----

----

**SERVICES      AGREEMENT**

**Gentium**

----

----

----

**SERVICES      AGREEMENT **

**BETWEEN      MDS PHARMA SERVICES**

**AND      **

**GENTIUM**

**PREAMBLE**

**Assago      (MI), Centro Direzionale Milanofiori, Strada 4, Palazzo A4,      Italy**
**Piazza      XX Settembre, 2, 22079 Villa Guardia (CO)-Italy**

**WITNESSETH:**

| **1** | **AFFILIATE:                DEFINED** |
|-------|---------------------------------------|

| **2** | **SCOPE                OF AGREEMENT**** ** |
|-------|-------------------------------------------------|

|   | **2.1** | **PURPOSE** |
|--------|---------|-------------|

----

|   | **2.2** | **MODIFICATION** |
|--------|---------|------------------|

|   | (i) | any                adjustment in fees resulting from the                change; |
|--------|-----|---------------------------------------------------------------------------------|

|   | (ii) | any                resulting planned changes in the                Agreement. |
|--------|------|-------------------------------------------------------------------------------|

|   | **2.3** | **PROTOCOL                / STUDY PLAN** |
|--------|---------|------------------------------------------|

|   | **2.3.1** | **DEFINITION** |
|--------|-----------|----------------|

----

|   | **2.3.2** | **PROTOCOL                OR STUDY PLAN DEVELOPMENT BY                MDSPS** |
|--------|-----------|-------------------------------------------------------------------------------|

| **3** | **DURATION** |
|-------|--------------|

| **4** | **RESOURCES                AND RESPONSIBILITIES** |
|-------|---------------------------------------------------|

|   | **4.1** | **RESOURCES                AND RESPONSIBILITIES OF                SPONSOR** |
|--------|---------|-----------------------------------------------------------------------------|

|   | (i) | sufficient                amount of all required Study Materials; |
|--------|-----|-------------------------------------------------------------------|

|   | (ii) | safety                data sheets for the Study Materials, where                available; |
|--------|------|--------------------------------------------------------------------------------------------|

|   | (iii) | sufficient                and comprehensive data as may be required by MDSPS concerning the                stability of the Study Materials, storage and safety                requirements; |
|--------|-------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | (iv) | final                version of the Clinical Trial Protocol in force on the Effective                date                indicating the title and date of Clinical                Trial; |
|--------|------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

----

|   | (v) | names                and contact information of all key                personnel; |
|--------|-----|-----------------------------------------------------------------------------------|

|   | (vi) | written                communication of any eventual bans or suspensions of the Clinical                Trial by                any applicable government or                organization. |
|--------|------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | **4.2** | **RESOURCES                AND RESPONSIBILITIES OF                MDSPS** |
|--------|---------|---------------------------------------------------------------------------|

|   | (i) | Materials                (other than the Study Materials described in Section                3.1); |
|--------|-----|----------------------------------------------------------------------------------------------------|

|   | (ii) | labor                necessary to conduct the Service as requested by                Sponsor; |
|--------|------|-----------------------------------------------------------------------------------------------|

|   | (iii) | data                generated from each Service, where                appropriate; |
|--------|-------|------------------------------------------------------------------------------------|

|   | (iv) | a                final report setting forth a full summary of the results of each                Service,                as requested; |
|--------|------|----------------------------------------------------------------------------------------------------------------------------------------|

|   | (v) | necessary                professional and support personnel for each Study or service                requested. |
|--------|-----|-----------------------------------------------------------------------------------------------------------------|

|   | **4.3** | **IDENTITY                OF PROJECT MATERIALS** |
|--------|---------|--------------------------------------------------|

|   | **4.4** | **DELAYS** |
|--------|---------|------------|

| **5** | **CONDUCT                OF SERVICE** |
|-------|---------------------------------------|

|   | **5.1** | **MDSPS                COMPLIANCE** |
|--------|---------|-------------------------------------|

----

|   | **5.2** | **SPONSOR                COMPLIANCE** |
|--------|---------|---------------------------------------|

|   | **5.3** | **QUALITY                CONTROLS** |
|--------|---------|-------------------------------------|

|   | **5.4** | **AUDITS                AND FACILITIES                EXAMINATION** |
|--------|---------|---------------------------------------------------------------------|

----

|   | **5.5** | **DEBARMENT                CERTIFICATION** |
|--------|---------|--------------------------------------------|

| **6** | **OWNERSHIP** |
|-------|---------------|

|   | **6.1** | **WORK                PRODUCT AND INVENTIONS** |
|--------|---------|------------------------------------------------|

|   | **6.2** | **PATENTS** |
|--------|---------|-------------|

----

|   | **6.3** | **PUBLICATIONS** |
|--------|---------|------------------|

|   | **6.4** | **USE                OF NAMES** |
|--------|---------|---------------------------------|

| **7** | **CONFIDENTIAL                INFORMATION** |
|-------|---------------------------------------------|

|   | **7.1** | **DEFINITION** |
|--------|---------|----------------|

|   | **7.2** | **DISCLOSURE** |
|--------|---------|----------------|

|   | **7.3** | **EXCEPTIONS** |
|--------|---------|----------------|

|   | (i) | Information                that is or becomes available to the public at the effective date                of the                present Agreement through no fault of the other                Party; |
|--------|-----|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | (ii) | Information                that, as of the time of disclosure to one Party, was already known                to and                in the lawful possession of the other, as evidenced by written                records; |
|--------|------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | (iii) | Information                obtained after the Effective Date of this Agreement hereof from a                third                party lawfully in possession of and with no limitation upon disclosure,                and having the right to disclose the                same; |
|--------|-------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | (iv) | Information                that is required to be disclosed pursuant to operation of                law. |
|--------|------|----------------------------------------------------------------------------------------------------------|

----

|   | **7.4** | **DURATION                OF OBLIGATION** |
|--------|---------|-------------------------------------------|

| **8** | **PAYMENT** |
|-------|-------------|

|   | **8.1** | **METHOD** |
|--------|---------|------------|

|   | **8.2** | **LONG                TERM STUDIES** |
|--------|---------|--------------------------------------|

|   | **8.3** | **CURRENCY                - EXCHANGE RATE** |
|--------|---------|---------------------------------------------|

----

|   | **8.4** | **DUE                DATE AND LATE FEES** |
|--------|---------|-------------------------------------------|

| **9** | **INDEMNIFICATION** |
|-------|---------------------|

|   | **9.1** | **BY                SPONSOR** |
|--------|---------|-------------------------------|

|   | **9.2** | **BY                MDSPS** |
|--------|---------|-----------------------------|

|   | 1. | Negligent                or intentionally wrongful acts of MDSPS during the conduct of a service;                or |
|--------|----|---------------------------------------------------------------------------------------------------------------------|

|   | 2. | Any                activity by MDSPS which is contrary to either this Agreement, written                relevant and material recommendations, information, instructions,                rules                and guidelines furnished by Sponsor for use in administration of                any                procedure described in this Agreement, federal laws and                regulations. |
|--------|----|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | **9.3** | **CONDITIONS                FOR INDEMNIFICATION** |
|--------|---------|---------------------------------------------------|

----

| **10** | **LIMITATION                OF LIABILITY / DAMAGES** |
|--------|------------------------------------------------------|

| **11** | **TERMINATION** |
|--------|-----------------|

|   | **11.1** | **BY                EITHER PARTY** |
|--------|----------|------------------------------------|

|   | **11.1.1** | **MATERIAL                BREACH** |
|--------|------------|------------------------------------|

|   | **11.1.2** | **SAFETY                OR EFFICACY HAZARD** |
|--------|------------|----------------------------------------------|

|   | **11.1.3** | **INSOLVENCY                AND/OR DISSOLUTION** |
|--------|------------|--------------------------------------------------|

|   | **11.2** | **BY                SPONSOR** |
|--------|----------|-------------------------------|

----

|   | **11.3** | **FORCE                MAJEURE** |
|--------|----------|----------------------------------|

|   | **11.4** | **SURVIVAL                OF OBLIGATIONS** |
|--------|----------|--------------------------------------------|

|   | **11.5** | **RETURN                OF ALL MATERIALS** |
|--------|----------|--------------------------------------------|

|   | **11.5.1** | **RETURN                OF SPONSOR’S MATERIALS** |
|--------|------------|--------------------------------------------------------|

|   | **11.5.2** | **RETURN                OF MDSPS’ MATERIALS** |
|--------|------------|-----------------------------------------------------|

----

| **12** | **TRANSFER                OF OBLIGATIONS** |
|--------|--------------------------------------------|

|   | **12.1** | **BETWEEN                THE PARTIES** |
|--------|----------|----------------------------------------|

|   | **12.2** | **ASSIGNMENT                TO SUB-CONTRACTORS** |
|--------|----------|--------------------------------------------------|

|   | - | Regulatory,                administrative and monitoring activities in Sweden to CRO                Norma. |
|--------|---|------------------------------------------------------------------------------------------------------------|

|   | - | Regulatory,                administrative and monitoring activities in Israel to Yael Marmor                (freelance CRA) |
|--------|---|-----------------------------------------------------------------------------------------------------------------------------|

|   | - | Import                license and drug supply in France to                LC2 |
|--------|---|-------------------------------------------------------------------------------|

|   | - | Import                license and drug supply to Utrecht Hospital in the Netherlands France                to a                Pharmacist in the Utrecht Hospital Import License and drug supply                to four                sites in Sweden to a Pharmacist in                Sweden |
|--------|---|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

| **13** | **INSURANCE** |
|--------|---------------|

----

| **14** | **LANGUAGE** |
|--------|--------------|

| **15** | **NOTICES** |
|--------|-------------|

|   | To                MDSPS:   | Manuela                LeoneGeneral                Manager, EuropeMDS                Pharma Services s.r.l.Assago                (MI),Centro                Direzionale Milanofiori,Strada                4,Palazzo                A4Italy |
|--------|----------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
|   |                       |                                                                                                                                                                                                                                       |
|   | Copy                to:    | Vice                President, Legal ServicesMDS                Pharma Services 621                Rose Street Lincoln,                NE 68502                                                                                            |
|   |                       |                                                                                                                                                                                                                                       |
|   | To                Gentium: | Massimo                IacobelliPiazza                XX Settembre, 2,22079                Villa Guardia (CO) - Italy                                                                                                                      |
|   |                       |                                                                                                                                                                                                                                       |

| **16** | **SEVERABILITY** |
|--------|------------------|

| **17** | **DISPUTE                AND ARBITRATION - APPLICABLE                LAW** |
|--------|----------------------------------------------------------------------------|

----

| **MDS                PHARMA SERVICES** |                                    |   | **GENTIUM** |
|----------------------------------------|-----------------------------------------|--------|-------------|
|                                   |                                    |   |        |   |
| By:                                    | /s/                Manuela Leone        |   | By:         | /s/                Laura Iris Ferro     |
|                                   | Signature                               |   |        | Signature |
|                                   |                                    |   |        |   |
|                                   | April                12, 2006           |   |        | March                17, 2006 |
|                                   | Date                                    |   |        | Date |
|                                   |                                    |   |        |   |
|                                   | Manuela                Leone            |   |        | Laura                Iris Ferro |
|                                   | Name                                    |   |        | Name |
|                                   |                                    |   |        |   |
|                                   | European                General Manager |   |        | Chief                Executive Officer  |
|                                   | Title                                   |   |        | Title |

| **GENTIUM** |                                   |   | **GENTIUM** |
|-------------|----------------------------------------|--------|-------------|
|        |                                   |   |        |   |
| By:         | /s/              Cary Grossman    |   | By:         | /s/              Massimo Iacobelli |
|        | Signature                              |   |        | Signature |
|        |                                   |   |        |   |
|        | April              6, 2006             |   |        | March                15, 2006 |
|        | Date                                   |   |        | Date |
|        |                                   |   |        |   |
|        | Cary                Grossman           |   |        | Massimo                Iacobelli |
|        | Name                                   |   |        | Name |
|        |                                   |   |        |   |
|        | Chief                Financial Officer |   |        | Scientific                Director |
|        | Title                                  |   |        | Title |

----

**APPENDIX      1 **

**PROTOCOL      OF THE CLINICAL TRIAL**

----

**APPENDIX      II **

**BUDGET**

----

**GENTIUM**

**VOD      - Defibrotide Study**

----

| *GENTIUM                - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                8* |  |
|--------------------------------------------------------------------------------------------------------|--|

| **EXECUTIVE                  SUMMARY** | **3**                                   |
|----------------------------------------|-----------------------------------------|
| **1.**                                 | **PROJECT                  DEFINITION** | **3** |
|                                   | **1.1.**                                | **Study                  Title** | **3** |
|                                   | **1.2.**                                | **Study                  Design** | **3** |
|                                   | **1.3.**                                | **Study                  Objectives** | **3** |
|                                   | **1.4.**                                | **Patient                  / Centre Numbers** | **3** |
|                                   | **1.5.**                                | **Study                  Timelines** | **3** |
| **2.**                                 | **STUDY                    MANAGEMENT** | **4** |
|                                   | **2.1.**                                | **Division                  of Responsibilities** | **4** |
|                                   | **2.2**                                 | **Project                  Team Approach** | **6** |
|                                   | **2.3.**                                | **Project                  Team Structure** | **7** |
| **3.**                                 | **SERVICES**                            | **8** |
|                                   | **3.1.**                                | **Study                  Set-up** | **8** |
|                                   |                                    | 3.1.1. | Project                  Definition Meeting | 8 |
|                                   |                                    | 3.1.2. | Project                  Team Training | 8 |
|                                   | **3.2.**                                | **Document                  Management** | **8** |
|                                   |                                    | 3.2.1. | Protocol                  / Informed Consent Form (ICF) familiarisation | 8 |
|                                   |                                    | 3.2.2. | Protocol                  Synopsis Translation in Sweden | 8 |
|                                   |                                    | 3.2.3. | ICF                  Adaptation and Translation | 8 |
|                                   |                                    | 3.2.4. | Case                  Report Form (CRF) Development | 9 |
|                                   |                                    | 3.2.5. | Operations                  Manual | 9 |
|                                   |                                    | 3.3. | Investigator                  Recruitment | 9 |
|                                   |                                    | 3.3.1. | EBMT                  - Investigators | 9 |
|                                   |                                    | 3.3.2. | Investigator                  Contracts / Hospital Conventions | 9 |
|                                   | **3.4.**                                | **Central                  Pharmacy / Import Supply** | **9** |
|                                   | **3.5.**                                | **Ethics                  Committee / Regulatory Submissions** | **9** |
|                                   |                                    | 3.5.1. | Organization                  of Regulatory Resources | 10 |
|                                   |                                    | 3.5.2. | Ethics                  Committees Amendment Submissions | 11 |
|                                   | **3.6.**                                | **Study                  Initiation** | **11** |
|                                   |                                    | 3.6.1. | Investigator                  Meeting | 11 |
|                                   |                                    | 3.6.2. | Site                  Initiation Visits | 11 |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|                                               | **3.7.**                             | **Monitoring                  Activities**          | **12**                                                                              |
|----------------------------------------------------|--------------------------------------|-----------------------------------------------------|-------------------------------------------------------------------------------------|
|                                               |                                 | 3.7.1.                                              | Monitoring                  Visits                                                  | 12 |
|                                               |                                 | 3.7.2.                                              | Telephone                  Contacts                                                 | 13 |
|                                               |                                 | 3.7.3.                                              | Correspondence                                                                      | 14 |
|                                               |                                 | 3.7.4.                                              | e-CRF                  Review and Query Management                                  | 14 |
|                                               |                                 | 3.7.5.                                              | COSMOS                  Set-up / Updates                                            | 14 |
|                                               |                                 | 3.7.6.                                              | Study                  File and Documentation Maintenance                           | 14 |
|                                               |                                 | 3.7.7.                                              | Serious                  Adverse Event (SAE) Reporting to Sponsor and Documentation | 15 |
|                                               |                                 | 3.7.8.                                              | Hospital                  Fee Payments (Optional)                                   | 15 |
|                                               | **3.8.**                             | **Study                  Close-out**                | **15**                                                                              |
|                                               |                                 | 3.8.1.                                              | Site                  Close-out Visits                                              | 15 |
|                                               |                                 | 3.8.2.                                              | Drug                  Reconciliation                                                | 15 |
|                                               | **3.9.**                             | **Project                  Management**             | **16**                                                                              |
|                                               |                                 | 3.9.1.                                              | Project                  Team Co-ordination                                         | 16 |
|                                               |                                 | 3.9.2.                                              | Reporting                  to Sponsor                                               | 16 |
|                                               |                                 | 3.9.3.                                              | MDS                  Pharma Express TM                                         | 16 |
|                                               |                                 | 3.9.4.                                              | Co-monitoring                  Visits (Optional)                                    | 19 |
|                                               |                                 | 3.9.5.                                              | Sponsor                  Contact                                                    | 19 |
|                                               |                                 | 3.9.6.                                              | Project                  Management of Austria, Germany and Switzerland (Optional)  | 19 |
| **4.**                                             | **SERVICE                  CHARGES** | **20**                                              |
|                                               | **4.1.**                             | **Project                  Assumptions**            | **20**                                                                              |
|                                               | **4.2.**                             | **Professional                  Fees**              | **20**                                                                              |
|                                               | **4.3.**                             | **Optional                  Costs**                 | **24**                                                                              |
|                                               | **4.4.**                             | **Variable                  Costs**                 | **25**                                                                              |
|                                               | **4.5.**                             | **Estimate                  of Pass-through Costs** | **26**                                                                              |
|                                               | **4.6.**                             | **Payment                  Schedule**               | **27**                                                                              |
| **APPENDIX                  1 - CURRICULUM VITAE** | **27**                               |

----

| *GENTIUM                - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                8* |  |
|--------------------------------------------------------------------------------------------------------|--|

**GENTIUM**
**Version      8**
*“Study      of the Incidence and Outcome of Veno-occlusive Disease (VOD) with the      Prophylactic Use of Defibrotide (DF, GENTIUM, Italy) in Paediatric Stem Cell      Transplantation.”*

**GENTIUM’s**

**TEAM      STABILITY**

**PROJECT      TEAM EXPERIENCE**

**Italian      office**
**GENTIUM**
**Agostino      Lazzaro**
*(Please      refer to his CV in appendix for more detail).*

**PROJECT      COMMUNICATION**

**GENTIUM**

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

**KEY      FACTS**

| **Countries**                                                                       | ITALY,                FRANCE, UK, NETHERLANDS, SWEDEN, ISRAEL, IRELAND |
|-------------------------------------------------------------------------------------|------------------------------------------------------------------------|
| **Services**                                                                        | CLINICAL                OPERATIONS, REGULATORY                AFFAIRS  |
| **N°                Centres**                                                  | 13                                                                     |
| **Total                N° Patients for ClinOps**                               | 117                                                                    |
| **Budget                (excluding VAT and Pass-****Through                costs)** | **562                741 €**                                     |

**MDS      Pharma Services will be pleased to discuss this bid with GENTIUM      team.**

----

| *GENTIUM                - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                8* |  |
|--------------------------------------------------------------------------------------------------------|--|

**GENTIUM**

**13**
**117**

| **COUNTRY**                   | **N°                CENTRES** | **N°                PATIENTS** |
|-------------------------------|------------------------------------|-------------------------------------|
| United                Kingdom | 2                                  | 18                                  |
| Ireland                       | 1                                  | 9                                   |
| Italy                         | 3                                  | 27                                  |
| Sweden                        | 4                                  | 36                                  |
| Netherlands                   | 1                                  | 9                                   |
| France                        | 1                                  | 9                                   |
| Israel                        | 1                                  | 9                                   |
| **TOTAL**                     | **13**                             | **117**                             |

|                                                  | **Timelines**                   |
|-------------------------------------------------------|---------------------------------|
| **w** Set-up                Activities           | End                October 2005 |
| **w** Regulatory                / EC Submissions | End                October 2005 |
| **w** First                Patient Included      | End                January 2006 |
| **w** Last                Patient Included       | End                January 2009 |
| **w** Last                Patient Last Visit     | End                August 2009  |
| **w** Study                Close-out             | End                October 2009 |

*NB      These timelines assume that Ethics Committee and Regulatory Authority approvals      are granted, and that the study drug is available on-site *
***before      First Patient In.***

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

| Responsibilities                                                      | GENTIUM                                                                | MDS                PharmaServices                 |
|-----------------------------------------------------------------------|------------------------------------------------------------------------|---------------------------------------------------|
| **Project                Definition Meeting**                         | **ü**                                                             | ü                                            |
| **Project                Team Training**                              |                                                                   | ü                                            |
| **Protocol                / Informed Consent Form (ICF) Development** | **ü**                                                             |                                              |
| **Protocol                / ICF Familiarisation**                     |                                                                   | ü                                            |
| **Protocol                Synopsis Translation**                      | **ü**                                                             | ü(Sweden                only)                |
| **ICF                Adaptation**                                     |                                                                   | ü(Ireland                and Sweden only)    |
| **ICF                Translation**                                    | **ü**                                                             | ü(Sweden                only)                |
| **Protocol                Submission to MoH**                         |                                                                   | ü(France                only)                |
| **CRF                Development**                                    | **ü****(e-CRF                development subcontracted**          |                                              |
| **Operations                Manual**                                  | **ü** **(To                be produced by a 3rd party CRO)** | ü (Review                only)          |
| **Investigator                Identification**                        | **ü**                                                             |                                              |
| **Qualification                Visits**                               | **ü**                                                             |                                              |
| **Hospital                Conventions**                               |                                                                   | ü                                            |
| **Regulatory                Submissions**                             | **ü**                                                             | ü(Ireland                and Sweden only)    |
| **Ethics                Committee Submissions**                       | **ü**                                                             | ü(Ireland                and Sweden only)    |
| **Ethics                Committee Submissions Follow-Up**             |                                                                   | ü(Support                only for UK)        |
| **Ethics                Committee Amendment Submissions**             | **ü****(Italy)**                                                  | ü(Except                Italy)               |
| **Investigator                Meetings: attendance and organisation** | **ü****(Organisation                sub-contracted)**             | ü(Attendance                and preparation) |
| **Study                Drug Packaging / Labelling / Distribution**    | **ü**                                                             |                                              |
| **Site                Initiation Visits**                             |                                                                   | ü                                            |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

| Responsibilities                                              | GENTIUM                           | MDS                PharmaServices                                 |
|---------------------------------------------------------------|-----------------------------------|-------------------------------------------------------------------|
| **Import                License**                             |                              | ü(The                Netherlands, Israel, France and Sweden) |
| **Contract                Negotiation with Central Pharmacy** |                              | ü(The                Netherlands and Sweden only)            |
| **Import                Supply Company**                      |                              | ü(France                (LC2) only)                          |
| **Routine                Monitoring Visits**                  |                              | ü                                                            |
| **Telephone                Contacts**                         |                              | ü                                                            |
| **Correspondence                with Sites**                  |                              | ü                                                            |
| **E-CRF                Review and Query Management**          |                              | ü                                                            |
| **COSMOS                Set-up / Updates**                    |                              | ü                                                            |
| **Study                File and Document Maintenance**        |                              | ü                                                            |
| **Serious                Adverse Event Reporting**            | **To                Authorities** | To                GENTIUM                                         |
| **Serious                Adverse Event Documentation**        |                              | ü                                                            |
| **Hospital                Fee Payments (*****optional*****)** |                              | ü                                                            |
| **Site                Close-out Visit**                       |                              | ü                                                            |
| **Project                Team Co-ordination**                 |                              | ü                                                            |
| **Reporting                to Sponsor**                       |                              | ü                                                            |
| **Sponsor                Contact**                            |                              | ü                                                            |
| **Data                Management**                            | **ü****(EBMT)**              |                                                              |
| **Statistics                Activities**                      | **ü****(EBMT)**              |                                                              |
| **Clinical                Study Report**                      | **ü****(EBMT)**              |                                                              |

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

**IPD**
**Italy**

**GENTIUM**
**s**

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

| **FTE**                        |
|--------------------------------|
| IPD                            | 0,21 |
| CRA                Italy       | 0,10 |
| CRA                France      | 0,03 |
| CRA                Netherlands | 0,04 |
| CRA                UK          | 0,07 |
| CRA                Sweden      | 0,13 |
| CRA                Ireland     | 0,04 |
| CRA                Israel      | 0,03 |
| CTA                            | 0,14 |

**Notes**

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

**All      MDS Pharma services will be provided in accordance with the MDS Pharma Services      SOPs, which are compliant with ICH GCP guidelines. All project team activities      are liable to be audited by the independent quality assurance division of MDS      Pharma Services.**

**3.1.1.**
**Project      Definition Meeting**

**IPD**
**GENTIUM’s**
**office**
**(Italy)**
**GENTIUM**

**3.1.2.**
**Project      Team Training**

**GENTIUM’s**
**office**
**GENTIUM**

**3.2.1.      Protocol / Informed Consent Form (ICF) familiarisation**

**GENTIUM**

**3.2.2.**
**Protocol      Synopsis Translation in Sweden**

**3.2.3.**
**ICF      Adaptation and Translation**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**3.2.4.**
**Case      Report Form (CRF) Development**

**GENTIUM**

**3.2.5.**
**Operations      Manual**

**3.3.1.**
**EBMT      - Investigators**

*European      Group for Blood and Marrow Transplantation*
**GENTIUM**

**3.3.2.**
**Investigator      Contracts / Hospital Conventions**

**except      for The Netherlands**
**GENTIUM**

**(Only      submissions in Ireland and Sweden will be managed by MDS Pharma Services. MDS      Pharma Services will also support Gentium for the submissions in France and      especially in UK).**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**3.5.1.      Organization of Regulatory Resources**

|   | Ø | Prepare                core study documentation (e.g. investigator brochure, IMP dossier,                IND) -                if required. |
|--------|--------|---------------------------------------------------------------------------------------------------------------------------------------------|

|   | Ø | Maintain                a country-by-country database of national regulatory and ethics data                requirements and processes. |
|--------|--------|-----------------------------------------------------------------------------------------------------------------------------------------|

|   | Ø | Co-ordinate                regulatory activities in conjunction with MDS project management                professionals. |
|--------|--------|---------------------------------------------------------------------------------------------------------------------------|

|   | Ø | Disseminate                emerging regulatory information to local regulatory advisers (see                below). |
|--------|--------|---------------------------------------------------------------------------------------------------------------------|

|   | Ø | Provide                support to local regulatory advisers in responding to ethics committee                and/or regulatory authority                questions. |
|--------|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   | Ø | Delivery                of training to local regulatory advisers when                appropriate. |
|--------|--------|---------------------------------------------------------------------------------------------------|

|   | Ø | Prepare                and submit regulatory and ethics committee packages in the local                country                concerned. |
|--------|--------|------------------------------------------------------------------------------------------------------------------------------------------|

|   | Ø | Respond                to any questions from the local ethics committees and/or regulatory                authority. |
|--------|--------|----------------------------------------------------------------------------------------------------------------------|

|   | Ø | Communicate                changes in country-specific regulatory and/or ethics requirements                to the                Regulatory Affairs Departments. |
|--------|--------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

| **Country** | **Approximate                Regulatory and****Ethics                Timelines** |
|-------------|----------------------------------------------------------------------------------|
| Ireland     | 2                months                                                          |
| Sweden      | 2                months                                                          |

**3.5.2.**
**Ethics      Committees Amendment Submissions**

**GENTlUM’s**
**GENTIUM**
**GENTIUM**

**3.6.1.      Investigator Meeting**

**one      Investigator Meeting**
**Germany**
**GENTIUM**

**GENTIUM**

**3.6.2.      Site Initiation Visits**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

|   |  ̈ | Review                with the investigators the protocol and                e-CRF, |
|--------|--------|-------------------------------------------------------------------------------------|

|   |  ̈ | Review                with the investigators the conduct of monitoring visits, and confirm                the                monitor’s continued access to study-related source                documents, |
|--------|--------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Review                with the investigators the requirements for Adverse Event                reporting, |
|--------|--------|-----------------------------------------------------------------------------------------------------------|

|   |  ̈ | Review** **with** **the** **investigators** **the** **requirements** **for** **drug** **storage** **and                accountability, |
|--------|--------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Supply                the investigators with a study file, in which all study-related documents                and correspondence will be archived, in accordance with ICH GCP                guidelines, |
|--------|--------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Retrieve                any document missing from MDS Pharma Services’ study                files, |
|--------|--------|----------------------------------------------------------------------------------------------------------|

|   |  ̈ | Review** **with** **the** **investigators** **their** **responsibilities** **concerning** **local                regulations, |
|--------|--------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Review                with the investigators laboratory                procedures, |
|--------|--------|------------------------------------------------------------------------------------|

|   |  ̈ | Stress                the importance of correctly obtaining informed consent from                patients, |
|--------|--------|------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Review                with the investigators their responsibilities for archiving study-related                documents according to applicable                regulations. |
|--------|--------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

**GENTIUM**

**3.7.1.      Monitoring Visits**

**6      times**
**7,5**

|   |  ̈ | Verify                all completed Electronic Case Report Forms (e-CRFs) and rectify any                errors                in accordance with ICH GCP                guidelines, |
|--------|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

|   |  ̈ | Verify                compliance with the protocol, |
|--------|--------|-----------------------------------------------------|

|   |  ̈ | Verify                critical study data, |
|--------|--------|--------------------------------------------|

|   |  ̈ | Verify                that patients have given their informed consent prior to inclusion                in the                study, |
|--------|--------|--------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Verify                documentation of all Adverse Events and compliance with the relevant                procedures, |
|--------|--------|-----------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Conduct                comprehensive source document verification (100% of demographic data,                study entry criteria, Adverse Events,** **concomitant                medication, key efficacy                parameters), |
|--------|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

**GENTIUM**

**3.7.2.**
**Telephone      Contacts**

|   |  ̈ | Study                progress, |
|--------|--------|--------------------------------|

|   |  ̈ | Queries,                in case of issues needing clarification or incomplete data further                to the                monitoring visit, |
|--------|--------|---------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Preparation                of corrections to be signed off at the next monitoring                visit, |
|--------|--------|---------------------------------------------------------------------------------------------------------|

|   |  ̈ | Information                on the overall study status, |
|--------|--------|---------------------------------------------------------|

|   |  ̈ | Investigator’s                motivation to deal with potential                problems, |
|--------|--------|------------------------------------------------------------------------------------------------|

|   |  ̈ | Adverse                Events, exchange of information. |
|--------|--------|---------------------------------------------------------|

**48**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**3.7.3.**
**Correspondence**

**3.7.4.**
**e-CRF      Review and Query Management**

**3.7.5.**
**COSMOS      Set-up / Updates**

**3.7.6.**
**Study      File and Documentation Maintenance**

**3.7.7.**
**Serious      Adverse Event (SAE) Reporting to Sponsor and Documentation**

**GENTIUM**

**GENTIUM**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**3.7.8.**
**Hospital      Fee Payments (**
***Optional***
**)**

**(except      for Italy)**
**GENTIUM**

**3.8.1.**
**Site      Close-out Visits**

|   |  ̈ | Verify                the study documentation, |
|--------|--------|------------------------------------------------|

|   |  ̈ | Verify                the suitability of study archives, |
|--------|--------|----------------------------------------------------------|

|   |  ̈ | Verify                the signing off of drug dispensing                logs, |
|--------|--------|-------------------------------------------------------------------------------|

|   |  ̈ | Retrieve                all unused study materials and return them to **GENTIUM**                for destruction, |
|--------|--------|-------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Confirm                with investigators that the study may be subject to                inspection. |
|--------|--------|-------------------------------------------------------------------------------------------------------|

**GENTIUM**

**3.8.2.      Drug Reconciliation**

**GENTIUM**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**3.9.1.      Project Team Co-ordination**

|   |  ̈ | Allocate                the appropriate resources to complete the study within the agreed                timelines, |
|--------|--------|---------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Co-ordinate                and supervise MDS Pharma Services’ project                team, |
|--------|--------|--------------------------------------------------------------------------------------------------|

|   |  ̈ | Motivate                MDS Pharma Services’ project team and investigators involved in the study, |
|--------|--------|----------------------------------------------------------------------------------------------------------|

|   |  ̈ | Respond                to recruitment rates from site to site, and initiate / co-ordinate                any                remedial action required to achieve the overall study recruitment                target                within the defined timelines, |
|--------|--------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|   |  ̈ | Oversee                the local distribution of study material and                documentation. |
|--------|--------|---------------------------------------------------------------------------------------------------|

**3.9.2.**
**Reporting      to Sponsor**

**GENTIUM**
**16      **

|   |  ̈ | Start-up,                regulatory status, |
|--------|--------|---------------------------------------------|

|   |  ̈ | Number                of investigators recruited into the                study, |
|--------|--------|---------------------------------------------------------------------------------|

|   |  ̈ | Inclusion                per site, |
|--------|--------|------------------------------------|

|   |  ̈ | Comparison                of planned and actual inclusions, |
|--------|--------|-------------------------------------------------------------|

|   |  ̈ | Number                of drop-outs, |
|--------|--------|-------------------------------------|

|   |  ̈ | Number                of protocol deviations, |
|--------|--------|-----------------------------------------------|

|   |  ̈ | Number                of SAEs / AEs, |
|--------|--------|--------------------------------------|

|   |  ̈ | Number                of monitoring visits performed, |
|--------|--------|-------------------------------------------------------|

|   |  ̈ | Number                of clean e-CRFs acquired, |
|--------|--------|-------------------------------------------------|

|   |  ̈ | Outstanding                administrative issues. |
|--------|--------|---------------------------------------------------|

**3.9.3.**
**MDS      Pharma Express TM**

**GENTIUM**
**MDS      Pharma Express TM**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

|  | · | An                  intuitive and user-friendly service that allows you to keep current                  on                  your studies without any delay. |
|--|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  | · | Provides                  real-time access to investigator and subject summary information                  with                  drill-down features, print-ready study status reports, site visit                  reports                  and site visit schedules. |
|--|--------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  | · | All                  study status information is extracted from MDS Pharma Services’                  operational systems and automatically published via a web                  interface. |
|--|--------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

**GENTIUM**
**GENTIUM**

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

**Sample      Overview of MDS PharmaExpressTM Reports:**

**Sample      MDS On-line Monitoring Report:**

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

**3.9.4.**
**Co-monitoring      Visits (**
***Optional***
**)**

**7**
**one**

**3.9.5.**
**Sponsor      Contact**

**GENTIUM**
**5**

**GENTIUM**
**2-3      times per month**

**3.9.6.**
**Project      Management of Austria, Germany and Switzerland (**
***Optional***
**)**

**GENTIUM**
**Austria**
**      Germany**
**Switzerland**
**GENTIUM**

----

| *GENTIUM                  - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                  8* |  |
|------------------------------------------------------------------------------------------------------------|--|

| **General                Assumptions**                                                                                                                                |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Total                number of patients                                                                                                                               | 117 |
| Total                number of centres                                                                                                                                | 13                (in 7 countries) |
| Number                of CRF pages                                                                                                                                    | 40 |
| Total                number of estimated SAEs                                                                                                                         | TBD |
| Total                study duration (months) -                Set-up -                Recruitment -                Treatment and follow-up -                Close-out | 48                3                36                7                2 |

|                                                                          | **No                of Units** | **Type                of Unit** | **Unit                Price (EUR)** | **TOTAL                (EUR)** | **Comments**                                                                                                                                                                                              |
|-------------------------------------------------------------------------------|--------------------------------|---------------------------------|-------------------------------------|--------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| **Study              Set-up**                                                 |                           |                            |                                | **21                328**      |                                                                                                                                                                                                      |
| Project                Definition Meeting                                     | 1                              | meeting                         | 1                704                | 1                704           | This                one-day meeting will take place in GENTIUM’s office in Italy. MDSPS’ IPD                will attend. Travel and accommodation costs not                included.          |
| Project                Team Training                                          | 1                              | meeting                         | 17                485               | 17                485          | This                one-day meeting will take place in GENTIUM’s office in Italy. MDSPS’ IPD                and CRAs will attend. Travel and accommodation costs not                included. |
| Team                Training (Webex)                                          | 1                              | training                        | 1                855                | 1                855           |                                                                                                                                                                                                      |
| Import                Supplier Company                                        | 1                              | contract                        | 284                                 | 284                            | In                France. IPD coordination only for contract negotiation.                                                                                                                                 |
| **Document                Management**                                        | **16              881**        |                            |
| Study                Document Familiarisation / Regulatory Master File Set-up | 1                              | dossier                         | 1                387                | 1                387           |                                                                                                                                                                                                      |
| Protocol                Familiarisation                                       | 15                             | team                members     | 291                                 | 4                359           | MDSPS                Team is composed of 1 IPD, 7 CRAs and 7 CTAs.                                                                                                                                        |
| Protocol                Synopsis Translation (Sweden only)                    | 1                              | language                        | 230                                 | 230                            | MDSPS                will subcontract the translation in Swedish to a professional agency.                Fees                are for coordination and review                only.                        |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|   | **No                      of Units** | **Type                      of Unit** | **Unit                      Price (EUR)** | **TOTAL                      (EUR)** | **Comments** |
|--------|--------------------------------------|---------------------------------------|-------------------------------------------|--------------------------------------|--------------|

| ICF                Adaptation and Translation                                  | 2                       | adaptation                with/without translation                                                                                                                                        | 550                  | 1                099  | MDSPS                will adapt the ICF in Ireland and Sweden. Additionally, MDSPS will                subcontract the translation in Swedish to a professional agency.                Fees are                for coordination and review only. |
|--------------------------------------------------------------------------------|-------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| CRF                Familiarisation                                             | 15                      | team                members                                                                                                                                                               | 291                  | 4                359  | MDSPS                Team is composed of 1 IPD, 7 CRAs and 7 CTAs.                                                                                                                                                                               |
| Operations                Manual                                               | 1                       | manual                                                                                                                                                                                    | 5                447 | 5                447  | MDSPS                IPD will participate to the Operating Manual development by the German                CRO. MDSPS’ CRA/CTA will also familiarise with the Operating                Manual.                                             |
| **Investigator                Recruitment**                                    | **20              316** | **All                Investigators are EBMT members. MDSPS will neither be responsible                for                investigators identification and                qualification.** |
| Hospital                Contracts / Conventions                                | 12                      | contracts                                                                                                                                                                                 | 1                061 | 12                727 | MDSPS                will not be responsible for hospitals contracts/conventions in The                Netherlands (not required).                                                                                                               |
| Central                Pharmacy Contract                                       | 3                       | contracts                                                                                                                                                                                 | 885                  | 2                655  | Negotiation                of the central pharmacy contracts in The Netherlands and                Sweden.                                                                                                                                       |
| Investigator                Meeting Preparation                                | 1                       | meeting                                                                                                                                                                                   | 2                662 | 2                662  |                                                                                                                                                                                                                                             |
| Investigator                Meeting Attendance                                 | 1                       | meeting                                                                                                                                                                                   | 2                272 | 2                272  | IPD                travel and attendance only.                                                                                                                                                                                                   |
| **EC                / Regulatory Submissions**                                 | **34              545** | **We                assumed that the IMP Dossier, the core EU application form and the                Investigator Brochure will be provided by                GENTIUM.**                 |
| CTA                Documentation Preparation (IMP                Dossier etc.) | 1                       | dossier                                                                                                                                                                                   | 4                624 | 4                624  | Corresponds                to time to compile the information from other submissions and to                support                GENTIUM during the regulatory process.                                                                         |
| Teleconferences                                                                | 32                      | hours                                                                                                                                                                                     | 124                  | 3                983  | As                the number of teleconferences is not clearly defined, we allocated                a                certain number of hours for this task.                                                                                      |
| Ethics                Committee Submissions                                    | 2                       | submissions                                                                                                                                                                               | 1                932 | 3                863  | MDSPS                will manage EC submissions in Ireland and Sweden only.                                                                                                                                                                      |
| Ethics                Committee Submissions                Follow-Up           | 2                       | submissions                                                                                                                                                                               | 764                  | 1                529  | MDSPS                will support GENTIUM submissions in UK (follow-up                only).                                                                                                                                                     |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|   | **No                      of Units** | **Type                      of Unit** | **Unit                      Price (EUR)** | **TOTAL                      (EUR)** | **Comments** |
|--------|--------------------------------------|---------------------------------------|-------------------------------------------|--------------------------------------|--------------|

| Ethics                Committee Amendment Submissions             | 10                        | submissions                   | 795                  | 7                946   | GENTIUM                will provide MDSPS with the final text of the amendment. MDSPS will                not                perform the submission in Italy.                                                                                                                                                                     |
|-------------------------------------------------------------------|---------------------------|-------------------------------|----------------------|------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Regulatory                Submissions                             | 2                         | submissions                   | 5                767 | 11                533  | MDSPS                will manage Regulatory submissions in Ireland and Sweden                only.                                                                                                                                                                                                                                |
| Protocol                Submission to                MoH (France) | 1                         | submission                    | 1                067 | 1                067   | Cost                to be adjusted according to the actual work performed.                                                                                                                                                                                                                                                        |
| **Study              Initiation**                                 | **24                722** |                          |
| Site                Initiation Visits                             | 13                        | visits                        | 1                711 | 22                247  |                                                                                                                                                                                                                                                                                                                              |
| Import                Licence Negotiation                         | 4                         | licence                       | 341                  | 1                362   | Negotiation                of the import licence for France, The Netherlands, Sweden and Israel.                Cost                for this task in UK and Ireland can be found in option                section.                                                                                                                |
| Drug                / Supplies Shipment Tracking                  | 13                        | shipments                     | 86                   | 1                113   | MDSPS                assumed 1 shipment per site.                                                                                                                                                                                                                                                                                 |
| **Monitoring                Activities**                          | **224              384**  |                          |
| Monitoring                Visits                                  | 78                        | visits                        | 1                679 | 130                927 | Corresponds                to 6 monitoring visits per site.                                                                                                                                                                                                                                                                       |
| Site                Communication                                 | 624                       | months                x sites | 52                   | 32                202  | Corresponds                to 13 sites during 48 months.                                                                                                                                                                                                                                                                          |
| e-CRF                Review / Query Management                    | 117                       | CRFs                          | 172                  | 20                126  |                                                                                                                                                                                                                                                                                                                              |
| COSMOS                Set-up / Updates                            | 117                       | patients                      | 54                   | 6                349   |                                                                                                                                                                                                                                                                                                                              |
| Filing                                                            | 48                        | months                        | 725                  | 34                780  | GENTIUM                will manage the TMF. MDSPS will only forward the essential documents                on a                regular basis to GENTIUM.                                                                                                                                                                          |
| **Study                Close-out**                                | **19              138**   |                          |
| Close-out                Visits                                   | 13                        | visits                        | 1                472 | 19                138  |                                                                                                                                                                                                                                                                                                                              |
| **Project                Management**                             | **201              427**  |                          |
| Project                Team Interaction                           | 48                        | months                        | 2                480 | 119                019 | Includes                IPD time to manage each country ( 1 hour per month per country managed)                and general on-going communication with CRAs (2 hours per CRA FTE).                Includes also between 0,5 and 1,5 CRA hours per month for interaction                with                the rest of the team.  |
| Project                Team Teleconferences                       | 16                        | teleconferences               | 999                  | 15                976  | Corresponds                to 1-hour teleconferences. The IPD will spend 1 hour for minutes                writing                after each teleconference. We assume monthly teleconference during                set-up                and closeout and 3-monthly teleconferences during the rest of the                study. |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|   | **No                      of Units** | **Type                      of Unit** | **Unit                      Price (EUR)** | **TOTAL                      (EUR)** | **Comments** |
|--------|--------------------------------------|---------------------------------------|-------------------------------------------|--------------------------------------|--------------|

| Status                Reports                                          | 16                       | reports | 1                489 | 23                832 | The                IPD will provide GENTIUM with 16 reports. This assumes 3 reports                during                the set-up, 2 reports during the closeout and 11 during the rest                of the                study.                 |
|------------------------------------------------------------------------|--------------------------|---------|----------------------|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sponsor                Meetings                                        | 5                        | meeting | 1                704 | 8                520  |                                                                                                                                                                                                                                                  |
| Sponsor                Communications                                  | 48                       | months  | 710                  | 34                080 | The                IPD will contact GENTIUM approximately 1,25 hours per week (2 hours                per                week during the set-up and close-out period and 1 hour per week during                the                rest of the study). |
| **TOTAL****(excluding                VAT and all pass-through costs)** | **562              741** |    |

|  |  ̈ | Due                to the particular setting of this study, MDS Pharma Services would                like to                inform **GENTIUM**                that the budget provided before is estimated.                MDS Pharma Services will invoice the actual production to **GENTIUM**,                in order to match the study specifications (competitive recruitment,                etc.). |
|--|--------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  |  ̈ | All                costs in this proposal exclude VAT and pass-through                costs. |
|--|--------|----------------------------------------------------------------------------------------------|

|  |  ̈ | Unit                costs are for information purposes                only. |
|--|--------|-----------------------------------------------------------------------------|

|  |  ̈ | These                fees will be valid for 60 days from the date of this proposal, after                which                they may be subject to change. |
|--|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  |  ̈ | If                this proposal is accepted within a 60-day period, the fees will be                valid                until **21st                April 2007**.                After this date, the fees will be subject to an annual increase not                to                exceed the “Indice Syntec.” |
|--|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  |  ̈ | MDS                Pharma Services would be prepared to begin preliminary activities                on this                project immediately upon receipt of a Letter of Intent from **GENTIUM**,                containing all the agreed terms and conditions, including an initial                fee                payment. A formal agreement will be negotiated and executed within                60 days                of receipt of the Letter of Intent, in order for MDS Pharma Services                to                proceed with the project. |
|--|--------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

|  |  ̈ | The                currency to be used for invoicing and payments is detailed in the                budget                attached. Where MDS Pharma Services incurs Pass-Through Expenses                or                Investigator Grants in a currency differing form that used for invoicing,                these will be translated using the exchange rates prevailing at the                invoice date. The initial exchange rates used as a basis for calculating                MDS Pharma Services’ professional fees (the “Budgeted Rates”) are: 1,44 €                for 1£ and 0,77 € for 1 $US. Each calendar quarter, the average actual                exchange rate (the “Current Rate”) will be computed for each currency,                based on the spot rates on the last day of each of the 3 months in                the                quarter under review, as quoted by the website, www.oanda.com.                If the amount invoiced for professional fees during the calendar                quarter                calculated at the Current Rates differs from that calculated at the                Budgeted Rates by more than two percent (2%), MDS Pharma Services                shall                issue a separate invoice or credit note for the                difference. |
|--|--------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|

----

| *GENTIUM                      - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                      8* |  |
|--------------------------------------------------------------------------------------------------------------------|--|

|                                                                        | **No                of Units** | **Type                of Unit** | **Unit                Price (EUR)** | **TOTAL****(EUR)**    | **Comments**                                                                                                                                                                                                                                                                                                                        |
|-----------------------------------------------------------------------------|--------------------------------|---------------------------------|-------------------------------------|-----------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| **Hospitals                Payments****costs**                              |                           |
| Payments                                                                    | 1                              | payment                         | 95                                  | -                     | Per                payment, except for Italy (directly managed by                Gentium).                                                                                                                                                                                                                                          |
| **Annual                Safety Reports**                                    |                           |
| Preparation                and submissions of annual reports to authorities | 1                              | report                          | TBD                                 | TBD                   |                                                                                                                                                                                                                                                                                                                                |
| **Training**                                                                |                           |
| Team                Training (Webex)                                        | 1                              | training                        | 1                855                | 1                855  |                                                                                                                                                                                                                                                                                                                                |
| **Investigator                Meeting**                                     |                           |
| Investigator                Meeting Organisation                            | 1                              | meeting                         | -                                   | 1                680  | MDSPS’                IPD will liaise with a meeting planner to organise a unique investigators                meeting in Germany. 2 investigators per site, MDSPS’ IPD and Gentium team                members will attend this one-day meeting. Please refer to pass-through                costs for meeting budget. |
| Investigator                Meeting Preparation                             | 1                              | meeting                         | -                                   | 2                662  |                                                                                                                                                                                                                                                                                                                                |
| Investigator                Meeting Attendance                              | 1                              | meeting                         | -                                   | 2                272  |
| **Project                Management****(Extra)**                            |                           |
| CoSMOS                updates and Filing                                    | -                              | -                               | -                                   | 9                837  | We                assumed 153 patients for CoSMOS updates and 48 months for                filing.                                                                                                                                                                                                                                  |
| Project                Team Training                                        | 1                              | meeting                         | 1                704                | 1                704  | We                assumed the preparation of one meeting to be held in MDSPS’ office in                Italy. All 3 (assumption) CRAs will participate.                                                                                                                                                                       |
| Project                Team Interaction                                     | 48                             | months                          | 1                142                | 54                800 | We                assumed a 3 CRA team and monthly teleconferences. The cost includes                teleconference minutes. Monthly teleconferences are required to manage                these additional countries (not MDSPS CRAs).                                                                                             |
| Reports                Review                                               | 136                            | reports                         | 71                                  | 9                656  | We                assumed 6 monitoring, 1 initiation and 1 close out visits per site                (17                sites in total).                                                                                                                                                                                             |
| Co-monitoring                visits                                         | 3                              | visits                          | 2                130                | 6                390  | One                visit per country/CRA. Pass-through costs not included.                                                                                                                                                                                                                                                          |
| Additional                cost for Status                Report writing     | 16                             | reports                         | 207                                 | 3                312  | Additional                time for IPD and CTA, to be included in line item Status Reports.                Monthly                reports will be required to manage these additional countries (not                directly monitored by MDSPS).                                                                                   |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|   | **No                      of Units** | **Type                      of Unit** | **Unit                      Price (EUR)** | **TOTAL****(EUR)** | **Comments** |
|--------|--------------------------------------|---------------------------------------|-------------------------------------------|--------------------|--------------|

| **Co-monitoring                visits**       |   |
|-----------------------------------------------|--------|
| Co-monitoring                visits           | 7      | visits | 2                130 | 14                910 | 1                co-monitoring visit per country. |
| **EC                Amendment****Submission** |   |
| Italy                                         | 1      | submission | 731 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| France                                        | 1      | submission | 737 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| Netherlands                                   | 1      | submission | 821 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| UK                                            | 1      | submission | 760 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| Sweden                                        | 1      | submission | 836 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| Ireland                                       | 1      | submission | 760 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| Israel                                        | 1      | submission | 761 |   | Gentium                will provide MDSPS with the final text of the                amendment. |
| **ICF                Adaptation**             |   |
| Italy                                         | 1      | adaptation | 360 |   |   |
| France                                        | 1      | adaptation | 380 |   |   |
| Netherlands                                   | 1      | adaptation | 460 |   |   |
| UK                                            | 1      | adaptation | 409 |   |   |
| Israel                                        | 1      | adaptation | 380 |   |   |

|                                                                                                      | **No                of Units** | **Type                of Unit**  | **Unit                Price (EUR)** | **TOTAL                (EUR)** | **Comments**                                                                                                |
|-----------------------------------------------------------------------------------------------------------|--------------------------------|----------------------------------|-------------------------------------|--------------------------------|-------------------------------------------------------------------------------------------------------------|
| **Study                Initiation**                                                                       |                           |
| Drug                / Supplies Shipment Tracking                                                          | 1                              | shipment                         | 86                                  |                           | Corresponds                to each additional shipment (1 per site costed in global                budget). |
| **SAEs                Reporting to Sponsor / SAE notification to****EC                and Investigators** |                           |
| Italy                                                                                                     | 1                              | SAE/                Notification | 180                                 |                           |                                                                                                        |
| France                                                                                                    | 1                              | SAE/                Notification | 190                                 |                           |                                                                                                        |
| Netherlands                                                                                               | 1                              | SAE/                Notification | 230                                 |                           |                                                                                                        |

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| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|   | **No                      of Units** | **Type                      of Unit** | **Unit                      Price (EUR)** | **TOTAL****(EUR)** | **Comments** |
|--------|--------------------------------------|---------------------------------------|-------------------------------------------|--------------------|--------------|

| UK                                    | l      | SAE/                Notification | 205                  |   |                                                                                                                                                                                                                                                                                                      |
|---------------------------------------|--------|----------------------------------|----------------------|--------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sweden                                | l      | SAE/                Notification | 230                  |   |                                                                                                                                                                                                                                                                                                      |
| Ireland                               | l      | SAE/                Notification | 205                  |   |                                                                                                                                                                                                                                                                                                      |
| Israel                                | 1      | SAE/                Notification | 190                  |   |                                                                                                                                                                                                                                                                                                      |
| **Project                Management** |   |
| Sponsor                Meeting        | l      | meeting                          | 1                704 |   | This                half-day meeting will take place in Gentium office in Italy. MDSPS’ IPD                will attend (2 hours for preparation, 4 hours for attendance and                2 hours                for meeting minutes). Travel and accommodation costs not                included. |
| **Monitoring                visits**  |   |
| Italy                                 | l      | visit                            | 1                511 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| France                                | 1      | visit                            | 1                211 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| Netherlands                           | l      | visit                            | 1                911 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| UK                                    | l      | visit                            | 1                175 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| Sweden                                | l      | visit                            | 1                911 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| Ireland                               | 1      | visit                            | 1                175 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |
| Israel                                | l      | visit                            | 1                401 |   | Includes                report review by the IPD.                                                                                                                                                                                                                                                         |

|                                                                     | **No                of****Units** | **Type                of****Unit**                 | **TOTAL****(EUR)**    | **Comments**                                                                                                                               |
|--------------------------------------------------------------------------|-----------------------------------|----------------------------------------------------|-----------------------|--------------------------------------------------------------------------------------------------------------------------------------------|
| **Translations**                                                         |                              |
| Protocol                Synopsis Translation (Sweden only)               | 1                                 | language                                           | TBD                   |                                                                                                                                       |
| ICF                Adaptation and Translation                            | 2                                 | adaptation                with/without translation | TBD                   |                                                                                                                                       |
| **Travel                (accommodation****not                included)** |                              |
| Project                definition meeting                                | 1                                 | meeting                                            | 110                   | This                one-day meeting will take place in Gentium office in Italy. MDSPS’ IPD                will attend.               |
| Sponsor                meeting                                           | 1                                 | meeting                                            | 110                   | This                half-day meeting will take place in Gentium office in Italy. MDSPS’ IPD                will attend.              |
| Project                team training                                     | 1                                 | meeting                                            | 6                864  | This                one-day meeting will take place in MDSPS’ office in Italy. MDSPS’ IPD and                CRAs will attend. |
| Initiation                and close-out visits                           | 26                                | visits                                             | 25                000 | 13                sites, 1 initiation and 1 close-out visit per site. 1 co-monitoring                (optional) visit per country.         |
| Monitoring                and co-monitoring visits                       | 85                                | visits                                             |

----

| *GENTIUM                    - VOD - Defibrotide Study - Proposal no. AA2618420 - Version                    8* |  |
|----------------------------------------------------------------------------------------------------------------|--|

|                                              | **No                of****Units** | **Type                of Unit** | **Total****(EUR)**    | **Comments**                                                                                                                                                                                                                                                  |
|---------------------------------------------------|-----------------------------------|---------------------------------|-----------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Monitoring              Activities                |                              |
| Hospitals                fees                     | 13                                | sites                           | TBD                   |                                                                                                                                                                                                                                                          |
| **Meeting                Planner**                |                              |
| Investigator                meeting               | TBD                               | TBD                             | TBD                   | MDSPS’                IPD will liaise with a meeting planner to organise a unique investigators                meeting in Germany. 2 investigators per site, MDSPS’ IPD and Gentium team                members will attend this one-day meeting. |
| **EC/Regulatory                Fees**             |                              |
| Sweden                                            | -                                 | -                               | 10                298 |                                                                                                                                                                                                                                                          |
| UK                                                | -                                 | -                               | TBD                   |                                                                                                                                                                                                                                                          |
| Ireland                                           | -                                 | -                               | 2                350  |                                                                                                                                                                                                                                                          |
| **Courier                and document shipments** |                              |
| Investigators                file                 | 13                                | sites                           | TBD                   |                                                                                                                                                                                                                                                          |
| Extra-ordinary                courier             | -                                 | -                               | TBD                   |                                                                                                                                                                                                                                                          |
| **Import                Drug Company**            | -                                 | -                               | TBD                   | France                only.                                                                                                                                                                                                                                   |
| **Central                Pharmacy**               | -                                 | -                               | TBD                   | The                Netherlands and Sweden only.                                                                                                                                                                                                               |

*These      pass-through costs will be invoiced to *
***GENTIUM***
*      as      incurred, plus a 5% handling charge. List for information only and not      exhaustive.*

**Professional      Fees**

*MDS      Pharma Services has invoiced to Gentium an upfront payment (*
***55      685***
*      Euros) at Letter of Intent signature. Once the upfront payment balances the      production, MDS Pharma Services will invoice the actual monthly      production.*

**Variable      / Optional costs and Pass-Through Costs**

*These      costs will be invoiced as incurred, on a monthly basis.*

**Agostino      Lazzaro**
**20**
**10**
**23**
**GENTIUM**
**s**

*Please      double click on the icon to open the file.*

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