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Corporate Presentation
   September 2011
Forward-Looking Statements



 The statements made in this presentation may contain certain forward-
 looking comments. Actual events or results may differ from the
 Company’s expectations. In addition to the matters described in the
 presentation, future actions by the European Agency for Evaluation of
 Medicinal Products, the U.S. Food and Drug Administration or
 equivalent regulatory authorities in other countries and results of
 pending or future clinical trials, as well as other risk factors outlined
 from time to time in the Company’s regulatory filings, may affect
 actual results achieved by the Company. The Alternative Investment
 Market (AIM) has not reviewed and does not accept responsibility for
 the adequacy or accuracy of this presentation.




                                                                             2
                                                                                 2
Background


•    Silence Therapeutics AG (formerly Atugen AG) was founded in 1998 as spin-off
     from RPI (later renamed to Sirna) and financed by MPM Capital, Apax and NVF
•    Target discovery and validation service company using antisense and delivery
     technologies -> over US$20m accum. service revenues from pharma companies
•    Developing delivery technologies for oligonucleotides since 1998
•    First AtuRNAi patent application filed in 2002, US patent granted in Nov. 2008
•    In 2005 reverse merger with SR Pharma plc (shell) listed on AIM, London
•    Renamed to Silence Therapeutics plc/AG in 2007 (LSE: SLN)
•    Acquired US siRNA therapeutics company Intradigm Corp. in January 2010
•    To date over £50m invested in RNAi platform
•    Well funded following successful £5.9m fundraising in May 2011
•    Current market cap. c.£11m -> technology value of only £5m
                                                                                      3
Overview


• World leader in the discovery, development and delivery of novel RNA interference
  (RNAi) therapeutics for the treatment of serious diseases
  − RNAi offers a unique new class of drugs that overcomes hurdles of existing drugs

• One of the sector’s most comprehensive RNAi platforms
  − Deliver to more target cells and tissues that anyone else (e.g. AtuPlex, DACC)

• One of the industry’s broadest RNAi clinical pipelines
  − Five of the 12 siRNA (& 4 of the 5 Phase II) clinical programs worldwide are based on Silence
    technology
  − Clinical and pre-clinical pipeline in diverse therapeutic areas – metabolic, pulmonary, vascular,
    oncology
  − Encouraging Phase I data on lead internal candidate Atu027 recently presented at ASCO

• Validating partnerships with leading global pharmaceutical companies
  − AstraZeneca, Pfizer/Quark, Novartis/Quark and Dainippon Sumitomo

• Broad intellectual property portfolio
  − Issued patents covering aspects of delivery, sequences and structures


                                                                                                        4
Silence Product Pipeline

                     Products     Indications             Partners       Target   Delivery   Pre-       Phase I   Phase II   Target Tissue /
                                                                                             Clinical                        Organ


                     PF-4523655   Diabetic Macular        Pfizer/Quark   RTP801   Naked                                      Local Delivery to the
                     (AtuRNAi)    Edema                                           siRNA                                      Eye
Partnered programs




                     PF-4523655   Age-related Macular     Pfizer/Quark   RTP801   Naked                                      Local Delivery to the
                     (AtuRNAi)    Degen                                           siRNA                                      Eye

                     QPI-1002     Prevention of Delayed   Novartis/      P53      Naked                                      Systemic Delivery to
                     (AtuRNAi)    Graft Function          Quark                   siRNA                                      the Kidney


                     QPI-1002     Acute Kidney Injury     Novartis/      P53      Naked                                      Systemic Delivery to
                     (AtuRNAi)                            Quark                   siRNA                                      the Kidney



                     Atu027       GI & Lung & other       Internal       PKN3     AtuPLEX                                    Systemic Delivery to
                     (AtuRNAi)    cancers                                                                                    Tumor Endothelium


                     Atu134       Solid Tumors            Internal                AtuPLEX                                    Systemic Delivery to
Internal programs




                     (AtuRNAi)                                                                                               Tumor Endothelium


                     Atu111       Acute Lung Injury       Internal                DACC                                       Systemic Delivery to
                     (AtuRNAi)                                                                                               Lung Endothelium


                     Atu195       Solid Tumors            Internal                AtuPLEX                                    Systemic Delivery to
                     (AtuRNAi)                                                                                               Tumor Endothelium



                            Almost half of all ongoing siRNA clinical trials are based
                                              on Silence technology                                                                              5
Current Partnership Overview

         Silence’s RNAi therapeutic platform has been
        validated through multiple major partnerships

          • AstraZeneca - $15M upfront payment with up to $400M in milestones
            plus sales royalties for five targets (2007, extended 2010)

          • AstraZeneca – Novel approaches to delivery of siRNA molecules (2008,
            extended 2010)

          • Pfizer/Quark – Phase II products for diabetic macular edema and age-
            related macular degeneration; $95M in milestones plus royalties (2006)

          • Novartis/Quark – Phase I/II products for acute renal failure and kidney
            transplantation; $82m in milestones plus royalties (2010)

          • Dainippon Sumitomo – siRNA delivery collaboration (2009, expanded
            2010)

                                                                                      6
Commercialisation Strategy


•   Out-license / co-develop internal candidates
    – e.g. Atu027 (in 2012), Atu111 (in 2012), Atu134 (TBD), Atu195 (TBD)

•   Form new collaborative alliances with pharmaceutical partners
    (target-specific)
    – e.g. AstraZeneca and Dainippon Sumitomo

•   Grant access to our proprietary technology platform (target-
    specific)
    – e.g. Quark/Pfizer and Quark/Novartis
    – securing near-term non-dilutive funding
    – build long-term platform value

•   Collaborate with biotech partners
    – e.g. for co-development of novel delivery approaches


                                                                            7
PF-4523655: Opthamology


•   Silence licensed AtuRNAi technology
    to Quark in 2004                              2010 Market size (AMD) $3.1bn

•   Pfizer licensed PF-’655 in 2006 from
    Quark                                                               DME
                                                                        24%


•   Milestones to Silence total $95m
     –   next milestone c$4m on phase III start

•   Phase II trial in diabetic macular
    oedema (DME) showed superiority
    over laser therapy
     –   Phase IIb to start in 2011                       AMD
                                                          76%

•   Phase II trial in age-related macular
    degeneration (AMD) data due in 2H11

•   Low single-digit effective royalty rate       Potential Market size (DME) $1bn+
    on end sales
                                                                          Source: company reports




                                                                                            8
QPI-1002: Renal disease


•   Silence licensed AtuRNAi technology
    to Quark in 2005                            2010 Market size (transplant) $4.4bn

•   Novartis signed $10m option for QPI-                              Neoral
    1002 in 2010                                                       19%


•   Milestones to Silence of c.$82m
                                                  Prograf
     –   next milestone $3-11m on exercise of
         option                                    42%                          Myfortic
                                                                                 10%
•   Phase II trial in prevention of delayed
    graft function (DGF) initiated
    September 2010 (results due 2012)

•   Phase II trial in acute kidney injury                           Cellcept
    (AKI) expected to commence 2H11                                  29%


•   Low single-digit effective royalty rate       Potential Market size (AKI) $1bn+
    on end sales

                                                                               Source: company reports




                                                                                                 9
Overcoming the Delivery Challenge




           AtuPLEX                     DBTC

Vascular endothelium                   Liver parenchyma
  • Cancer & Metastasis                • Hepatocellular carcinoma
        • Inflammation                 • Ischemia Reperfusion Injury
                                       • Fulminant Fibrosis



                                       DACC

                                       Pulmonary endothelium
                                       • Acute lung injury/ARDS
                                       • Pulmonary Hypertension
                                       • Infection & Inflammation




                                                                    10
Atu027/Atu134: Market opportunity


•   Anti-angiogenic market worth $8.2bn
                                                 2010 Market size (oncology) $53bn
•   Both Atu027 and Atu134 are anti-
    angiogenic drugs
                                                            Anti-
•   Atu027 is only RNAi anti-angiogenic                 angiogenics,
    drug in clinical development                             8.2


•   Atu027 will be used in the setting of                                        Chemotherapy,
    highly vascularised tumours; prostate,                                           19.3
    lung, ovarian & melanoma                     Hormone
                                               Therapies, 8.9
•   Results of on-going phase I trial
    expected at end 2011

•   Interim data to be presented at ASCO,                 Other             Other small
    June 2011                                         antibodies, 10       molecules, 6.7

•   Partner Atu027 in 2012
     –   upfront, milestones and royalties                                       Source: company reports




               Anti-angiogenic – works by disrupting blood supply to tumours                      11
Atu027 deal structure


                                                                                  Big Pharm a alliances 2005-9


•   Plan to partner in 2012




                                          Upfront payment ($m)
                                                                 35
                                                                 30
                                                                 25
•   Partnering discussions initiated                             20
                                                                 15
                                                                 10
•   Typical deal structure                                        5

     –   Upfronts (double digit $m’s)                             0
                                                                       Lead      Preclinical   Phase I   Phase II    Phase III

     –   Milestones (significant)
     –   Royalties (double digit %)
                                                                                    Early stage deals 2005-9



•   Variations                                                   200


     –   Global rights                                           150
                                        Payments ($m)
     –   Regional rights                                         100
     –   Ex-US/Eu rights
                                                                 50
     –   Opt-in rights
                                                                  0
                                                                       Upfront           R&D        Milestones        Equity




                                                                                                                 Source: RECAP Deloitte
Atu027: Strong preclinical efficacy data


•   Atu027 ‘silences’ the production of         0   20 - 45                   46 days
    PKN3                                                                       Atu027
     –   PKN3 is a key regulator of blood and                                  Avastin
         lymph vessel formation

•   Inhibition of PKN3 leads to:
                                                                                    Vehicle
     –   reduced oxygen supply to tumour
     –   reduced tumour growth/metastases

•   Efficacy of Atu027 demonstrated in
    multiple cancer animal models                                                   Atu027
                                                                                    VEGF-R-siRNA-lipoplex
     –   data published in peer reviewed                                            Avastin
         journals                                                                   VEGF-R-siRNA-lipoplex
                                                                                     + Avastin
                                                                                     Atu027 + Avastin
•   Atu027 has been shown to knock-
    down protein and mRNA expression of
    PKN3 in animal models

•   Impressive data led to start of Phase I
    trial in 2009                                       DU-146 prostate Xenograft (N = 8)
                                                            Twice weekly treatment
                                                                                                   13
Atu027: Phase I results promising


      BEFORE                                                                 AFTER




      Baseline (pre-treatment)                                                1 week after 8th repeated treatment
      Note: vanished metastatic lesion in the left lower lobe of the lung (circle)



•   Data from Cohort 6: First dose level where efficacy was predicted based on preclinical work
    Of three patients treated:
                   – one patient showed tumour shrinkage (above)

                   – one patient showed stable disease at end of treatment phase

                   – one patient discontinued treatment for non-drug related reasons

                                                                                                                    14
Atu134: Strong preclinical efficacy data

•   Atu134 has demonstrated efficacy in a                            In preclinical studies
    variety of preclinical cancer models
     –   Orthotopic models                                       Atu134 significantly reduced
     –   Ectopic models                                                 tumour growth

•   Atu134 has demonstrated strong                               4000
                                                                                  * p=0.003
    efficacy against primary tumour
                                                                                        * p=0.002 * p=0.014




                                            Tumor volume [mm3]
                                                                 3000

•   Targets CD31 – well validated target
                                                                 2000

•   GMP manufacturing commencing
                                                                 1000


•   Preclinical toxicology testing due to                           0
    start early in 2012                                                 Sucrose   Luciferase    CD31      control

                                                                                               (Atu134)

•   IND filing expected in 2012                                         Breast (mammary fat pad)

•   Plan to partner during Phase I
     – target double digit royalty rate
                                                                                                                    15
Atu111: treatment of acute lung injury


•   Acute lung injury (ALI) is an area of high
    unmet medical need

•   Significant market opportunity
     –   Pneumonia is 2nd highest cause of hospital
         admissions
     –   Pneumonia treatment costs $8bn/yr in US
         alone (mortality rate 12-30%)
     –   ALI principle cause of mortality

•   DACC delivery system provides                     Organ distribution after delivery of siRNA with DACC
    exquisitely selective delivery to lung                                   125
    (see chart)

                                                      siRNA [%ID/g tissue]
                                                                             100

                                                                              75
•   DACC delivery system leads to prolonged
                                                                              50
    knock-down
                                                                              25
     –   potential for only one dose in ALI
                                                                               0

•   Aim to partner in 2012
     – target high single digit royalties
                                                                                                      16
DBTC: Targeting the Liver


•   Proprietary lipid-based formulation
    targeting liver

•   Significant market opportunities
     –   Liver cancer
     –   Ischemia reperfusion injury
     –   fibrosis

•   DBTC delivers siRNAs primarily to liver
    (see chart)                                      Organ distribution after delivery of siRNA with DBTC

                                                                        70
•   DTBC delivery system leads to persistent

                                                   siRNA [%ID/tissue]
                                                                        60
    knock-down                                                          50
     –   Single dose knocks down gene expression                        40
         for up to 1 wk                                                 30
                                                                        20
                                                                        10
•   DTBC well tolerated                                                  0
     –   Dosed up to 8.3mg/kg


                                                                             no functional delivery of siRNA to spleen
                                                                                  no knockdown in spleen tissue.         17
Burn rate significantly reduced in 2H10


£000s                        1H10A          2H10A     2010A
Revenue                       716            1,650    2,366

R&D spend                    (4,401)        (1,420)   (5,821)

Admin costs                  (3,227)        (1,976)   (5,203)

Operating loss               (6,912)        (1,746)   (8,658)

Other income/(exp.)           (142)            5       (137)

Loss before tax              (7,054)        (1,741)   (8,795)

Loss after tax               (7,054)        (1,741)   (8,795)



Net cash                     6,836           3,567    3,567


                      ~ £5.9m raised in May 2011 ~              18
Expected Milestones for 2011


Update on progress of Atu027                                    Jan. 2011

Update on PF-’655 in diabetic macular oedema (DME)              Mar. 2011

Full year results for 2010                                      April 2011

Fundraising                                                     May 2011

Present interim Phase I data of Atu027 at ASCO                  June 2011

Completion of Phase II trial of PF-’655 in AMD (Pfizer/Quark)   2H11

Start of Phase IIb trial of PF-’655 in DME (Quark)              2H11

Extension of Dainippon Sumitomo collaboration                   2H11

Start of Phase II trial of QPI-1002 in AKI (Quark/Novartis)     2H11

Further issuance of Zamore patents                              2H11

Completion of Atu027 trial                                      2H11

                                                     19                      19
Corporate plans 2011-13

Event                                                     Timing   Status
Complete fundraising                                      1H11     Completed May 2011
Present interim Phase I results at ASCO                   1H11     Completed June 2011
Complete Atu027 ‘in patient’ Phase I                      2H11
Milestone on delivery of final results in collaboration   2H11     Non-dilutive funding opportunity
Announce Atu027 clinical plans                            2H11
Complete restructuring                                    2H11
Present Phase I final results of Atu027                   1H12
‘Platform technology deal’                                1H12     Non-dilutive funding opportunity
Initiate Atu027 Phase Ib                                  1H12
License DACC/Atu111                                       2H12     Non-dilutive funding opportunity
File IND for Atu134                                       2H12
License Atu027                                            2H12     Non-dilutive funding opportunity
Start Atu134 Phase I                                      2H12
Complete ‘in-patient’ Atu027 Phase Ib                     1H13
File IND on third internal drug candidate                 1H13
Announce Atu027 Phase Ib results                          2H13
Complete Atu134 Phase I study                             2H13
Start Atu027 Phase II trial                               2H13                                        20
Management


Experienced team with proven pharmaceutical development track
   record

 — Max Herrmann ACA, acting Chief Executive Officer and CFO
   Intercytex Group PLC, Onyx Pharmaceuticals, ING

 — Klaus Giese, Ph.D., Chief Scientific Officer
   Chiron Corporation, UCSF and Max-Planck Institute

 — Thomas Christély, Chief Operating Officer,
   OXO Chemie Inc., Löschen & Partner, Enskilda Securities

 — Jörg Kaufmann, Ph.D., VP Research
   Chiron, Howard Hughes Medical Institute

                                                                21
Summary


• World leader in the discovery, development and delivery of novel RNA interference
 (RNAi) therapeutics for the treatment of serious diseases

• One of the sector’s most comprehensive platforms for the discovery, development and
 delivery of targeted RNAi Therapeutics

• One of the industry’s broadest RNAi clinical pipelines addressing diverse therapeutic
 areas

• Validating partnerships with leading global pharmaceutical companies

• Broad intellectual property portfolio

• Strong upcoming newsflow

• Well funded following successful £5.9m fundraising in May 2011




                                                                                          22
                                                                                           22
APPENDIX
m



                                Atu027: Gene knock-down of PKN3
                                confirmed in preclinical studies

                                  Plasma level of siRNA strand (1st infusion)                                          Protein knock down in lung tissue (Western blot)

                                1000                                 1.0mg/kg                                                                      sucrose            0.3          1.0       3.0mg/kg
    antisense strand [pmol/ml




                                                                     0.3mg/kg
                                                                                                                       animal #                     1      2      3     4      5         6   7     8




                                                                                             antisense strand [ng/ml
                                                                                      1000
                                 100
                                                                     0.1mg/kg
             plasma]




                                                                                                                       PKN3




                                                                                                     plasma]
                                                                     0.03mg/kg
                                  10
                                                                     3.0mg/kg         10                               p110
                                   1
                                                                                                                       Actin
                                   0                                                  0
                                       0    4       8      12       16    20     24
                                                        time [h]

                                   RNAi in lung tissue (5‘-RACE)                                                       mRNA knock down in lung tissue (B-DNA)
                                  Sucrose 0.3mg/kg



                                                                                                                        hPKN3/hPPIB mRNA
                                                                                                                                           1.2

                                                            229 bp 16S rRNA 5´-RACE
                                                                                                                                           0.8
                                                                    (internal control)

                                                                                                                                           0.4
                                                           166 bp    PKN3 RNAi 5´-RACE

                                                                                                                                           0.0
                                                                                                                                                 vehicle   0.03        0.1         0.3       1.0       3.0
                                    cleavage site                                                                                                control                    mg/kg ATU027/23H
                                   verified                                                                                                                                                                  24
Atu027: Phase I Study Design

•    Atu027 - targeting PKN3 for the
     treatment of advanced solid cancer
      •   PKN3 is a key regulator during angiogenesis and
          lymphangiogeneis


•    Prospective, open label, single-centre,
     dose finding study
      •   Male and female subjects with advanced or
          metastatic solid tumors not amenable to
          curative standard therapy
      •   Approx 33 subjects - 3-6 subjects per dose level
      •   11 dose levels, dose escalation: modified
          Fibonacci Scheme


•    Treatment: 4h i.v. infusion

•    24 patients treated (end March 2011)




                                                             25
                                                              25
We have achieved Predictable
                                   Pharmacokinetics For Atu027

                                               Cynomolgus Monkey                                                                                        Human

                                         4 h infusion                                                                            4 h infusion
                                   120                                                                                     120                                      0.180 mg/kg
A strand concentration in plasma




                                                                      0.3 mg/kg




                                                                                        A strand concentration in plasma
 - mean of dose groups [ng/mL]




                                                                                                                                                                    0.120 mg/kg




                                                                                         - mean of dose groups [ng/mL]
                                                                      0.1 mg/kg                                                                                     0.072 mg/kg
                                                                      0.03 mg/kg                                                                                    0.036 mg/kg
                                    80                                                                                      80
                                                                                                                                                                    0.018 mg/kg
                                                                                                                                          *
                                                                                                                                      *                             0.009 mg/kg
                                                                                                                                                                    0.003 mg/kg
                                    40                                                                                      40                                      0.001 mg/kg



                                     0                                                                                       0
                                         0        4     8        12      16   20   24                                             0           4   8        12      16       20       24
                                                            Time [hours]                                                                              Time [hours]
                                             In vitro: IC50 ≈ 1 to 10 nM                                                                                      * Final/verfied data pending




                                                   Predictable PK tells that Atu027 is behaving in humans as
                                                                 it did in pre-clinical models
Atu027: Positive Phase I Data to Date


•   Phase I trial on-going – expected to complete
    2H2011
−   No dose limiting toxicities to date, dose escalation continuing
                                                                                             Atu027 - Dose (mg/kg)
                                                                         Dose level
•   Generally well tolerated to date                                                      (based on the siRNA content)

−   173+ doses administered to 24 patients across 8 dose levels       1 (starting dose)              0.001
−   Up to 26 doses administered to a single patient (study
                                                                             2                       0.003
    followed by compassionate use)
−    No cytokine activation observed                                         3                       0.009

                                                                             4                       0.018
•   No pre-medication required
                                                                             5                       0.036

•   > 210 timepoints analysed for complement                                 6                       0.072

    system and cytokine activation                                           7                       0.120

                                                                             8                       0.180
•   Limited Atu027-related transient activation of
                                                                             9                       0.253
    the alternative pathway of the complement
    system - (as published and expected for                                  10                      0.336

    liposomal formulations) not dose dependant                               11                      0.447



•   Human plasma PK shows dose dependent
    increase with no evidence of drug accumulation
    during repeated treatment

                                                                                                                         27
Atu134 (CD31/PECAM-1): A well
validated target




                                28
Efficacy of Atu134 in Various
                     Ectopic Tumor Xenograft Models


                                                                                            3200                                                                 1600
                                                           sucrose
                                                           siRNALuc-                                                                                                                                     sucrose
                     800                                                                                                       sucrose
                                                           lipoplex




                                                                                                                                            Tumor volume [mm³]
                                                                       Tumor volume [mm3]
Tumor volume [mm3]




                                                                                                                                                                 1200
                                                                                            2200
                                                                                                                               siRNAPTEN-
                     600                                   Atu134                                                              lipoplex
                                                                                                                                                                 800
                                                                                                                                                                                                         Atu134
                                                                                            1200
                     400
                                                                                                                               Atu134                            400


                     200                                                                     200                                                                   0
                           24   26    28   30   32    34                                           12      14    16      18                                             25      31     37     43    49
                           Days post cell challenge                                                 Days post cell challenge                                                 Days post cell challenge



                                 PC-3 s.c.                                                          3Y1-RasV12 s.c.                                                             DU-145 s.c.


                                          Atu134 shows anti-tumor activity in different established
                                     subcutanuous tumor xenografts in comparison to control treatment.

                                                                                                        Silence Therapeutics                                                                                   29
Thank you

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Silence Therapeutics - Gene Silencing - Corporate Presentation September 2011

  • 1. Corporate Presentation September 2011
  • 2. Forward-Looking Statements The statements made in this presentation may contain certain forward- looking comments. Actual events or results may differ from the Company’s expectations. In addition to the matters described in the presentation, future actions by the European Agency for Evaluation of Medicinal Products, the U.S. Food and Drug Administration or equivalent regulatory authorities in other countries and results of pending or future clinical trials, as well as other risk factors outlined from time to time in the Company’s regulatory filings, may affect actual results achieved by the Company. The Alternative Investment Market (AIM) has not reviewed and does not accept responsibility for the adequacy or accuracy of this presentation. 2 2
  • 3. Background • Silence Therapeutics AG (formerly Atugen AG) was founded in 1998 as spin-off from RPI (later renamed to Sirna) and financed by MPM Capital, Apax and NVF • Target discovery and validation service company using antisense and delivery technologies -> over US$20m accum. service revenues from pharma companies • Developing delivery technologies for oligonucleotides since 1998 • First AtuRNAi patent application filed in 2002, US patent granted in Nov. 2008 • In 2005 reverse merger with SR Pharma plc (shell) listed on AIM, London • Renamed to Silence Therapeutics plc/AG in 2007 (LSE: SLN) • Acquired US siRNA therapeutics company Intradigm Corp. in January 2010 • To date over £50m invested in RNAi platform • Well funded following successful £5.9m fundraising in May 2011 • Current market cap. c.£11m -> technology value of only £5m 3
  • 4. Overview • World leader in the discovery, development and delivery of novel RNA interference (RNAi) therapeutics for the treatment of serious diseases − RNAi offers a unique new class of drugs that overcomes hurdles of existing drugs • One of the sector’s most comprehensive RNAi platforms − Deliver to more target cells and tissues that anyone else (e.g. AtuPlex, DACC) • One of the industry’s broadest RNAi clinical pipelines − Five of the 12 siRNA (& 4 of the 5 Phase II) clinical programs worldwide are based on Silence technology − Clinical and pre-clinical pipeline in diverse therapeutic areas – metabolic, pulmonary, vascular, oncology − Encouraging Phase I data on lead internal candidate Atu027 recently presented at ASCO • Validating partnerships with leading global pharmaceutical companies − AstraZeneca, Pfizer/Quark, Novartis/Quark and Dainippon Sumitomo • Broad intellectual property portfolio − Issued patents covering aspects of delivery, sequences and structures 4
  • 5. Silence Product Pipeline Products Indications Partners Target Delivery Pre- Phase I Phase II Target Tissue / Clinical Organ PF-4523655 Diabetic Macular Pfizer/Quark RTP801 Naked Local Delivery to the (AtuRNAi) Edema siRNA Eye Partnered programs PF-4523655 Age-related Macular Pfizer/Quark RTP801 Naked Local Delivery to the (AtuRNAi) Degen siRNA Eye QPI-1002 Prevention of Delayed Novartis/ P53 Naked Systemic Delivery to (AtuRNAi) Graft Function Quark siRNA the Kidney QPI-1002 Acute Kidney Injury Novartis/ P53 Naked Systemic Delivery to (AtuRNAi) Quark siRNA the Kidney Atu027 GI & Lung & other Internal PKN3 AtuPLEX Systemic Delivery to (AtuRNAi) cancers Tumor Endothelium Atu134 Solid Tumors Internal AtuPLEX Systemic Delivery to Internal programs (AtuRNAi) Tumor Endothelium Atu111 Acute Lung Injury Internal DACC Systemic Delivery to (AtuRNAi) Lung Endothelium Atu195 Solid Tumors Internal AtuPLEX Systemic Delivery to (AtuRNAi) Tumor Endothelium Almost half of all ongoing siRNA clinical trials are based on Silence technology 5
  • 6. Current Partnership Overview Silence’s RNAi therapeutic platform has been validated through multiple major partnerships • AstraZeneca - $15M upfront payment with up to $400M in milestones plus sales royalties for five targets (2007, extended 2010) • AstraZeneca – Novel approaches to delivery of siRNA molecules (2008, extended 2010) • Pfizer/Quark – Phase II products for diabetic macular edema and age- related macular degeneration; $95M in milestones plus royalties (2006) • Novartis/Quark – Phase I/II products for acute renal failure and kidney transplantation; $82m in milestones plus royalties (2010) • Dainippon Sumitomo – siRNA delivery collaboration (2009, expanded 2010) 6
  • 7. Commercialisation Strategy • Out-license / co-develop internal candidates – e.g. Atu027 (in 2012), Atu111 (in 2012), Atu134 (TBD), Atu195 (TBD) • Form new collaborative alliances with pharmaceutical partners (target-specific) – e.g. AstraZeneca and Dainippon Sumitomo • Grant access to our proprietary technology platform (target- specific) – e.g. Quark/Pfizer and Quark/Novartis – securing near-term non-dilutive funding – build long-term platform value • Collaborate with biotech partners – e.g. for co-development of novel delivery approaches 7
  • 8. PF-4523655: Opthamology • Silence licensed AtuRNAi technology to Quark in 2004 2010 Market size (AMD) $3.1bn • Pfizer licensed PF-’655 in 2006 from Quark DME 24% • Milestones to Silence total $95m – next milestone c$4m on phase III start • Phase II trial in diabetic macular oedema (DME) showed superiority over laser therapy – Phase IIb to start in 2011 AMD 76% • Phase II trial in age-related macular degeneration (AMD) data due in 2H11 • Low single-digit effective royalty rate Potential Market size (DME) $1bn+ on end sales Source: company reports 8
  • 9. QPI-1002: Renal disease • Silence licensed AtuRNAi technology to Quark in 2005 2010 Market size (transplant) $4.4bn • Novartis signed $10m option for QPI- Neoral 1002 in 2010 19% • Milestones to Silence of c.$82m Prograf – next milestone $3-11m on exercise of option 42% Myfortic 10% • Phase II trial in prevention of delayed graft function (DGF) initiated September 2010 (results due 2012) • Phase II trial in acute kidney injury Cellcept (AKI) expected to commence 2H11 29% • Low single-digit effective royalty rate Potential Market size (AKI) $1bn+ on end sales Source: company reports 9
  • 10. Overcoming the Delivery Challenge AtuPLEX DBTC Vascular endothelium Liver parenchyma • Cancer & Metastasis • Hepatocellular carcinoma • Inflammation • Ischemia Reperfusion Injury • Fulminant Fibrosis DACC Pulmonary endothelium • Acute lung injury/ARDS • Pulmonary Hypertension • Infection & Inflammation 10
  • 11. Atu027/Atu134: Market opportunity • Anti-angiogenic market worth $8.2bn 2010 Market size (oncology) $53bn • Both Atu027 and Atu134 are anti- angiogenic drugs Anti- • Atu027 is only RNAi anti-angiogenic angiogenics, drug in clinical development 8.2 • Atu027 will be used in the setting of Chemotherapy, highly vascularised tumours; prostate, 19.3 lung, ovarian & melanoma Hormone Therapies, 8.9 • Results of on-going phase I trial expected at end 2011 • Interim data to be presented at ASCO, Other Other small June 2011 antibodies, 10 molecules, 6.7 • Partner Atu027 in 2012 – upfront, milestones and royalties Source: company reports Anti-angiogenic – works by disrupting blood supply to tumours 11
  • 12. Atu027 deal structure Big Pharm a alliances 2005-9 • Plan to partner in 2012 Upfront payment ($m) 35 30 25 • Partnering discussions initiated 20 15 10 • Typical deal structure 5 – Upfronts (double digit $m’s) 0 Lead Preclinical Phase I Phase II Phase III – Milestones (significant) – Royalties (double digit %) Early stage deals 2005-9 • Variations 200 – Global rights 150 Payments ($m) – Regional rights 100 – Ex-US/Eu rights 50 – Opt-in rights 0 Upfront R&D Milestones Equity Source: RECAP Deloitte
  • 13. Atu027: Strong preclinical efficacy data • Atu027 ‘silences’ the production of 0 20 - 45 46 days PKN3 Atu027 – PKN3 is a key regulator of blood and Avastin lymph vessel formation • Inhibition of PKN3 leads to: Vehicle – reduced oxygen supply to tumour – reduced tumour growth/metastases • Efficacy of Atu027 demonstrated in multiple cancer animal models Atu027 VEGF-R-siRNA-lipoplex – data published in peer reviewed Avastin journals VEGF-R-siRNA-lipoplex + Avastin Atu027 + Avastin • Atu027 has been shown to knock- down protein and mRNA expression of PKN3 in animal models • Impressive data led to start of Phase I trial in 2009 DU-146 prostate Xenograft (N = 8) Twice weekly treatment 13
  • 14. Atu027: Phase I results promising BEFORE AFTER Baseline (pre-treatment) 1 week after 8th repeated treatment Note: vanished metastatic lesion in the left lower lobe of the lung (circle) • Data from Cohort 6: First dose level where efficacy was predicted based on preclinical work Of three patients treated: – one patient showed tumour shrinkage (above) – one patient showed stable disease at end of treatment phase – one patient discontinued treatment for non-drug related reasons 14
  • 15. Atu134: Strong preclinical efficacy data • Atu134 has demonstrated efficacy in a In preclinical studies variety of preclinical cancer models – Orthotopic models Atu134 significantly reduced – Ectopic models tumour growth • Atu134 has demonstrated strong 4000 * p=0.003 efficacy against primary tumour * p=0.002 * p=0.014 Tumor volume [mm3] 3000 • Targets CD31 – well validated target 2000 • GMP manufacturing commencing 1000 • Preclinical toxicology testing due to 0 start early in 2012 Sucrose Luciferase CD31 control (Atu134) • IND filing expected in 2012 Breast (mammary fat pad) • Plan to partner during Phase I – target double digit royalty rate 15
  • 16. Atu111: treatment of acute lung injury • Acute lung injury (ALI) is an area of high unmet medical need • Significant market opportunity – Pneumonia is 2nd highest cause of hospital admissions – Pneumonia treatment costs $8bn/yr in US alone (mortality rate 12-30%) – ALI principle cause of mortality • DACC delivery system provides Organ distribution after delivery of siRNA with DACC exquisitely selective delivery to lung 125 (see chart) siRNA [%ID/g tissue] 100 75 • DACC delivery system leads to prolonged 50 knock-down 25 – potential for only one dose in ALI 0 • Aim to partner in 2012 – target high single digit royalties 16
  • 17. DBTC: Targeting the Liver • Proprietary lipid-based formulation targeting liver • Significant market opportunities – Liver cancer – Ischemia reperfusion injury – fibrosis • DBTC delivers siRNAs primarily to liver (see chart) Organ distribution after delivery of siRNA with DBTC 70 • DTBC delivery system leads to persistent siRNA [%ID/tissue] 60 knock-down 50 – Single dose knocks down gene expression 40 for up to 1 wk 30 20 10 • DTBC well tolerated 0 – Dosed up to 8.3mg/kg no functional delivery of siRNA to spleen no knockdown in spleen tissue. 17
  • 18. Burn rate significantly reduced in 2H10 £000s 1H10A 2H10A 2010A Revenue 716 1,650 2,366 R&D spend (4,401) (1,420) (5,821) Admin costs (3,227) (1,976) (5,203) Operating loss (6,912) (1,746) (8,658) Other income/(exp.) (142) 5 (137) Loss before tax (7,054) (1,741) (8,795) Loss after tax (7,054) (1,741) (8,795) Net cash 6,836 3,567 3,567 ~ £5.9m raised in May 2011 ~ 18
  • 19. Expected Milestones for 2011 Update on progress of Atu027 Jan. 2011 Update on PF-’655 in diabetic macular oedema (DME) Mar. 2011 Full year results for 2010 April 2011 Fundraising May 2011 Present interim Phase I data of Atu027 at ASCO June 2011 Completion of Phase II trial of PF-’655 in AMD (Pfizer/Quark) 2H11 Start of Phase IIb trial of PF-’655 in DME (Quark) 2H11 Extension of Dainippon Sumitomo collaboration 2H11 Start of Phase II trial of QPI-1002 in AKI (Quark/Novartis) 2H11 Further issuance of Zamore patents 2H11 Completion of Atu027 trial 2H11 19 19
  • 20. Corporate plans 2011-13 Event Timing Status Complete fundraising 1H11 Completed May 2011 Present interim Phase I results at ASCO 1H11 Completed June 2011 Complete Atu027 ‘in patient’ Phase I 2H11 Milestone on delivery of final results in collaboration 2H11 Non-dilutive funding opportunity Announce Atu027 clinical plans 2H11 Complete restructuring 2H11 Present Phase I final results of Atu027 1H12 ‘Platform technology deal’ 1H12 Non-dilutive funding opportunity Initiate Atu027 Phase Ib 1H12 License DACC/Atu111 2H12 Non-dilutive funding opportunity File IND for Atu134 2H12 License Atu027 2H12 Non-dilutive funding opportunity Start Atu134 Phase I 2H12 Complete ‘in-patient’ Atu027 Phase Ib 1H13 File IND on third internal drug candidate 1H13 Announce Atu027 Phase Ib results 2H13 Complete Atu134 Phase I study 2H13 Start Atu027 Phase II trial 2H13 20
  • 21. Management Experienced team with proven pharmaceutical development track record — Max Herrmann ACA, acting Chief Executive Officer and CFO Intercytex Group PLC, Onyx Pharmaceuticals, ING — Klaus Giese, Ph.D., Chief Scientific Officer Chiron Corporation, UCSF and Max-Planck Institute — Thomas Christély, Chief Operating Officer, OXO Chemie Inc., Löschen & Partner, Enskilda Securities — Jörg Kaufmann, Ph.D., VP Research Chiron, Howard Hughes Medical Institute 21
  • 22. Summary • World leader in the discovery, development and delivery of novel RNA interference (RNAi) therapeutics for the treatment of serious diseases • One of the sector’s most comprehensive platforms for the discovery, development and delivery of targeted RNAi Therapeutics • One of the industry’s broadest RNAi clinical pipelines addressing diverse therapeutic areas • Validating partnerships with leading global pharmaceutical companies • Broad intellectual property portfolio • Strong upcoming newsflow • Well funded following successful £5.9m fundraising in May 2011 22 22
  • 24. m Atu027: Gene knock-down of PKN3 confirmed in preclinical studies Plasma level of siRNA strand (1st infusion) Protein knock down in lung tissue (Western blot) 1000 1.0mg/kg sucrose 0.3 1.0 3.0mg/kg antisense strand [pmol/ml 0.3mg/kg animal # 1 2 3 4 5 6 7 8 antisense strand [ng/ml 1000 100 0.1mg/kg plasma] PKN3 plasma] 0.03mg/kg 10 3.0mg/kg 10 p110 1 Actin 0 0 0 4 8 12 16 20 24 time [h] RNAi in lung tissue (5‘-RACE) mRNA knock down in lung tissue (B-DNA) Sucrose 0.3mg/kg hPKN3/hPPIB mRNA 1.2 229 bp 16S rRNA 5´-RACE 0.8 (internal control) 0.4 166 bp PKN3 RNAi 5´-RACE 0.0 vehicle 0.03 0.1 0.3 1.0 3.0 cleavage site control mg/kg ATU027/23H verified 24
  • 25. Atu027: Phase I Study Design • Atu027 - targeting PKN3 for the treatment of advanced solid cancer • PKN3 is a key regulator during angiogenesis and lymphangiogeneis • Prospective, open label, single-centre, dose finding study • Male and female subjects with advanced or metastatic solid tumors not amenable to curative standard therapy • Approx 33 subjects - 3-6 subjects per dose level • 11 dose levels, dose escalation: modified Fibonacci Scheme • Treatment: 4h i.v. infusion • 24 patients treated (end March 2011) 25 25
  • 26. We have achieved Predictable Pharmacokinetics For Atu027 Cynomolgus Monkey Human 4 h infusion 4 h infusion 120 120 0.180 mg/kg A strand concentration in plasma 0.3 mg/kg A strand concentration in plasma - mean of dose groups [ng/mL] 0.120 mg/kg - mean of dose groups [ng/mL] 0.1 mg/kg 0.072 mg/kg 0.03 mg/kg 0.036 mg/kg 80 80 0.018 mg/kg * * 0.009 mg/kg 0.003 mg/kg 40 40 0.001 mg/kg 0 0 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Time [hours] Time [hours] In vitro: IC50 ≈ 1 to 10 nM * Final/verfied data pending Predictable PK tells that Atu027 is behaving in humans as it did in pre-clinical models
  • 27. Atu027: Positive Phase I Data to Date • Phase I trial on-going – expected to complete 2H2011 − No dose limiting toxicities to date, dose escalation continuing Atu027 - Dose (mg/kg) Dose level • Generally well tolerated to date (based on the siRNA content) − 173+ doses administered to 24 patients across 8 dose levels 1 (starting dose) 0.001 − Up to 26 doses administered to a single patient (study 2 0.003 followed by compassionate use) − No cytokine activation observed 3 0.009 4 0.018 • No pre-medication required 5 0.036 • > 210 timepoints analysed for complement 6 0.072 system and cytokine activation 7 0.120 8 0.180 • Limited Atu027-related transient activation of 9 0.253 the alternative pathway of the complement system - (as published and expected for 10 0.336 liposomal formulations) not dose dependant 11 0.447 • Human plasma PK shows dose dependent increase with no evidence of drug accumulation during repeated treatment 27
  • 28. Atu134 (CD31/PECAM-1): A well validated target 28
  • 29. Efficacy of Atu134 in Various Ectopic Tumor Xenograft Models 3200 1600 sucrose siRNALuc- sucrose 800 sucrose lipoplex Tumor volume [mm³] Tumor volume [mm3] Tumor volume [mm3] 1200 2200 siRNAPTEN- 600 Atu134 lipoplex 800 Atu134 1200 400 Atu134 400 200 200 0 24 26 28 30 32 34 12 14 16 18 25 31 37 43 49 Days post cell challenge Days post cell challenge Days post cell challenge PC-3 s.c. 3Y1-RasV12 s.c. DU-145 s.c. Atu134 shows anti-tumor activity in different established subcutanuous tumor xenografts in comparison to control treatment. Silence Therapeutics 29