Silence Therapeutics

The company possesses one of the most comprehensive and sophisticated RNAi therapeutic platforms comprised of proprietary delivery technologies, potent siRNA sequences and innovative siRNA structural features – the three areas the company believes to be critical to building, protecting and commercializing RNAi therapeutics. This platform is protected by Silence’s strong intellectual property portfolio which includes more than 200 issued and pending patent applications worldwide.

Additionally, Silence is a clear leader in the development of RNAi clinical candidates, possessing a pipeline that includes a total of five different internal and partnered programs in the clinic.  With at least half of the siRNA programs currently in clinical development worldwide based on Silence's technology, the company’s clinical pipeline validates not only the strength of the company's proprietary technology but also the team of researchers that has guided the development path.

A final key validation of Silence’s leadership position in RNAi is the company’s multiple major partnerships with global pharmaceutical companies.  The partnerships with companies such as AstraZeneca, Pfizer/Quark Pharma and Dainippon Sumitomo further demonstrate the credibility of Silence’s technologies.

THERAPEUTIC PLATFORM

Overview
As a result of its recent merger with Intradigm Corporation, Silence now possesses one of the most comprehensive platforms in RNAi therapeutic development.

The company holds a powerful and strategic position in each of the three areas believed to be critical to building, protecting and commercializing RNAi therapeutics:

    * Proprietary Delivery Technologies
    * Potent siRNA Sequences
    * Innovative siRNA Structural Features

Delivery Technology

To achieve the goal of systemic delivery of RNAi therapeutics, Silence possesses a range of complementary siRNA delivery technologies which include both polymer and lipid platforms.

AtuPlex/AtuFect Delivery Platform
Silence has developed a proprietary lipid delivery technology (also known as lipoplex technology) called AtuPlex.  This unique platform is based on proprietary lipid components called AtuFect which embed siRNA into multiple lipid bi-layer structures.  The resulting nanoparticle structure consists of the siRNA combined with a cationic lipid, fusiogenic lipid and PEG.  To date, the AtuPlex technology has demonstrated the ability to increase:

    *  Systemic delivery to endothelium, liver and other tissues
    * Functional intracellular uptake (endosomal release) of siRNA compared with “naked” delivery
    * Bioavailability and circulation time



Furthermore, the nanoparticles generated with the AtuPlex technology are capable of being lyophilized which allows for easier transport and handling in hospitals and long-term stability.

The company believes that the AtuPlex platform is ideal for the development of anti-angiogenic and/or anti-vascular therapies aimed at treating solid cancer and cardiovascular diseases.
PolyTran™ Delivery Platform

Silence possesses a proprietary technology for creating nanoparticles that combine active siRNA molecules with the company’s novel PolyTran biodegradable peptide-based polymers. These PolyTran polymers have been optimized for efficient siRNA delivery, providing the nanoparticles created by Silence with the following attributes:

    * Ability to enable systemic administration of RNAi therapeutics
    * Capability to facilitate intracellular delivery of siRNA payload under pharmaceutically relevant conditions
    * Flexibility to incorporate siRNA sequences (independent of length, end structure or chemical modification) against any disease target.

Silence’s lipoplexes and nanoparticles are modular, allowing them to be easily modified by PEGylation or the attachment of targeting moieties.  This flexibility further enhances the delivery features of the nanoparticles by increasing their half-life and reducing immunogenicity (PEGylation) and enabling delivery directly to targeted cells (targeting ligands).

Sequence Library
The ability to effectively select appropriate disease targets plays a critical role in the development and optimization of RNAi therapeutics.

KEY SEQUENCE FEATURES

    * Double Blunt-Ended
    * Versatile Lengths Including 19, 21, 23 and 25 Base-Pairs
    * High Potency
    * Optimized Molecular Structure
    * Cross-Species Homology

         

To maximize target selection success, Silence weighs a number of critical considerations including the role the target plays in disease modification, the cell type in which the target is expressed and other IP-related considerations in developing a therapeutic against the target.

Through diligent scientific research based on both bioinformatics algorithms and unique know-how, Silence has compiled a library of proprietary siRNA sequences against more than 50 high-value disease targets.  The company has built a strong intellectual property position around its sequence library, including protection for certain specific disease targets.

Structual Modification
To further strengthen its position within the RNAi therapeutics space, Silence has engaged in pursuing valuable structural modifications for its proprietary siRNA sequences.

These modifications are designed to improve both the efficacy and safety of these sequences, while also offering an increased depth of patent protection. The company’s work in this area involves two distinct approaches to structural modification.

AtuRNAi
Silence has developed a proprietary siRNA containing only naturally-occurring RNA which has been chemically modified to result in a chemically stabilized molecule.  This stabilized siRNA, known as AtuRNAi, offers a number of key advantages including:

    * Stability against nuclease degradation, offering longer half-life, lower doses and less frequent administration
    * Absence of toxic metabolites due to the inclusion of only naturally occurring building blocks
    * Lower manufacturing costs
    * Increased yield and more rapid synthesis due to improved process development

Zamore "Design Rules"
Silence has three exclusive licenses from the University of Massachusetts that provide access to issued and pending patents associated with the Zamore "Design Rules".  Access to this technology offers Silence additional insight into methods for increasing siRNA potency and reducing off-target effects of its therapeutics.
For more information CLICK HERE




For further information on the PIPELINE CLICK HERE


INTELLECTUAL PROPERTY
Silence has built a strong and diverse intellectual property portfolio including proprietary siRNA delivery technologies, potent siRNA sequences and key siRNA structural features, as well as specific high-value disease targets.

The company believes that this IP portfolio strategically provides a proprietary position in the RNAi therapeutics space.

At present, the company’s global patent portfolio includes over 200 issued and pending patent applications. Key assets include three exclusive licenses to the issued and pending patents associated with the Zamore "Design Rules" from the University of Massachusetts, as well as a license to the Fire & Mello patent.

For further information on INTELLECTUAL PROPERTY CLICK HERE

COLLABORATIONS
A key component of Silence’s business strategy is the establishment of additional high-value partnerships with the leading pharmaceutical companies.
       
Silence believes that the company’s comprehensive RNAi therapeutic platform can support and advance multiple partnerships with the pharmaceutical industry across a diverse range of therapeutic opportunities.  In particular, the company’s broad range of complementary siRNA delivery technologies allows Silence to offer potential partners a choice of solutions for the delivery of RNAi molecules to diseased tissue - one of the main challenges in the emerging field of RNAi therapeutics.

The company’s unique RNAi therapeutic platform has drawn the attention of many leading pharmaceutical companies worldwide and Silence is actively engaged in partnering discussions spanning a range of new and exciting development opportunities.

For further information on COLLABORATIONS CLICK HERE


SCIENCE OF RNAi
RNA interference (RNAi) is a natural cellular process of gene silencing that occurs in almost all organisms. One type of RNAi is siRNA which relies upon short double-stranded RNA (< 30 base pairs) that induce sequence-specific silencing of target disease genes through specific degradation of the mRNA responsible for protein synthesis.

The result of this process is the silencing or shutting down of a target gene protein product. In a therapeutic setting, siRNAs are delivered to target cells to halt the production of disease-causing proteins.

To learn more about the science of RNAi, please visit the following sites dedicated to this topic:

    * PBS’ NOVA Series: http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html
    * Nature: http://www.nature.com/nature/focus/rnai/

For further information on SCIENCE OF RNAi CLICK HERE

Board of Directors

JERRY RANDALL
Position: Chairman
Mr. Randall is a qualified chartered accountant and previously served as the chief financial officer of Sinclair Pharmaceuticals plc which he joined in 2000 as part of a management buy-in team. Prior to this, Mr. Randall worked in corporate finance with Gambit Corporate Finance and had previously been involved in two other buy-ins. He acted as adviser to both private and quoted companies between 1993 and 2000, in both the capacity of nominated adviser and in practice with KPMG. During this period, he was involved in a number of flotations and transactions on the Official List, Unlisted Securities Market and the Alternative Investment Market, as well as raising private equity.

ANNETTE CLANCY
Position: Non-Executive Director
Ms. Clancy has had a distinguished career spanning 30 years with GlaxoSmithKline (GSK). She has 15 years experience in business development, leading GSK's global transactions and alliance management teams for the past three years, and during her tenure she and her team have been responsible for concluding a large number of research, development and commercial business collaborations on behalf of GSK. Prior to her role in business development, Ms. Clancy held a number of positions in clinical research, research and development project management and commercialization. Ms. Clancy has a BSc (Hons) in pharmacology from Bath University.

PHILIP HAWORTH, JD, Ph.D.
Position: Chief Executive Officer
Dr. Haworth was appointed chief executive officer of Silence Therapeutics in January 2010, following the company’s merger with Intradigm Corporation.  Prior to this role, Dr. Haworth served as CEO of Intradigm, following his tenure as the company’s vice president of business development. He joined Intradigm in 2007, having spent the previous 15 years in senior business development roles at several leading biotechnology companies including Genencor International, COR Therapeutics and Affymax/Affymetrix, among others. In these positions, he led the identification and negotiation of numerous collaborative and licensing agreements with a range of global and regional pharmaceutical companies. He most recently served as vice president, business development at Codexis, Inc. He possesses deep deal–making expertise that spans establishing discovery and development partnerships, technology and product in– and out–licensing, mergers and acquisitions, and financing support.

Dr. Haworth earned his J.D. from Stanford University Law School and his Ph.D. in biochemistry from the University of Manchester in the U.K. He also received his bachelor’s degree with first class honors in physiology and biochemistry from the University of Southampton in the U.K.

JAMES N. TOPPER, M.D., Ph.D
Position: Non-Executive Director
Dr. Topper is a general partner at Frazier Healthcare Ventures’ Palo Alto office and was the chairman of the board of Intradigm from May 2006 to the date of the merger with Silence Therapeutics. Since joining Frazier Healthcare in 2003, Dr. Topper has led several biopharma investments including Arête Therapeutics, Cotherix, and MacuSight. Dr. Topper is also an advisory board member to the Harvard-Partners Center for Genetics and Genomics. Prior to joining Frazier Healthcare, he served as head of the cardiovascular research and development franchise at Millennium Pharmaceuticals and ran Millennium San Francisco (formerly COR Therapeutics). Prior to the merger of COR and Millennium, he served as the Vice President of Biology at COR and was responsible for managing all of its research activities.

Dr. Topper received his MD and Ph D in Biophysics from Stanford University School of Medicine in 1991. He completed his postgraduate training in Internal Medicine and Cardiovascular Disease at the Brigham and Women’s Hospital in Boston and is board certified in both disciplines. While there, he completed a research fellowship in the Vascular Research Division in the department of Pathology. He then joined the faculty of Harvard Medical School from 1997 to 1998, and subsequently Stanford University as an Assistant Professor of Medicine (Cardiovascular) in July 1998. He has authored over 50 publications and was the recipient of a Howard Hughes Scholars Award while on the faculty at Stanford University. He continues to hold an appointment as a Clinical Assistant Professor of Medicine at Stanford University.

DAVID MACK, Ph. D
Position: Non-Executive Director
Dr. Mack is a director at Alta Partners where he led the investment in Angiosyn as a director and acting CEO (acquired by Pfizer in 2005). He joined Intradigm’s board in May 2006 and served on that board until the merger with Silence Therapeutics. He is currently on the board of directors of Aerie Pharmaceuticals, Ceregene and Proacta. Prior to Alta, Dr. Mack co-founded and served as Vice President of Genomics Research at Eos Biotechnology (acquired by Protein Design Labs in 2003). From 1995 to 1997, he served at Affymetrix as Head of Cancer Biology where he oversaw the development and application of DNA array technology in the areas of oncology and inflammation. He was also a pivotal member of the Polymerase Chain Reaction (PCR) invention group at Cetus (now Chiron) in the mid 1980s.

Dr. Mack has co-authored more than 30 scientific articles and reviews, including papers published in Cell, Science and Nature, and he is an inventor on 21 US patents. He was an American Cancer Society postdoctoral fellow at Stanford University School of Medicine in Microbiology and Immunology. Dr. Mack received his Ph.D. in 1992 from the University of Chicago where he was a Howard Hughes fellow in Molecular Genetics and Cell Biology. He holds a Bachelor of Arts in Molecular Biology from University of California, Berkeley.

DAVID U'PRICHARD, Ph.D.
Position: Non-Executive Director
Dr. U'Prichard was, from 1999 to 2003, chief executive officer and a member of the board of directors of 3-Dimensional Pharmaceuticals, Inc. ("3DP"). During that time, he took 3DP public and secured large collaborations with Bristol-Myers Squibb and Johnson & Johnson. In March 2003, 3DP become a part of Johnson & Johnson Pharmaceutical R&D. From 1997 to 1999, Dr. U'Prichard served as chairman of research and development at SmithKline Beecham. While at SmithKline Beecham, Dr. U'Prichard oversaw the entry of approximately ten compounds into global development, the international registration of the diabetes drug Avandia® and the entry of four compounds into Phase III trials and six compounds into early clinical trials; additionally, he instituted several major restructuring efforts at the company. Prior to SmithKline Beecham, he worked for ICI/Zeneca from 1986 to 1997, as executive vice president and international research director from 1994 to 1997.

Senior Management Team

PHILIP HAWORTH, JD, Ph.D.
Position: Chief Executive Officer
Dr. Haworth was appointed chief executive officer of Silence Therapeutics in January 2010, following the company’s merger with Intradigm Corporation.  Prior to this role, Dr. Haworth served as CEO of Intradigm, following his tenure as the company’s vice president of business development. He joined Intradigm in 2007, having spent the previous 15 years in senior business development roles at several leading biotechnology companies including Genencor International, COR Therapeutics and Affymax/Affymetrix, among others. In these positions, he led the identification and negotiation of numerous collaborative and licensing agreements with a range of global and regional pharmaceutical companies. He most recently served as vice president, business development at Codexis, Inc. He possesses deep deal–making expertise that spans establishing discovery and development partnerships, technology and product in– and out–licensing, mergers and acquisitions, and financing support.

Dr. Haworth earned his J.D. from Stanford University Law School and his Ph.D. in biochemistry from the University of Manchester in the U.K. He also received his bachelor’s degree with first class honors in physiology and biochemistry from the University of Southampton in the U.K.

MAX HERRMANN
Position: Chief Financial Officer and Company Secretary
Mr. Herrmann possesses more than 20 years of biotechnology and pharmaceutical industry experience having held key management positions with leading development stage companies, as well as several investment banks.  In these roles, he has been involved in raising more than $300M for biotechnology companies in the United States and Europe.  Most recently Mr. Herrmann served as CFO of Intercytex Group plc, a publicly traded company focused on the emerging area of regenerative medicine.  Before joining Intercytex, he spent over ten years as a sell-side equity analyst, most recently as managing director and head of European pharmaceutical and biotechnology research at ING.  He has also held the position of financial controller for US-based Onyx Pharmaceuticals Inc and currently serves on the boards of Regenerative Medicine Assets Limited, as well as the company’s subsidiaries Intercytex Ltd. and Axordia Ltd.

Mr. Herrmann qualified as a Chartered Accountant with Arthur Andersen in 1993. He holds a degree in microbiology from the University of Kent.

KLAUS GIESE, Ph.D.
Position: Chief Scientific Officer
Dr. Giese has over 19 years of relevant experience in both the U.S. and Europe, including the management of more than 20 international collaborations with pharmaceutical and biotech companies and more than five years in cross-border management as CSO.  Dr. Giese joined Silence Therapeutics AG in 1999, where he continues his position as CSO. Prior to Silence Therapeutics, Dr. Giese was group leader at Chiron Corporation from 1994 to 1998 and was responsible for coordinating and managing a portion of Chiron's obesity and oncology program. His efforts in this program included the development of several different gene expression profiling approaches and the development of a novel high-throughput screening assay to identify inhibitors of HIV-1 transcription. Prior to joining Chiron, Dr. Giese acted as research scientist and postdoctoral fellow at the Howard Hughes Medical Institute, University of California, San Francisco, as well as at the Max-Planck-Institute for Molecular Genetics in Berlin. Dr. Giese studied biochemistry at the Free University of Berlin, where he also received his Ph.D.

MICHAEL RILEY, JD, M.Sc.
Position: Vice President of Intellectual Property & Corporate Development
Mr. Riley joined Silence in January 2010 as part of the company’s merger with Intradigm.  In the same position with Intradigm, he lead the company’s operations (finance, legal, HR & IT) while also holding responsibility for all intellectual property activities. Mr. Riley brings with him over 15 years of scientific, operational, intellectual property (legal) and international business experience. Most recently he held various positions in Europe and the U.S. with Amgen, Abgenix and Celltech Group PLC.

Mr. Riley obtained his JD with distinction from University of North Dakota School of law, and his M Sc from University of North Dakota School of Medicine, Department of Biochemistry and Molecular Biology.

THOMAS CHRISTÉLY
Position: Chief Operating Officer
Thomas Christély has more than 19 years experience in finance and corporate and business development. His track record includes multiple financing transactions, as well as M&A, divestments and strategic restructurings and more than nine years in cross-border management at board level. Mr. Christély joined Silence Therapeutics AG (Atugen AG) in 2001 as CFO and became COO in 2002 prior to being appointed its CEO in 2006. From 1996 to 2000, he held the position of senior vice president and CFO at OXO Chemie AG, a Swiss pharmaceutical company, and founded its subsidiary OXO Chemie, Inc., in San Francisco, where he stayed from 1997 to 2000. Mr. Christély was managing partner of the investment firm Löschen & Partner in Hamburg and Moscow, from 1992 to 1995 and worked in mergers and acquisitions of Enskilda Corporate Finance in London from 1989 to 1992. Mr. Christély has worked for two international accounting and consultancy firms and for the Commission of the European Union in Brussels. After his studies in Hamburg and Geneva, he received degrees in business administration (equivalent to MBA) and law from the University of Hamburg and was admitted as attorney-at-law.

Updated from Silence therapeutics website 12.09.11