**Exhibit 10.1**

 

*****Text Omitted and FiledSeparatelyConfidential Treatment RequestedUnder 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 andexisting under the laws of Canada and wholly-owned subsidiary of Shire, havingits 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 ofDelaware, having its principal office at 8899 University Center Lane, Suite400, San Diego, California 92122, U.S.A, and **Cytovia, Inc.** (***“Cytovia”***), acorporation incorporated and existing under the laws of the State of Delawareand a wholly-owned subsidiary of Maxim, having the same principal office asMaxim (Maxim and Cytovia are hereinafter collectively referred to as ***“MPI”***), is enteredinto as of January 26th, 2005 (the ***“Amendment Date”***).  Capitalized terms used but not otherwisedefined herein shall have the meanings provided in the Agreement.

 

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

 

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

** **

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

 

**5.1****          ClinicalTrial, 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 theachievement of each of the respective clinical trial, regulatory approval, andcommercialization milestones by MPI or its Affiliate in a Major Market whereMPI has not granted development or commercialization rights with respect toProducts to any Sublicensee, *provided that*, **[...***...]**shall **[...***...]**be payable under this Section 5.1 (*i.e.*, the maximum amount that may bepayable pursuant to this Section 5.1 is **[...***...]**,notwithstanding the total number of Products developed or indications pursuedor approved or the number of Major Markets in which any Product is developed orapproved; and (ii) in the event that a Product shall be discontinued afterany milestone shall have been paid, such milestone shall be credited againstthe milestone due for any Product subsequently pursued.  In the event that a subsequent milestoneshall be triggered where a prior milestone has not been triggered (for example,Phase III trials shall be initiated without prior initiation of Phase IItrials), then both milestones shall be payable upon the happening of thesubsequent milestone.  For purposes ofclarification, if any of the milestones set forth in this Section 5.1 isachieved by a Sublicensee, no milestone payment shall be due under thisSection 5.1 with respect thereto.

 

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| **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 ishereby amended and restated to read in its entirety as follows:

 

**5.2****          Royalties.**  In all countries of the Territory in whichthere exists a Valid Patent Claim that would, but for the license grantedhereunder or under the Agreement, be infringed by the manufacture, use or saleof the Product as commercialized by MPI or its Affiliate (so long as any claimcovering manufacture excludes others from selling the Product as commercializedby 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 **[...***...]**ofNet 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 SBIa royalty of **[...***...]**of Net Salesof the Product by MPI and its Affiliates (but not by Sublicensees), for amaximum of ten (10) years following Launch. In addition, such **[...***...]**royaltyshall 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 coveringmanufacture, use or sale of such Product as commercialized by MPI or itsAffiliate has expired prior to such ten (10) year period.

 

**5.2.1****      **However, if the Valid Patent Claim arisesfrom a pending patent application, then payments at the **[...***...]**royalty level shall onlybe required for a period of five (5) years from first publication, or, in thosecountries where governmental agencies do not publish patent applications, for aperiod of five (5) years from filing.  Inthe event that the said patent application does not mature into an issuedpatent within this five (5) year period of time, such a patent claim will nolonger be deemed a Valid Patent Claim and SBI shall refund (or in lieu of suchrefund, 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 forthabove for countries where there is no Valid Patent Claim.  In the event that SBI opts for a set-offrather than an immediate refund of amounts owed to MPI, the amount owed shallaccrue interest from the date due, and thus the set-off shall also

 

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include such interest to be computed for such unpaid amount on the lastday of each calendar quarter (accruing quarterly) at the prime or otherequivalent rate of Citibank for the last day of the calendar quarter, or thehighest interest rate permissible under applicable law, whichever islower.  In the event that a Valid PatentClaim covering the Product as commercialized by MPI or its Affiliate shallissue in a country where royalty was paid at the **[...***...]**level as a result of pendency of a patent applicationfor 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 theroyalty payable at the **[...***...]**leveland that paid at the **[...***...]**levelfor 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 ofCitibank on the last day of each calendar quarter, or the highest interest ratepermissible under applicable law, whichever is lower, until payment of suchamount by MPI.

 

**3.****             EntireAgreement. **The Agreement, as amended by this Amendment, embodies the entireunderstanding of the parties and shall supersede all previouscommunications, representations and understandings, whether oral, written orotherwise, between the parties relating to the subject matter hereof.  Exceptas specifically amended by this Amendment, the terms and conditions of the Agreement shall remain in full forceand effect.

 

**4.****             GoverningLaw. **This Amendment and itsexecution, validity and interpretation shall be governed in all respects inaccordance with the laws of the State of New York, the United States ofAmerica, other than its conflict of law rules except for Section 5-1401 ofthe New York General Obligations Law. The Parties expressly exclude any application of the United NationsConvention on Contract for the Sale of Goods to this Amendment.

 

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

 

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**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 |                   |   |   |
|                                  |                        |                        |  |  |  |  |

 

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