Executive Sponsor

Sponsorship and Exhibition Opportunities

To find out more on the sponsorship and exhibition opportunities, please contactLily Chong: Tel: +44 (0) 207 017 5011 Fax +44 (0) 207 017 5656 Email: lily.chong@informa.com

Access Industry Decision MakersEuroTIDES 2006 conference and exhibition provides an ideal opportunity to gain exposure for your products and services, to all of those involved with the Oligonuleotide,RNAi and Peptide Manufacturing and Drug Development Industry. With a number of lead generating, networking and branding opportunities available, you will be able toaccess senior level decision makers across Europe, USA and Asia.

Post-Conference Workshop Thursday 7 December 2006

EuroTIDES 2006 Exhibition 5-6 December 2006

Avecia Biotechnology are the world's leading and most experiencedcontract manufacturer of oligonucleotides for DNA medicines. Working ona range of programmes for many customers across the USA and Europe,

Avecia serves the full drug development pipeline with capabilities in process development, analyticalmethod development, scale-up, validation and manufacture at all phases and scales.

Associate SponsorGirindus, member of Solvay Organics, is a leading manufacturer of cGMP Oligonucleotides fortherapeutic and cosmetic use. Solvay Organics combines its organic fluorine chemistry withPeptisyntha´s innovative peptide technologies and Girindus expertise in oligonucleotides. Girindusis outstanding in offering two production methods, solid-phase and a one-of-a-kind solution-

phase for efficient manufacture of large volumes. Girindus operates cGMP oligonucleotide production facilities in Ohioand Germany, which support API supplies from clinical into market.Visit www.girindus.com for more information.

Conference Padfolio SponsorAmerican International Chemical’s Advanced Technology Division is dedicated to theexpanding fields of Oligonucleotide chemistries. AIC is a leader in the Activator marketoffering 5-Ethylthio-1H-tetrazole, 5-Benzylmercaptotetrazole and licensed 4,5-

Dicyanoimidazole. AIC also offers a wide variety of DNA and RNA synthesis reagents including: SpecialtyPhosphoramidites, Thiolating Reagents, Custom Synthesis, and Synthesis Supports.

Biopharmaceutical Production Series SponsorSAFC Biosciences develops, manufactures and markets cell culturereagents, specialty chemicals, bioproducts and biodisposables toorganizations involved in developing and manufacturing

biopharmaceuticals. An industry leader providing reliable products and customized services for more than 30years, SAFC Biosciences has GMP, ISO certified manufacturing and distribution facilities in the United States,Europe and Australia

Pall’s leading edge filtration, separation and purification technologies and serviceshelp to facilitate the drug discovery, development and production process to getinnovative drugs to the market faster. Throughout the Life Sciences, Pall filtration,

chromatography, sampling, monitoring and quality assurance products, together with technical services invalidation, assays and process optimization are applicable to laboratory and pilot-scale development,production, aseptic processing, biologicals, bioprocessing, fermentation and downstream processing.

Featured Exhibitors

Registration: 09.30 Start: 10.00 End: 16.00 Lunch, morning and afternoon breaks are included

NETWORKING OPPORTUNITIES

HIGH SPEED NETWORKINGTuesday 5 December 2006 at 16.00 (During afternoon tea break)

• With HIGH SPEED NETWORKING you can make more new business contacts inone session than most people will make in 6 months!

• Network with other professionals, one on one, a few minutes at a time• Leave with a pocket full of business cards and a ton of new business connections!• Chances are you'll meet lots of people you wish

you had more time with. At the end of the firstday of the conference, continue networking atthe drinks reception in the exhibition hall plusalso attend the optional dinner boat cruise

Registration will be on Tuesday 6th Decemberduring the first break of the conference

Present a Poster at the Conference

Would you like to share yourresearch with your peers and the key industry leaders?

Posters must relate to the congress theme and should illustrate novel science,technologies and supporting data. You must be booked on as a delegate tobe able to present a poster. To apply please email Louisa Pickering at:louisa.pickering@informa.com and submit your abstract of 200 words or less,written in English, listing the principle author and completing all the contactdetails (organisation, mailing address, E-mail, phone, fax, poster, title, additionalauthors). Last date for submission of poster is 5th November 2006. In order tosecure the Poster Board, a fee of £99 will be required (Academics are free).

5

Session 1: Solid-phase synthesis and deprotection methods• RNA synthesis: pros and cons of TBDMS, TOM, ACE and Cpep chemistry• Chemical modifications and conjugates: e.g. phosphorothioates, 2'-O-

methyls, 2’-fluoros, LNA, etc.; attachment of lipophilic groups, peptides,proteins, PEG, fluorescent dyes, etc.

• Scale-up related issues and analysis of run files to identify problems

Session 2:Purification methods• HPLC: anion-exchange and reversed phase• Gel filtration• Desalting methods: precipitation, gel filtration and ultrafiltration

Session 3:Analytical methods and quality control• Analytical HPLC• Capillary gel electrophoresis• Mass spectroscopy and LC-MS• Endotoxin control

Session 4:Regulatory issues • siRNA and aptamers• More complex products such as nanoparticles and conjugates of

aptamers with PEG• Additional QC requirements

Workshop Leaders:Dr Brian Sproat, Chief Scientific Officer, RNA-TEC, BelgiumDr Susan Srivatsa, President, ElixinPharma, USA Thomas Rupp, Application Support Specialist, GE Healthcare, Germany

WORKSHOP CQ3008WsiRNA, Aptamers and their Conjugates: Synthesis, Purification, Analysis and Regulatory Issues

EuroTIDES 2006Monday 4 – Wednesday 6 December 2006Radisson SAS Hamburg, Germany www.ls-informa/eurotides

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■■ EuroTIDES 3 DAY CONF 11.00am 23-26 Oct 06

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Keynote Presentations:

• The Versatility of Oligonucleotides as Potential DrugsProfessor Fritz Eckstein, Max-Planck-Institute forExperimental Medicine, Germany

• Clinical Development of the Anti-Nucleolin Aptamer AS1411Dr Chris Smyth, Head of Research,Antisoma, UK

• The Phosphorothioate-stimulated Delivery of siRNA toMammalian Cells Via Caveosomes Ends in the Golgi Apparatus

Professor Georg Sczakiel, Institute for Molecular Medicine,University of Lübeck, Germany

Advisors:• Professor Masad Damha,

Department of Chemistry,McGill University, Canada

• Dr Mark Douglas,Strategy and IP Manager,Avecia Biotechnology, UK

• Dr Troels Koch,Vice President Chemistry,Santaris Pharma A/S, Denmark

• Dr Michael McLean,Chief Executive Officer,Oligovas, France

• Dr Thomas Rupp,Application Support Specialist,Protein Separations,GE Healthcare Bio-SciencesEurope GmbH, Germany

• Dr Yogesh S. Sanghvi,President, Rasayan Inc., USA

• Dr Brian Sproat,Chief Scientific Officer,RNA-TEC, Belgium

• Dr Susan Srivatsa,President, ElixinPharma, USA

• Professor Cy Stein,Professor of Medicine,Albert Einstein College ofMedicine, USA

www.ls-informa/eurotidesPart of Informa Life Sciences Group – The leading provider of scientific, technological and business information

Life Sciences

Oligonucleotide, RNAi and Peptides for the DrugDevelopment and Manufacturing Industry

IBC’s 7th Annual Conference

2006

Media Partners:

Thursday 7 December 2006

• siRNA, Aptamers and their Conjugates: Synthesis, Purification, Analysis and Regulatory Issues

Separately Bookable Session on:

Tools for a Start-Up Company- How to Take a Product Through to Development

Conference: Monday 4 to Wednesday 6 December 2006Exhibition: Tuesday 5 and Wednesday 6 December 2006Workshop: Thursday 7 December 2006Location: Radisson SAS Hamburg, Germany

Reduced Pricefor Start-upand SmallBiotech!!

Monday 4 December 2006

Attend this tailor-made session, designed specifically with key information on how to take your product through development to market• Taking oligonucleotides into the clinic economically• What legal and regulatory issues should be considered?• Access to affordable oligonucleotides

Post-Conference Workshop

Executive Sponsor:

Separately Bookable Morning Session on:

Tools for a Start- Up Company- How to Take a Product Through to Development

EuroTIDES Conference Research Development of Oligonucleotides, RNAi and Peptides

08.30 Registration for the Start-up Session ONLY and Morning Coffee

09.00 Chairperson’s Opening Remarks

09.05 Taking oligonucleotides into the clinic economicallyThe majority of start-up biotechnology companies raise as much money as they can, as early as they can, to develop their first clinical candidate. Oligovax hasfollowed a different model and yet we have advanced our lead compound into arandomised Phase II trial.This presentation will explore the possibilities for reaching clinical proof of concept without early stage dilutive financing.Dr Michael J. McLean, Chief Executive Officer, Oligovax, France

09.30 What legal issues should be considered in the start-up phase?The role of patents and IP rights in general, as potential constraints on freedom tooperate, as an essential credibility factor and as critical negotiating chips in licensingthird party technology in or exploiting the company's own IP to gain an early incomestream Lorna Brazell, Partner, Bird and Bird, UK

09.55 Access to affordable oligonucleotides for start-up companiesDespite of the significant improvements in oligonucleotide synthesis technologiesduring the last decade, the cost of manufacturing oligonucleotides remains high today.For a start-up company with limited funds, access to affordable oligonucleotide mayappear to be a surmountable challenge. This presentation will offer the guidelines forthe selection of low- cost CMO’s and the calculations of the cost of goods. Technicalinformation on how to be street-smart and save $$ while shopping for oligonucleotideswill be discussed.Dr Yogesh S. Sanghvi, President, Rasayan Inc., USA

10.25 What are the regulatory issues to consider?Development of oligonucleotide therapeutics in a start-up environment poses special challenges. In order to succeed, it is important to be fully aware of the evolving expectations of the regulatory agencies in various regions. This presentationwill provide strategies, from an industry perspective, to effectively meet the CMCregulatory requirements in a virtual/semi-virtual start-up environment.Dr G. Susan Srivatsa, President, ElixinPharma, USA

10.50 Morning Tea and Coffee

10.00 Registration for EuroTIDES and Morning Coffee

KEYNOTE PRESENTATION11.00 The versatility of oligonucleotides as potential drugs

There is a considerable range of oligonucleotides which have the potential to becleaving mRNA. Although the mechanisms differ for the various oligonucleotides, they have a number of problems in common, some of which can be solved by chemical modification such as enzymatic instability or avoiding certain side effects. Efficient cellular delivery, however, still awaits improvement as does specific cell targeting. Many oligonucleotides have been tested in animal models some are in different stages of clinical trials.Although many of these look very promising, the number of approved drugs is minimal up to now.Professor Fritz Eckstein, Max-Planck-Institute for Experimental Medicine,Germany

11.40 Industry angle of aptamers and other effective biomoleculesAptamers bridge target validation with drug discovery since they either can be used to identify functionally equivalent small molecule lead compounds in HTS programs or can even be turned into drugs themselves. Another class of biomolecules which qualify as pharmaceutical candidates are MicrobodiesTM.These highly soluble and selective proteins are even smaller in size (28 to 45 amino acids) and composed of a predefined pseudo-knot structure, which provides excellent stability for this protein group. Thus, Microbodies™ combine the selectivity of biologic therapeutics with the ease of handling and storage of small molecule pharmacologicals. This will be demonstrated by two case studies on MicrobodyTM-based product development.Dr Michael Blind, Chief Scientific Officer, NascaCell Technologies AG,Germany

12.10 Biotech Start-up SessionOpportunities for start-up companies to host a short presentation to the EuroTIDES audienceFor more information please contact louisa.pickering@informa.com

12.40 Lunch for Delegates and Speakers

14.00 Synthesis and biochemical properties of borane phosphonate DNAWe have discovered chemical methods for the synthesis of DNA containing phosphonoacetate, phosphonoformate, and borane phosphonate internucleotidelinkages. For all three analogs any combination of the four natural bases as wellas phosphate internucleotide linkages are possible. So far we have found thatphosphonoacetate DNA can be used, in the absence of cationic lipids, for thetransport of RNA/DNA into cells. Additionally all three analogs are resistant tonuclease degradation and form duplexes with complementary oligonucleotides.Phosphonoacetate and borane phosphonate DNA stimulate RNase H activity.Professor Marvin Caruthers, Department of Chemistry and Biochemistry,University of Colorado, USA

14.30 SisiRNA – Novel siRNA-like constructsThe novel molecular design “sisiRNA” for gene silencing is introduced.Among the characteristics of the sisiRNA technology are the following:

- the gene-silencing effect is strong and long-lasting- the number of off-target effects are reduced- the use of heavily modified antisense strands is made possible- the pharmacokinetics of the sisiRNA constructs can be modulated by

multiple conjugationThe gene silencing effect of unmodified-, LNA-modified and 2’-O-alkyl-modified sisiRNA constructs will be compared with the effects of traditional siRNA and siLNA constructs.Professor Jesper Wengel, Nucleic Acid Center, Department of Chemistry,University of Southern Denmark, Denmark

15.00 New PNA analogues: Synthesis and applicationsPNA are oligonucleotide mimics containing a pseudopeptide backbone.Despite their high affinity and specificity of binding toward complementary DNA and RNA and their stability to nuclease and protease, they show low solubility in aqueous environment, scarce ability to cross cell membranes.Furthermore the lack of charge on the backbone reduces their ability to interact with proteins. With the aim of obtaining PNA analogues with higher solubility in aqueous solutions and increased affinity to protein, we synthesisedPNA monomers with modifications at the g _position of the backbone. Moleculardynamic simulations on duplexes formed by a modified PNA and itscomplementary DNA reveal details on the effect of the PNA backbonestereochemistry on the hybridisation to DNA.Dr Alessandra Romanelli, University of Naples “Federico II”, Italy

15.30 Afternoon Tea and Coffee

16.10 Structure and mechanism of ribozymesThe chemical mechanism of ribozymes are gradually becoming clear. We are investigating this by a combination of structural analysis, single-molecule iophysics to observe the reactions and chemical genetic approaches to dissect the participating elements. From this the participation of nucleobases ingeneral acid-base catalysis is emerging in a number of nucleolytic ribozymes, nda general picture is emerging.Professor David Lilley, MSI/WTB complex, University of Dundee, UK

16.40 Pushing the boundaries of RNA chemistry to optimise RNAiOver the last several years our lab has focused on identifying the breadth of siRNA chemical modifications (and modification patterns) that are tolerated by theRNAi mechanism. This medicinal chemistry approach has allowed the identification of enhancements that substantially alter and improve some of thebasic characteristics of siRNA specificity, functionality, stability, and delivery. Thistalk will focus on work that combined siRNA bioinformatics and chemistry todisable one of the arms of the RNAi pathway responsible for off- targeting andtouch on chemical formulation strategies that enhance membrane uptake andcellular delivery Dr Anastasia Khvorova, Chief Scientific Officer, Vice President, Research and Development, Dharmacon, Inc, USA

17.10 Mechanism of action of defibrotide, a phosphodiester oligonucleotide therapeutic Defibrotide has a very high affinity (30 and 40 nM respectively)for bFGF and PDGF-BB. These affinities decrease dramatically when the average length of DF isreduced (35-40mer). Furthermore, DF is able to mobilise bFGF and PDGF-BB, fromtheir low affinity, glycosaminoglycan-binding sites on bovine corneal endothelialmatrix, without blocking their binding to cellular high affinity binding sites. Thesedata suggest that DF modulates the effects of endothelial damage by mobilisingendothelial cell growth- promoting cytokines, and as such represents an entirelynovel mode of oligonucleotide therapeutics.Professor Cy Stein, Professor of Medicine, Albert Einstein College of Medicine,USA

17.40 Strategies towards ribozyme mediated correction of genetic disordersKnockdown of transcripts encoding gene products that are pathogenic to the cellhas proven a potential strategy in fighting malignancies or viral infections.Treatment of inherited diseases however, requires correcting the disorder rather than destroying it. The lecture will introduce a novel strategy for ribozyme driven RNA repair.Professor Sabine Müller, Department of Biochemistry, Ernst Moritz Arndt University Greifswald, Germany

18.10 End of Day One

D A Y O N E • M O N D A Y 4 D E C E M B E R 2 0 0 6

2

08.30 Morning Coffee

09.00 Chairperson’s Opening RemarksProfessor Cy Stein, Professor of Medicine, Albert Einstein College of Medicine, USA

09.05 Pre-clinical development of siRNA ATU027 using the AtuPLEX delivery systemWe established the AtuPLEX, a liposomal formulation (AuFECT) of stabilised siRNA (AtuRNAi), asa versatile strategy for functional RNAi in the mouse vascular endothelium. Hence, the AtuPLEXopens the opportunity for employing RNAi to modulate the tumor vasculature in an anti-angiogenic strategy for cancer therapy. The AtuPLEX technology is currently being applied inAtugen’s therapeutic development program considering different AtuRNAi lead molecules fordiverse indications in oncology.Dr Joerg Kaufmann, Senior Director New Technologies, Atugen AG (SR Pharma plcsubsidiary), Germany

09.25 in vivo data of the chemokine-binding Spiegelmer NOX-E36The RNA-Spiegelmer NOX-E36 is a high-affinity binder to a proinflammatory chemokine. NOX-E36 is currently in preclinical development targeted at the treatment of renalinflammation. Data will be presented on the biophysical and biological characterisation of NOX-E36 and analogues thereof. Discussion of in vivo studies with NOX-E36 will focus onbiodistribution, pharmacokinetic profile and on first efficacy data in rodents.Dr Stefan Vonhoff, Production Manager, Noxxon Pharma AG, Germany

09.45 Neuropeptide development: Preclinical challenges in pharmacokinetics andpharmacodynamics--lessons learned from NAP peptideOne of the challenges of neuropeptide drug development is understanding the mechanism andkinetics by which peptide enter the central nervous system, including selection of the route ofadministration based on pharmacokinetics and pharmacodynamics. NAPVSIPQ is aneuroprotective peptide with broad-spectrum preclinical efficacy, currently in clinicaldevelopment for Alzheimer’s disease and mild cognitive impairment. Examples from the NAPdevelopment program will be used to illustrate how these challenges can be addressed.Bruce H. Morimoto, Vice President, Drug Development, Allon Therapeutics Inc, Canada

10.05 RNAi: A new strategy for treating ocular hypertension and glaucomaTo study the effect of topical administration of siRNA on intraocular pressure (IOP) New ZealandWhite rabbits were used. In this model more than twenty different siRNA targeting differentgenes involved in IOP have been tested. The reduction of IOP by siRNAs treatment shows ageneralised long lasting effect when compared to commercial drugs. Our goal is find a newtreatment for ocular hypertension and glaucoma.Dr Ana Isabel Jiménez, Sylentis S.A, Madrid Spain

10.25 Morning Tea, Coffee and Poster/Exhibition Viewing Time

11.00 Clinical and preclinical development of TLR nucleic acid agonistsColey’s B-Class oligodeoxynucleotide (ODN) PF-3512676 (also known as CPG7909 or Promune)is in pivotal phase 3 registration trials in first-line advanced lung cancer. After having achievedhighly encouraging results in a randomised multinational phase 2 trial in first-line non-small celllung cancer and objective responses in other advanced tumors. The C-Class ODN Actilon(CPG10101) designed to induce a broad anti-HCV activity is currently in phase 2 combinationtrials in the treatment of chronic hepatitis C virus infection based on positive activity observedboth as single-agent and in combination therapy of HCV.Dr Jörg Vollmer, Senior Director Discovery and Development, Coley Pharmaceutical GmbH,Langenfeld, Germany

11.20 RNAi therapeutics from a norwegian perspective – partnering of academic andcommercial sectorsSiRNAsense focuses on the first critical steps in development of RNAi therapeutics within thefields of cancer and neuroscience, using its in-house expertise to pre-validate targets, andidentify and optimise lead siRNA drug candidates for pre-clinical development. Results of mousemodel experiments and other pre-clinical data from the metastasis project will be presented.Dr Mohammed Amarzguioui, Research Director, siRNAsense, Norway

11.40 Locked Nucleic Acid: Developed for microRNA and mRNA targeted drugs • An update on the development of LNA antisense therapeutics• New targets addressed by LNA and comparisons with other chemistries• Uptake, distribution and PK of LNA oligonucleotides• Potency and efficacy of microRNA inhibitionDr Troels Koch, Vice President Drug Discovery and Manufacturing, Santaris Pharma A/S,Denmark

12.00 Progress on clinical and preclinical studies of DefibrotideClinical studies have suggested that Defibrotide improves survival in patients with severehepatic Veno-Occlusive Disease (VOD) following hematopoietic stem cell transplant (SCT).Results from a multicenter dose-finding phase II clinical trial conducted in the US showed asurvival rate of 40% after 100 days. Recent data from in vivo studies in human MultipleMyeloma xenografts in SCID/NOD mice showed that Defibrotide increase the responsiveness ofMultiple Myeloma cells to cytotoxic chemotherapeutics, such as Melphalan orCyclophosphamide.Massimo Iacobelli, MD – Scientific Director, Gentium S.p.A, Italy

12.20 Synthetic Lipohexapeptides: A novel class of anti-infectiveThe development of synthetic peptides as anti-infectives has been challenging despite theirbroad spectrum, novel mechanism of action, lack of resistance induction and cidal activity. Theproblems have been a function of their large size (and therefore cost), high positive charge,protease susceptibility and inhibition by biological environments such as serum. We havedeveloped a series of lipohexapeptides that in vivo out-perform the more traditionalantimicrobial peptide and address all of the issues listed above.Dr Timothy Falla, Chief Scientific Officer, Helix BioMedix, Inc., USA

12.40 Technology TutorialTechnology providers will host interactive tutorials, which are educational and address the benefits of their technology in the field of oligonucleotides, RNAi and peptide technology, if youwould like to host a tutorial, please contact lily.chong@informa.com

EXHIBITION HALL OPENS

Pre-Clinical Updates

13.10 Lunch and Poster/Exhibition Viewing Time

KEYNOTE PRESENTATION 14.20 Clinical development of the anti-nucleolin aptamer AS1411

AS1411 was the first aptamer to start clinical trials for cancer. It is a DNA aptamer which bindsto nucleolin, a protein expressed on the cell surface in various malignancies. Promising phase Ifindings have been reported in renal cancer patients, and preclinical data suggest potential forbroader application.Dr Chris Smyth, Head of Research, Antisoma, UK

14.40 Monarsen, an orally deliverable orphan antisense drug with multileveled modes of actionMonarsen, a 3’-oxymethylated orally deliverable orphan Antisense drug, selectivity suppressesthe levels of a normally rare mRNA transcript encoding for “readthrough” acetylcholinesterase.In brain and blood cells, Monarsen suppresses stress symptoms while modifying TLR9-mediatedsignaling. In patients with the autoimmune disease Myasthenia gravis, Monarsen at nanomolardoses facilitates neuromuscular activity.Dr Hermona Soreq, Dean, The Faculty of Science, The Hebrew University of Jerusalem,Israel

15.00 Update on Hematide™, a synthetic PEGylated peptide for the treatment of anemiaHematide is a novel synthetic peptidic compound that acts as a potent erythropoiesis-stimulating agent. Extensive chemical optimisation and PEGylation afforded PK and PDproperties that provide extended duration of action. Human clinical trials are underway toestablish that Hematide could be administered via injection once every 4 weeks. A summary ofthe preclinical and Phase 2 clinical results for the treatment of anemia will be described.Dr Christopher P. Holmes, Senior Director, Chemistry, Affymax, Inc., USA

15.20 AVT- 01 - a new decoy ODN approach for the treatment of asthmaAvontec`s AVT-01 decoy ODN is a 18 base pairs double stranded ODN with a partialphosphorothioate backbone. AVT-01 decoy ODN`s anti-inflammatory potential has beendemonstrated in several animal models of inflammation and it easily penetrates cells withoutthe help of transfection agents. A pilot phase IIa study was conducted (single doses of 3 and 10mg). It was well tolerated and exerted a clinically meaningful effect on the reduction of airwayhyper-responsiveness after AMP challenge.Dr Wolfgang Barth, Vice President Product Development, Avontec, Germany

15.40 TPI-ASM8 and TPI-PDE100 – Multi-targeted AON approaches for the treatment of lunginflammatory diseasesWe have developed using a multi-antisense approach, novel anti-inflammatory compounds forlung inflammatory conditions. Data on TPI-ASM8, the first RNA-targeted medicine for whichefficacy in a human phase 2 Asthma study has been demonstrated, and an overview of TPI-PDE100, a novel anti-inflammatory approach for COPD will be presented.Dr Luc Paquet, Vice President, Discovery, Topigen Pharmaceutiques Inc, Canada

16.00 Afternoon Tea and Coffee

16.00 Join us for HIGH SPEED NETWORKING (See page 5 for details)

16.40 Recent advances in aptamer developmentStructural stability, nuclease resistance and target binding affinity can be drastically improved byselective introduction of nucleotide base and backbone modifications. Furthermore, PK anddistribution parameters can be fine-tuned by attaching high-molecular weight PEG groups.Recent data with an emphasis on aptamer synthesis, advanced analytical methods, formulation,and CMC considerations are presented.Dr Markus Kurz, Associate Director, Chemistry, Archemix Corp., USA

17.00 The TGF-beta2 inhibitor AP 12009 in clinical development against malignant glioma andother solid tumorsThe TGF-beta2 inhibitor AP 12009 is being developed for the treatment of patients suffering from advanced cancer including malignant glioma, pancreatic carcinoma,melanoma, and colorectal carcinoma. Data from currently ongoing clinical Phase I/II and PhaseIIb trials will be presented.Dr Reimar Schlingensiepen, Managing Director, Antisense Pharma GmbH, Germany

17.20 Liraglutide: Efficacious lowering of blood glucose by once daily administration of thisGLP-1 analogLiraglutide is an analog of GLP-1 designed for optimal efficacy by once daily administration. A very long half-life (13 h in man) was achieved by acylation with natural fattyacids, leading to albumin binding and self-association. A structure activity relationship wasestablished. Liraglutide has been shown to effectively lower blood glucose and body weight in anumber of animal models as well as in type 2 diabetes patients. Liraglutide is currently in phase3 clinical development.Lotte Bjerre Knudsen, Senior Principal Scientist, Liraglutide Scientific Coordinator, NovoNordisk A/S, Denmark

17.40 How does chemistry make complex oligonucleotides more affordable?An oligonucleotide N3’- P5’-thio-phosphoramidate lipid conjugate, (GRN163L) was developed aspotent and specific telomerase inhibitor. We have developed a new synthetic approach to thekey 3’-aminonucleoside-derived building blocks for preparation of GRN163L. GRN163L iscurrently in a multi-center Phase I/II and Phase I studies in patients with CLL and with solidtumors, respectively.Dr Sergei Gryaznov, Director and Senior Research Fellow, Geron Corporation, USA

18.00 Development of Icatibant: A specific bradykinin B2 receptor antagonist Results on recent developments of Icatibant as a potent and specific peptidomimetic bradykininB2 receptor antagonist will be presented.More than 1000 individuals have been treated in various clinical trials worldwide including 2double blind randomized phase III clinical trials for hereditary angioedema.Dr Jochen Knolle, Head of R&D, Jerini AG, Germany

18.20 End of Day Two, Followed by a Drinks Reception in the Exhibition HallDrinks Recption Sponsor:

Clinical Updates

Clinical and Pre-Clinical Development of Oligonucleotides, RNAi and Peptides

D A Y T W O • T U E S D A Y 5 D E C E M B E R 2 0 0 6

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08.30 Morning Coffee

09.00 Chairperson’s Opening Remarks

09.10 Chiral amino acid analysis of peptides: Techniques, validation, advantages and limitationsMeasurement of the racemate content is an important aspect of the determination of the purity ofpeptidic products. A technique for quantitation of the racemate content of peptide-bound aminoacids is presented, eliminating the contribution of racemisation during hydrolysis. Validation showsthe capability of the method. Limitation and characteristics for some amino acids will bediscussed as well as possible solutions.Dr Juergen K.P. Gerhardt, General Manager, C.A.T. GmbH&Co KG, Germany

09.40 Improved technologies for controlled release of peptides or PEGylated peptides andoligonucleotidesEncapsulating PEGylated bioactive molecules in PLGA microspheres results in release kinetics thatare controlled by PLGA degradation rather than PEG hydrodynamic radius. High drug content, lowburst, excellent stability and full bioactivity allow for weekly dosing of PEG-insulin microspheresfor maintenance of basal insulin levels in diabetic rats. Microspheres encapsulating a PEGylatedaptamer provide efficacious intraocular pegaptanib levels for several months after intravitrealinjection.Dr Paul G. Schmidt, Chief Scientific Officer, PR Pharmaceuticals, Inc., USA

10.10 Morning Tea, Coffee and Poster/Exhibition Viewing Time

10.50 Development of a non-invasive, an intranasal alternative to insulin injectionNastech is currently developing anintranasal formulation insulin as an alternative to injections.Aqueous formulations were screened employing an in vitro tissue model to measuretransepitheleal electrical resistance (TER), permeation, cytotoxicity and cell viability. Formulationswere identified providing TER reduction concomitant with dramatically increased permeationcompared to simple formulations.Dr Rick Costantino, Director, Formulations, Nastech Pharmaceutical Company Inc., USA

11.20 PROMAXX technology for pulmonary delivery of proteins and peptidesThe PROMAXX microsphere technology has been applied to a number of therapeutic proteins andpeptides for delivery via the pulmonary route. Animal data will be presented. To increaseefficiency of formulation development a rapid screening system was developed.A project management based approach to successful collaboration with partner will be presented.Dr Julia Rashba-Step, Director, R&D, Epic Therapeutics, Inc., A Wholly Owned Subsidiary ofBaxter Healthcare, USA

11.50 Peptide API's manufacturing challenges through more complex molecules and changingregulatory environment (For more information please visit www.informa-ls.com/eurotides)Dr Alain Scarso, Vice President, Head of R&D, Lonza Braine SA, Belgium

12.20 Technology TutorialPseudoproline dipeptides in peptide synthesisPseudoproline dipeptides are extremely powerful tools for enhancing the synthetic efficiency inFmoc-solid phase peptide synthesis (SPPS). Using concrete examples from our own researchlaboratories, as well as from academic and industrial scientists, we will demonstrate the use ofthese building blocks not only in the synthesis of demanding peptides, but also inracemisationfree fragment condensations.Dr Bodo Baumeister, Marketing Manager, Novabiochem, Switzerland

12.50 Lunch and Poster/Exhibition Viewing Time

Meet the Poster Presenters in the Exhibition Hall

TRACK TWO: Challenges with Manufacturing of Peptides

Critical Manufacturing and Regulatory Challenges for Oligonucleotides and Peptides

D A Y T H R E E • W E D N E S D A Y 6 D E C E M B E R 2 0 0 6

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14.00 Chairperson’s Opening Remarks

14.05 European regulatory perspectives on oligonucleotides and peptidesThis presentation will provide a short overview about the European Regulatory System. Advice is givenon how companies can interact with European Regulatory Agencies during the development of a newdrug product. Since peptide and oligonucleotide drug products are subject to a variety of regulatoryrequirements issues to be considered during product development and the preparation of the CMCpart for the marketing authorisation application are discussed.Dr René Thurmer, Pharmaceutical Expert, Unit Pharmaceutical Biotechnology, BfArM- FederalInstitute for Drugs and Medical Devices, Germany

KEYNOTE PRESENTATION 14.35 The phosphorothioate-stimulated delivery of siRNA to mammalian cells via caveosomes ends

in the Golgi apparatus: Relationship between sub-cellular localisation and biological activityRecently we reported that phosphorothioate (PTO)-derived oligonucleotides stimulate the physicalcellular uptake of siRNA in trans in human cells. This is reflected by an apparent dose-dependentsiRNA-mediated suppression of lamin A/C in primary human HUVEC cells. The PTO-stimulated cellularuptake in trans is concentration-dependent, length-dependent, related to the phosphorothioatechemistry but not sequence-specific. The use of specific inhibitors of various uptake pathways andfluorescence microscopy strongly favor a caveolin-mediated uptake mechanism and accumulation ofsiRNA in the Golgi apparatus.Proffessor Georg Sczakiel, Institute for Molecular Medicine, University of Lübeck, Germany

15.05 Make it happen: Therapeutic delivery of oligonucleotides.Efficient and safe delivery of oligonucleotides is recognised as being the major hurdle towardstherapeutic development of siRNA, antisense or decoys. Novosom AG is addressing this issue with itsSmarticles technology, a pH-responsive liposome technology. Data will be presented for therapeuticanimal models in cancer and inflammatory diseases.Steffen Panzner, Chief Executive Officer, Novosom, Germany

15.35 Cationic peptide delivery agents: Different routes are chosenA large variety of cationic peptides and peptide analogues and mimetics that improve cellular uptakeand in some cases also in vivo bioavailability of conjugated drugs, have been discovered over the pastdecade. It is now generally acknowledged that the main route of cell entry is through endosomes.Using a PNA antisense splice correction model system and several endosome disruptive agents aswell as inhibitors of specific endosome processes, we find that these agents affect the activity ofdifferent cationic peptides differently, thereby indicating distinct differences of their (endosomal)route(s) of cellular entry.Professor Peter Nielsen, Department of Medical Biochemistry and Genetics, University ofCopenhagen, Denmark

16.05 Afternoon Tea and Coffee

16.35 Drug delivery system induced-gene expression: The potential for enhancing siRNA potencyKnowledege of the transcriptional effects of drug delivery systems may be used to enhance thepotency of existing siRNAs by combining inhibitory effects of the two components. How this might beimpact on the clinical application of siRNAs will be highlighted.Professor Saghir Akhtar, Chair in Drug Delivery and Director, Centre for Genome-based Therapeutics(CGT), Welsh School of Pharmacy, Cardiff University, UK

17.05 Nanoparticle siRNA delivery for inhibitions of neovascularisation and tumor growthWe have developed two polymer-based nanoparticle systems, HKP and RPP, for both local andsystemic siRNA deliveries. Using HKP-siRNA particle we achieved significant anti-angiogenesisactivity in mouse ocular models through local delivery and potent anti-tumor efficacy in mousexenograft model through systemic delivery.Dr Martin Woodle, Chief Scientific Officer, Intradigm Corporation, USA

17.35 Chemical design of small interefering RNA (siRNA) and improved polymeric delivery systemsThe effectiveness of a drug is determined mainly by its in vivo stability, the ability to migrate throughthe body and reach its molecular target sites in therapeutically relevant levels. Through optimisation ofthe chemical design and improved polymeric nanocarriers we have improved the efficacy of siRNAboth in vitro and for in vivo applications.Professor Jørgen Kjems, Department of Molecular Biology, University of Aarhus, Denmark

18.05 End of Conference

08.30 Morning Coffee

09.00 Chairperson’s Opening RemarksDr Mark Douglas, Strategy and IP Manager, Avecia Biotechnology, UK

09.10 Economics of 1st, 2nd, 3rd and 4th generation oligonucleotidesDuring the past fifteen years we have witnessed a variety of chemically modified oligonucleotidesenter clinical trials where each advancing generation appears to be more complex anddemanding in their manufacturing. As a result, the economics of the latest generation ofoligonucleotide synthesis is heading in the wrong direction. Implementation of the lessons learntfrom the manufacturing of 1st generation phosphorothioate oligonucleotides to the futuregeneration may turn the curve in the right direction. Various strategies to stay ahead of the curvewill be presented.Dr Yogesh S. Sanghvi, President, Rasayan Inc., USA

09.40 Approaches to characterisation of oligonucleotidesSome aspects of characterisation can be approached considering oligonucleotides as a class ofcompounds while other characterisation techniques are more molecule specific. Examples will begiven, and the utility of extinction coefficients and the use of impurity analysis by LCMS to guideprocess improvements will be highlighted.Dr Dennis Michaud, Director of Analytical Development, Avecia Biotechnology, USA

10.10 Morning Tea, Coffee and Poster/Exhibition Viewing Time

10.50 Identification of impurities in oligonucleotide therapeuticsThe identification of impurities in drug substances and products is an important aspect of drugdevelopment. The presentation describes a general approach to impurity identification inoligonucleotides. Techniques such as liquid chromatography-electrospray mass spectrometry,high-resolution mass spectrometry, NMR spectroscopy, and enzymatic and chemical degradationare discussed and illustrated by reference to real-life examples. The role played by syntheticorganic chemistry in impurity characterisation is highlighted.Dr Daniel Capaldi, Executive Director, Development Chemistry, Isis Pharmaceuticals Inc., USA

11.20 LC-UV-MS analysis of oligonucleotides: Ultra performance chromatographyWe developed fast and mass spectrometry (MS) compatible methods of analysis ofoligonucleotides using ultra performance liquid chromatography (UPLC). The UPLC advantage isthat it provides highly efficient analyses without post-column peak broadening. Despite the poorseparation selectivity, the baseline resolution is often achieved. LC-MS applications for RNAi andphosphorothioate therapeutic oligos are discussed.Martin Gilar, Life Sciences R&D, Waters Corporation, USA

11.50 Purification the heart of oligo manufacturingPhosphoramidite synthesis for assemble of oligonucleotides is well established and generallyaccepted as the preferred method for synthesis of DNA or RNA natural and modified oligos.There are however multiple approaches that can be applied for the purification of the crude oligonucleotides. The impact of the purification process on the overall oligo manufacturing process, product quality and cost will discussed.Michael J. Fazio, Scientist, Dowpharma, USA

12.20 Technology TutorialTechnology providers will host interactive tutorials, which are educational and address thebenefits of their btechnology in the field of oligonucleotides, RNAi and peptide technology, if youwould like to host a tutorial, please contact lily.chong@informa.com

12.20 Lunch and Poster/Exhibition Viewing Time

Meet the Poster Presenters in the Exhibition Hall

TRACK ONE: Challenges with Manufacturing of Oligonucleotides

Joint Afternoon Session

Challenges and Strategies for Oligonucleotide and Peptide Delivery