory Note to a Competitor (as defined below) without the prior
written consent of the Company.  In
addition and in any event, the Holder shall be obligated to comply with all
applicable restrictions on transfer under applicable federal and state
securities laws. For purposes of this Note, “Competitor” shall mean any party
engaged, directly or indirectly, in drug development for therapies for spinal cord
injuries or multiple sclerosis.”

 

(e)                                  All references to “Committee Termination”
shall become references to “Board Termination” and all references to
“Committee” shall become references to the “Board of Directors of the
Company”).

 

3.4                                 Acorda Registration Rights
Agreement

 

(a)                                  Acorda hereby agrees that the amendments to
the Acorda Registration Rights Agreement set forth in this Clause 3.4
constitute a superseding agreement between Acorda and Elan that does not
require the consent of the other parties to the Acorda Registration Rights
Agreement.

 

(b)                                 Acorda agrees that the legend set forth in
Section 2(b) of the Acorda Registration Rights Agreement shall be amended and
restated to read in its entirety as follows:

 

“THESE SECURITIES ARE
SUBJECT TO CERTAIN RESTRICTIONS ON TRANSFER AS SET FORTH IN AN AGREEMENT
BETWEEN THE

 

6

 

COMPANY AND THE STOCKHOLDER,
A COPY OF WHICH IS ON FILE WITH THE SECRETARY OF THE COMPANY.”

 

(c)                                  Acorda agrees that the restrictions set forth
in Section 3 of the Acorda Registration Rights Agreement shall not apply to
Elan or its transferees of any Restricted Securities (as defined in the Acorda
Registration Rights Agreement); provided, however, Elan agrees to provide
written notice to Acorda of any transfer of Restricted Securities to a third
party which notice shall set forth the name of the relevant transferee, the
date of such transfer and the Restricted Securities transferred and which such
notice shall also be accompanied by, if requested by Acorda, at Elan’s expense,
an unqualified written opinion of legal counsel who shall and whose legal
opinion shall be satisfactory to Acorda, which opinion shall be addressed to
Acorda to the effect that the proposed transfer of the Restricted Securities
may be effected without registration under the Securities Act of 1933, as
amended.

 

(d)                                 Acorda agrees that the reference to 100,000
shares in Section 13 of the Acorda Registration Rights Agreement shall be
subject to adjustment for stock splits, combinations, reclassifications and
other similar events.

 

3.5                                 Second Closing Warrant.  The
first two sentences of Section 10 (Transfers) of the Second Closing Warrant are
hereby deleted and replaced in their entirety with the following:

 

“This Warrant may be transferred
or assigned by the Warrantholder, in whole or in part, subject to compliance by
the Warrantholder with all applicable federal and state securities laws,
without the prior written consent of the Company; provided, however, any
assignee or transferee of this Warrant (“permitted assignee”) shall be required
to accept this Warrant subject to all rights and obligations of the
Warrantholder as set forth herein.”

 

4.                                       Board Observation Right.  Subject to
earlier termination as provided herein, as long as Elan holds not less than
2,200,000 shares of Acorda’s outstanding common stock on a fully-diluted basis
(subject to stock splits, combinations, reclassifications and other similar
events), Elan shall have the right to have an observer (the “Elan Observer”)
present at two meetings each year of Acorda’s board of directors, the
determination of which meetings to be at Acorda’s sole discretion. The Elan
Observer may be excused from any meeting or discussion by the Board of
Directors to the extent that the Board may deem it to be inappropriate, in the
judgment of the Board, for the Elan Observer to be present during any such
meeting or discussion.  The
out-of-pocket expenses of the Elan Observer with respect to attending such
meetings will be reimbursed by Acorda to the same extent that Acorda reimburses
such expenses of its Directors. Elan may transfer its right to the Elan
Observer to any third party to which it sells, transfers or assigns not less
than 2,200,000 shares of Acorda’s outstanding common stock on a fully-diluted
basis (subject to stock splits, combinations, reclassifications and other
similar events). The observer right provided for herein shall terminate upon
the earlier to occur of (i) the closing of an initial public offering of
Acorda’s securities or (ii) the date upon which Elan

 

7

 

or its transferee ceases to
own five percent (5%) or more of Acorda’s outstanding common stock on a
fully-diluted basis.

 

5.                                       General

 

5.1                                 Governing law and
jurisdiction:

 

(a)                                  This Agreement shall be governed by and
construed in accordance with the laws of the State of New York, without
regard to conflicts of law principles under the laws of the State of New York.

 

(b)                                 For the purposes of this Agreement, the
Parties submit to the nonexclusive jurisdiction of the State and Federal Courts
of New York.

 

5.2                                 Assignment:

 

(a)                                  Subject to Clause 5.2(b), this Agreement
shall not be assigned by any Party without the prior written consent of the
others, save that any Party:

 

(i)             may assign this Agreement in whole or in part
and delegate its duties hereunder to its Affiliate or Affiliates without such
consent; and

(ii)          may assign its rights and obligations to a successor (whether by
merger, consolidation, reorganization or other similar event) or purchaser of
all or substantially all of its assets relating to such Party’s technology
related to this Agreement, provided that such successor or purchaser has agreed
in writing to assume all of such Party’s rights and obligations hereunder and a
copy of such assumption is provided to the other Parties.

 

(b)                                 For the avoidance of doubt, nothing in this
Clause 5.2 shall affect the provisions governing assignment of securities set
forth elsewhere in this Agreement.

 

5.3                                 Notices:

 

(a)                                  Any notice to be given under this Agreement
shall be sent in writing in English by registered airmail, internationally
recognized courier or telefaxed to the following addresses:

 

	
  If to Acorda at:

  
	
   

  
	
  Acorda Therapeutics, Inc.

  
	
  15 Skyline Drive

  
	
  Hawthorne, NY  10532

  

 

8

 

	
  Facsimile:

  
	
  Attention: 

  	
  President

  
	
   

  
	
  If to MS R&D or Acorda,

  with a copy to:

  
	
   

  
	
  Wilson, Sonsini, Goodrich & Rosati

  
	
  650 Page Mill Road

  
	
  Palo Alto, CA  94304

  
	
  Facsimile: 650-493-6811

  
	
  Attention: 

  	
  Douglas Collom

  
	
   

  
	
  If to Elan and/or EIS at:

  
	
   

  
	
  Elan Corporation, plc

  
	
  Elan International Services, Ltd.

  
	
  C/o Elan International Services, Ltd.

  
	
  102 St. James Court

  
	
  Flatts,

  
	
  Smiths FL04

  
	
  Bermuda

  
	
  Attention: 

  	
  Secretary

  
	
  Telephone: 

  	
  441 292 9169

  
	
  Fax: 

  	
  441 292 2224

  

 

or to such other address(es)
and telefax numbers as may from time to time be notified by any Party to the
others hereunder.

 

(c)                                  Any notice sent by mail shall be deemed to
have been delivered within seven (7) working days after dispatch or delivery to
the relevant courier and notice sent by fax shall be deemed to have been
delivered upon confirmation receipt. 
Notice of change of address shall be effective upon receipt.

 

5.4                                 Waiver.  No
waiver of any right under this Agreement shall be deemed effective unless
contained in a written document signed by the Party charged with such waiver,
and no waiver of any breach or failure to perform shall be deemed to be a
waiver of any future breach or failure to perform or of any other right arising
under this Agreement.

 

5.5                                 Severability.  If
any provision in this Agreement is agreed by the Parties to be, or is deemed to
be, or becomes invalid, illegal, void or unenforceable under any law that is
applicable hereto:

 

(a)                                  such provision will be deemed amended to
conform to applicable laws so as to be valid and enforceable; or

 

9

 

(b)                                 if it cannot be so amended without materially
altering the intention of the Parties, it will be deleted, with effect from the
date of this Agreement or such earlier date as the Parties may agree, and the
validity, legality and enforceability of the remaining provisions of this
Agreement shall not be impaired or affected in any way.

 

5.6                                 Further Assurances.  At
the request of any of the Parties, the other Party or Parties shall (and shall
use reasonable efforts to procure that any other necessary parties shall)
execute and perform all such documents, acts and things as may reasonably be
required subsequent to the signing of this Agreement for assuring to or vesting
in the requesting Party the full benefit of the terms hereof.

 

5.7                                 Successors.  This
Agreement shall be binding upon and inure to the benefit of the Parties hereto
and their respective successors and permitted assigns.

 

5.8                                 Amendments.  No
amendment, modification or addition hereto shall be effective or binding on any
Party unless set forth in writing and executed by a duly authorized
representative of each Party.

 

5.8                                 Counterparts. This Agreement may be executed in any number
of counterparts, each of which when so executed shall be deemed to be an
original and all of which when taken together shall constitute this Agreement.

 

5.9                                 Costs.  Each
Party shall bear its own costs and expenses in connection with the transactions
contemplated by this Agreement.

 

5.10                           Force Majeure.  No
Party to this Agreement shall be liable for failure or delay in the performance
of any of its obligations hereunder if such failure or delay results from Force
Majeure, but any such failure or delay shall be remedied by such Party as soon
as practicable.

 

5.11                           Relationship of the Parties.      The Parties are independent contractors under
this Agreement.  Nothing herein
contained shall be deemed to create or establish an employment, agency, joint
venture, or partnership relationship between the Parties or any of their agents
or employees, or any other legal arrangement that would impose liability upon
one Party for the act or failure to act of another Party.  No Party shall have any express or implied
power to enter into any contracts, commitments or negotiations or to incur any
liabilities in the name of, or on behalf of, another Party, or to bind another
Party in any respect whatsoever.

 

5.11                           Entire Agreement.

 

(a)                                  This Agreement, the Amended Finance Documents,
the 1998 Securities Purchase Agreement, the Termination Agreement and the
Restated Elan License set forth all of the agreements and understandings
between the

 

10

 

Parties with respect to the
subject matter hereof.  There are no
agreements or understandings with respect to the subject matter hereof, either
oral or written, between the Parties other than as set forth in such agreements
and documents.

 

(b)                                 No provision of this Agreement shall be
construed so as to negate, modify or affect in any way the provisions of any
other agreement between the Parties unless specifically provided herein and
only to the extent so specified.

 

(c)                                  Other than as expressly set forth herein, the
Amended Finance Documents remain in full force and effect and all future
references to them shall be deemed to give effect to the amendments set forth
herein.

 

THE REMAINDER OF THIS PAGE

HAS BEEN INTENTIONALLY LEFT BLANK.

 

11

 

IN WITNESS
WHEREOF the Parties
have executed this Agreement.

 

	
  SIGNED

  
	
   

  
	
   

  
	
  Elan Corporation, plc

  
	
   

  
	
  Monksland Holdings BV

  
	
   

  
	
  BY:

  	
  /s/ Klaas van Blanken

  	
   

  
	
   

  	
   

  	
   

  
	
  BY:

  	
  /s/ Pieter Bos

  	
   

  
	
   

  	
  Name: Monksland Holdings BV

  
	
   

  	
  Title: Proxyholder

  
	
   

  
	
   

  
	
  SIGNED

  
	
   

  
	
  Elan International Services, Ltd

  
	
   

  
	
   

  
	
  BY:

  	
  /s/ Debra Buryj

  	
   

  
	
   

  	
  Name: Debra Buryj

  
	
   

  	
  Title: Vice President

  
	
   

  
	
   

  
	
  SIGNED

  
	
   

  
	
  Acorda Therapeutics, Inc.

  
	
   

  
	
   

  
	
  BY:

  	
  /s/ Ron Cohen

  	
   

  
	
   

  	
  Name:  Ron Cohen

  
	
   

  	
  Title:  President & Chief
  Executive Officer

  
					

 

12Exhibit
10.26

 

Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.

 

Fampridine
Tablets (10mg, 15mg, 20mg, 25mg)

Technical Transfer Program Proposal for 

Commercial Registration

 

 

For

 

Acorda
Therapeutics

 

 

Proposal
No. ELN-FQ-0001-1002-R4

 

Dated:  February 26, 2003

 

 

Confidential

 

 

TABLE OF
CONTENTS

 

	
  1.0

  	
  Project
  Scope

  
	
   

  	
   

  
	
  2.0

  	
  Environmental,
  Health and Safety

  
	
   

  	
   

  
	
  3.0

  	
  Analytical Development

  
	
   

  	
   

  
	
   

  	
  3.1

  	
  Cleaning
  Residuals Assay (Method Development and Validation)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.2

  	
  Drug
  Substance Potency and Related Substance Assay (Method Transfer)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.3

  	
  Drug
  Substance – Particle Size (Method Transfer)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.4

  	
  Drug
  Substance – Residual Solvent Assay (Method Verification)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.5

  	
  Drug
  Substance – Moisture by KF (Verification)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.6

  	
  Drug
  Product Potency & Related Substance Assay, Two Methods (Method Transfer)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.7

  	
  Dissolution Assay
  (Method Validation)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.8

  	
  Drug
  Product – Moisture by KF (Verification)

  
	
   

  	
   

  	
   

  
	
   

  	
  3.9

  	
  Release Testing
  of the Drug Substance, per Lot

  
	
   

  	
   

  	
   

  
	
  4.0

  	
  Feasibility Manufacturing

  
	
   

  	
   

  
	
  5.0

  	
  Registration Manufacturing

  
	
   

  	
   

  
	
  6.0

  	
  Stability - Registration

  
	
   

  	
   

  
	
  7.0

  	
  Project
  Management

  
	
   

  	
   

  
	
  8.0

  	
  Assumptions,
  Terms and Conditions

  
	
   

  	
   

  
	
  Appendix A: Budget Summary

  
	
   

  
	
  Appendix B:
  High Level Timeline

  

 

2

 

Patheon Proposal #
ELN-FQ-0001-1002-R4

29-Feb-03

 

1.0          Project Scope

 

Patheon Inc. (“Patheon”) will perform manufacturing and analytical
services in order to manufacture Fampridine Tablets (10mg, 15mg, 20mg, 25mg)
for Acorda Therapeutics (“Client”). 
Analytical methods will be assessed to support the manufacturing
program.

 

The Budget Summary for this proposal is presented in Appendix A.

 

Patheon will commence the activities described in this proposal
following the execution of the Contract by both parties.

 

Reference standards for Fampridine and impurities and tablet samples
will be provided by the Client.  Source
technical documents (e.g., current Elan methods, validation reports, and master
batch records, etc) and an HPLC column for initiation of method familiarization
activities will be provided by the Client. 
Patheon will be responsible for the generation of documentation and
protocols required to support methods familiarization, methods transfer,
manufacturing studies, and process transfer activities to be performed as part
of this proposal.  The Client will
review and approve all protocols generated by Patheon prior to execution of
studies with the exception of the Clean Residuals Assay method.  Patheon will provide final reports at key
stages in the project, as indicated in this proposal.  The Client will review and approve final reports.

 

2.0          Environmental,
Health and Safety

 

Prior to the commencement of analytical method development, formulation
development and manufacturing activities, a thorough review by Patheon of the
Environmental, Health and Safety (EH&S) requirements for Fampridine will be
completed.  The fee assumes the EH&S
review will determine that Fampridine can be safely handled at Patheon.  A summary report for this evaluation will be
provided to the Client.

 

3.0          Analytical
Development

 

Patheon will perform the required method familiarization, method
transfer, method development and/or method validation work required to support
the manufacture of Fampridine Tablets. 
Patheon is responsible for preparing all protocols.  The Client will review and approve all
protocols prior to execution of the work. Upon completion of individual
studies, Patheon will prepare final reports to document results of all studies
with the exception of the Clean Residuals Assay method.  The Client will review and approve all
reports before moving forward with activities that rely on results of the
activities that are the subject of a report.

 

3

 

3.1          Cleaning Residuals Assay (Method
Development and Validation)

 

Patheon will develop and validate the test methods required for testing
cleaning residuals and swab samples in order to support the manufacturing
program.  Analytical protocols and
report will be prepared by Patheon.  The
development and validation will challenge the following parameters:

 

•                  System
Suitability

•                  Linearity

•                  LOD

•                  LOQ

•                  Recovery
/ Accuracy

•                  Repeatability

•                  Intermediate
Precision

•                  Robustness

•                  Specificity

•                  Stability

 

3.2          Drug Substance Potency and Related
Substance Assay (Method Transfer)

 

Patheon will transfer the test method required for drug substance
testing in order to support the manufacturing program. The Client will supply
Patheon in advance with the relevant Validation data to allow Patheon to set
acceptance criteria for the protocol. Method Transfer protocols will be
prepared by Patheon and submitted to the Client for approval prior to execution.  A final report documenting the methods
transfer results will be prepared by Patheon and submitted to the Client for
approval prior to use of the method for release testing. The method transfer
will challenge the following parameters:

 

•                  System
Suitability

•                  LOD
and LOQ

•                  Specificity

•                  Repeatability

•                  Reproducibility

•                  Robustness

 

3.3          Drug Substance – Particle Size (Method
Transfer)

 

Patheon will transfer the test method required for drug substance
particle size testing in order to support the manufacturing program. The Client
will supply Patheon in advance with the relevant Validation data to allow
Patheon to set acceptance criteria for the protocol. Method Transfer protocols
will be prepared by Patheon and submitted to the Client for approval prior to execution.   A final report documenting the methods
transfer results will be prepared by Patheon and submitted to the Client for
approval prior to use of the method for release testing. The method transfer
will challenge the following parameters:

 

•                  Reproducibility

•                  Robustness

•                  Repeatability

 

4

 

3.4          Drug Substance – Residual Solvent Assay
(Method Verification)

 

Patheon will verify the test method required for drug substance
residual solvent testing in order to support the manufacturing program.
Analytical protocols will be prepared by Patheon and submitted to the Client
for approval prior to execution.  A
final report documenting the method verification results will be prepared by
Patheon and submitted to the Client for approval prior to use of the method for
release testing. The method verification will evaluate the following
parameters:

 

•                 System
Suitability

•                 LOD
and LOQ

•                 Specificity

•                 Repeatability

•                 Reproducibility

 

3.5          Drug Substance – Moisture by KF (Verification)

 

Patheon will verify the test method (up to 6 samples) required for drug
substance moisture testing to ensure the method is precise and accurate in
order to support the manufacturing program. Analytical protocols will be
prepared by Patheon and submitted to the Client for approval prior to
execution. A final report documenting the method verification results will be
prepared by Patheon and submitted to the Client for approval prior to use of
the method for release testing.

 

3.6                               Drug Product Potency & Related
Substance Assay, Two Methods (Method Transfer)

 

Patheon will perform method familiarization for the methods in advance
of methods transfer.  A report
documenting the method familiarization results will be prepared by Patheon and
submitted to the Client for approval prior to commencement of method transfer
studies.  The client will supply Patheon
with the relevant validation data to allow Patheon to set acceptance criteria
for the protocol

 

Patheon will transfer the test methods required for drug product
potency and related substances testing in order to support the manufacturing
program.  It is noted that in addition
to testing the coated finished product using Methods 1 and Method 2, a separate
HPLC method will be used for the following:

 

•                  content
uniformity testing,

•                  assay
of the uncoated tablets

•                  blend
homogeneity testing.

•                  Unit
dose testing

 

Method Transfer protocols will be prepared by Patheon and submitted to
the Client for approval prior to execution. Final reports documenting the method
transfer results will be prepared by

 

5

 

Patheon and submitted to the Client for approval prior to use of the
methods for testing.  The transfer will
challenge the following parameters:

 

•                  System
Suitability

•                  LOD
and LOQ

•                  Specificity

•                  Repeatability

•                  Reproducibility

•                  Robustness

 

3.7          Dissolution Assay (Method Validation)

 

Patheon will perform full validation of the method required for testing
dissolution of the drug product in order to support the manufacturing
program.  Analytical protocols will be
prepared by Patheon and submitted to the Client for approval prior to
execution.  A final report documenting
the method validation results will be prepared by Patheon and submitted to the
Client for approval prior to use of the method for release testing. The
validation will be performed according to ICH guideline requirements typically:

 

•                  System
Suitability

•                  Linearity
& Range

•                  Accuracy

•                  Precision
(Reproducibility)

•                  Robustness
of dissolution parameters & HPLC Methodology

•                  Specificity

•                  Solution
Stability

 

3.8          Drug Product – Moisture by KF
(Verification)

 

Patheon will verify the test method (up to 6 samples) required for drug
product moisture testing to ensure that the method is   precise and accurate in order to support the manufacturing
program. Analytical protocols will be prepared by Patheon and submitted to the
Client for approval prior to execution. A final report documenting the method
verification results will be prepared by Patheon and submitted to the Client
for approval prior to use of the method for release testing.

 

3.9          Release Testing of the Drug Substance,
per Lot

 

Patheon will test drug substance for receiving and releasing for
manufacture as per Client’s CoA or as specified by Client instruction.

 

Note:

Release testing of the excipients and drug product has been included as
“Analytical Support” under each section of the manufacturing.

 

6

 

4.0          Feasibility
Manufacturing

 

Patheon will manufacture up to three feasibility batches of Fampridine
Tablets at the 10mg strength.  These
batches will be approximately 50 kilograms each and will not be manufactured
back-to-back.  A protocol to evaluate
blend times, tablet press parameters and coating parameters will be prepared by
Patheon and submitted to the Client for approval prior to execution of the
feasibility study.  The protocol will
specify a detailed sampling plan and acceptance criteria.

 

All excipients will undergo complete analytical release testing in
compliance with USP/NF (if the Client requires additional testing on the
excipients, this will be addressed and costed separately as an amendment to
this proposal).  Patheon will prepare a
master batch record(s), which will be provided to the Client for approval prior
to manufacturing and specifies manufacturing procedures and acceptance
criteria.

 

The feasibility batches will not be GMP batches and will not undergo a
full QA review; the batches will be bulk packaged. A report documenting the
results of the feasibility studies will be prepared by Patheon and submitted to
the Client for approval prior to proceeding to the registration batch
production phase of this proposal.

 

Feasibility Manufacturing Process Train (50 kilograms):

 

•                  325L
Gallay

•                  Beta
Press

•                  Vector
Lab Coater

•                  Comil

 

The following in-process and finished product testing is based upon the
described tests.  

 

Blend Analysis

 

•                  Blend
Homogeneity / uniformity of dosage (total of 10 samples)

•                  Composite
sample Assay

•                  Flow
Properties

•                  Bulk
and Tap Densities (Including one sieve analysis)

 

Coated Tablet
Analysis:

 

•                  Appearance

•                  Weight
Variation

•                  Potency
& Related Substances

•                  Identification

•                  Dissolution
Profile

•                  Physical
Parameters (hardness and friability)

•                  Moisture
(KF)

 

7

 

Uncoated Tablet Analysis:

 

•                  Content
Uniformity (As per USP)

•                  Physical
Parameters (Note Weight thickness and hardness will be evaluated as part of
in-process monitoring these are performed as part of the process) – hardness
and friability

•                  Appearance

•                  Moisture
(KF)

 

5.0                               Registration Manufacturing

 

Patheon will manufacture twelve registration batches of Fampridine
Tablets (three of each tablet strength) that are colored and debossed
tablets.  These batches will be
approximately 50 kilograms each and may be manufactured back-to-back.
Processing parameters will be based on recommendations from the feasibility
study.  All excipients will undergo
complete analytical release testing in compliance with USP/NF (if the Client
requires addition testing on the excipients, this will be addressed and costed
separately as an amendment to this proposal). 
Patheon will prepare a protocol and provide the protocol to the Client
for approval prior to execution of the registration batch production work.  The protocol will specify a detailed
sampling plan and acceptance criteria. Patheon will prepare master batch
records, which will be provided to the Client for approval prior to
manufacturing; the batch records will specify manufacturing procedures and
acceptance criteria.

 

The registration batches will be manufactured in accordance with cGMPs
and will undergo a full QA review by Patheon. 
The batches will be packaged as follows by Patheon (packaging
configuration split to be determined by Client):

 

	
  10mg Tablets

  	
   

  	
  HDPE Bottles of 14’s and 60’s

  
	
  15mg Tablets

  	
   

  	
  HDPE Bottles of 14’s and 60’s

  
	
  20mg Tablets

  	
   

  	
  HDPE Bottles of 14’s, 60’s and 180’s

  
	
  25mg Tablets

  	
   

  	
  HDPE Bottles of 14’s, 60’s and 180’s

  

 

(all packaging configurations will include desiccant, filler and
induction seal)

 

Registration Manufacturing Process Train (50 kilograms):

 

•                  325L
Gallay

•                  Beta
Press

•                  Vector
Lab Coater

•                  Comil

 

8

 

The following in-process and finished product testing will be
conducted.

 

Blend Analysis:

 

•                  Blend
Homogeneity/uniformity of dosage (total of 10 samples)

•                  Composite
sample assay, appearance, and ID

•                  Flow
Properties

•                  Bulk
and Tap Densities (Including one sieve analysis)

 

Coated Tablet Analysis:

 

•                  Appearance

•                  Potency
& Related Substances

•                  Identification

•                  Dissolution
Profile

•                  Physical
Parameters (hardness and friability)

•                  Moisture
(KF)

•                  Uniformity
of dosage

 

Uncoated Tablet Analysis:

 

•                  Weight
Variation

•                  Physical
Parameters (hardness,  and friability)

•                  Appearance
ID

•                  Moisture
(KF)

•                  Assay

 

Patheon will provide copies of executed batch records to the Client
with the associated completed sampling protocol and summary of results.  The Client will review the batch records
prior to initiation of registration stability studies by Patheon.

 

6.0          Stability
- Registration

 

For quoting purposes a non-matrix approach has been suggested to
monitor the 30 lots (12 Registration batches, two packaging formats for the 10
and 15mg strengths, and three packaging formats for 20 and 25mg strengths of
Fampridine Tablets) as per ICH guidelines.

 

Additional samples will be stored as contingency samples if required to
generate data for long-term stability of the product.

 

The following storage conditions and test-points are suggested for
testing:

 

•                                          1,
2, 3 and 6 months for 40°C ±
2°C
/ 75% ± 5% RH

•                                          1,
2, 3, 6, 9, and 12 months for 30°C ±
2°C
/ 60% ± 5% RH*

•                                          3,
6, 9, 12, 18, 24 and 36 months for 25°C ±
2°C
/ 60% ± 5% RH

•                                          Contingency
samples at 5°C, Ambient RH*

 

(* Tested only if required due to significant changes in the next level
condition)

 

9

 

The analytical data used for the release of each lot manufactured at
Patheon will be considered as initial (T=0) data if samples are placed on
stability within 30 days of batch release.

 

Cost efficiencies for analytical testing have been built into the
stability program based upon the number of samples pulled in a given
month.  The fee for this stability
program assumes that all lots will be placed on stability at the same
time.  If these lots are not placed on
stability at the same time, the fee will be adjusted accordingly through an
Amendment to Proposal. The number of Pulls and costing is based on the
assumption that no testing is required at 30°C/60%RH.

 

	
  Pullpoint Month

  	
   

  	
  1

  	
   

  	
  2

  	
   

  	
  3

  	
   

  	
  6

  	
   

  	
  9

  	
   

  	
  12

  	
   

  	
  18

  	
   

  	
  24

  	
   

  	
  36

  
	
  Number of Samples Pulled

  	
   

  	
  30

  	
   

  	
  30

  	
   

  	
  60

  	
   

  	
  60

  	
   

  	
  30

  	
   

  	
  30

  	
   

  	
  30

  	
   

  	
  30

  	
   

  	
  30

  

 

Therefore, the stability sample breakdown is:

 

•                  0
Single Sample Pullpoints (0 Samples)

•                  0
Double Sample Pullpoints (0 Samples)

•                  0
More Than Two Sample Pullpoints (0 Samples)

•                  0
More Than Five Sample Pullpoints (330 Samples)

•                  9
More Than Ten Sample Pullpoints (330 Samples)

 

The following standard tests are usually performed as part of the
Stability Program:

 

•                  Potency
&Related Substances

•                  Dissolution
Profile

•                  Physical
Appearance

•                  Moisture

•                  Hardness

•                  Friability

 

This estimate is based on a full ICH program.  Patheon will prepare the ICH stability protocol.  The protocol will be approved by the Client
prior to initiation of the stability studies. 
Patheon will provide results to the Client for each test interval that
has been reviewed by Patheon quality assurance.  Patheon will prepare a report at the 3 and 6 month test stations
and will prepare reports at every subsequent 6 month test station thereafter
(or at each 12 month test interval, as appropriate, based upon the protocol).

 

There is the possibility to reduce the fees for this work based on the
mutual agreement between Patheon and the Client to matrix the testing design.  The final cost is to be determined.

 

7.0          Project
Management

 

Patheon will provide project management support to monitor the progress
of the project against established timelines and will update the Client of
changes in events. The project manager will coordinate regular biweekly
teleconference meetings and quarterly face-to-face meetings.  The fee for project management is
incorporated in the breakdown of each activity.

 

10

 

8.0          Assumptions,
Terms and Conditions

 

1.             Development Activities:  Patheon shall undertake
and perform the product development work described in this Proposal (the
“Development Activities”) which when accepted by CLIENT shall become a contract
binding on Patheon and CLIENT (the “Contract”).  Notwithstanding the foregoing, CLIENT and Patheon acknowledge
that certain changes are contemplated in the scope of the Development
Activities the details and costs of which will be negotiated at a later date.
No changes, deletions or additions to the Development Activities will be
considered valid without prior written agreement between CLIENT and
Patheon.  Patheon shall notify Client,
in advance of incurring any costs, when additional development activities by
Patheon, beyond the Development Activities set forth in this Proposal, become
necessary due to unforeseen events. 
Patheon shall not perform any additional development activities without
CLIENT approval of such related costs.

 

It is assumed that, based on the information available to Patheon at
this time, Patheon can safely perform the Development Activities at its Toronto
Region Operations facility.  If it is
determined by Patheon’s Environmental Health and Safety personnel that any of
the active ingredients are a Category III or Category IV compound, an
occupational exposure level, then an air sampling method will be required at
CLIENT’s expense prior to commercialization. 
Patheon reserves the right, in its sole and absolute discretion, to
conduct an air sampling method on Category I and II compounds, at such price
and upon such terms as may be mutually agreed to between the parties prior to
commercialization.

 

1.1           “Intellectual
Property”: includes, without limitation, rights in patents, patent
applications, trade-marks, trade-mark applications, trade-names, confidential
information, trade secrets, inventions, copyrights, industrial designs.

 

1.2           Grant of
Non-Exclusive License to Patheon: 
The CLIENT hereby grants to Patheon, for the term of the Contract, a
royalty-free, non-exclusive license to use Client’s Intellectual Property for
the performance of the Development Activities. 
The nonexclusive license granted herein shall be limited to Intellectual
Property of the CLIENT that is necessary for the performance of the Development
Activities and Patheon shall not use such Intellectual Property for any other
purpose than performance of the Development Activities.  The non-exclusive license shall not include
any right not expressly stated hereunder. 
CLIENT represents and warrants that as of the date of the Contract to
the best of its knowledge, without conducting any inquiry, that the Development
Activities performed by Patheon will not, to the best of CLIENT’s belief,
infringe any Intellectual Property held by any third party.

 

2.             Supply of Products:

 

(a)           CLIENT shall supply Patheon with
sufficient bulk quantities of the active ingredients and certain excipients for
Patheon’s use in conducting the Development Activities under this
Proposal.  Such ingredients and excipients
shall by supplied by CLIENT at its expense.

 

11

 

Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have been
separately filed with the Commission.

 

(b)           Patheon shall purchase all other
materials required to conduct the Development Activities.  CLIENT shall pay Patheon’s direct cost
thereof plus an additional [**] as a handling charge upon receipt of an invoice
detailing such costs.  Prior to making
any such purchases in excess of [**], Patheon shall obtain CLIENT
approval.  In addition, Patheon shall
obtain prior client approval for each and every purchase of other materials
once the total amount invoiced to CLIENT during performance of the Development
Activities exceeds [**].

 

3.             Payment
for Service:

 

(a)           CLIENT shall pay Patheon for the
services to be provided during the term of this Proposal in such amounts and in
such manner as set forth in this Proposal. 
All amounts quoted are in USD funds and are valid for sixty (60) days
from the date of this Proposal.  All
amounts quoted are subject to review by Patheon of all product specifications,
development reports and, Environmental, Health and Safety assessment.  One review with changes is included in the
fee for final reports.  Any additional
changes shall be invoiced separately at the then prevailing hourly rates.

 

(b)           Project specific items, which include
but are not limited to special equipment, change parts, excipients, laboratory
columns and reagents, tooling etc., obtained by Patheon from third party
suppliers as well as services to be provided by any third party suppliers are
subject to prior CLIENT approval, and will be billed back to CLIENT upon
Patheon’s receipt of invoice from any supplier of Patheon.  The purchase of project specific items and
services are subject to the same prior approval requirements in Section 2 (b)
of the Contract.

 

(c)           Each Patheon invoice shall be due and
payable within thirty (30) days of the date of such invoice.

 

4.             Deposit:  Prior to the commencement
of any Development Activities by Patheon pursuant to this Proposal, Patheon
shall have received from CLIENT a deposit in the amount set out in the Project
Summary.  This deposit amount will be
held by Patheon as a deposit until the Development Activities, as modified from
time to time, are fully completed or until this Contract expires or is
terminated for whatever reason.  The
deposit amount shall be credited towards the final invoice for the
Project.  Patheon may apply this deposit
amount against any accounts overdue in excess of 60 days of the date of the
invoice.  In addition, Patheon may, at
its option, suspend all Development Activities until such time the outstanding
amounts have been paid in full and the original deposit amount has been
replenished.

 

5.             Term and Termination:  This Contract will take
effect on the date of execution and shall continue until completion by Patheon
of the Development Activities.  Either
party may terminate this Contract if the other party is in material breach of
any provisions thereof and the breaching party fails to remedy any such breach
within thirty (30) days of the notice of such breach by the non-breaching
party. Additionally, CLIENT shall have the right to terminate this Contract
immediately for any business reason.

 

In either such case, Patheon shall cease performance of the Development
Activities upon termination and CLIENT shall pay to Patheon:  (i) any fees and expenses due to Patheon for
the

 

12

 

services rendered up to the date of termination; (ii) all actual costs
incurred by Patheon to complete activities associated with the termination and
close of the Project; and (iii) any additional costs incurred by Patheon in
connection with the Project that are required to fulfill applicable regulatory
and contractual requirements.  Any
re-scheduling of the Development Activities requested by CLIENT beyond one
hundred twenty (120) days, notwithstanding a request made pursuant to Section
8.8, shall be deemed to be a termination.

 

All materials and supplies shall be picked up within five (5) business
days of termination otherwise, a $20.00 per square foot per month surcharge
will be assessed for storage.

 

6.             Confidential Information:  All proprietary or
confidential information of either party that is disclosed or otherwise made
known to the other party as a result of the Development Activities performed
under this Contract shall be considered confidential property of the disclosing
party (the “Confidential Information”). 
The Confidential Information shall be used by the receiving party, its
employees and external advisors only for the purpose of performing the receiving
party’s obligations hereunder.  For
purposes of this paragraph, Confidential Information shall not be deemed to
include any information that is (i) known to the receiving party at the time of
the disclosure, as evidenced by its written records prior to disclosure by the
disclosing party; (ii) is or becomes available publicly other than as a result
of a breach of this Contract by the receiving party, (iii) obtained from a
third party lawfully in possession of such information and under no obligation
to maintain such information confidential or (iv) independently developed by
the receiving party without use of the Confidential Information.

 

Each party agrees that it will not reveal, publish or otherwise
disclose the Confidential Information of the other party to any third party
without prior written consent of the disclosing party.  However, disclosure of Confidential
Information may be made if required by law or by any regulatory or governmental
authority to which the receiving party or any of its respective affiliates may
be subject, in each case, on prior written notice to the disclosing party, so
that the disclosing party may determine whether to seek a protective order or
other appropriate remedy.  This
obligation of confidentiality and non-disclosure shall remain in effect for a
period of ten (10) years after the effective date of termination of this
Contract.

 

7.             Inventions, Etc.:  All data, information and
Intellectual Property generated or derived by Patheon as a result of
Development Activities performed by Patheon under this Contract, to the extent
it is specific to the development, manufacture, use and sale of the CLIENT’s
product the subject of the Development Activities (“CLIENT’s Product”) shall be
and remain the exclusive property of CLIENT. 
In addition, any data, information and Intellectual Property generated
or derived by Patheon through the use of CLIENT’s Intellectual Property that is
not a result of the Development Activities performed by Patheon shall be the
exclusive property of CLIENT.  On the
other hand, all data information and Intellectual Property generated or derived
by Patheon as a result of Development Activities performed by Patheon under
this Contract, which is not specific to the development the development,
manufacture, use and sale of the CLIENT’S product and has application beyond
the CLIENT’s Product shall be and remain the exclusive property of
Patheon.  Notwithstanding the foregoing,
CLIENT acknowledges that Patheon possesses certain inventions, processes,
know-how, trade secrets, other intellectual properties and other assets,
including but not limited to, analytical methods, computer technical expertise
and

 

13

 

software which have been independently developed by
Patheon (collectively “Patheon Property”). 
CLIENT and Patheon agree that any Patheon Property or improvement
thereto which are used, improved, modified or developed by Patheon under or
during the term of this Contract, is the product of Patheon’s technical
expertise possessed and developed by Patheon prior to or during performance of
this Contract and are the sole and exclusive property of Patheon.

 

8.             Errors
and Omissions:  In the event of
a material error by Patheon in the performance of the Development Activities,
CLIENT shall have the option to request Patheon to (1) repeat the service at
Patheon’s own costs provided that CLIENT provides the active ingredient, or (2)
reimburse CLIENT for the price for that particular service, excluding the cost
of the active ingredient.  In any event,
Patheon shall not reimburse the amount of the active ingredient.

 

9.             Indemnification:

 

(a)           CLIENT shall defend, indemnify and
hold harmless Patheon and its affiliates and their respective directors,
officers, employees and agents (together with Patheon, the “Patheon Indemnitees”)
from and against any and all claims, actions, causes of action, damages,
liabilities, expenses including reasonable attorneys’ fees and expenses
(collectively, “Losses”) to and in favour of third parties (other than
affiliates) resulting from, relating to, or arising from: (i) any breach by
CLIENT of any of its obligations under this Contract; and (ii) the Intellectual
Property rights of third parties except to the extent such Losses are: (I)
determined to have resulted from the negligence or willful misconduct of
Patheon; or (2) for which Patheon is obligated to indemnify the CLIENT
Indemnitees pursuant to Section 9(b).

 

(b)           Patheon shall defend, indemnify and
hold harmless CLIENT and its affiliates and their respective directors,
officers, employees and agents (together with CLIENT, the “CLIENT Indemnitees”)
from and against any and all Losses resulting from, relating to, or arising
from any breach by Patheon of any of its obligations under this Contract except
to the extent such Losses are: (i) determined to have resulted from negligence
or willful misconduct of CLIENT; or (ii) for which CLIENT is obligated to
indemnify the Patheon Indemnitees pursuant to Section 9(a).

 

(c)           Under no circumstances whatsoever
shall either party be liable to the other in contract, tort, negligence, or
breach of statutory duty for any otherwise for any indirect or consequential
damages.

 

10.          Indemnification
Procedures:  In the event that
either party seeks indemnification, it shall inform the other party of the claim
as soon as reasonably practicable after it receives notice thereof and, shall
permit the other party, at that party’s cost, to assume direction and control
of the defense of the claim, and shall cooperate as reasonably requested (at
the expense of the other party), in defense of the claim.  Neither party shall settle or otherwise
compromise any claim or suit in any manner that adversely affects that other
party hereunder or imposes obligations on the other party in addition to those
set forth in this Contract, without prior written consent of the other party,
which consent shall not be unreasonably withheld or delayed.

 

14

 

11.          Miscellaneous:  This Contract contains the entire
understanding of the parties with respect to the subject matter herein and
supersedes all previous agreements (oral and written), negotiations and
discussions.  The parties may modify or
amend the provisions hereof only by an instrument in writing duly executed by
both of the parties.  Neither this
Contract, nor any of either party’s rights hereunder, may be assigned or
otherwise transferred by either party without the prior written consent of the
other party.  Any attempt to assign the
rights or obligations under this Contract shall be void. This Contract shall be
deemed to be made in the State of New York and shall be interpreted and
enforced in accordance with the laws of the State of New York, without regard
to conflict of law principles.  The
parties hereby submit to the jurisdiction of the state and federal courts
located within the State of New York. 
The obligation of the parties contained in Sections 6, 7, 8, 9 and 10
shall survive the expiration or earlier termination of this Contract.

 

Patheon and CLIENT have executed this Contract in duplicate by the duly
authorized officers of each party.

 

	
  Acorda Therapeutics

  	
   

  	
  Patheon Inc.

  
	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Mitchell Katz

  	
   

  	
   

  	
  By:

  	
  /s/ Nick A. DiPietro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Name:

  	
  Mitchell Katz, PhD

  	
   

  	
   

  	
  Name:

  	
  Nick A. DiPietro

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Vice President, Clinical Programs

  	
   

  	
   

  	
  Title:

  	
  President & COO

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Date:

  	
  3/28/03

  	
   

  	
   

  	
  Date:

  	
  4/7/03

  	
   

  

 

15

 

Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.

 

Appendix A: Budget Summary

 

THE
FOLLOWING COSTS ARE ALL QUOTED IN:                              USD

 

	
  2.0
  ENVIRONMENTAL HEALTH AND SAFETY

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  ACTIVITY

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  PRICE

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  EH&S
  Assessment ($3,000 per active)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.0
  ANALYTICAL DEVELOPMENT

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  ACTIVITY  SHIFTS

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  	
   

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.1
    Cleaning Residuals Assay (Method Development and Validation)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
  3.2
    Drug Substance Potency & Related Substances (Method Transfer)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.3
    Drug Substance - Particle Size (Method Transfer)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.4   Drug Substance - Residual Solvents
  Assay (Method Verification)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.5
    Drug Substance - Moisture by KF (MethodVerification)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.6   Drug Product Potency & Related
  Substances Assay (Method Transfer)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.7   Dissolution (Validation)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.8   Drug Product - Moisture by KF
  (Method Verification)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  3.9   Full Release testing of the Drug
  Substance (per Lot)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Protocol/benchwork

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Final Report

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  TOTAL
  (Analytical Development)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  4.0 FEASIBILITY MANUFACTURING -
  OPTIMIZATION BATCHES

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  ACTIVITY

  	
   

  	
  SHIFTS

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  	
  SHIFTS

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Certain 
  portions of this Exhibit have been omitted pursuant to a request for
  confidentiality. Such omitted 

  portions, which are marked with brackets
  [     ] and an asterisk*, have been separately filed
  with the 

  Commission.

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Per
  Batch:

  	
  Manufacturing

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Bulk Packaging

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Analytical
  Support

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  Project Support

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
  TOTAL
  (Three Feasibility Batches)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  

 

16

 

Certain portions of this Exhibit have been omitted pursuant to a
request for confidentiality. Such omitted portions, which are marked with
brackets [   ] and an asterisk*, have
been separately filed with the Commission.

 

	
  5.0 REGISTRATION MANUFACTURING

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ACTIVITY

  	
   

  	
  SHIFTS

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  	
  SHIFTS

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Per
  Batch:

  	
   

  	
  Manufacturing

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Packaging

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical
  Support

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Project Support

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
  First
  Batch

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
  11

  	
  Additional
  Batches Manufactured Back-to-Back from First Batch

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Cost
  Savings Per Additional Batch:

  	
   

  	
  3.5

  	
   

  	
  Shifts/

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Cost
  Per Additional Batch:

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
  OPTIONAL:
  For 4 Registration Batches Manufacture
  Back-to-Back the Cost will be $249,820

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Bulk Hold Time
  Study (per Strength - one Timepoint)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TOTAL
  (Registration Manufacturing)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  6.0 STABILITY - REGISTRATION

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  ACTIVITY

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  HOURS

  	
   

  	
  PRICE

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Number of Lots

  	
  24

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Total Samples

  	
  264

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  Cost per
  Sample

  	
   

  	
  # of Samples

  	
   

  	
  Subtotal

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical
  Support (1 sample per pullpoint)

  	
   

  	
  $

  	
  [**]

  	
   

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical Support
  (2 samples per pullpoint)

  	
   

  	
  $

  	
  [**]

  	
   

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical
  Support (2+ samples per pullpoint)

  	
   

  	
  $

  	
  [**]

  	
   

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical
  Support (5+ samples per pullpoint)

  	
   

  	
  $

  	
  [**]

  	
   

  	
  0

  	
   

  	
  $

  	
  0

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  Analytical
  Support (10+ samples per pullpoint)

  	
   

  	
  $

  	
  [**]

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  TOTAL
  (Stability - Validation)

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  [**]

  	
   

  	
   

  	
  [**]

  	
   

  
	
  BUDGET TOTAL *

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  USD

  	
   

  	
   

  	
  [**]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Deposit

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  	
  $

  	
  [**]

  	
   

  
																							

 

* The manufacturing cost given in this proposal is based upon the
assumption that the drug substance is classified as a high potency material in
accordance with Patheon’s Categorization System.  If it is determined through Patheon’s Environmental Health and
Safety Review that the drug substance is not categorized as a high potency
material, the manufacturing cost will be revised through a Change of Scope to
reflect handling charges for a low potency product.

 

17

 

Appendix
B: High Level Timeline

(2 pages)

 

The attached High Level Timeline is presented at this stage as a
projected estimate of the duration and achievable milestones, based upon
Patheon’s experience and history.  The
High Level Timeline should not be taken as part of an agreed legal deliverable
of this proposal.

 

Once the project has been awarded to Patheon and the relevant legal
documentation is in place, a revised Timeline detailing set milestones and
duration of deliverables will be agreed upon between Patheon and the
Client.  The revised Timeline would
likely have a similar duration and would be based upon resources and the
availability of manufacturing time at the initiation of the project.

 

18

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