Silence Therapeutics Corporate Factsheet, March 2012, including: > Pipeline of internal and partnered product candidates for RNAi therapeutics > Partnerships and Collaborations > Patented siRNA Delivery Technologies > Structural Features of siRNA sequences > Intellectual Property

1. Silence Therapeutics plc (AIM: SLN) is a leader
in the discovery, development and delivery of
RNA interference (RNAi) Therapeutics for the
treatment of serious diseases.
Silence’s RNAi therapeutic platform comprises of proprietary delivery technologies, short
interfering RNA (siRNA) sequences and innovative siRNA structural features that are critical Stock Information*
in building, protecting and commercialising RNAi therapeutics -considered one of the most Ticker: AIM:SLN
exciting and significant medial breakthroughs of recent years. Market Cap (GBP): £13.9million
Market Cap (USD): $22.8million
About RNAi * as of 14 Feb, 2012
RNAi is a natural cellular process that occurs in almost all organisms and results in the
silencing or shutting down of a target gene protein product. In an effort to combat a
wide range of diseases, therapeutics that exploit the RNAi process are being developed
Corporate Highlights
to halt the production of disease-causing proteins. One of the sector’s most
comprehensive RNAi platforms:
Silence’s Pipeline I Unparalleled, proprietary delivery
platforms
Silence has developed a broad pipeline of internal and partnered I Potent siRNA sequences
product candidates. I Innovative siRNA structural features
Silence’s technology serves as an important foundation in almost half of the siRNA programs in
clinical development worldwide, demonstrating the company is a clear sector leader. Silence’s
Robust clinical pipeline of siRNA
impressive pipeline of products not only validates the strength of the company’s technology but
therapeutics:
also the depth of knowledge that has guided the development path. I 5 clinical programs ongoing with partners
and/or internally
Products Partners Target Delivery Market Discovery Pre- PhaseI PhaseII PhaseIIb
Tissue/ method size Clinical I Nearly half of the siRNA clinical programs
Organ ($m) worldwide incorporate Silence’s
technology
RTP801
PF-4523655
– Local Delivery to $1bn+
I Atu027 is one of most clinically advanced
Diabetic Macular Naked sIRNA
the Eye (potential) RNAi therapeutics in oncology
Edema
I Indications include metabolic, pulmonary
PF-4523655 and vascular diseases, as well as cancer
RTP801
Age-related $3.1bn
– Local Delivery Naked sIRNA
Macular (2010)
to the Eye
Degeneration
Validating partnerships
QPI-1002
Prevention of
P53 – Systematic
$4.4bn with leading pharmaceutical
Delivery to the Naked sIRNA
Delayed Graft
Kidney
(2010) companies:
Function
I Dainippon Sumitomo
P53 – Systematic
QPI-1002
Delivery to the $1bn+
I Pfizer/Quark
Acute Kidney Naked sIRNA
Injury
Kidney (potential) I Quark/Novartis
I AstraZeneca
PKN3 – Systematic $8.2bn+
Atu027
Delivery to Tumor AtuPLEX (angiogenesis
Solid Tumors
Endothelium mkt 2010)
Robust, global intellectual
property portfolio providing a
Systematic
Atu111 $1bn+
Acute Lung Injury
Delivery to Lung DACC
potential
strong proprietary position:
Endothelium
I Issued US, EU and Japanese patents
Systematic
covering critical aspects of delivery,
Liver diseases Delivery to Liver
DBTC Undisclosed sequences and structures
(DBTC programs) Hepatocytes and
Endothelium
P53 – Systematic
Lung diseases
Delivery to the DACC Undisclosed
(DACC system)
Kidney
2012 Goals
Silence’s Partnerships I Complete Phase I clinical trial for Atu027
I Present final Phase I results on Atu027
I Pfizer/Quark – Phase II products for diabetic macular edema and age-related macular I Advance preclinical programs for Liver &
degeneration; $95M in milestones plus royalties Lung diseases
I Quark/Novartis (option) – Phase II study ongoing in kidney transplantation; Phase I study I Complete new corporate alliance
complete in acute kidney injury; $82M in milestones plus royalties
I Initiate Phase II trial of Atu027
I Dainippon Sumitomo – siRNA delivery collaboration
I AstraZeneca – $15m upfront; siRNA research and delivery collaboration
(research phase now complete)

2. RNAi Therapeutic Platform
Silence’s siRNA Delivery Technologies
Silences believes a single approach will not be sufficient to universally overcome the RNAi delivery
Structural Features challenge. To achieve the goal of systemic delivery of RNAi therapeutics, Silence possesses a range of
and IP complementary siRNA delivery technologies.
AtuPLEX™ Delivery system
The AtuPLEX™ delivery system is Silence’s most advanced lipid based siRNA formulation. It is designed
for a broad delivery to vascular endothelium and shows a high RNAi activity making it ideal for the
development of anti-angiogenic/anti-vascular therapies.
High-Value siRNA siRNA Delivery
DACC Delivery system
Sequences and IP Technologies and IP The DACC system represents a novel lipid-based formulation family which delivers siRNA efficiently
to the vascular endothelium of the lung. Silence considers this delivery system as being exceptionally
well suited to address lung-specific diseases e.g. acute lung injury/ARDS. The DACC system has
demonstrated sustained gene silencing - a single dose is sufficient to inhibit target gene expression in
Management Team lungs for up to a month.
ANTONY SEDGWICK
Chief Executive Officer
DBTC Delivery system
MAX HERRMANN
Chief Financial Officer Delivery of siRNA to the liver has also been achieved by other delivery systems - but instead of merely
targeting liver hepatocytes, Silence’s DBTC formulations target both liver hepatocytes and vascular
KLAUS GIESE, Ph.D. endothelial cells of the liver. This unique feature opens up much broader therapeutic opportunities.
Chief Scientific Officer
GEORGE BUCHNER
VP Business Development Successful siRNA delivery with Silence’s technology
JÖRG KAUFFMAN
VP Research & Development AtuRNAi™ Local and systemic delivery Phase II
AtuPLEX™ Systemic delivery to endothelial cells in blood vessels Phase I
RNAi Delivery Challenge DACC Systemic delivery to lung endothelial cells Preclinical
The challenges of systemic RNAi DBTC Systemic delivery to hepatocytes Preclinical
delivery are well documented
and include numerous biological
barriers that limit an RNAi
therapeutic’s ability to reach its
“target” safely and effectively. Silence’s Structural Features
Silence structurally modifies its proprietary siRNA sequences to improve their efficacy
and safety, while also offering an increased depth of patent protection. Two examples of
Silence’s Delivery Solutions this work are:
Silence’s sophisticated and flexible AtuRNAi™
delivery technologies provide
Proprietary siRNA sequences containing the only naturally-occurring chemical modification
the Company with unmatched
(2’-O-methyl) to result in a stabilized molecule.
potential to develop solutions
for successfully delivering RNAi
molecules to specific tissues thus Zamore “Design Rules”
allowing specific therapeutic Technology in-licensed from UMass provides insight into methods for increasing siRNA
benefits. This versatility positions potency and reducing off-target effects of its therapeutics.
Silence to be a partner of choice for
pharmaceutical and biotechnology
companies currently working in, or
seeking to enter, the RNAi field.
Silence’s Intellectual Property
Silence Therapeutics is executing a proactive strategy to continue to build and strengthen a
global, diverse and competitive intellectual property portfolio that provides the Company and
its partners with a strong proprietary position in the RNAi therapeutics space. The Company
believes that it will continue to make significant progress in these efforts as it expects
additional RNAi patents to be issued in Japan, the United States and Europe during 2012. At
present, Silence’s global patent portfolio contains issued patents and pending applications
covering strategic areas of RNAi therapeutic development including multiple proprietary
siRNA delivery technologies, AtuRNAi (chemical modification, blunt ended), specific siRNA
sequences and Zamore design rules.
The Royal Institution of Great Britain, 21 Albemarle Street, London W1S 4BS, United Kingdom
t: +44 (0) 20 7491 6520 www.silence-therapeutics.com e: london@silence-therapeutics.com