Exhibit 10.1


 


***Text Omitted and Filed
Separately

Confidential Treatment Requested

Under 17 C.F.R. §§ 200.80(b)(4),

200.83 and 240.24b-2


 


FIRST AMENDMENT TO 

LICENSE AGREEMENT


 


This First Amendment (the
“Amendment”) to the License Agreement
dated March 1, 2004 (the “Agreement”) by and between: (a) on the one hand, Shire BioChem Inc. (“SBI”), a corporation organized and
existing under the laws of Canada and wholly-owned subsidiary of Shire, having
its principal office at 275 Armand-Frappier Boulevard, Laval, Quebec,
Canada H7V 4A7; and (b) on the other hand, Maxim Pharmaceuticals, Inc. (“Maxim”),
a corporation incorporated and existing under the laws of the State of
Delaware, having its principal office at 8899 University Center Lane, Suite
400, San Diego, California 92122, U.S.A, and Cytovia, Inc. (“Cytovia”), a
corporation incorporated and existing under the laws of the State of Delaware
and a wholly-owned subsidiary of Maxim, having the same principal office as
Maxim (Maxim and Cytovia are hereinafter collectively referred to as “MPI”), is entered
into as of January 26th, 2005 (the “Amendment Date”).  Capitalized terms used but not otherwise
defined herein shall have the meanings provided in the Agreement.


 


Whereas,
the parties wish to amend certain provisions of the Agreement, subject to the
terms and conditions set forth herein.


 


Now, Therefore,
in consideration of the foregoing premises and the mutual covenants contained
herein and other good and valuable consideration, the receipt and sufficiency
of which are hereby acknowledged, the parties agree as follows:


 


1.             Amendment to Section 5.1.  Section 5.1 of the Agreement is
hereby amended and restated to read in its entirety as follows:


 


5.1          Clinical
Trial, Regulatory Approval and Commercialization Milestone Payments.  MPI shall make payments to SBI in U.S.
dollars as set forth within the table below within thirty (30) days after the
achievement of each of the respective clinical trial, regulatory approval, and
commercialization milestones by MPI or its Affiliate in a Major Market where
MPI has not granted development or commercialization rights with respect to
Products to any Sublicensee, provided that, [...***...] shall [...***...] be payable under this Section 5.1 (i.e., the maximum amount that may be
payable pursuant to this Section 5.1 is [...***...],
notwithstanding the total number of Products developed or indications pursued
or approved or the number of Major Markets in which any Product is developed or
approved; and (ii) in the event that a Product shall be discontinued after
any milestone shall have been paid, such milestone shall be credited against
the milestone due for any Product subsequently pursued.  In the event that a subsequent milestone
shall be triggered where a prior milestone has not been triggered (for example,
Phase III trials shall be initiated without prior initiation of Phase II
trials), then both milestones shall be payable upon the happening of the
subsequent milestone.  For purposes of
clarification, if any of the milestones set forth in this Section 5.1 is
achieved by a Sublicensee, no milestone payment shall be due under this
Section 5.1 with respect thereto.


 










*Confidential Treatment Requested


 


1





















 


	
  MILESTONE

  	
   

  	
  PAYMENT

  
	
   

  	
   

  	
   

  
	
  1.  First dosing of a human subject with a
  Product in a Major Market

  	
   

  	
  [...***...]

  
	
   

  	
   

  	
   

  
	
  2.  Initiation of a Phase II Clinical Trial of a
  Product in a Major Market

  	
   

  	
  [...***...]

  
	
   

  	
   

  	
   

  
	
  3.  Initiation of a Phase III Clinical Trial of
  a Product in a Major Market

  	
   

  	
  [...***...]

  
	
   

  	
   

  	
   

  
	
  4.  Fist NDA filing for a Product in a Major
  Market

  	
   

  	
  [...***...]

  
	
   

  	
   

  	
   

  
	
  5.  First commercial sale of a Product in a
  Major Market

  	
   

  	
  [...***...]

  



 


2.             Amendment to Section 5.2.  Section 5.2 of the Agreement is
hereby amended and restated to read in its entirety as follows:


 


5.2          Royalties.  In all countries of the Territory in which
there exists a Valid Patent Claim that would, but for the license granted
hereunder or under the Agreement, be infringed by the manufacture, use or sale
of the Product as commercialized by MPI or its Affiliate (so long as any claim
covering manufacture excludes others from selling the Product as commercialized
by MPI or its Affiliate in the country in question), MPI shall pay to SBI
(subject to the remaining terms and conditions of this Section 5.2)
following Launch a royalty of [...***...] of
Net Sales of the Product by MPI and its Affiliates (but not by Sublicensees)
for so long as such a Valid Patent Claim shall exist in such country.  In all other countries, MPI shall pay to SBI
a royalty of [...***...] of Net Sales
of the Product by MPI and its Affiliates (but not by Sublicensees), for a
maximum of ten (10) years following Launch. 
In addition, such [...***...] royalty
shall also apply with respect to a Product for the remainder of such ten (10)
year period in any country where such a Valid Patent Claim covering
manufacture, use or sale of such Product as commercialized by MPI or its
Affiliate has expired prior to such ten (10) year period.


 


5.2.1       However, if the Valid Patent Claim arises
from a pending patent application, then payments at the 

[...***...] royalty level shall only
be required for a period of five (5) years from first publication, or, in those
countries where governmental agencies do not publish patent applications, for a
period of five (5) years from filing.  In
the event that the said patent application does not mature into an issued
patent within this five (5) year period of time, such a patent claim will no
longer be deemed a Valid Patent Claim and SBI shall refund (or in lieu of such
refund, MPI may set off such amount against any payments owed by MPI to SBI)
one-half of any corresponding payments made at the [...***...] royalty rate so as to yield the rate of [...***...] of Net Sales of Product set forth
above for countries where there is no Valid Patent Claim.  In the event that SBI opts for a set-off
rather than an immediate refund of amounts owed to MPI, the amount owed shall
accrue interest from the date due, and thus the set-off shall also


 










*Confidential Treatment Requested


 


2





















 


include such interest to be computed for such unpaid amount on the last
day of each calendar quarter (accruing quarterly) at the prime or other
equivalent rate of Citibank for the last day of the calendar quarter, or the
highest interest rate permissible under applicable law, whichever is
lower.  In the event that a Valid Patent
Claim covering the Product as commercialized by MPI or its Affiliate shall
issue in a country where royalty was paid at the [...***...] level as a result of pendency of a patent application
for more than five (5) years as provided herein, then MPI shall pay to SBI
(taking into account any refunds made by SBI) the difference between the
royalty payable at the [...***...] level
and that paid at the [...***...] level
for the period of the reduced royalty payments until issue of the Patent,
together with interest on such amount at the prime or other equivalent rate of
Citibank on the last day of each calendar quarter, or the highest interest rate
permissible under applicable law, whichever is lower, until payment of such
amount by MPI.


 


3.             Entire
Agreement.  The Agreement, as amended by this Amendment, embodies the entire
understanding of the parties and shall supersede all previous
communications, representations and understandings, whether oral, written or
otherwise, between the parties relating to the subject matter hereof.  Except
as specifically amended by this Amendment, the terms and conditions of the Agreement shall remain in full force
and effect.


 


4.             Governing
Law.  This Amendment and its
execution, validity and interpretation shall be governed in all respects in
accordance with the laws of the State of New York, the United States of
America, other than its conflict of law rules except for Section 5-1401 of
the New York General Obligations Law. 
The Parties expressly exclude any application of the United Nations
Convention on Contract for the Sale of Goods to this Amendment.


 


5.             Counterparts.  This Amendment may be executed in
counterparts, each of which shall be deemed an original document, and all of
which, together with this writing, shall be deemed one instrument.


 










*Confidential Treatment Requested


 


3





















 


In Witness Whereof,
the parties hereto have duly executed this Amendment as of the Amendment Date.


 


	
  Maxim
  Pharmaceuticals, Inc.

  	
   

  	
  SHIRE BIOCHEM Inc.

  
	
   

  	
   

  	
   

  	
   

  	
   

  	 

	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Larry G. Stambaugh

  	
   

  	
  By:

  	
  /s/ Claude Perron

  	
   

  
	
  Name:

  	
  Larry G. Stambaugh

  	
   

  	
  Name:

  	
  Claude Perron

  	
   

  
	
  Title:

  	
  Chairman and President

  	
   

  	
  Title:

  	
  Vice President and General Manager

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  Cytovia, Inc.

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  
	
  By:

  	
  /s/ Larry G. Stambaugh

  	
   

  	
   

  	
   

  
	
  Name:

  	
  Larry G. Stambaugh

  	
   

  	
   

  	
   

  
	
  Title:

  	
  Chairman and President

  	
   

  	
   

  	
   

  
							



 


4