Corporate PresentationSeptember 2011

22

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

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

• 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

Overview

5

Almost half of all ongoing siRNA clinical trials are based on Silence technology

Products Indications Partners Target Delivery Pre-

Clinical

Phase I Phase II Target Tissue /

Organ

Partn

ere

d p

rogra

ms

PF-4523655

(AtuRNAi)

Diabetic Macular

Edema

Pfizer/Quark RTP801 Naked

siRNA

Local Delivery to the

Eye

PF-4523655 (AtuRNAi)

Age-related Macular

Degen

Pfizer/Quark RTP801 Naked

siRNA

Local Delivery to the

Eye

QPI-1002 (AtuRNAi)

Prevention of Delayed

Graft Function

Novartis/

Quark

P53 Naked

siRNA

Systemic Delivery to the Kidney

QPI-1002 (AtuRNAi)

Acute Kidney Injury Novartis/

Quark

P53 Naked

siRNA

Systemic Delivery to the Kidney

Inte

rnal p

rogra

ms

Atu027

(AtuRNAi)

GI & Lung & other

cancers

Internal PKN3 AtuPLEX Systemic Delivery to

Tumor Endothelium

Atu134

(AtuRNAi)

Solid Tumors Internal AtuPLEX Systemic Delivery to

Tumor Endothelium

Atu111

(AtuRNAi)

Acute Lung Injury Internal DACC Systemic Delivery to

Lung Endothelium

Atu195

(AtuRNAi)

Solid Tumors Internal AtuPLEX Systemic Delivery to

Tumor Endothelium

Silence Product Pipeline

6

Current Partnership Overview

• 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)

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

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

• Pfizer licensed PF-’655 in 2006 from Quark

• 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

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

• Low single-digit effective royalty rate on end sales

2010 Market size (AMD) $3.1bn

Potential Market size (DME) $1bn+

DME

24%

AMD

76%

Source: company reports

8

QPI-1002: Renal disease

• Silence licensed AtuRNAi technology to Quark in 2005

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

• Milestones to Silence of c.$82m– next milestone $3-11m on exercise of

option

• Phase II trial in prevention of delayed graft function (DGF) initiated September 2010 (results due 2012)

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

• Low single-digit effective royalty rate on end sales

2010 Market size (transplant) $4.4bn

Potential Market size (AKI) $1bn+

Neoral

19%

Myfortic

10%

Cellcept

29%

Prograf

42%

Source: company reports

9

AtuPLEX

Vascular endothelium• Cancer & Metastasis

• Inflammation

DBTC

Liver parenchyma• Hepatocellular carcinoma

• Ischemia Reperfusion Injury

• Fulminant Fibrosis

DACC

Pulmonary endothelium• Acute lung injury/ARDS

• Pulmonary Hypertension

• Infection & Inflammation

Overcoming the Delivery Challenge

10

Atu027/Atu134: Market opportunity

• Anti-angiogenic market worth $8.2bn

• Both Atu027 and Atu134 are anti-angiogenic drugs

• Atu027 is only RNAi anti-angiogenic drug in clinical development

• Atu027 will be used in the setting of highly vascularised tumours; prostate, lung, ovarian & melanoma

• Results of on-going phase I trial expected at end 2011

• Interim data to be presented at ASCO, June 2011

• Partner Atu027 in 2012 – upfront, milestones and royalties

Anti-angiogenic – works by disrupting blood supply to tumours

2010 Market size (oncology) $53bn

Chemotherapy,

19.3

Other small

molecules, 6.7

Other

antibodies, 10

Hormone

Therapies, 8.9

Anti-

angiogenics,

8.2

Source: company reports

11

Atu027 deal structure

• Plan to partner in 2012

• Partnering discussions initiated

• Typical deal structure

– Upfronts (double digit $m’s)

– Milestones (significant)

– Royalties (double digit %)

• Variations

– Global rights

– Regional rights

– Ex-US/Eu rights

– Opt-in rights

0

5

10

15

20

25

30

35

Lead Preclinical Phase I Phase II Phase III

Big Pharma alliances 2005-9

0

50

100

150

200

Upfront R&D Milestones Equity

Early stage deals 2005-9

Upfr

ont

paym

ent

($m

)Paym

ents

($m

)

Source: RECAP Deloitte

13

Atu027: Strong preclinical efficacy data

DU-146 prostate Xenograft (N = 8)

Twice weekly treatment

0 20 - 45 46 days

Atu027

Avastin

Vehicle

Atu027

VEGF-R-siRNA-lipoplex

Avastin

Atu027 + Avastin

VEGF-R-siRNA-lipoplex

+ Avastin

• Atu027 ‘silences’ the production of PKN3

– PKN3 is a key regulator of blood and lymph vessel formation

• Inhibition of PKN3 leads to:

– reduced oxygen supply to tumour

– reduced tumour growth/metastases

• Efficacy of Atu027 demonstrated in multiple cancer animal models

– data published in peer reviewed journals

• 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

• 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

1 week after 8th repeated treatmentBaseline (pre-treatment)

Note: vanished metastatic lesion in the left lower lobe of the lung (circle)

BEFORE AFTER

Atu027: Phase I results promising

14

0

1000

2000

3000

4000

Sucrose Luciferase CD31 control

(Atu134)T

um

or

volu

me [

mm

3]

Breast (mammary fat pad)

* p=0.003

* p=0.002 * p=0.014

Atu134: Strong preclinical efficacy data

• Atu134 has demonstrated efficacy in a variety of preclinical cancer models

– Orthotopic models

– Ectopic models

• Atu134 has demonstrated strong efficacy against primary tumour

• Targets CD31 – well validated target

• GMP manufacturing commencing

• Preclinical toxicology testing due to start early in 2012

• IND filing expected in 2012

• Plan to partner during Phase I

– target double digit royalty rate

In preclinical studies

Atu134 significantly reduced

tumour growth

15

Organ distribution after delivery of siRNA with DACC

Atu111: treatment of acute lung injury

0

25

50

75

100

125

siRN

A [

%ID

/g t

issu

e]

16

• 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 exquisitely selective delivery to lung (see chart)

• DACC delivery system leads to prolonged knock-down

– potential for only one dose in ALI

• Aim to partner in 2012

– target high single digit royalties

0

10

20

30

40

50

60

70

Organ distribution after delivery of siRNA with DBTC

siRN

A [

%ID

/ti

ssue]

DBTC: Targeting the Liver

no functional delivery of siRNA to spleen

no knockdown in spleen tissue. 17

• Proprietary lipid-based formulation targeting liver

• Significant market opportunities

– Liver cancer

– Ischemia reperfusion injury

– fibrosis

• DBTC delivers siRNAs primarily to liver (see chart)

• DTBC delivery system leads to persistent knock-down

– Single dose knocks down gene expression for up to 1 wk

• DTBC well tolerated

– Dosed up to 8.3mg/kg

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

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

2222

Summary

22

• 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

APPENDIX

0.0

0.4

0.8

1.2

vehicle 0.03 0.1 0.3 1.0 3.0

control mg/kg ATU027/23H

hP

KN

3/h

PP

IB m

RN

A

v000m

animal # 1 2 3 4 5 6 7 8

sucrose 0.3 1.0 3.0mg/kg

PKN3

p110

Actin

Protein knock down in lung tissue (Western blot)

mRNA knock down in lung tissue (B-DNA)

Plasma level of siRNA strand (1st infusion)

0

1

10

100

1000

0 4 8 12 16 20 24

time [h]

an

tise

nse

str

an

d [p

mo

l/m

l

pla

sm

a]

0

10

1000

an

tise

nse

str

an

d [n

g/m

l

pla

sm

a]

1.0mg/kg

0.3mg/kg

0.1mg/kg

0.03mg/kg

3.0mg/kg

Sucrose 0.3mg/kg

166 bp PKN3 RNAi 5´-RACE

229 bp 16S rRNA 5´-RACE

(internal control)

cleavage site

verified

RNAi in lung tissue (5‘-RACE)

Atu027: Gene knock-down of PKN3

confirmed in preclinical studies

24

25

Atu027: Phase I Study Design

25

• 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)

0

40

80

120

0 4 8 12 16 20 24

Cynomolgus Monkey Human

0

40

80

120

0 4 8 12 16 20 24

A s

trand c

oncentr

ati

on in p

lasm

a

-m

ean o

f dose

gro

ups

[ng/m

L]

Time [hours]

0.3 mg/kg

0.1 mg/kg

0.03 mg/kg

4 h infusion 4 h infusion

A s

trand c

oncentr

ati

on in p

lasm

a

-m

ean o

f dose

gro

ups

[ng/m

L]

Time [hours]

0.180 mg/kg

0.120 mg/kg

0.072 mg/kg

0.036 mg/kg

0.018 mg/kg

0.009 mg/kg

0.003 mg/kg

0.001 mg/kg

**

* Final/verfied data pending

We have achieved Predictable

Pharmacokinetics For Atu027

Predictable PK tells that Atu027 is behaving in humans as

it did in pre-clinical models

In vitro: IC50 ≈ 1 to 10 nM

27

Dose levelAtu027 - Dose (mg/kg)

(based on the siRNA content)

1 (starting dose) 0.001

2 0.003

3 0.009

4 0.018

5 0.036

6 0.072

7 0.120

8 0.180

9 0.253

10 0.336

11 0.447

Atu027: Positive Phase I Data to Date

27

• Phase I trial on-going – expected to complete 2H2011

− No dose limiting toxicities to date, dose escalation continuing

• Generally well tolerated to date− 173+ doses administered to 24 patients across 8 dose levels

− Up to 26 doses administered to a single patient (study

followed by compassionate use)

− No cytokine activation observed

• No pre-medication required

• > 210 timepoints analysed for complement system and cytokine activation

• Limited Atu027-related transient activation of the alternative pathway of the complement system - (as published and expected for liposomal formulations) not dose dependant

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

28

Atu134 (CD31/PECAM-1): A well

validated target

200

400

600

800

24 26 28 30 32 34

Tum

or

volu

me [

mm

3]

Days post cell challenge

Silence Therapeutics

200

1200

2200

3200

12 14 16 18

Tum

or

volu

me [

mm

3]

Days post cell challenge

sucrose

siRNAPTEN-

lipoplex

Atu134

3Y1-RasV12 s.c.

Atu134

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

0

400

800

1200

1600

25 31 37 43 49

Tum

or

volu

me

[mm

³]

Days post cell challenge

sucrose

Atu134

Atu134 shows anti-tumor activity in different established

subcutanuous tumor xenografts in comparison to control treatment.

sucrosesiRNALuc-

lipoplex

29

Efficacy of Atu134 in Various

Ectopic Tumor Xenograft Models

Thank you