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MolMed S.p.A

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					                                Innovative
                          therapeutics f
                          th        ti for
                            the treatment
                                 of cancer




MolMed S.p.A.
R&D and business update

October 19, 2010
                                                                              Agenda

   14.00 h: MolMed R&D and business update presentation
      •   Executive summary
      •   Clinical development pipeline
      •   Research, development and GMP production
      •             strategy,
          Business strategy financials and milestones
      •   Closing remarks

   14.45 h: Q&A session

   15.15 h: Closure

   MolMed speakers
      •   Claudio Bordignon, Chairman and Chief Executive Officer
      •                    ,                        p
          Antonio Lambiase, Director Clinical Development
      •   Holger Neecke, Director Business Development & Investor Relations




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                            Forward-looking statements


The presentation contains certain forward-looking statements.
Although the Company believes its expectations are based on reasonable assumptions, these
forward-looking statements are subject to numerous risks and uncertainties, including
scientific, business, economic and financial factors, which could cause actual results to differ
materially from those anticipated in the forward-looking statements.
The company assumes no responsibility to update forward-looking statements or adapt them to
future events or developments.

This presentation is not an offer of securities for sale in any country or jurisdiction, including
the United States. Securities may not be sold to the public in the United States, in Australia, in
Canada, in Japan, or in other relevant jurisdictions without complying with local registration
requirements and other legal restrictions.

Declaration by the official Corporate Financial Reporting Manager:
The undersigned herewith attests, pursuant to Article 154-bis, paragraph 2 of the Italian
                                                   58/1998),
Consolidated Law on Finance (Legislative Decree 58/1998) that the accounting disclosure
contained in this presentation matches documentary evidence, corporate books, and
accounting records.
Enrico Cappelli, Chief Financial Officer, official Corporate Financial Reporting Manager


MolMed S.p.A. – R&D and business update, October 19, 2010                                        3
                                                            Presentation - table of contents


1. Executive summary – Claudio Bordignon

2. Clinical development pipeline
            TK
            NGR-hTNF

3. Research, development and GMP production

4. Business strategy, financials and milestones

            k
5 Cl i remarks
5. Closing




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                     Late-stage company focused on oncology

   Two investigational therapeutics in Phase III
      •                                                                     tumours,
           A fully proprietary selective vascular targeting agent for solid tumours in Phase III
           for mesothelioma
      •    A cell-based therapy for a novel approach to HSCT, in Phase III for high-risk leukaemia
           - Partnered in Asia with Takara Bio Inc.
   Experienced management team with strong board and scientific advisors
   Publicly listed in Milan (MLM)
      •    IPO in March 2008
      •    Share capital increase completed in August 2010
   Solid investor base
   Strong link to and roots in the San Raffaele Institute
      •    Option right to projects in the field of oncology

   Current staff 83, of which 62 dedicated to R&D




MolMed S.p.A. – R&D and business update, October 19, 2010                                          5
                                 Completed share capital increase: use of proceeds

    Gross proceeds of the completed share capital increase: € 58 million

    Use of proceeds:

      •Fund the clinical and industrial development of the Company’s most
                                              p               p y
         advanced product candidates, NGR-hTNF and TK

      •Strengthen R&D pipeline
      •Allow flexibility in development of MolMed’s products




MolMed S.p.A. – R&D and business update, October 19, 2010                        6
                                                            MolMed clinical development pipeline


Product       Indication (trial code)                                      Phase I   Phase II   Phase III
TK              g                  (     ,
              High-risk leukaemia (TK007, TK008))
              Leukaemia/Japan [by partner Takara Bio]
NGR-hTNF Solid tumours MTD (EORTC 16041)
              Solid tumours [low dose] (NGR002)
              Colorectal cancer (NGR006)
single agent
              Hepatocarcinoma (NGR008)
              Mesothelioma (NGR010, NGR015)
                    t mo rs
              Solid tumours [high dose] (NGR013)
              Solid tumours (NGR003)
              Small cell lung cancer (NGR007)
+ doxorubicin
              Ovarian cancer (NGR012)
              Sarcomas
+ Xelox       Colorectal cancer (NGR005)
+ cisplatin   Solid tumours (NGR004)
  cis/gem     Lung cancer/NSCLC (NGR014)
+ cis/pem

Legenda for clinical trials:          planned           ongoing    completed



MolMed S.p.A. – R&D and business update, October 19, 2010                                                   7
                                                            Key achievements in the last 6 months


                 TK

   Long-term findings of Phase II trial TK007 in high-risk leukaemia:
      • Renewal of thymic functionality
      • Direct anti-leukaemia effect
           NGR-hTNF
   Start of Phase III trial NGR015 in mesothelioma
   IND clearance of Phase III trial NGR015 by the FDA
   Results of Phase II trial NGR007 in small-cell lung cancer (+ doxorubicin)
   Results of Phase II trial NGR012 in ovarian cancer (+ doxorubicin)
   First data (recruitment and safety) of randomised Phase II trial NGR014 in non-
       ll ll lung cancer
   small cell l
   Full papers in major clinical journals on results of 4 Phase II trials:
      •   as monotherapy in colorectal cancer, liver cancer and mesothelioma
      •   in combination with Xelox in colorectal cancer

MolMed S.p.A. – R&D and business update, October 19, 2010                                       8
                                                            Presentation - table of contents


1. Executive summary

2. Clinical development pipeline
            TK – Claudio Bordignon
            NGR-hTNF

3. Research, development and GMP production

4. Business strategy, financials and milestones

5. Closing remarks




MolMed S.p.A. – R&D and business update, October 19, 2010
                                           TK opens the door of bone marrow transplant
                                                                      to more patients

   Indication:
    • High-risk acute leu ae a ( 5,000 pat e ts yea in Europe, No t America a d Japa )
        g    s        leukaemia (~25,000 patients/year  u ope, North  e ca and Japan*)
   Current therapy:
    • Pharmacotherapy: patients become disease free, but usually relapse within 1-2 years
    • Only established cure: haematopoietic stem cell transplant (HSCT) from a fully matched
        donor
   Unmet need:
    • ~50% of patients candidate to HSCT miss a fully matched donor
       50% f     i        did             i     f ll      h dd
    • HSCT from partially compatible donors (haplo-HSCT) is limited by either high risk of
        graft-versus-host disease (GvHD) or delayed immune-reconstitution

         TK, an adjunctive cell therapy, overcomes the limits of haplo-HSCT




*Globocan 2008, Company estimates
MolMed S.p.A. – R&D and business update, October 19, 2010                                    10
                                                   TK: patient-specific cell therapy based on
                                                        genetically engineered donor T cells

  TK: donor T cells transduced with the TK gene (TK cells) are infused into the patient
                 Donor
        Haematopoietic                                                                  Graft versus Infection
       Stem Cells (HSC)          HSC transplant               TK infusion   TK cells            (GvI)
                                    (day 0)                    (day +28)
                                                                                         Graft versus Leukaemia
                                                                                                   (GvL)

                                                             Patient                   Graft versus Host Disease
                                   Hospital                                                      (GvHD)
           Haplo-
          id   i l
          identical
            donor                        Donor T cells transduction,
                                          selection and expansion                            Abrogation by
                                                                                           administration of
                                                                                              ganciclovir

                   Donor                                                    TK cells
                                                    HSV-TK
                   T cells
                                                     y
                                   MolMed GMP facility



    TK provides a fully functional immune system to the patient while preventing
                                      post-transplant immune-suppression
            GvHD without the need of post transplant immune suppression

MolMed S.p.A. – R&D and business update, October 19, 2010                                                          11
                                                                      Key results of Phase I/II trial TK007

    Results published in 2009 by The Lancet Oncology
       TK007 trial data2
                                                  22 no TK cells infusion
           ITT population:
             50 patients                                                                       6 not immune-reconstituted
                  haplo-HSCT
        receiving haplo HSCT                            infused
                                                     28 i f d
                                                    with TK cells                         22 immune-reconstituted (IR)
                                                                                                    (>100 CD3+ cells/ml)

                                                             haplo-HSCT data
                                                                                                      TK007 IR patients
                                                                (EBMT survey,
                                                                                                          (22 patients) 2
                                                                266 patients) 1
        Median age                                                 35 years                                 56 years
        Transplant-related mortality
                                                                      50%                                      14%
        (at 50 months from HSCT)
        Leukaemia relapse                                           20-30%                                     10%
        4-year disease-free survival                                20-30%                                     45%
        GvHD:
           occurrence                                                 n.a.                                     50%
           control                                                                                             100%

Sources: 1Ciceri et al. Blood, 2008 November 1;112(9):3574-3581, 2Ciceri, Bonini et al., Lancet Oncol. 2009 May 1;10:489-500
MolMed S.p.A. – R&D and business update, October 19, 2010                                                                      12
                           Ongoing Phase III trial in high-risk leukaemia (TK008)


                     Recruiting adult patients (age ≥ 18 years):
                         High-risk leukaemia (AML or ALL) in 1 or subsequent CR
                         Candidate to haplo-HSCT
                                                            N 152
                                                            N=152

                                                       Randomisation
                                                            3:1
                                 n=101                                    n=51

                           Haplo-HSCT + TK                             Haplo-HSCT

                                            Primary endpoint:
                                       Transplant-related mortality
                                          Secondary endpoints:
                          Disease-free survival, overall survival, relapse, safety




MolMed S.p.A. – R&D and business update, October 19, 2010                            13
                                                            EMA and FDA interactions for TK

EMA:
    2003: Orphan Drug designation for haematological malignancies
    2007: Protocol assistance for Phase III trial TK008
                                           p    (CAT) classified TK as “cell
    2009: EMA Commtittee for Advanced Therapies (   )
    therapy”

FDA:
    2005: Orphan Drug designation for haematological malignancies
    April 2010, IND filed for the conduction of Phase 3 clinical trial:
       •   Suggestion to use Disease Free Survival as primary endpoint
       •   Compatible with EMA registration strategy: TRM and OS endpoints
       •            follow-up
           1H 2011: follow up meeting with FDA
       •   Recombinant DNA Advisory Committee: positive opinion received




MolMed S.p.A. – R&D and business update, October 19, 2010                                 14
                       TK manufacturing process: automation project ongoing

   Current manufacturing process conducted in semi-automatic closed system

   Feasibility study for fully-automated closed system (→ manufacturing
   machine) completed

   Process automation project started in June 2010 with two partners
      •    Awarded a € 1.4 million grant from
           Regione Lombardia to partially                   TK-manufacturing machine: feasibility study
                                                            TK manufacturing
           cover R&D costs incurred


             Investment in process
             automation graduated
              following progress of
              Phase III trial TK008




MolMed S.p.A. – R&D and business update, October 19, 2010                                                 15
                                                            Presentation - table of contents


1. Executive summary

2. Clinical development pipeline
            TK
            NGR-hTNF – Claudio Bordignon, Antonio Lambiase

3. Research, development and GMP production

4. Business strategy, financials and milestones

5. Closing remarks




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                               NGR-hTNF at a glance


   First-in-class vascular targeting agent (VTA)
   Unique mechanism of action:
   U i       h i     f ti
    • Selective targeting of tumour blood vessels
    • Increases intra-tumour chemotherapy uptake
   Indications: vascularised solid tumors including both orphan and
   broad indications
   Unmet need:
    • Lack of therapies effective against advanced-stage solid tumors
    • Low toxicity treatment


         NGR-hTNF: new targeted biologic with promising anti-tumour activity
                           and favourable safety profile




MolMed S.p.A. – R&D and business update, October 19, 2010                         17
                                    NGR-hTNF: a novel vascular targeting agent with
                                       broad therapeutic potential in solid tumours

   Vascular targeting peptide (NGR) fused to human cytokine TNF (Tumour Necrosis
         )
   Factor)
   Structure of NGR-hTNF monomer




                                                              Human TNF:
                                                                Binds to TNF receptors (TNF-
                                                                RI and TNF-RII) on vascular
                                                                endothelium
  Cyclic CNGRCG peptide:                                        Strong antitumour effect
                                                                S          i         ff
     targets CD13, a receptor                                   Destroys blood vessel function
     present on tumour neo-
                                                                Approved as anticancer drug,
     vasculature
                                                                but toxicity limits application
                                                                           y         pp
                                                                to isolated limb perfusion
                                 Resolution: 2.8 Å




MolMed S.p.A. – R&D and business update, October 19, 2010                                     18
                                                            Clinical development as monotherapy

                              0.2→1.6 µg/m2                                  0.2→60 µg/m2                         60→225 µg/m2
 Ph I


                              NGR002: N=16                                 EORTC16041: N=70                       NGR013: N=32
                                 OBD: 0 8
                                      0.8                                       MTD: 45                       (prem ↑ inf) - No DLTs
                                                                                                              (prem-↑




                                                                                                                                       ation therapy
 Ph Ib




                                                                   NGR004          NGR003
                                                                     N=22           N=15
 P




                                                                  + Cisplatin       + Doxo

                 NGR010         NGR008     NGR006
 Ph II




                  N=57           N=40       N=46




                                                                                                                                 Combina
                  MPM            HCC        CRC
 P




                   2nd line     2nd line   ≥3rd line
                   apy




                                                       NGR005: N=24      NGR007: N=28         NGR012: N=37
 Ph IIb

           Monothera




                                                       0.8/45
                                                       0 8/45 + Xelox      0 8 + Doxo
                                                                           0.8                 0.8
                                                                                               0 8 + Doxo
                                                        CRC ≥ 3rd line    SCLC 2nd line         OC 2nd line
 Ph II R




                                                               NGR014: N=102                                     NGR016: N=96
                                                                             0.8
                                                              Cispl-chemo ± 0 8                                  0.8/45
                                                                                                                 0 8/45 ± Doxo
           M




                                                                NSCLC 1st line                                    STS 2nd line


              NGR015: N=390
 Ph III




                      0.8
                BIC ± 0 8
  h




               MPM 2 nd line                                             Completed           Ongoing      Planned


MolMed S.p.A. – R&D and business update, October 19, 2010                                                                                    19
                          Summary of completed Phase II trials as monotherapy

   3 single-arm trials completed in pre-treated patients with advanced-stage disease
   with 2 dosing schedules tested (triweekly and weekly)

   Very favourable safety profile:
    • Side effects essentially limited to constitutional symptoms (chills) during first infusions
    • No long term toxicity observed (up to 2 years of continuing administrations)
         long-term
    • Lack of grade 3 or 4 drug-related toxicities
     t tu ou act v ty observed:
   Antitumour activity obse ved:
    • In mesothelioma (trial NGR010): More prolonged clinical benefit with treatment
        frequency intensification (weekly instead of triweekly)
    • In colorectal cancer (trial NGR006): Median overall survival doubled as compared to
        Best Supportive Care data reported in literature
    • In liver cancer (trial NGR008): One complete response obtained – Patient is disease-free
        since May 2008



            Results published in 2010 as f ll papers in primary clinical journals
            R   lt    bli h d i          full        i    i      li i l j      l

MolMed S.p.A. – R&D and business update, October 19, 2010                                           20
                       NGR010: Phase II trial as monotherapy in mesothelioma


    57 pemetrexed-pretreated patients                                   Overall Survival by disease status (n=57)
                                                                                            100                Pts with disease control
    0 8 µg/m2 q3w (n=43) or weekly (n=14)
    0.8                                                                                                        Pts with disease progression
                                                                                            80
    Disease control rate: 26 (46%)




                                                                         Percent survival
                                                                                                                       Median Overall Survival:
       • 1 PR + 25 SD                                                                       60                         16,5 versus 8,3 months

    M di PFS: 2 8 months
    Median PFS 2.8    h




                                                                               t
                                                                                            40

       • In pts with disease control: 4.7 months                                            20

    Median OS: 12.1 months                                                                    0
                                                                                                  0   6   12      18       24     30     36
                                                                                                               Time (months)
 PFS and OS by schedule in all patients (n=57) and in patients with disease control (n=26)
                                                            weekly
                                                            triweekly




Updated from Gregorc V et al, JCO 2010
MolMed S.p.A. – R&D and business update, October 19, 2010                                                                                         21
                            NGR015: Phase III trial in mesothelioma (second line)


    Inclusion criteria:                                      Indication: Patients pre-treated with a
       • Only 1 prior regimen
            y p         g                                          pemetrexed based regimen
                                                                   pemetrexed-based
       • PS 0-2
     Stratification:                                                          NGR-hTNF 0.8 µg/m2 weekly
       • PS (0 v 1-2)
                 1 2)                                         n=195                     + BIC
       • Candidate for chemo (yes v no)
                                                            Random
    Primary endpoint: Overall survival                                                    Placebo
                                                              n=195                        + BIC
    Secondary endpoints:
    S    d      d i
       • Progression-free survival
       • Disease control rate and duration                    BIC: Best Investigator’s Choice = current
       • Safety                                               treatment option in clinical practice
       • Quality of life                                      Includes either best supportive care
       • Medical care utilisation                             alone or combined with single-agent
                                                              chemotherapy (doxorubicin,
                                                              gemcitabine, or vinorelbine)
       First patient treated in April 2010
      IND cleared by the FDA in May 2010                        N=390 - Double-blind, placebo-controlled
                                                                    HR for OS: 0.73 (α=.05; β=.20)



Gregorc V et al, JCO 2010
MolMed S.p.A. – R&D and business update, October 19, 2010                                                  22
                                                      EMA and FDA interactions for NGR-hTNF

EMA:
    2008: Orphan Drug designation for malignant mesothelioma
    2008: Protocol Assistance for:
       •   Manufacturing development of drug product, and comparability assessment
       •   Phase III clinical t i l d i f mesothelioma
           Ph         li i l trial design for th li
    2009: Orphan Drug designation for primary liver cancer
    2011: Planned follow-up request to Protocol Assistance of 2008

FDA:
    2008: Orphan Drug designation for malignant mesothelioma
    2009: Orphan Drug designation for primary liver cancer
    2010 (April): IND filed for the conduction of Phase 3 clinical trial in mesothelioma
    2010 (May): IND clearance received
         (M )        l            i d
       •   General comments and recommendations received on future BLA
       •   Meetings regarding clinical development and CMC are planned in 1H 2011



MolMed S.p.A. – R&D and business update, October 19, 2010                                  23
                                                   Clinical development in combination therapy

                              0.2→1.6 µg/m2                                  0.2→60 µg/m2                         60→225 µg/m2
 Ph I


                              NGR002: N=16                                 EORTC16041: N=70                       NGR013: N=32
                                 OBD: 0 8
                                      0.8                                       MTD: 45                       (prem ↑ inf) - No DLTs
                                                                                                              (prem-↑




                                                                                                                                       ation therapy
 Ph Ib




                                                                   NGR004          NGR003
                                                                     N=22           N=15
 P




                                                                  + Cisplatin       + Doxo

                 NGR010         NGR008     NGR006
 Ph II




                  N=57           N=40       N=46




                                                                                                                                 Combina
                  MPM            HCC        CRC
 P




                   2nd line     2nd line   ≥3rd line
                   apy




                                                       NGR005: N=24      NGR007: N=28         NGR012: N=37
 Ph IIb

           Monothera




                                                       0.8/45
                                                       0 8/45 + Xelox      0 8 + Doxo
                                                                           0.8                 0.8
                                                                                               0 8 + Doxo
                                                        CRC ≥ 3rd line    SCLC 2nd line         OC 2nd line
 Ph II R




                                                               NGR014: N=102                                     NGR016: N=96
                                                                             0.8
                                                              Cispl-chemo ± 0 8                                  0.8/45
                                                                                                                 0 8/45 ± Doxo
           M




                                                                NSCLC 1st line                                    STS 2nd line


              NGR015: N=390
 Ph III




                      0.8
                BIC ± 0 8
  h




               MPM 2 nd line                                             Completed           Ongoing      Planned


MolMed S.p.A. – R&D and business update, October 19, 2010                                                                                    24
                                                                 NGR005: Phase II with Xelox in
                                                            pre-treated colorectal cancer (CRC)

    Single-arm, sequential cohort study                                  Waterfall plot at 0.8 and 45 μg/m2
     . μg     (p                  , );
    0.8 μg/m2 (prior lines: median, 3); n=12
                                                                                                   NGR-hTNF 0.8 μg/m2 + Xelox
    45   μg/m2     (prior lines: median, 2); n=12




                                                                Max. chang in target lesions (%)
                                                                                                   NGR-hTNF 45 μg/m2 + Xelox

    Activity at 0.8 μg/m2:
      • 1 PR & 5 SD ( di d ti 4 6
                     (median duration: 4.6
        months)
      • 3-month PFS rate: 50%
      • 3 patients with PFS > PFS on last regimen




                                                                         ge
    Activity at 45 μg/m2:
      • 6 SD (median duration: 3.6 months)
      • 3-month PFS rate: 33%

                  Antitumour activity mainly observed in the low-dose cohort:
                        further confirmation of low dose as optimal dose



Mammoliti S et al, Ann Onc 2010
MolMed S.p.A. – R&D and business update, October 19, 2010                                                                       25
                                                             NGR007: Phase II with doxorubicin in
                                                            relapsed small-cell lung cancer (SCLC)

    Prior therapies: median, 1 (1-3)                               RR by prior platinum sensitivity
    Prior platinum sensitivity
      • Refractory/resistant: 58%
      • Sensitive relapsed: 42%
    Response rate (RR)
      • Partial response (PR): 23%
      • Disease control (DC): 54%
    Median PFS: 3.2 months
                                63
    Median PFS in pts with DC: 6.3 months

   Nonhaematological toxicity                                      Maximal change in target lesions




Abstract 446P ESMO 2010 (poster)
MolMed S.p.A. – R&D and business update, October 19, 2010                                             26
                                                             NGR007: Phase II with doxorubicin in
                                                            relapsed small-cell lung cancer (SCLC)

    Prior therapies: median, 1 (1-3)                               RR by prior platinum sensitivity
    Prior platinum sensitivity
      • Refractory/resistant: 58%
      • Sensitive relapsed: 42%
    Response rate (RR)
      • Partial response (PR): 23%
      • Disease control (DC): 54%
    Median PFS: 3.2 months
                                63
    Median PFS in pts with DC: 6.3 months

   Nonhaematological toxicity                                      Maximal change in target lesions




               Similar antitumour activity observed in both platinum-resistant
                               and platinum-sensitive patients
Abstract 446P ESMO 2010 (poster)
MolMed S.p.A. – R&D and business update, October 19, 2010                                             27
                                                            NGR012: Phase II with doxorubicin in
                                                                 recurrent ovarian cancer (OC)

   17 patients analysed (37 enrolled)                             Maximal change in target lesions
      • Prior regimens: median,            1 (1-5)
      • Refractory resistant (RR):
        Refractory-resistant                 65%
      • Partially sensitive (PS):            35%
   Cycles in combination: median, 6
   Response rate:
      p
      • Partial response (PR): 6 (35%)
      • Stable disease (SD): 6 (35%)
      • Disease control rate: 12 (70%)
               5.0
   Median PFS: 5 0 months
    • 4.9 in RR and 12.0 in PR
    • 7.0 in patients with disease control
                                                                  Progression-free survival
 Tolerability profile




Abstract 982P ESMO 2010 (poster)
MolMed S.p.A. – R&D and business update, October 19, 2010                                            28
                                                            NGR012: Phase II with doxorubicin in
                                                                 recurrent ovarian cancer (OC)

   17 patients analysed (37 enrolled)                             Maximal change in target lesions
      • Prior regimens: median,            1 (1-5)
      • Refractory resistant (RR):
        Refractory-resistant                 65%
      • Partially sensitive (PS):            35%
   Cycles in combination: median, 6
   Response rate:
      p
      • Partial response (PR): 6 (35%)
      • Stable disease (SD): 6 (35%)
      • Disease control rate: 12 (70%)
               5.0
   Median PFS: 5 0 months
    • 4.9 in RR and 12.0 in PR
    • 7.0 in patients with disease control
                                                                  Progression-free survival
 Tolerability profile




    Overall primary endpoint - 6 responses out of 37 patients - already met after
                           first study stage (17 patients)
Abstract 982P ESMO 2010 (poster)
MolMed S.p.A. – R&D and business update, October 19, 2010                                            29
                       NGR014: Random Ph II trial with cisplatin-based chemo
                              in first-line non-small-cell lung cancer (NSCLC)

  NGR014 trial design

                                                                    NGR-hTNF 0 8
                                                                    NGR hTNF 0.8 µg/m2 q3w
                                               n=51                           +
                                                                       Chemotherapy(∗)
         NO prior therapy
         Performance status
         0-2                                                             Chemotherapy(∗)
                                               n=51

                                                            (∗) According to histology:
                                                               Cisplatin/gemcitabine (squamous)
                                                               Cisplatin/pemetrexed (
                                                               Ci l ti /     t                  )
                                                                                  d (nonsquamous)


       p                  p     y      y              p
    65 patients enrolled, primary analsysis for PFS expected in mid 2011
    In patients with squamous histology, no safety signals of bleeding
    (hemoptysis or hematemesis) in the experimental arm



MolMed S.p.A. – R&D and business update, October 19, 2010                                           30
                                                                                      Clinical development plan

                              0.2→1.6 µg/m2                                   0.2→60 µg/m2                         60→225 µg/m2
 Ph I


                              NGR002: N=16                                  EORTC16041: N=70                       NGR013: N=32
                                 OBD: 0 8
                                      0.8                                        MTD: 45                       (prem ↑ inf) - No DLTs
                                                                                                               (prem-↑




                                                                                                                                         ation therapy
 Ph Ib




                                                                    NGR004          NGR003
                                                                      N=22           N=15
 P




                                                                   + Cisplatin       + Doxo

                 NGR010         NGR008     NGR006
 Ph II




                  N=57           N=40       N=46




                                                                                                                                   Combina
                  MPM            HCC        CRC
 P




                   2nd line     2nd line   ≥3rd line
                   apy




                                                        NGR005: N=24      NGR007: N=28         NGR012: N=37
 Ph IIb

           Monothera




                                                        0.8/45
                                                        0 8/45 + Xelox      0 8 + Doxo
                                                                            0.8                 0.8
                                                                                                0 8 + Doxo
                                                         CRC ≥ 3rd line    SCLC 2nd line         OC 2nd line
 Ph II R




                                 NGR019: N=100                  NGR014: N=102                 NGR018: N=100       NGR016: N=96
                                0.8
                                0 8 (maintenance)                             0.8
                                                               Cispl-chemo ± 0 8                        0.8
                                                                                                Doxo ± 0 8        0.8/45
                                                                                                                  0 8/45 ± Doxo
           M




                                    MPM 1st line                 NSCLC 1st line                 OC 2nd line        STS 2nd line


              NGR015: N=390                     NGR0..: N=…
 Ph III




                      0.8
                BIC ± 0 8                          S
                                                   Secondd
  h




               MPM 2 nd line                     indication               Completed           Ongoing      Planned         New trials


MolMed S.p.A. – R&D and business update, October 19, 2010                                                                                      31
                                                            Presentation - table of contents


1. Executive summary

2. Clinical development pipeline
            NGR-hTNF
            TK

3. Research, development and GMP production - Claudio Bordignon

4. Business strategy, financials and milestones

            k
5 Cl i remarks
5. Closing




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                Insight into NGR-hTNF mechanism of action

    Specific targeting of angiogenic tumour vessels

    Impairment of survival signals and induction of programmed cell death
    (apoptosis) of tumour blood vessel endothelial cells

    Effects on tumor blood vessels and tumor environment

    No increase in Bone Marrow-derived Cell (BMDC) infiltrates at tumour site and
    in circulating growth factors, which stimulate tumour angiogenesis, re-growth
    after therapy and metastasis




            Significant anti-vascular and anti-tumour activity without inducing
                        detrimental counter-regulatory mechanisms

MolMed S.p.A. – R&D and business update, October 19, 2010                               33
                                                            Vascular/tumour targeting programme

    NGR-IFNγ - candidate drug in preclinical development:
       •   specific targeting of angiogenic tumour vessels mediated by the interactions between
           NGR/IFNγ and CD13/IFN-R
       •   lack of targeting on healthy tissues
       •      i         i i in h b           f   j      i ff
           antitumor activity i the absence of major toxic effects
       •   antitumor activity at low dose in mouse models of lymphoma, colon carcinoma and
           prostate carcinoma
       •   multiple administration prolonged survival of prostate carcinoma-bearing mice


    New leads - Identification and validation of new vascular/tumour targeting
    moieties and of appropriate effector moieties to be conjugated or used in
    combination:
       •                                                                   specificity
           Three new targeting peptides identified with high stability and specificit for either
                  ne                                ith      stabilit
           vascular or tumour targets
       •   Molecules with anti-tumour properties selected, including a class of kinase
           inhibitors

MolMed S.p.A. – R&D and business update, October 19, 2010                                      34
                                                             GMP production in cell & gene therapy

     In-house GMP manufacturing facility authorised since 2003


     Manufacturing of genetically modified patient-specific cells
        •    Production of TK for Phase III
        •    Services to third parties: tailored solutions for cell & gene
             therapy projects


     Major collaborations for clinical trials:
        •                                              genetic diseases
             Telethon Foundation: gene therapy of rare g
                                  g         py
        •    San Raffaele/TIGET: gene therapy of inherited immunodeficiency
        •    EU-FP7 projects: PERSIST, OPTISTEM, ATTRACT, CELL-PID


     Major development projects:
        •        y            y            production p
             Fully automated system for TK p          process
        •    Lentivirus vector platform for gene therapy products
 MolMed S.p.A. – R&D and business update, October 19, 2010
35                                                                                               35
                                                            Presentation - table of contents


1. Executive summary

2. Clinical development pipeline
            NGR-hTNF
            TK

3. Research, development and GMP production

4. Business strategy, financials and milestones – Holger Neecke

            k
5 Cl i remarks
5. Closing




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                            TK: a breakthrough therapy

     TK advantages assessed in Phase II:
     • No donor T cell depletion, no post-transplant immunosuppression
                                     post transplant
     • Early and effective immune-reconstitution
     • Reduction of transplant-related mortality
     • Protection from relapse (
                            p (Graft versus Leukemia)  )
     Safety:
     • Prompt control of GvHD
     • No adverse events related to gene transfer procedure
     Manufacturing: automated cell processing machine for market in development
     Orphan Drug designation: high-risk acute leukemia in EU and US
       p       g     g          g
     Market potential: ~12.500 high-risk acute leukemia patients without fully
     compatible donor


         TK enables haplo-HSCT, the only potential cure for leukaemia patients
                            lacking a fully matched donor

MolMed S.p.A. – R&D and business update, October 19, 2010                            37
                                               NGR-hTNF: a unique treatment opportunity


    Multiple applications within cancer treatment algorithms:
     • Antitumour activity observed so far in five indications tested in Phase II
     • Active as single agent and in combination with chemotherapy
    Favourable toxicity profile, better than competitors:
     • vs. other VTAs: no cardiovascular toxicity
     • vs. anti-angiogenics: no gastro-intestinal perforations, bleeding,
        thromboembolisms
    Pharmaceutical development: manufacturing process for Phase III & MAA
    developed by Avecia Biologics, now MSD Biologics
    Orphan Drug designation: mesothelioma and liver cancer in EU and US
    Market potential: ~1.4 million patients/year in Europe, North America and
    Japan in the six indications tested in Phase II


               New treatment option for both orphan and broad indications
                       as single agent and in combination therapy


MolMed S.p.A. – R&D and business update, October 19, 2010                             38
                                             Business model: innovation & risk mitigation


          MM core assets & competencies                               Diversifying assets
                  Cell & gene therapeutics                  Vascular/tumour targeting biological drugs


                                TK                                         NGR-hTNF
                          Cell therapy                                Recombinant protein
        Orphan indication with high unmet need                   Many indications, broad markets
                 Patient-specific medicine                            Potential blockbuster



                      Business model                                    Business model
           O    industrial    d ti
           Own i d t i l production and  d                           Production out-sourced
        commercialisation capabilities planned
                                                                 Partner development and
       Partnered with Takara Bio for Japan/Asia             commercialisation with pharma/biotech




                         Two technology platforms and two business models
                                     for di     ifi d i li
                                     f a diversified pipeline

MolMed S.p.A. – R&D and business update, October 19, 2010                                                39
                                                                                Cash to support
                                                                product development programmes

MolMed financials 1H 2010 (€ thousand)

                                                            FY 2007    FY 2008    FY 2009    1H 2010


Revenues & other income                                       3,814      3,963      4,712        1,178

Operating costs                                             (16,763)   (23,073)   (22,519)     (9,683)

R   lt for the i d
Result f th period                                          (12,696)
                                                            (12 696)   (17,446)
                                                                       (17 446)   (17,169)
                                                                                  (17 169)     (8,642)
                                                                                               (8 642)



Net fi
    financial position
          i l    ii                                             666
                                                              5,666     35,281
                                                                        3 28       19,567
                                                                                    9 6        ∗12,259
                                                                                                 22 9


                 ∗ Before share capital increase, completed in August 2010:
                                  € 58 million gross proceeds
               that will be used to support development of product candidates



MolMed S.p.A. – R&D and business update, October 19, 2010                                              40
                                                                                      Shareholders structure

   Listed on Milan Stock Exchange (MTA, standard segment) since March 5, 2008:
   Financials:
      • Capital raised at IPO: € 56 million (gross proceeds)
      • Share capital increase in 2010: € 58 million (gross proceeds)
      • Market cap (Oct 18, 2010): € 93.5 million
      • Average volume (last 3 months): 2.3 million shares
      • Issued shares: 210 415 616
                       210,415,616
                                                       Shareholders (Sep 15, 2010)

                                                                          Fininvest S.p.A. 23.956%
                                                                                                                           S.p.A.
                                                                                                          Science Park Raf S p A
                                                                                                                 10.494%
                                                                                                                 H-Equity S.r.l.
                                                                                                                     4.064%
                                                                                                                 H-Invest S.p.A.
                                                                                                                 H Invest S p A
                                                                                                                     4.064%
                                                                                                          Airain Lda
                                                                                       Delfin Jefferies    7.111%
                                                             Free float
                                                                                       S à r l Int. Ltd
                                                                                       S.à r.l.
                                                              41.021%
                                                                                       4.300% 4.990%

MolMed S.p.A. – R&D and business update, October 19, 2010                                                                          41
                                                     Achievements and milestones 2010-2013


                                              TK                                     NGR-hTNF
    2010          Long-term
                ✓ Long term findings Phase II trial TK007:        ✓   Start Phase III trial in MPM
                      GvL and thymic renewal                      ✓   FDA IND clearance of Phase III in MPM
                      Expand Phase III trial TK008:               ✓ Results of Phase II trial + doxo in SCLC
                                p
                         In Europe                                ✓ Results of Phase II trial + doxo in OC
                         In US                                      First data of random Phase II trial +
                                                                  ✓
                      First data (safety) Phase III trial TK008     cisplatin-chemo in NSCLC
                                                                  ✓ Full papers of completed Phase II trials
                                                                      Start random Phase II trial + doxo in STS
    2011              Update on Phase III trial TK008                 Results of random Phase II trial +
                                                                      cisplatin-chemo in NSCLC
                                                                      First data (safety) of Phase III trial in
                                                                      MPM
                                                                      Start random Phase II trial in OC and in
                                                                      MPM (maintenance)
                                                                      Start Phase III trial in second indication
    2012              BLA filing                                      Results of random Phase II trials in STS,
                                                                      OC and MPM (maint.)
    2013                                                              BLA filing for MPM

MolMed S.p.A. – R&D and business update, October 19, 2010                                                          42
                                                            Presentation - table of contents


1. Executive summary

2. Clinical development pipeline
            NGR-hTNF
            TK

3. Research, development and GMP production

4. Business strategy, financials and milestones

            k Claudio B di
5 Cl i remarks – Cl di Bordignon
5. Closing




MolMed S.p.A. – R&D and business update, October 19, 2010
                                                                         Strong position for growth


    Unique investigational therapeutics in oncology in Phase III
    Diversified, risk-mitigating technology platforms
    Di    ifi d i k i i i           h l      l f
    Cash to support product development programmes
    Opportunity to feed research pipeline through option right from San Raffaele



                                                            Late-stage
                                                             pipeline
                                                                             Leader in
                                  Proven
                                                                          oncology clinical
                                innovation
                                                                           development
                                                                                              Public company
  Experienced
                                                                                                with strong
  management
                                                                                               investor base




MolMed S.p.A. – R&D and business update, October 19, 2010                                                  44
                                                                  Innovative
                                                            therapeutics f
                                                            th        ti for
                                                              the treatment
                                                                   of cancer




Q
Q&A session


MolMed S.p.A. – R&D and business update, October 19, 2010
                                                            MolMed update events 4Q 2010


 Financial calendar
        b
   November 11                                   l        f      2010
                                         Financial report for Q3 20 0




 Business meetings
   November 2-4                                           p                     p ,        (USA)
                                         Windhover’s Therapeutic Area Partnerships, Boston (   )
   November 15-17                        Bio Europe 2010, München (Germany)


 Clinical meetings
   December 4-7                          ASH Annual Meeting, Orlando (USA)




MolMed S.p.A. – R&D and business update, October 19, 2010                                          46
Contact:                                                          Innovative
Claudio Bordignon, Chairman and CEO                         therapeutics f
                                                            th        ti for
MolMed S.p.A.
Via Olgettina, 58 - 20132 Milan, Italy
                                                              the treatment
phone: +39 0221277 1
            0221277.1                                              of cancer
fax: +39 0221277.325
e-mail: investor.relations@molmed.com




          y       y
    Thank you very much
     for your attention

MolMed S.p.A. – R&D and business update, October 19, 2010

				
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