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Exhibit 10.15    
    


 
 

LICENSE AND SUPPLY AGREEMENT    
    By and Between    
    GENTIUM S.p.A.    
    AND    
    SIGMA-TAU INDUSTRIE FARMACEUTICHE RIUNITE SpA    
    Dated as of December 7th, 2001    









 
 
 

TABLE OF CONTENTS    
    



	SECTION I—DEFINITIONS	 	4
	

SECTION II—LICENSE	
 	

7
	2.1	 	License Grant	 	7
	2.2	 	Trademarks	 	7
	2.3	 	Development	 	8
	2.4	 	Reservation of Ownership	 	8
	2.5	 	Gentium Know-How	 	8
	

SECTION III—DEVELOPMENT	
 	

8
	3.1	 	Development Activities	 	8
	3.2	 	Cooperation	 	8
	3.3	 	Variations	 	9
	3.4	 	Discontinuation	 	9
	

SECTION IV—REGULATORY MATTERS	
 	

10
	4.1	 	Regulatory Matters	 	10
	4.2	 	Manufacturing Facilities	 	10
	4.3	 	Meetings	 	10
	4.4	 	Clinical Studies	 	10
	

SECTION V—CONSIDERATION	
 	

10
	5.1	 	ST's Contribution in the Development	 	10
	5.2	 	Licensing Fee	 	11
	5.3	 	Royalty Payments	 	11
	5.4	 	Inspection	 	11
	

SECTION VI—MARKETING	
 	

11
	6.1	 	Marketing Obligation	 	11
	6.2	 	Recalls and Other Remedial Actions	 	12
	6.3	 	Safety Agreement	 	12
	6.4	 	Compliance with Law	 	12
	

SECTION VII—PROMOTIONAL MATERIAL AND PRODUCT PACKAGING	
 	

13
	7.1	 	Promotional Materials; Promotion of Finished Product	 	13
	7.2	 	Product Packaging	 	13
	7.3	 	Quality Audit	 	13
	

SECTION VIII—SUPPLY	
 	

14
	8.1	 	Finished Product Supply	 	14
	8.2	 	Terms of Sale	 	14
	8.3	 	Forecasts	 	14
	8.4	 	Finished Product Quality Control	 	14
	8.5	 	Inspection of Finished Product Shipped	 	15
	

SECTION IX—NEW PRODUCT	
 	

15
	9.1	 	Development of the New Product	 	15
	9.2	 	First Refusal Right	 	15
	

SECTION X—TERM AND TERMINATION	
 	

16
	10.1	 	Term	 	16
	10.2	 	Termination; General	 	16
	10.3	 	Survival of Obligations	 	17
	10.4	 	Effect of Termination	 	17
	 	 	 	 	 



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SECTION XI—CONFIDENTIAL INFORMATION	
 	

17
	11.1	 	Confidential Information	 	17
	11.2	 	Injunctive Relief	 	18
	11.3	 	Publication	 	18
	

SECTION XII—DISPUTE RESOLUTION	
 	

18
	12.1	 	Dispute Resolution	 	18
	12.2	 	Jurisdiction	 	19
	

SECTION XIII—REPRESENTATION AND WARRANTIES	
 	

19
	13.1	 	Intellectual Property	 	19
	13.2	 	Gentium Indemnification	 	20
	13.3	 	ST Indemnification	 	20
	13.4	 	Disclaimer	 	20
	

SECTION XIV—MISCELLANEOUS	
 	

20
	14.1	 	Governing Law	 	20
	14.2	 	Waiver	 	20
	14.3	 	Notices	 	21
	14.4	 	Force Majeure	 	21
	14.5	 	Entire Agreement	 	21
	14.6	 	Amendments	 	21
	14.7	 	Headings	 	21
	14.8	 	Severability	 	21
	14.9	 	Registration and Filing of the Agreement	 	22
	14.10	 	Assignment	 	22
	14.11	 	Successors and Assigns	 	22
	14.12	 	Counterparts	 	22
	14.13	 	Third-Party Beneficiaries	 	22
	14.14	 	Relationship of the Parties	 	22
	14.15	 	LIMITATION OF DAMAGES	 	22
	14.16	 	Taxes	 	23
	14.17	 	Payment Currency	 	23
	

Schedule 1—Patent	
 	

24
	Schedule 2—ST's Contribution in the Development	 	25
	Schedule 3—Development Activities	 	26
	Schedule 4—Tasks and Works for FDA's Approval of Gentium's Plant	 	27
	Schedule 5—Supply Price and Terms	 	28
	Schedule 6—Product Specifications	 	29




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LICENSE AND SUPPLY AGREEMENT    
    


        THIS AGREEMENT ("Agreement"), dated as of December 7th, 2001 (the "Effective Date"), by and between Gentium
S.p.A, a corporation organized under the laws of Italy and having a principal place of business at Piazza XX Settembre, 2, Villa Guardia (Como), Italy, capital stock Euro
5.000.000.- fully paid-up, registered with the Company register of Como No 29927, Fiscal Code and VAT Code No. 02098100130("Gentium"), and  Sigma-Tau Industrie Farmaceutiche Riunite SpA, a
corporation organized under the laws of Italy and having its registered offices at Viale
Shakespeare 47, 00144 Rome, Italy, capital stock Euro 15.860.000 fully paid-up, registered with the Company register of Rome No 1468/57, Fiscal Code No. 00410650584 and VAT Code
No. 00885531004 ("ST") (with each of Gentium and ST referred to herein individually as a "Party" and collectively as the "Parties"). 


        WHEREAS,
Gentium and its Affiliates have certain rights in the Territory in and to the Compound, which enable Gentium to make, have made, use, and sell the Product; 


        WHEREAS,
Gentium and its Affiliates desire to cooperate with ST to Market the Product in the Territory; 



        WHEREAS,
ST possesses expertise in the development and marketing of pharmaceutical products through its R&D and technical operations department as well as its Affiliates' sales
representatives and sales channels in the Territory; 


        NOW,
THEREFORE, in consideration of the following mutual promises and obligations, and for other good and valuable consideration, the adequacy and sufficiency of which are hereby
acknowledged, the Parties agree as follows: 


 
 

SECTION I—DEFINITIONS    
    


        Capitalized terms used in this Agreement, whether used in the singular or plural, except as expressly set forth herein, shall have the meanings set forth below: 


	1.1
	"Affiliate" shall mean, with respect to any Person, any other Person which controls, is controlled by, or is under common control with
such Person. A Person shall be deemed to control another Person if such Person possesses, directly or indirectly, the power to direct or cause the direction of the management and policies of such
Person, whether through the ownership of voting securities, by contract or otherwise.



	1.2
	"Agreement" shall have the meaning set forth in the introductory paragraph.



	1.3
	"Approval" shall mean the approval, registration, license or authorization from FDA required for the manufacture, Development,
Marketing, sale, storage or transport of the Product in the Territory.



	1.4
	"Business Day" shall mean any day other than a Saturday or a Sunday or any day of the month of August or a day on which commercial
banks either in New York City, NY, USA, or Milan, Italy, are authorized or required by Law to remain closed. "Business Hours" shall mean the time period
encompassed between 9 a.m. and 5 p.m. of a Business Day.



	1.5
	"Compound" shall mean the active ingredient whose International Non-proprietary Name (INN) is defibrotide, including
isomers and polymorphs thereof and salts of the foregoing.



	1.6
	"Confidential Information" shall mean all information or materials possessed or developed by either Gentium or ST or their respective
Affiliates, whether developed before or after the Effective Date, in relation to Development, promotion, marketing, distributing and selling any Product hereunder, including, without limitation,
information or materials on substances, formulations, techniques, technology, equipment, data, reports, Know-How, sources for supply, patent position and business plans;  provided however, that
Confidential Information shall not include information 


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or
material that is (i) already in the public domain as of the Effective Date by reason of prior publication or otherwise; (ii) received by a receiving Party on an unrestricted basis
from a Third Party other than the disclosing Party, where such Third Party is authorized to disclose such information; (iii) part of the public domain after the Effective Date through no act,
omission or fault of the receiving Party; or (iv) similar in nature to the purported confidential information but has been independently created. 



	1.7
	"Develop" shall mean to engage in research or development activities (including, without limitation, clinical trials) or to have any of
those activities performed, and "Development" shall have a corresponding meaning.



	1.8
	"Effective Date" shall have the meaning set forth in the introductory paragraph.



	1.9
	"FDA" shall mean the United States Food and Drug Administration and any successor agency thereto.



	1.10
	"Finished Product" shall mean Product which has been formulated, finished and secondarily packaged by Gentium (or its designated Third
Party(ies) manufacturer(s)) in accordance with the Product Specifications. Once the relevant first refusal right leads to a licence agreement for any New Product, such New Product will be deemed to be
included in this definition of Finished Product.



	1.11
	"Force Majeure" shall have the meaning set forth in Article 14.4.



	1.12
	"Good Manufacturing Practices" or "GMP" shall mean current Good Manufacturing Practices (including without limitation good
distribution practices and guidelines) as such term is defined from time to time by the FDA or other relevant Governmental Authority having jurisdiction over the manufacture, distribution or sale of
the Product in the Territory or where the Product is manufactured pursuant to its regulations, guidelines or otherwise.



	1.13
	"Governmental Authority" shall mean any court, agency, authority, department, regulatory body or other instrumentality of any
government or country or of any national, federal, state, provincial, regional, county, city or other political subdivision of any such government or any supranational organization of which any such
country is a member.



	1.14
	"IND" shall mean an Investigational New Drug Application filed with the FDA including but not limited to the case where a new drug is
designated as an "orphan drug" under Federal and State Laws applicable in the U.S.A..



	1.15
	"Know-How" shall mean any and all proprietary technical information, know-how, data, test results, knowledge,
techniques, discoveries, inventions, specifications, designs, regulatory filings, and other information (whether or not patentable) which are now or hereafter during the Term owned, licensed or
otherwise held by a Party or its Affiliates with the rights to license or sublicense the same and that relate to the Product or the Development, manufacture, use, offer for sale or sale thereof.



	1.16
	"Law" shall mean all laws, statutes, rules, regulations, orders, judgments, injunctions and/or ordinances of any Governmental
Authority.



	1.17
	"Market"/"Marketing" shall mean the distribution, sale and marketing of the Finished Product, supplied by Gentium or its designated
Affiliate, which is to be conducted independently and under the Trademark by ST or a ST Affiliate in the Territory in accordance with the terms and conditions of this Agreement.



	1.18
	"NDA" shall mean a New Drug Application filed with the FDA, including but not limited to the case where a new drug is designated as an
"orphan drug" under U.S. Federal and State Laws. 


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	1.19
	"Net Sales" shall mean the invoice price billed by ST or its Affiliates to Third Parties on sales of the Finished Product in bona fide
arm's length transactions, less value added or excise taxes of a similar nature paid on the sale of the Finished Product. Sales from ST or its Affiliates to their Affiliates shall be excluded from the
calculation of Net Sales until the sale by the Affiliate to unaffiliated third party, at which time Net Sales shall be calculated as if ST had made such sale to the unaffiliated third party on the
same terms as the sale by the Affiliate.



	1.20
	"New Product" shall mean (a) any pharmaceutical form of the Product other than "intravenous"; (b) a pharmaceutical
product containing the Compound as the active ingredient and intended for: (i) the prophylaxis of veno-occlusive disease; or (ii) the mobilisation of hematopoietic
progenitors/stem cells.



	1.21
	"Packaging Specifications" shall mean the specifications as determined by the Parties for the packaging of the Product, such
specifications to comply with all applicable current Good Manufacturing Practices, all applicable requirements necessary for FDA Approval, and any other such applicable Laws.



	1.22
	"Party" shall have the meaning set forth in the introductory paragraph.



	1.23
	"Patent" shall mean any of the issued patents and patent applications listed in Schedule 1, until such issued patents and
patent applications have not been declared invalid in the Territory in a final nonappellable order, which, for purposes of this Agreement, shall include reissue patents, patent term extensions,
supplementary protection certificates, re-examination certificates and the like, and also any other patent applications and patents which will be licensed to or owned by Gentium or its
Affiliates during the Term and that contains at least one claim that encompasses or embraces the Compound per se or a process for production relating to the Compound or a use of the Compound.



	1.24
	"Patent Rights" shall mean those rights of Gentium and its Affiliates under the Patents.



	1.25
	"Person" shall mean and include an individual, partnership, joint venture, limited liability company, a corporation, a firm, a trust,
an unincorporated organization and a government or other department or agency thereof.



	1.26
	"Product" shall mean a pharmaceutical product in intravenous formulation containing Compound as the active ingredient and intended
only for the treatment of hematopoietic stem cell transplant patients with hepatic veno-occlusive disease.



	1.27
	"Product Launch" shall mean, with respect to the Territory, the first date of commercial sale of Product (including sale for Treatment
IND once the Net Sales of the Product have reached US$ 500,000 or after six months from the first sale for Treatment IND, whichever comes first) to Third Parties in the Territory.



	1.28
	"Product Specifications" shall mean the specifications for the Product, such specifications to comply with all applicable current Good
Manufacturing Practices, all applicable requirements for Approval. The Product Specifications shall be completed upon Approval and included in Exhibit 6 hereof. Gentium may modify the Product
Specifications from time to time, subject to Approval and Good Manufacturing Practices.



	1.29
	"Promotional Material" shall have the meaning set forth in Article 7.1.



	1.30
	"Safety Agreement" shall have the meaning set forth in Article 6.4.



	1.31
	"Term" shall have the meaning set forth in Article 10.1.



	1.32
	"Territory" shall mean the United States of America.



	1.33
	"Third Party" shall mean any Person other than Gentium or ST or any Affiliate of either Party. 


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	1.34
	"Trademark" shall mean the trademark or such other trademarks, trade names, logos, trade dress and/or indicia of origin owned by
Gentium or any of its Affiliates, which are licensed to ST pursuant to Articles 2.2(a) and (b) for the purpose of identifying the Finished Product to be marketed by ST or its Affiliates in
Territory.



	1.35
	"Treatment IND" shall mean the treatment use of an investigational new drug pursuant to US 21 CFR § 312.34. 


 
 

SECTION II—LICENSE    
    


        2.1    License grant.    



        Subject
to the terms of this Agreement, including without limitation Article 9.2.2, the exceptions set forth in Article 2.4 below and the rights retained by Gentium and its
Affiliates hereunder in connection with the Product, Gentium grants to ST, for the Term, the exclusive, non-transferable, non divisible licence under the Patent Rights and the
Know-How to Market the Finished Product in the Territory, with the right to sub-license its rights to one of its Affiliates in the Territory. 


        2.2    Trademarks.    



        (a)   All
packaging, labelling, advertising and Promotional Material used in connection with Marketing the Finished Product by ST shall feature the Trademark. ST shall not
(i) use more than one trademark in connection with the Finished Product in the Territory, (ii) sell the Finished Product under its generic name, or (iii) use any trademark which
is confusingly similar or is a colorable imitation of the Trademark. 


        (b)   For
the purpose of the Article 2.2(a), Gentium, subject to Article 9.2.2, shall grant ST in the Territory exclusive, non-transferable, non
divisible license to use such Trademark in the Territory during the Term in connection with the Finished Product for purposes of this Agreement. 



        (i)    ST
acknowledges that it will acquire no rights to Trademark or any other Gentium trademark by virtue of its use, or the use by its Affiliates, of the Trademark or any
such Gentium trademark pursuant to this Agreement. Gentium shall own and retain all rights to association of trademark, service marks, copyrights, or goodwill associated therewith, and all use of a
Trademark by ST (or its Affiliate sublicensees) shall, at all times, inure to the benefit of Gentium. ST hereby agrees to use the Trademark solely in a manner that does not deleteriously affect the
rights of Gentium. All uses of the Trademark or any Gentium trademark by ST shall comply with applicable Law. 



        (ii)   ST
shall, upon request from Gentium, assist Gentium in any action reasonably necessary or desirable to protect Gentium's rights in the Trademark used or intended to be
used hereunder by ST in the Territory. 


        (iii)  Upon
request by Gentium, ST shall execute such documents as may reasonably be required by Gentium for the purpose of recording any license granted under this
Article 2.2 with any Governmental Authority. 


        (iv)  If
either Party or its Affiliates learn of a claim or assertion that the use of the Trademark infringes or otherwise violates the intellectual or industrial property
rights of any Third Party or that any Third Party violates the intellectual or industrial property rights of Gentium or its Affiliates in the Trademark, then the Party (or its Affiliate) becoming so
informed shall promptly, but in all events within ten (10) calendar days thereof, notify the other Parties to this Agreement of this claim or assertion. At its sole discretion, Gentium shall
conduct all infringement actions relating to the Trademark at its own expense and shall be entitled to any and all damages, costs and fees awarded and any amounts paid in settlement as a result of
such action. ST and its 



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Affiliates
shall assist Gentium and cooperate in any such infringement litigation at Gentium's reasonable request. 


        (v)   If
so requested in writing by Gentium, ST shall discontinue the use of the Trademark or any other Gentium trademark upon notice that such use is, on a good faith and
documented basis, an infringement of such Third Party's rights. All liability arising out of ST's continuing use of the Trademark or any other Gentium trademark shall be borne by ST. In such an event,
ST and Gentium shall attempt in good faith to agree on a new Trademark that is acceptable to both Parties for use in the Territory. 


        (vi)  Each
Party shall retain all right, title and interest in and to its respective corporate logos. 




        2.3    Development    


        Without
prejudice to Article 4.4 hereof, during the Term, ST shall not engage in any Development activities, including, without limitation, clinical trials, with respect to the
Product without the express prior written consent of Gentium; for Phase IV clinical trials the need of Gentium's consent will be limited to the relevant protocol. Nothing in this Agreement shall be
deemed to be an express or implied license under any of Gentium's intellectual property to undertake any such Development activities. 


        2.4    Reservation of Ownership.    


        Except
for rights specifically granted to ST in this Agreement, Gentium shall own and retain all right title, and interest in the Compound, Product, the Patent Rights, the Trademark, any
Know-How developed by Gentium pursuant to, or prior to, this Agreement, and all rights not specifically granted herein to ST. 


        2.5    Gentium Know-How.    


        Gentium
shall periodically disclose to ST in a timely manner in order to permit the purpose of this Agreement to be fully realized, its Know-How, and other information in its
possession or control relating to the Compound and the Product, and which it may lawfully disclose. Gentium shall also provide reasonable technical assistance to ST to permit ST to use the
Know-How. 


        During
the Term, ST shall inform Gentium in writing of any Know-How developed by ST or its Affiliates ("ST Know-How"). ST agrees to grant Gentium an exclusive but
for ST license to use the ST Know-How worldwide except, during the Term, the Territory, with the right to sublicense. Such license shall be royalty-free, unless the ST
Know-How is patentable, in which case the Parties shall negotiate in good faith the relevant terms and conditions for the grant of said license. 


 
 

SECTION III—DEVELOPMENT    
    


        3.1    Development Activities    


        Gentium
shall use all commercially reasonable efforts to continue the Development of the Product in accordance with the timing set forth in Schedule 3 hereof, provided however
that Gentium shall have reasonable flexibility in conducting the Development of the Product and in committing to it its resources. The Parties shall consult each other on a regular basis to check the
progress made on the activities listed in Schedule 3. Gentium shall be excused from any delay in completion of a stage due to an action or failure by ST or to any action or failure to act by
FDA or any other Governmental Authority whose Approval is reasonably necessary to permit Gentium to perform its activities. 


        3.2    Cooperation    


        ST
shall actively cooperate with Gentium for the Development of the Product providing its expertise and allocating to said cooperation appropriate resources. Each Party shall nominate a
Person 


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who
shall be responsible for coordinating all activities and matters arising from the Development of the Product and to whom all reports, information, instructions and other communications from either
Party shall be addressed. ST shall have the right at any time to have its representatives observe said activities and documents of Gentium relating thereto at Gentium premises upon prior reasonable
notice during Business Hours, and Gentium shall seek ST's previous agreement on the plan, milestones and schedule of the Development of the Product and on the relevant submissions to FDA or any other
Governmental Authority. Any disagreement which could not be resolved by the Persons responsible for the coordination of the Development work, shall be referred to the senior management of the Parties. 


        3.3    Variations    


        Either
Party shall promptly inform the other Party as soon as it becomes aware of any event which is likely to cause a variation or materially impair the continuation of the Development
of the Product. If such event (including but not limited to unforeseen requests by FDA or any other Governmental Authority), notwithstanding the exercise of due care, is likely to cause a material
increase of the budget allocated for the Development of the Product and/or the schedule thereof, the Parties shall discuss in good faith a revision of the Development plan and the terms and conditions
of this Agreement (including but not limited to the Consideration provided for in Section V). In the event that the Parties shall not agree upon the continuation of the Development of the
Product within thirty (30) Business Days of the starting of the negotiation, each Party shall have the right to terminate this Agreement by thirty (30) days written notice to the other
Party. 


        3.4    Discontinuation.    



        The
failure to meet an estimated completion date shall not constitute a breach of this Agreement if Gentium is using all reasonable efforts to complete a stage. However, in the event
that (i) Gentium unilaterally discontinues the Development of the Product; or (ii) this Agreement is terminated pursuant to Article 3.3 above; and Gentium, within
thirty-six (36) months of the termination resumes the Development of the Product, substantially availing itself of the stages previously completed, either independently or with a
Third Party, then Gentium shall promptly reimburse ST for all sums paid by ST according to Article 5.1 hereof, increased by the interest calculated at the Italian legal rate from the dates of
each payment. Gentium shall promptly notify ST of its decision(s) to discontinue or resume the Development of the Product and shall provide ST with any and all documentation reasonably necessary to
competently prove such discontinuation and resuming. 


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SECTION IV—REGULATORY MATTERS    
    


        4.1    Regulatory Matters.    


        Gentium
(through its Affiliates as appropriate) shall use all reasonable efforts in order to obtain, in its own name and at Gentium's expense, all Approvals necessary for Marketing the
Product in the Territory, including the IND, according to the timing set forth in Schedule 3 hereto. All Approval applications, Approvals, supporting documentation and data relating to the
Product shall be deemed the property of Gentium or its designated Affiliate and shall be treated by the Parties and their respective Affiliates as Confidential Information of Gentium. Gentium, subject
to Article 9.2.2, hereby grants to ST an exclusive, non transferable, non divisible, license to use any Approval obtained by Gentium in the Territory for purposes of this Agreement. 


        4.2    Manufacturing facilities.    


        The
Parties acknowledge that the Approval by FDA of the Gentium plant in Villa Guardia (Como), Italy, which will be obtained and maintained by Gentium in its own name and at its own
expenses, is part of the Approvals. Schedule 4 outlines the tasks and the works concurrently envisaged by the Parties, on a good faith and basis in order to obtain Approval of the Gentium
plant. Gentium shall use all reasonable efforts to complete said tasks and works consistently with Schedule 3 and the provisions of Article 3.1 and shall keep ST timely and properly
informed of such activities. Gentium shall be excused from any delay in completion of a task or work due to an action or failure to act by ST or to any action or failure to act by FDA or any other
Governmental Authority whose Approval is reasonably necessary to permit Gentium to perform said task and works. The failure to meet an estimated completion date shall not constitute a breach of this
Agreement if Gentium is using all reasonable efforts to complete a task or work. Article 3.4 shall apply, mutatis mutandis, to the tasks and
works outlined in Exhibit 4. 


        4.3    Meetings.    


        In
the event that ST or Gentium or any of their respective Affiliates receive any request from a Governmental Authority for a meeting, conference or discussions concerning the Product,
or any
Approval application or Approval relating to the Product in the Territory, each Party shall immediately notify the other of such request, and the Parties shall determine and agree upon in good faith
the manner in which the Parties should respond to any such request. It is understood by the Parties that if attendance at any meeting, conference or discussion with a Governmental Authority in the
Territory is strictly limited, attendance shall be based on expertise in relation to the Product. 


        4.4    Clinical Studies.    


        If,
after an Approval is obtained in the Territory, additional clinical studies are required by a Governmental Authority in the Territory or deemed necessary by the Parties, subject to
Article 2.3 hereof, the Parties and their respective Affiliates shall cooperate to perform such studies and shall share the costs of such studies if so agreed by the Parties at the time the
studies become necessary. 


 
 

SECTION V—CONSIDERATION    
    


        5.1    ST's contribution to the Development.    



        In
consideration for and as a contribution to Gentium's initiation of the Development and costs incurred in connection therewith, the sharing of Gentium's technical and clinical data
necessary or useful to conduct same, Gentium generating the Know-How and have its plant approved by the FDA according to Article 4.2 above, the first refusal rights granted under
Article 9.2 below, ST shall pay to Gentium the amounts specified in Schedule 2 hereto on the dates specified therein and, when appropriate, upon receiving the relevant documentation
showing the occurrence. Such payments shall 


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be
non-refundable, subject to the provisions of Article 3.4 hereof. No other compensation or reimbursement, whatsoever shall be due by ST for the Development of the Product. 


        5.2    Licensing Fee.    


        In
consideration of the rights granted hereunder in the Territory for the Product, ST shall pay Gentium a seven percent (7%) royalty on the Net Sales. 


        5.3    Royalty Payments.    



        Royalty
payments shall be determined in United States currency and ST shall pay or cause to be paid to Gentium in United States currency within forty-five (45) days
following the last day of each calendar quarter during the Term, royalties which have accrued to Gentium during such calendar quarter. Each payment shall be accompanied by a reasonably detailed
accounting of the Net Sales, the payment due and ST method of calculating such payment. 


        5.4    Inspection.    


        Gentium
shall have the right, during the Term and for a period of two (2) years following any termination of this Agreement, to have a public accountant, to whom ST has no
reasonable objection, examine the relevant books and records of ST during Business Hours to determine whether appropriate accounting and payment have been made by ST hereunder. ST shall retain any
such books and records for the period of time subject to Gentium's right of inspection. 


 
 

SECTION VI—MARKETING    
    


        6.1    Marketing Obligations.    



        ST
shall commit a commercially reasonable level of resources to promote and sell the Finished Product in the Territory. ST shall refrain, outside the Territory, from seeking actively
customers for the Finished Product by whatever means, and from establishing branches and maintaining any distribution facilities engaged in Marketing the Finished Product. 


        6.2    Recalls and Other Remedial Action.    


        (a)   ST
shall have the right to initiate any recall, withdrawal or other remedial action regarding the Finished Product in the Territory, but only where such recall,
withdrawal or other remedial action is due to or caused by the negligence, misconduct or misrepresentation of ST or any of its Affiliates, or by ST's breach of the terms of, or failure to meet its
obligations under, this Agreement, including, without limitation, with regard to the packaging for transport, transport, storage, distribution and promotion of the Finished Product by ST. 


        (b)   Except
as set forth in Article 6.3(a), Gentium, through its designated Affiliates, as appropriate, shall have the right to initiate any recall, withdrawal or
other remedial action regarding the Product in the Territory. Before Gentium, through its local Affiliates, as appropriate, initiates any recall or withdrawal, the Parties shall immediately discuss in
good faith the reasons therefor. 


        (c)   If
ST is aware that a recall, withdrawal or other remedial action is or may be required in the Territory, ST shall immediately notify Gentium in writing with a
follow-up telephone call. 


        (d)   ST
shall, at all times, maintain an effective tracking system for the Finished Product and an effective system for the recall or withdrawal of the Finished Product in
the Territory. ST shall inform Gentium of such system, which shall be subject to Gentium's approval. 



        (e)   In
the event of a recall, withdrawal or other remedial action, the implementing Party and its Affiliates shall be given any and all necessary assistance by the other
Party and its Affiliates. 


11







 



        (f)    Gentium
shall be responsible for all of the direct and indirect costs of a recall, withdrawal or other remedial action, which is the result of a failure to comply with
Product Specifications due to the negligence or misconduct of Gentium or its Affiliates or is made according to Article 6.3 (b) above. To the extent that the recall is due to or caused
by the negligence, misconduct or misrepresentation of ST or any of its Affiliates, or by ST's breach of the terms of, or failure to meet its obligations under this Agreement (including, without
limitation, with regard to the packaging for transport, transport, storage, distribution and promotion of the Product), ST shall be responsible for all costs associated with the recall. 


        6.3    Safety Agreement.    



        Both
Parties agree to be bound by a Safety Agreement to be agreed between the designated safety representatives of the Parties within four (4) months of the Effective Date. Such
Safety Agreement shall include provisions for post-Approval pharma-covigilance and related post-Approval activities. Each party agrees to give the other any and all necessary
or reasonably requested assistance in order to comply with all post-Approval requirements, including but not limited to, quarterly reports, semi-annual reports and annual
reports, company registration and drug listing. 


        6.4    Compliance with Law.    



        Notwithstanding
anything to the contrary in this Agreement, each Party shall comply (and shall cause its Affiliates to comply) with all applicable Laws, including, without limitation,
all applicable Laws with respect to the Marketing of pharmaceutical products in the Territory. No Party or any of its Affiliates shall be required to undertake any activity which violates, or which it
believes, in good faith, may violate, any Law in the Territory and/or elsewhere. 


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SECTION VII—PROMOTIONAL MATERIAL AND PRODUCT PACKAGING    
    


        7.1    Promotional Materials; Promotion of Finished Product.    



        (a)   ST
will develop its own promotional, advertising, communication and educational materials relating to the Finished Product (collectively, "Promotional Materials")
strictly based on the clinical data for the Product. ST shall bear all of its own costs and expenses of advertising and promotion for the Finished Product in the Territory. ST shall promote the
Finished Product and provide information about the Finished Product as permitted by the Laws of the Territory through the distribution of Promotional Materials. ST nor its Affiliates shall make any
medical claim for the Finished Product beyond the scope of the Approvals then in effect for the Product. 


        (b)   Subject
to the provisions of Article 7.1 (a) above, in order to ensure consistency of Promotional Material with the scientific and clinical profile of the
Product, ST shall only use Promotional Materials which have been approved in writing by Gentium (or its designated Affiliate) as to the accuracy of their technical, scientific and medical content. ST
shall submit to Gentium (or its designated Affiliate) all Promotional Materials before their proposed use. Gentium (or its designated Affiliate) shall be deemed to have approved such Promotional
Materials if it does not raise any objections thereto within 10 (ten) Business Days of submission of the relevant Promotional Materials. In the event that Gentium (or its designated Affiliate) raises
any objection to any Promotional Materials, ST and Gentium (or its designated Affiliate) shall discuss and agree timely in good faith upon appropriate amendments to such Promotional Materials
consistent with the scientific and clinical profile of the Product. 




        7.2    Product Packaging.    



        The
Parties, subject to the Packaging Specifications, shall agree upon and develop the packaging and package inserts for the Finished Product. The Parties agree further that: 



        (a)   Each
Finished Product shall be packaged in accordance with the Packaging Specifications as reflected in the NDA and other Approvals for the Product. 


        (b)   Each
Finished Product shall be packaged in accordance, in all material respects, with all Laws applicable to the packaging of the Product, including, without limitation,
all GMP requirements. ST shall sell the Finished Product and distribute the Finished Product only with labels, printed packaging materials and inserts, the format, content and type (including the
appearance of the relevant Gentium company name as licensor) which shall have been submitted to and approved by Gentium in writing, such approval not to be unreasonably withheld or delayed. 




        7.3    Quality Audit.    


        ST
shall conduct its activities pursuant to this Agreement, including storage and distribution of the Finished Product, in compliance with the Law, the Good Manufacturing Practices and
all FDA post-Approval requirements. ST shall make that all records and reference samples related to the Finished Product, available for inspection by Gentium or its designated Affiliate
during Business Hours. Such inspection shall be announced by Gentium to ST in writing at least two weeks prior to the proposed date of inspection. Records made available for inspection hereunder shall
include records relevant to assessing the quality of a Finished Product in the event of a complaint or a suspected defect. Inspection by Gentium or its designated Affiliate shall be conducted only by
qualified personnel from Gentium or its designated Affiliate and shall be limited to determining whether there is compliance with this Agreement, any Approvals, Good Manufacturing Practices and other
requirements of applicable Laws. ST shall obtain and maintain, all at its cost, all licenses, consents and Approvals of applicable Governmental Authorities or Third Parties necessary or desirable in
connection with its activities. 


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SECTION VIII—SUPPLY    
    


        8.1    Finished Product Supply    



        ST
shall purchase from Gentium all its requirements of Product for Marketing the same in the Territory, according to the terms and conditions set forth in Schedule 5 hereto.
Gentium or its designated Affiliate shall be the exclusive supplier of the Finished Product to ST in the Territory. Gentium undertakes to supply ST with all its requirements of the Finished Product in
the Territory during the Term. The Finished Product supplied to ST will conform to the Product Specifications. 


        8.2    Terms of Sale    



        Gentium
or its designated Affiliate shall supply the Finished Product to ST in the Territory on terms and conditions set forth in Schedule 5 hereto. 


        8.3    Forecasts.    



        (a)   ST
shall deliver to Gentium at the beginning of every month a report which forecasts the requirements of ST for the Finished Product for the next twenty-four
(24) months in quarterly intervals, the portion of the forecast for the immediately upcoming three (3) months being considered a firm commitment. ST shall place firm orders for Finished
Product not later than ninety (90) days prior to the desired delivery date from Gentium in Villa Guardia (Como), Italy. Each order shall be for a number of full batches of Finished Product, the
quantities for any batch to be communicated to ST as soon as available and part batches of Finished Product shall not be ordered by ST unless previously agreed upon between the Parties. 


        (b)   Notwithstanding
anything else in this Agreement, in the event that and so long as Gentium or its designated Affiliate is unable to provide an adequate supply of properly
forecasted amounts of the Finished Product in spite of having acted with documented reasonable diligence to satisfy its supply obligation ("Gentium non-ability"): (i) Gentium shall
immediately notify ST by giving also proper evidence of the reason of such occurrence and Gentium's obligation to supply the Finished Product shall be suspended;  provided, that Gentium shall continue to
exercise reasonable diligence to satisfy its supply obligation by also allocating then-existing
inventory equitably between ST, Gentium and other distributors; (ii) Gentium shall do its best in order to find a timely and proper alternative to Gentium non-ability, leaving
unchanged the economic terms and conditions at which ST will be supplied; (iii) should Gentium be unable to find a proper alternative to or to cure Gentium non-ability within ninety
(90) days of ST receiving the notification above, ST shall have the right to manufacture the Product so long as the Gentium non-ability lasts and ST shall be released from its purchase
obligations under Article 8.1. Provided that Gentium complies with (i) (ii) (iii) above, Gentium shall not be liable for any damages related to, arising out of or in connection
with Gentium non-ability, whether such damages be claimed in tort or contract and whether direct or indirect, special, consequential or otherwise. Notwithstanding the foregoing, under no
circumstances shall Gentium be obligated to deliver the total quantity of Finished Product ordered by ST if such quantity exceeds, by twenty percent (20%) or more, the firm commitment given by ST in
the report sent to Gentium in the immediately preceding quarter, but Gentium shall use all reasonable efforts to supply ST with the quantities exceeding the forecast, provided however that the
quantities exceeding the forecast shall not be considered in determining the Gentium non-ability. 




        8.4    Finished Product Quality Control.    


        Gentium
shall endeavor to provide proper quality assurance and quality control procedures regarding the Finished Product. Gentium, and any Third Party manufacturer or supplier acting on
its behalf, shall retain batch data records and quality control certificates for each batch of the Finished Product and, if requested by ST, will promptly provide such information to ST. Such records
shall be 


14







 



retained
for the longest period required by applicable Law. The Finished Product will be supplied to ST together with the relevant certificate of analysis and any other documentation required so that
the Finished Product is ready for sale. 


        8.5    Inspection of Finished Product Shipped.    



        Within
thirty (30) days after receipt of any shipment of Finished Product, ST will be entitled to check the quantity of Finished Product received and inspect the Finished Product
to verify that it complies with the Product Specifications. In the event the Finished Product supplied by Gentium or its designated Affiliate is less than the quantity ordered or does not conform with
the Product Specifications, ST shall inform Gentium of such fact in writing within thirty (30) days from receipt of the non-conforming Finished Product. Unless such notice relates
to a quantity shortfall, without the prior written consent of Gentium, ST and its Affiliates shall not use the alleged non-conforming Finished Product. Gentium shall replace all such
non-conforming Finished Product free of charge as promptly as practicable. Such replacement cost shall constitute the entire liability of Gentium and its Affiliates for nonconforming
Finished Product. Should Gentium contest any evidence given by ST concerning the non-conformity, both Parties shall immediately and jointly carry out the necessary analysis to verify
whether ST's complaint is justified. In the event the parties are unable to reach an agreement as to ST's complaint, the matter at stake will be submitted to an independent laboratory, chosen by
mutual agreement by the parties, which decision shall be binding and which costs shall be borne by the party who is found at fault. 


 
 

SECTION IX—NEW PRODUCT, FIRST REFUSAL RIGHTS    
    


        9.1    Development of the New Product.    


        Gentium
shall have the right to conduct upon its own initiative the Development of any New Product and shall keep ST timely and accurately informed of any such activity. Gentium shall
discretionally study and review all the available technical, chemical, pharmacological and clinical data and market information relating to the New Product to determine the feasibility and the
prospective of the Development, Approval and manufacture in commercial quantities of the New Product. 


        9.2    First Refusal Right.    


        Gentium
hereby grants to ST exclusive irrevocable rights of first refusal for an exclusive license to Market the New Product in the Territory. Such first refusal right shall be exercised
according to the following terms: 



        9.2.1    Offer.    At any time after the Effective Date, should Gentium decide to offer Marketing rights on the New
Product in the Territory, Gentium shall notify in writing to ST a proposal of an agreement granting ST the relevant license. Such proposal shall include: (a) a description of the then current
status of the Development of the New Product; (b) an outline of the investigations, tasks, and time required to achieve the Approval of the New Product in the Territory; (c) the economic
terms and conditions for the license and supply of the New Product. Gentium hereby agrees that it shall not offer Marketing rights on the New Product in the Territory prior to the lapse of a
12-month period from the Effective Date. 


        9.2.2    Negotiation.    Within thirty (30) days of the notification of the proposal from Gentium pursuant to
Article 9.2.1, Gentium and ST shall engage in good faith discussions in order to negotiate the relevant agreement. In the event the Parties do not reach an agreement within ninety
(90) days of the notification of the proposal from Gentium pursuant to Article 9.2.1, or within the agreed upon extension of said 90-day term, Gentium shall be free to offer
the New Product and the Product to any Third Party provided that such Third Party accepts the same terms and conditions already offered for the New
Product to, and refused by ST. 



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        9.2.3    Within the 60-day period following the expiration of the 90-day period referenced to in
Article 9.2.2 above, ST shall have the right (a) to continue the license granted by Gentium to ST pursuant to Section II and Article 4.1 on a semi-exclusive
basis; or (b) to request that Gentium, upon the execution of the license agreement between Gentium and the Third Party (the "Third Party License Agreement") (which event shall be notified by
Gentium to ST promptly after its occurrence), buy out all Marketing rights then owned by ST or its Affiliate and all business and goodwill associated to the Product ("ST put right"). In the event that
ST does not exercise either the right to continue the license on a semi-exclusive basis or, alternatively, it does not exercise the ST put right, Gentium shall have within the following
60-day period the right to buy out all Marketing rights then owned by ST or its Affiliate and all business and goodwill associated to the Product ("Gentium call right").    


        9.2.4    The price for Gentium's buying out all Marketing rights then owned by ST or its Affiliate and all business and goodwill
associated to the Product shall be determined as follows: (a) the Net Sales of the twelve (12) months preceding the expiration of the 90-day period provided for in
Article 9.2.2 above multiplied by 2.2 (two times point two); or, in the event that the execution of the Third Party License Agreement occurs before a 12-month period from the Launch
has elapsed, (b) the amount of the contribution actually paid by ST pursuant to Article 5.1, increased by the interest calculated at Italian legal rate from the dates of each payment.
Said price shall be paid: (a) in case of the exercise of the Gentium call right, within ten (10) business days of Gentium exercising the Gentium call right; (b) in case of
exercise of the ST put right, upon the first commercial sale of the New Product by the Third Party; provided however that ST shall have the right to continue selling the Product in the Territory and
Gentium shall continue to supply ST with the Product until the first commercial sale of the New Product by the Third Party.    



        If
neither Party exercises the Gentium call right or the ST put right within 120 days of the 90-day term provided above in Article 9.2.2 or any extension
thereof, then ST shall be deemed to have exercised the right to continue the license granted by Gentium to ST pursuant Section II and Article 4.1 on a semi-exclusive basis. 



 
 

SECTION X—TERM AND TERMINATION    
    


        10.1    Term.    



        This
Agreement shall be effective from the Effective Date until: (i) the eighth anniversary of the Product Launch; or (ii) the expiration of the US Patent n. 5,223,609 or
any extension thereof, whichever occurs later. 


        10.2    Termination: General.    


        Subject
to Article 3.3, this Agreement shall be terminable forthwith, upon written notice, if one or more of the following events should occur: 



        (a)   by
either Party, if the other Party commits a material breach of this Agreement that is material to the transactions contemplated by this Agreement, which breach shall
not have been remedied within ninety (90) days from the other Party giving written notice requiring such breach to be remedied; provided, that
any such termination shall be without prejudice to the terminating Party's rights at law, at equity and otherwise; 


        (b)   by
either Party, due to the other Party's negligence, willful misconduct or misrepresentation in connection with this Agreement resulting in material harm to the
terminating Party (or its Affiliates); provided, that any such termination shall be without prejudice to the terminating Party's rights at law, at
equity and otherwise; 



16









  




        (c)   by
either Party, if the other Party or the business of the other Party including, in whole or in part, the activities and the goodwill contemplated by this Agreement, is
assigned or controlled by a Person other than the Person(s) owning or controlling such other Party as of the Effective Date; provided however that this right of termination shall not apply if the
affected Party or the business of such Party remains vested in the individuals or their family members (limited to spouse and direct relatives under Italian Law) who ultimately own or control Gentium
or ST as of the Effective Date. 




        10.3    Survival of Obligations.    



        Notwithstanding
any termination of this Agreement, (a) neither Gentium nor ST shall be relieved of any obligations incumbent upon such Party and already enforceable prior to such
termination, and (b) the obligations of the Parties with respect to the protection and nondisclosure of Confidential Information in accordance with Section XI, as well as other
provisions which by their nature are intended to survive any such termination, shall survive and continue to be enforceable. Upon any termination of this Agreement, Gentium and ST shall, and shall
ensure that their respective Affiliates shall promptly destroy (subject to written certification of the destruction) or return to the other Party all written Confidential Information, and all copies
thereof (except one copy which may be kept in a Party's restricted file for record-keeping purposes only), belonging to such other Party and ST shall have no further right with respect to, and shall
cease all activities related to Marketing of the Product in the Territory. 


        10.4    Effect of Termination.    


        Notwithstanding
any other rights or obligations a Party may have under this Agreement, or under Law, upon termination of this Agreement by Gentium under Article 10.2 above:
(i) all requisite Approvals, authorizations, permits, licenses, filings, registrations; (ii) any Approval applications thereof; and (iii) any other regulatory records obtained
pursuant to this Agreement, in the Territory, shall be assigned to, and exclusively owned by Gentium. The Parties and their Affiliates shall cooperate in informing relevant Governmental Authorities of
the cessation of ST's activities in relation to the Product and use of the Trademark. 


        Upon
termination of this Agreement by ST under Article 10.2, ST shall, at its sole discretion: i) sell to Gentium the Product in ST's inventory at the price paid to Gentium
for the supply for the finished Product; or ii) continue to sell the Product in ST's inventory for a period not exceeding six (6) months. 


        Upon
termination of this Agreement by Gentium under Article 10.2, Gentium shall, at its sole discretion: i) re-purchase the Product in ST's inventory at the
price paid by ST for the supply for the finished Product; or ii) let ST continue to sell the Product in ST's inventory for a period not exceeding six (6) months. 


        Upon
the natural expiry of this Agreement, ST or its Affiliate shall have the right to continue to use the Approvals and the Trademark in the Territory, (a) paying a royalty of
two percent (2%) on the Net Sales; or (b) royalty-free if and as long as the Parties agree on the continuation of the supply
provisions provided for in Section VIII and terms and conditions thereof. 


 
 

SECTION XI—CONFIDENTIAL INFORMATION    
    


        11.1    Confidential Information.    


        (a)   Each
of Gentium and ST acknowledges that all Confidential Information provided by the other Party or its respective Affiliates is confidential and proprietary to such
other Party or its respective Affiliates and agrees to (i) maintain such information in confidence during the Term and any extended Term of this Agreement and for a period of seven
(7) years thereafter and (ii) during the 


17







 



Term,
use such information solely for the purpose of performing its respective obligations hereunder. Each of Gentium and ST covenants that neither it nor any of its respective Affiliates shall
disclose any such information except to its employees, agents or any other Person under its authorization; provided, such employees, agents or Persons
under its authorization are subject in writing to substantially the same confidentiality obligations as the Parties and their respective Affiliates. The foregoing confidentiality obligations shall not
apply to Confidential Information which is required to be disclosed to a Governmental Authority by applicable Law, in which case the disclosing Party shall promptly notify the other Party of such
disclosure and the procedures, such as a protective order, instituted to protect the confidentiality of the Confidential Information to be disclosed. 


        (b)   ST
agrees that prior to dissemination or disclosure by it or any of its Affiliates of any technical or scientific information which may contain Confidential Information
owned or developed by either Party relating to the Compound or the Product it shall provide to Gentium an advance copy of any such proposed publication or dissemination prior to submission for
publication. Gentium shall have a reasonable opportunity to recommend any changes it reasonably believes are necessary to preserve Confidential Information and the incorporation of such recommended
changes shall not be unreasonably refused. If Gentium informs ST, within thirty (30) days of receipt of an advance copy of a proposed publication, that such publication in its reasonable
judgment could be expected to have a material adverse effect on the commercial value of any technical or scientific Confidential Information, then ST shall delay or prevent such publication as
proposed by Gentium. In the case of inventions, the delay shall be sufficiently long to permit the timely preparation and filing of a patent application(s) or application(s) for a certificate of
invention on the information involved. 


        11.2    Injunctive Relief.    


        Each
Party acknowledges that damages resulting from disclosure of the Confidential Information would be an inadequate remedy and that, notwithstanding the provisions of
Section XII, in the event of any such disclosure or any indication of an intent to disclose such information, the Party (or its Affiliates) owning such information shall be entitled to seek, by
way of private litigation, injunctive relief or other equitable relief in addition to any and all remedies available at law or in equity, including the recovery of damages and reasonable attorneys'
fees. 


        11.3    Publication.    


        During
the Term and any extension thereof, Gentium and ST agree not to issue any press releases or public announcements concerning this Agreement (and to ensure that their respective
Affiliates do not do so) without the prior written consent of the other Party to the form, timing and content of any such release or announcement, except as required by a Governmental Authority and
applicable Law. Neither Party shall unreasonably withhold or delay its consent to any such press release or announcement. Except as required by Law or any agreements under which Gentium or its
Affiliates holds the Compound Patent Rights, neither Party (or their respective Affiliates) shall disclose to any Third Party, under any circumstances, any financial terms of this Agreement that have
not been previously disclosed publicly pursuant to this Section XI without the prior written consent of the other Party, which consent shall not be unreasonably withheld or delayed. 


 
 

SECTION XII—DISPUTE RESOLUTION    
    


        12.1    Dispute Resolution.    



        The
Parties agree that, subject to Article 11.2, they, including their Affiliates, as applicable, shall use commercially reasonable efforts to resolve any dispute, controversy or
claim arising out of or relating to this Agreement or the validity, breach, termination or interpretation thereof, by good faith negotiation and discussion. 


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        12.2    Jurisdiction.    



        (a)   Subject
to Article 12.1, in the event that the Parties are unable to resolve any dispute, controversy or claim between the Parties arising out of or relating to
this Agreement or the validity, breach, termination or interpretation thereof, through the procedures described in Article 12.1 above, the dispute, controversy or claim shall be finally settled
by the Court of Milan (Italy), which shall have the exclusive jurisdiction. 


 
 

SECTION XIII—REPRESENTATIONS AND WARRANTIES    
    


        13.1    Intellectual Property.    


        (a)   Gentium
represents and warrants to ST that, as of the Effective Date, (i) to the best of its knowledge, it owns or has all necessary licenses or rights in the
Territory to use the subject matter claimed by any Patent, (ii) to the best of its knowledge, neither the manufacturing of any Product nor the promotion, marketing and sale of any Product by
the Parties in the Territory will infringe upon any valid rights of any other Person and neither Gentium nor any of its Affiliates has received any written notice alleging any such infringement,
(iii) the rights granted to ST hereunder do not, to Gentium' knowledge, conflict with rights granted by Gentium to any Third Party and (iv) neither Gentium nor any of its Affiliates has
received any notice concerning the institution or possible institution of any interference, opposition, reexamination, reissue, revocation or nullification involving any Patent or any administrative
proceeding challenging the validity of any Patent. 


        (b)   In
the event that patent infringement proceedings are commenced by a Third Party against ST or ST's distributors or agents (collectively "Indemnitees") for alleged
infringement by any of them in the Territory of a patent which covers an invention alleged to encompass the manufacture, use or sale of the Product, ST shall notify Gentium promptly of the
commencement thereof. Gentium agrees to defend, indemnify and hold harmless ST from liability to any Third Party for costs (including attorneys' fees) and damages awarded against Indemnitees for such
infringement of said patents of the Third Party, provided Gentium has been given the opportunity to defend such suit at its own expense. This
indemnification and hold harmless provision by Gentium shall in no case exceed an amount equal to the Licensing Fees received by Gentium pursuant to Article 5.2. 


        (c)   If
ST and Gentium should agree (or failing agreement, should an independent patent counsel appointed by Gentium advise) that a patent owned by or licensed to a Third
Party would be infringed by the activities performed by the Indemnitees under this Agreement, then Gentium shall use all reasonable endeavors to obtain at its expense a license under such patent from
the owner or licensee thereof which would enable Indemnitees to continue their activities under this Agreement. Should Gentium not obtain such license for Indemnitees, ST may directly negotiate and
obtain such license from the Third Party, in which event Gentium may credit in full any royalty paid to the Third Party for such license against any amount of royalties Indemnitees would otherwise owe
Gentium under this Agreement. 


        (d)   Each
Party shall promptly notify the other Party of any possible infringement by a Third Party of any Patent Rights. Gentium shall have the right but not the obligation
to commence proceedings in respect to such infringement and agrees to permit ST to join as a co-plaintiff if ST so desires. If Gentium fails to so commence proceedings within ninety
(90) days of infringement's notice, ST shall entitled to prosecute the infringers at its expense and Gentium shall lend ST any reasonable assistance. Recoveries in any patent infringement
proceeding shall be for the benefit of both Parties proportionately to the expenses incurred by each of them in connection with such proceedings. 


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        13.2    Gentium Indemnification.    


        Gentium
shall indemnify ST from all liability to Third Parties or expenses of litigation (including attorneys' fees) resulting from or arising out of (a) clinical trials of the
Product; (b) the negligent or intentionally wrongful acts or omissions of Gentium; (c) the Development, manufacturing, handling, possession or use of the Compound, Product and Finished
Product by Gentium, its Affiliate or its designee, unless such liability arising out of or resulting from this Article 13.2 results from or arises out of (i) the breach or
misrepresentation by ST of its warranties or obligations hereunder or (ii) the negligent or intentionally wrongful acts or omissions by ST. 


        13.3    ST Indemnification.    


        ST
shall indemnify Gentium from all liability to Third Parties or expenses of litigation (including attorneys' fees) resulting from or arising out of (a) promotion, distribution,
sale, handling, possession or use of the Finished Product by ST; (b) the negligent or intentionally wrongful acts or omissions of ST; or (c) the breach or misrepresentation by ST of its
warranties or obligations hereunder; unless such liability arising out of or resulting from this Article 13.3 results from or arises out of (i) the breach or misrepresentation by Gentium
of its warranties or obligations hereunder or (ii) the negligent or intentionally wrongful acts or omissions by Gentium. 


        13.4    Disclaimer.    


        Except
as expressly set forth herein, no Party makes any express or implied warranties, statutory or otherwise, concerning the value, adequacy, freedom from fault of, other quality,
efficiency, stability, characteristics or usefulness of, or merchantability, or fitness for a particular purpose of, any Product; provided,  however,
nothing contained in this Section XIII shall be deemed a waiver of, or be deemed to limit, the obligations of each Party hereunder or
under any other agreement between the Parties. 


 
 

SECTION XIV—MISCELLANEOUS    
    


        14.1    Governing Law.    


        This
Agreement shall be governed by and construed in accordance with the Laws of Italy. 


        14.2    Waiver.    



        Waiver
by a Party of a breach hereunder by the other Party shall not be construed as a waiver of any succeeding breach of the same or any other provision. No delay or omission by a Party
in exercising or availing itself of any right, power or privilege hereunder shall preclude the later exercise of any such right, power or privilege by such Party. No waiver shall be effective unless
made in writing with specific reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the Party granting the waiver. 


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        14.3    Notices.    


        All
notices, instructions and other communications hereunder or in connection herewith shall be in writing, shall be sent to the address of the relevant Party set forth in the
introductory paragraph of this Agreement, and shall be (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent via
a reputable international overnight courier service, or (d) sent by facsimile transmission (except in the case of notices of termination, which should be sent by a, b or c). Any such notice,
instruction or communication shall be delivered in the case of (a) upon receipt, (b) and (c) upon signature of the receipt by the receiving Party, and (d) when transmitted
with electronic confirmation of receipt, if such transmission is on a Business Day, or otherwise, on the next Business Day following such transmission. Either Party may change its address by giving
notice to the other Party in the manner provided above. 


        14.4    Force Majeure.    



        In
the event of strikes, lock-outs or other industrial disturbances, rebellions, mutinies, epidemics, landslides, lightning, earthquakes, fires, storms, floods, sinking,
drought, civil disturbances, explosions, acts or decisions of duly constituted municipal, state or national Governmental Authorities or of courts of Law, as well as impossibility to obtain equipment,
supplies, fuel or other required materials, in spite of having acted with reasonable diligence, or by reason of any other causes, which are not under the control of the Party requesting the abatement
of performance, or causes due to unexpected circumstances which may not be possible to eliminate or overcome with due diligence by such Party ("Force Majeure"), the Parties agree that, if either
Gentium or ST finds itself wholly or partially unable to fulfill its respective obligations in this Agreement by reasons of Force Majeure, the Party affected will advise the other Party in writing of
its inability to perform, giving a detailed explanation of the occurrence of the event which excuses performance immediately after the cause or event has occurred. If such notice is given, the
performance of the Party giving the notification shall be abated, and any time deadlines shall be extended for so long as performance may be prevented by Force Majeure. Subject to Article 8.3
(b), should one party fail to perform and fulfill its obligations stated above for more than ninety (90) consecutive days or more, the parties agree to negotiate in good faith either
(i) to resolve the contingencies or find an alternative solution, if possible; (ii) to extend by mutual agreement the time period to resolve, eliminate, cure or overcome such
contingencies; or (iii) to terminate this Agreement upon the terms and conditions agreed upon at that time. 


        14.5    Entire Agreement.    


        This
Agreement (including Schedules) contains the complete understanding of the Parties with respect to the subject matter hereof and supersedes all prior understandings and writings
relating to the Product. 


        14.6    Amendments.    


        No
provision in this Agreement shall be supplemented, deleted or amended except by a written document duly executed by Gentium and ST. 


        14.7    Headings.    


        Headings
in this Agreement are for convenience of reference only and shall not be considered in construing this Agreement. 


        14.8    Severability.    


        If
any provision of this Agreement is held unenforceable by a court or tribunal of competent jurisdiction because it is invalid or conflicts with any Law of any relevant jurisdiction,
the validity of the remaining provisions shall not be affected. The Parties shall negotiate a substitute provision that, to the extent possible, accomplishes the original business purpose. 


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        14.9    Registration and Filing of the Agreement.    


        To
the extent, if any, that a Party concludes in good faith that it is required to file or register this Agreement or a notification thereof with any Governmental Authority in accordance
with applicable Law, such Party may do so; provided, however, that it provides the other Party with no
less than ten (10) Business Days' written notice of its intent to do so, and discusses in good faith with such other Party its reasons for doing so. In such situation, the Parties will request
confidential treatment of sensitive provisions of this Agreement, to the extent permitted by Law. The Parties shall promptly inform each other as to the activities or inquiries of any such
Governmental Authority relating to this Agreement and shall cooperate to respond to any request for further information therefrom. 


        14.10    Assignment.    


        Except
as otherwise expressly provided herein, neither this Agreement nor any of the rights or obligations hereunder may be assigned by either Gentium or ST without (a) the prior
written consent of ST in the case of any assignment by Gentium or (b) the prior written consent of Gentium in the case of an assignment by ST, except in each case, subject to
Article 10.3(d), to an Affiliate of the assigning Party
or to any other party who acquires all or substantially all of the business of the assigning Party by merger, sale or assets or otherwise, so long as (a) such Affiliate or other Party agrees in
writing to be bound by the terms of this Agreement; and (b) such Affiliate remains an Affiliate of the Assigning Party. Any attempted assignment in violation hereof shall be void. 


        14.11    Successors and Assigns.    


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


        14.12    Counterparts.    


        This
Agreement may be executed in any number of counterparts, each of which shall be deemed an original but all of which together shall constitute one and the same instrument. 



        14.13    Third-Party Beneficiaries.    


        None
of the provisions of this Agreement shall be for the benefit of or enforceable by any Third Party including, without limitation, any creditor of any Party hereto. No such Third
Party shall obtain any right under any provision of this Agreement or shall by reason of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against any
Party hereto. 


        14.14    Relationship of the Parties.    



        Each
Party shall bear its own costs incurred in the performance of its obligations hereunder without charge or expense to the other except as expressly provided in this Agreement.
Neither Gentium nor ST shall have any responsibility for the hiring, termination or compensation of the other Party's employees or for any employee compensation or benefits of the other Party's
employees. No employee or representative of a Party shall have any authority to bind or obligate the other Party to this Agreement for any sum or in any manner whatsoever, or to create or impose any
contractual or other liability on the other Party without said Party's approval. For all purposes, and notwithstanding any other provision of this Agreement to the contrary, ST's legal relationship
under this Agreement to Gentium shall be that of independent contractor. Nothing in this Agreement shall be construed to establish a relationship of partners or joint venturers. 


        14.15    LIMITATION OF DAMAGES.    


        IN
NO EVENT SHALL ST OR GENTIUM BE LIABLE FOR SPECIAL, INDIRECT, INCIDENTAL OR CONSEQUENTIAL DAMAGES (INCLUDING, WITHOUT LIMITATION, 


22







 



LOSS
OF PROFITS) SUFFERED BY THE OTHER PARTY, EXCEPT TO THE EXTENT OF INDIRECT DAMAGES PAID TO A THIRD PARTY AS PART OF A THIRD PARTY CLAIM. 


        14.16    Taxes.    


        Any
withholding or other taxes, if any, that either Party or its Affiliates are required by Law to withhold or pay on behalf of the other Party, with respect to any payments to it
hereunder, shall be deducted from such payments and paid contemporaneously with the remittance to the other Party; provided, however, that the
withholding Party shall furnish the other Party with proper evidence of the taxes so paid. Each Party shall furnish the other Party with appropriate documents to secure application of the most
favorable rate of withholding tax under applicable Law. 


        14.17    Payment Currency.    


        All
amounts due under this Agreement and any Ancillary Agreement shall be paid to the designated Party in the currency mutually agreed by the Parties for that purpose or, in the event
that no such currency has been agreed by the Parties, in the currency of United States of America. 


        IN
WITNESS WHEREOF, the Parties hereto have caused this Agreement to be signed in duplicate by their respective proper officers. 



	Gentium S.p.A.	 	 
	

By	

/s/  LAURA IRIS FERRO      
	
 	

 
	Name: Laura Iris Ferro MD

Title: Sole Administrator & C.E.O.	 	 
	

Sigma-Tau Industrie Farmaceutiche Riunite SpA	
 	

 
	

By	

/s/  EMILIO PLATE      
	
 	

 
	Name: Dr. Emilio Plate

Title: Chief Operating Officer	 	 




23









   
Schedule 1 


PATENT



US
Pat. 5,223,609; 


US
Pat. 4,985,552; 


US
Pat. 5,646,127; 



US
Pat. 5,646,268: 


PCT/EP01/04105. 


24







 

Schedule 2



ST's Contribution in the Development  


ST
shall pay the total amount of US$ 4,900,000 (United States Dollars four million nine hundred thousand) as follows upon receipt of the relevant invoices: 



US$
1,000,000 within December 31, 2001. 


US$
850,000 within April 30, 2002. 


US$
200,000 within 30 (thirty) days of the end of dose-finding study. 


US$
1,600,000 within thirty (30) days of the issuing of the IND number. 


US$
350,000 within thirty (30) days of the IND issuing for the Phase III pivotal study. 


US$
350,000 within thirty (30) days of the end of the Phase III pivotal study. 


US$
550,000 within thirty (30) days of obtaining the NDA and other Approval necessary for the Product to be Marketed in the Territory by a ST Affiliate. 


25







 

Schedule 3



Development
activities 



	Activity
 
	 	Timing
 

	Dose finding Study Completion	 	3Q 2002
	FDA pre-IND Meeting	 	3Q 2002
	IND submission	 	1Q 2003
	Phase III Pivotal Study	 	Start: 2Q 2003

End: 2Q 2004
	FDA Pre-NDA meeting	 	1Q 2004
	NDA submission	 	2Q 2004
	NDA supplement	 	4Q 2004
	Approval	 	4Q 2005




26









   Schedule 4 


Tasks and works for FDA's Approval of Gentium's Plant



Qualification of Slaughter House

Holding Tank Purchase

Holding Tank Qualification

Existing Mucosa Extraction-Collection Equipment qualification

Delivery Container Modification

Delivery Container Qualification

COMPLETION OF WORKS—1Q 2003 


Upstream Processing

Purchase and Installation of Acid/Base Holding Tanks

Purchase of an Elevator for Movement of Materials

Water Treatment System (Purified Warew and WFI)

Establishment of a Controlled Access to Manufacturing Areas

Scale Purchase and Qualification

Pumps Purchase and Qualification

Modification of Reactor R25

Filter Press System Revision

Installation of SS 316 connectors

Holding Tank S32 Modification

Construction and Installation of a Lipid Interface Detection System

R8 & R9 Tanks modification

New Closed Tank for Clarified Filtrate from Filter Press FP4

Installation for new Piping Connections

Installation of Controlled Environment for Salt addition

New Reactor Purchase and Installation

Purchase of new Piping for the Ultrafilter

Purchase and Installation of a new Tank for Ultrafiltrate Collection

COMPLETION OF WORKS—1Q 2003 


Down Stream Processing

Purchase System to Measure Volume of Process Solutions

R26 Modifications (Insulation, pH System, Piping)

Purchase and Installation of:

SS Tank for Mixing EDTA and NaOH

Scale for the Measurement of added Ingredients

Hopper to add Clarcel FLOMA to the System

HC1 PVC Holding Tank

Closure System to contain the Equipment

Purchase new UF Membranes

Improve area Lighting

Purchasing and Installation of an Enclosure for addition into R21

Installation of a closure for tank used for UF Membrane Washing

Install SS 316 Piping for R2

Purchasing and Installation of Pumps for NaOH and Acetic Acid

Construction of a closed Area to house the Equipment on the roof of the Clean Room

Purchasing and Installation of a Milling Machine

Purchasing of SS Containers for the DS 


Qualification
of all the Equipment (New and Existing)

COMPLETION OF WORKS—1Q 2003 


27







 

Schedule 5



Supply
Price and Terms 


        1.     Gentium
agrees to sell (directly or through its designated Affiliate,) to ST, and ST agrees to purchase from Gentium (or its designated Affiliate), ST's requirements of
Finished Product at a price equal to thirty-one percent (31%) of ST's Net Sales in the Territory (provided,  however, that in no event shall such price fall
below € 50 (Euro 50) per unit of Finished Product) Delivery of
Finished Products shall be EXW (ICC Incoterms 2000) Gentium' manufacturing facility in Villa Guardia, (Como), Italy. 


        2.     The
Parties shall calculate and agree on estimated prices of the Finished Product for the first year of the Term. Thereafter, the estimated prices of the Finished Product
will be based on Net Sales in the Territory during the preceding year. 


        3.     Payment
will be made to Gentium (or as directed by Gentium) within forty-five (45) days of the relevant invoice date or ST's receipt of the Finished
Product, whichever shall occur later. 


        4.     Within
thirty (30) days after the end of each calendar quarter (except for the first year following Product Launch,
where calculation shall be effected at the end of the year), ST's Net Sales shall be calculated based upon the reports provided pursuant to Article 5.3, and an adjustment of the differences
between the price for the Finished Product originally charged for the Finished Product and thirty-one percent (31%) of Net Sales shall be paid by one Party to the other as appropriate. 


        5.     Should
any events unforeseen by, and beyond the control of, the Parties occur that alter Gentium' (or its Affiliates') and/or ST's costs hereunder and materially and
detrimentally affect its economic return on the Finished Product as contemplated on the Effective Date hereof, the Parties shall consult together in order to revise the applicable prices and delivery
terms or other terms of this Agreement on a fair basis. 


28







 

Schedule 6



Product
Specifications 


To
be completed as soon as available. 


29











QuickLinks



Exhibit 10.15


LICENSE AND SUPPLY AGREEMENT By and Between GENTIUM S.p.A. AND SIGMA-TAU INDUSTRIE FARMACEUTICHE RIUNITE SpA Dated as of December 7th, 2001

TABLE OF CONTENTS


LICENSE AND SUPPLY AGREEMENT

SECTION I—DEFINITIONS


SECTION II—LICENSE

SECTION III—DEVELOPMENT


SECTION IV—REGULATORY MATTERS

SECTION V—CONSIDERATION

SECTION VI—MARKETING



SECTION VII—PROMOTIONAL MATERIAL AND PRODUCT PACKAGING

SECTION VIII—SUPPLY

SECTION IX—NEW PRODUCT, FIRST REFUSAL RIGHTS

SECTION X—TERM AND TERMINATION


SECTION XI—CONFIDENTIAL INFORMATION

SECTION XII—DISPUTE RESOLUTION

SECTION XIII—REPRESENTATIONS AND WARRANTIES

SECTION XIV—MISCELLANEOUS