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Unaudited Preliminary Results 2011

21 March 2012
New Team members with Proven Track Record of building value
For shareholders



   – Anthony Sedgwick, Ph.D., Chief Executive Officer
     ( Biotech Entrepreneur Novacta, Daniolabs, Cambridge Biotechnology, Roche)




   – George Büchner, Ph.D., Head of Business development
     (Novacta, Haptogen, Pharma Ventures)




                                                                                  2
2011 Highlights

 –   Positive interim data presented at ASCO
      – Data showed excellent safety and indications of potential efficacy

 –   Leadership position validated by three new partnerships
      – Top 10 pharma company, InteRNA Technologies and miRNA Therapeutics
      – Further deal signed with miRagen Inc in January 2012

 –   Positive clinical results from partners
     – Quark and Pfizer positive Phase II results in diabetic macular oedema

 –   Organisation streamlined
      – Californian facility was closed, Board membership reduced

 –   Enhanced commercial focus
      – New business development team recruited

 –   Intellectual property strengthened
     – PKN3 patent issued in Japan, Zamore re-issued in US, Tuschl I clarified (Europe)

 –   Fundraising of £5.51m (net of expenses) in May 2011
     – To fund development of pipeline and investment in RNAi technology platform




                                                                                          3
2011 Post year-end Highlights


   –   Dr Tony Sedgwick was promoted to Chief Executive Officer

   –   Deal announced with miRagen Therapeutics for the delivery of microRNAs using
       the DBTC liver delivery systems
        – Silence's second deal on DBTC and third for microRNAs

   – Creation of a Scientific Advisory Board
       – Two Key Opinion Leaders in the area of liver disease –announced today




                                                                                      4
RNAi – James Watsons vision 2012




                                   5
An Overview of Silence Therapeutics


 •   European Biotechnology Company
 •   Listed on LSE (AIM) with operations
     centralised in Berlin
 •   Cutting Edge technology- RNAi (Ribose
     Nucleic acid Interference)
 •   Experienced New Management Tony
     Sedgwick CEO –Geo Buchner Business
 Several value drivers:
 •   External Milestones and Royalties (Quark)
 •   Internal Phase I First in Class Cancer Therapy
     (To be completed
     mid-2012)
 •   Low cost preclinical Pipeline
 •   Strong IP (e.g. AtuRNAi, Licenses
     to Fire & Mello and Zamore Patents)
 •   One of only 2 companies with prosecuted
     patents in area




                                                      6
What is RNAi


 Transformative technology




                             7
RNAi can “Silence” Undruggable problem genes


                        22,000 genes




                               Human Genome
                          At the origin of numerous
                                   diseases

                          The RNAi technology
                        can target ALL OF THEM



  Targets that can be
                                                      Stabilised AtuRNAi
   blocked by small
                                                      Naked can target All
  molecule drugs or
                                                             Genes
      antibodies



                                                                             8
Two value drivers: External and Internal




                                           9
Potential External revenue streams




   Novartis               Pfizer           Pfizer/Quark           Novartis/Quark

$3-11 million          $4 million          $85 million            $71-77 million




     2012                  2014                    Remaining milestones




                 Total milestone potential: approx $170 million

  PLUS further potential milestone payments from the AstraZeneca collaborations

                                                                                   10
Commercial landscape:
Delivering the great promise of RNAi



                  Delivery              Development of
                 challenges            successful delivery
                 Identified                solutions




           siRNA
           technology
           trigger




                                                             11
And Internal value drivers…




                              12
Silences AtuRNAi plus Disease “bespoke”
delivery system makes a drug




                                          13
Atu027: New Cancer treatment in Phase I




 • Atu027 ‘silences’ the
   production of PKN3 a Key
   regulator of blood and lymph
   vessel formation


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




                                          14
Atu027 is RNAi against PKN3 plus Atuplex




                                           15
Atu027: successfully progressed to a phase I




                                Investment



                                               16
Atu027 is safe in man and could be a new
medicine for treating difficult cancers




 •   Atu027 Phase I interim data demonstrates safety (ASCO 2011)

 •   10 out of 27 patients showed stable disease after treatment period

 •   Atu027 very well tolerated - effective dose exceeded

 •   Phase I results expected to report in mid-2012

 •   Biomarker data currently under evaluation

 •   Looking for Co development partner

 •   Validates AtuPLEX™ delivery technology



                                                                          17
AtuRNAi plus DACC system makes a drug for treating
lung Cancer and life threatening lung disease




                                                     18
Silence´s DACC delivery system: targets siRNAs to the lungs



 •   Address lung-specific diseases
     e.g. acute lunG
     injury/ARDS/Cancer by
     delivering siRNA primarily to
     the lungs

 •   Single dose sufficient to inhibit
     target gene

 •   Expression in the lungs for up
     to a month

 •   Atu111 in preclinical




                                                              19
AtuRNAi plus DBTC system makes a drug for treating
liver Cancer and life threatening liver disease




                                                     20
Silence´s DBTC: targets siRNAs to the liver



 • Address liver-specific diseases
   e.g. HCC, ischemia reperfusion
   injury

 • Single dose inhibits gene
   expression in the liver for up to 1
   week

 • Well tolerated (up to 8.3 mg/kg)

 • Preclinical studies ongoing




                                              21
Silence’s Revenue Stream




                           22
Two value drivers: External and Internal




                                           23
Silence Power………………….




•   New Management with proven track record

•   Cutting Edge technology

•   First in Class RNAi new cancer therapy

•   One of only two companies with Prosecuted patents in area

•   Lean organisation

•   Pipeline of drugs and deals

•   Undervalued




                                                                24
Results for 2011



    GBP ‘000s                  2011       2010
                             unaudited   audited
    Revenue                    694        2,366

    R&D spend                 (3,361)    (5,821)

    Admin costs               (2,647)    (5,203)

   Restructuring costs         (472)        -

    Operating loss            (5,786)    (8,658)

    Other income/(expense)      49        (137)

    Loss after tax            (5,737)    (8,795)



    Net cash                   3,688      3,567




                                                   25
Newsflow 2012




   Update on AstraZeneca collaboration                               January 2012

   Sign delivery collaboration with miRagen                          January 2012

   Start of Phase IIb trial of PF’-655 in DME (Quark/Pfizer)         1Q 2012

   Sign further collaboration agreements                             1H 2012

   Completion of enrolment in Atu027 trial                           1H 2012

   Start of Phase II trial of QPI-1002 in AKI (Quark/Novartis)       1H 2012

   Publication of white paper on delivery technologies               1H 2012

   Completion of Atu027 phase I trial                                Mid 2012

   Completion of phase II trial of QPI-1002 delayed graft function   2H 2012

   Start of phase Ib/II trial of Atu027                              2H 2012

   Further patent issuances                                          2H 2012




                                                                                    26
Disclaimer



                 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.




                                                                       27
Key peers




            28

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Silence Therapeutics Unaudited Preliminary Results 2011

  • 1. Unaudited Preliminary Results 2011 21 March 2012
  • 2. New Team members with Proven Track Record of building value For shareholders – Anthony Sedgwick, Ph.D., Chief Executive Officer ( Biotech Entrepreneur Novacta, Daniolabs, Cambridge Biotechnology, Roche) – George Büchner, Ph.D., Head of Business development (Novacta, Haptogen, Pharma Ventures) 2
  • 3. 2011 Highlights – Positive interim data presented at ASCO – Data showed excellent safety and indications of potential efficacy – Leadership position validated by three new partnerships – Top 10 pharma company, InteRNA Technologies and miRNA Therapeutics – Further deal signed with miRagen Inc in January 2012 – Positive clinical results from partners – Quark and Pfizer positive Phase II results in diabetic macular oedema – Organisation streamlined – Californian facility was closed, Board membership reduced – Enhanced commercial focus – New business development team recruited – Intellectual property strengthened – PKN3 patent issued in Japan, Zamore re-issued in US, Tuschl I clarified (Europe) – Fundraising of £5.51m (net of expenses) in May 2011 – To fund development of pipeline and investment in RNAi technology platform 3
  • 4. 2011 Post year-end Highlights – Dr Tony Sedgwick was promoted to Chief Executive Officer – Deal announced with miRagen Therapeutics for the delivery of microRNAs using the DBTC liver delivery systems – Silence's second deal on DBTC and third for microRNAs – Creation of a Scientific Advisory Board – Two Key Opinion Leaders in the area of liver disease –announced today 4
  • 5. RNAi – James Watsons vision 2012 5
  • 6. An Overview of Silence Therapeutics • European Biotechnology Company • Listed on LSE (AIM) with operations centralised in Berlin • Cutting Edge technology- RNAi (Ribose Nucleic acid Interference) • Experienced New Management Tony Sedgwick CEO –Geo Buchner Business Several value drivers: • External Milestones and Royalties (Quark) • Internal Phase I First in Class Cancer Therapy (To be completed mid-2012) • Low cost preclinical Pipeline • Strong IP (e.g. AtuRNAi, Licenses to Fire & Mello and Zamore Patents) • One of only 2 companies with prosecuted patents in area 6
  • 7. What is RNAi Transformative technology 7
  • 8. RNAi can “Silence” Undruggable problem genes 22,000 genes Human Genome At the origin of numerous diseases The RNAi technology can target ALL OF THEM Targets that can be Stabilised AtuRNAi blocked by small Naked can target All molecule drugs or Genes antibodies 8
  • 9. Two value drivers: External and Internal 9
  • 10. Potential External revenue streams Novartis Pfizer Pfizer/Quark Novartis/Quark $3-11 million $4 million $85 million $71-77 million 2012 2014 Remaining milestones Total milestone potential: approx $170 million PLUS further potential milestone payments from the AstraZeneca collaborations 10
  • 11. Commercial landscape: Delivering the great promise of RNAi Delivery Development of challenges successful delivery Identified solutions siRNA technology trigger 11
  • 12. And Internal value drivers… 12
  • 13. Silences AtuRNAi plus Disease “bespoke” delivery system makes a drug 13
  • 14. Atu027: New Cancer treatment in Phase I • Atu027 ‘silences’ the production of PKN3 a Key regulator of blood and lymph vessel formation • Inhibition of PKN3 leads to: • reduced oxygen supply to tumour • reduced tumour growth/metastases 14
  • 15. Atu027 is RNAi against PKN3 plus Atuplex 15
  • 16. Atu027: successfully progressed to a phase I Investment 16
  • 17. Atu027 is safe in man and could be a new medicine for treating difficult cancers • Atu027 Phase I interim data demonstrates safety (ASCO 2011) • 10 out of 27 patients showed stable disease after treatment period • Atu027 very well tolerated - effective dose exceeded • Phase I results expected to report in mid-2012 • Biomarker data currently under evaluation • Looking for Co development partner • Validates AtuPLEX™ delivery technology 17
  • 18. AtuRNAi plus DACC system makes a drug for treating lung Cancer and life threatening lung disease 18
  • 19. Silence´s DACC delivery system: targets siRNAs to the lungs • Address lung-specific diseases e.g. acute lunG injury/ARDS/Cancer by delivering siRNA primarily to the lungs • Single dose sufficient to inhibit target gene • Expression in the lungs for up to a month • Atu111 in preclinical 19
  • 20. AtuRNAi plus DBTC system makes a drug for treating liver Cancer and life threatening liver disease 20
  • 21. Silence´s DBTC: targets siRNAs to the liver • Address liver-specific diseases e.g. HCC, ischemia reperfusion injury • Single dose inhibits gene expression in the liver for up to 1 week • Well tolerated (up to 8.3 mg/kg) • Preclinical studies ongoing 21
  • 23. Two value drivers: External and Internal 23
  • 24. Silence Power…………………. • New Management with proven track record • Cutting Edge technology • First in Class RNAi new cancer therapy • One of only two companies with Prosecuted patents in area • Lean organisation • Pipeline of drugs and deals • Undervalued 24
  • 25. Results for 2011 GBP ‘000s 2011 2010 unaudited audited Revenue 694 2,366 R&D spend (3,361) (5,821) Admin costs (2,647) (5,203) Restructuring costs (472) - Operating loss (5,786) (8,658) Other income/(expense) 49 (137) Loss after tax (5,737) (8,795) Net cash 3,688 3,567 25
  • 26. Newsflow 2012 Update on AstraZeneca collaboration January 2012 Sign delivery collaboration with miRagen January 2012 Start of Phase IIb trial of PF’-655 in DME (Quark/Pfizer) 1Q 2012 Sign further collaboration agreements 1H 2012 Completion of enrolment in Atu027 trial 1H 2012 Start of Phase II trial of QPI-1002 in AKI (Quark/Novartis) 1H 2012 Publication of white paper on delivery technologies 1H 2012 Completion of Atu027 phase I trial Mid 2012 Completion of phase II trial of QPI-1002 delayed graft function 2H 2012 Start of phase Ib/II trial of Atu027 2H 2012 Further patent issuances 2H 2012 26
  • 27. Disclaimer 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. 27
  • 28. Key peers 28