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Wednesday, October 17
7:30 am Registration Opens
RNAi’s IN PRECLINICAL AND
CLINICAL DEVELOPMENT
2:10 pm Chairperson’s Remarks
Akshay Vaishnaw, M.D., Ph.D., Vice President, Clinical Research, Alnylam
Pharmaceuticals, Inc.
2:15 Development of Antiviral siRNAs for Pandemic Influenza
Steven Quay, Ph.D., Chairman, President and CEO, Nastech Pharmaceutical
Company, Inc.
Small interfering RNAs (siRNAs) targeting the conserved
regions of influenza viral genes reduce viral replication in vitro and in
vivo and may provide an effective early treatment or prophylaxis by delivery
to the upper respiratory / nasal mucosa. Administration of anti-cytokine siRNAs
to deep lung tissue will play a critical role in treating later stages of
disease when host inflammatory activities are activated. Optimal siRNA
formulations for respiratory delivery may permit use of lower doses, reduced
dosing frequency, and a longer duration of effect, thus providing a viable
therapeutic approach to treat, and possibly prevent, pandemic flu. Recent
Nastech developments highlighting improved target specificity, delivery
formulations, and safety properties of siRNA therapeutics will be discussed,
including;
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Reduction of off-target effects of siRNAs
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Potential synergies and reduced toxicity using combinations
of selected lipids and peptides for delivery
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The potential for reduction of interferon response induced
by siRNA using peptide delivery agents
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Therapeutic advantages using Dicer substrates
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Development of cell-specific siRNA targeting agents through
the use of combinatorial peptide libraries expressing structured miniproteins.
2:45 Progress and Challenges of Using RNAi for the Treatment of HIV
Infection
John J. Rossi, Ph.D., Chair & Professor, Molecular Biology, City of Hope
Beckman Research Institute
RNAi as a therapeutic modality is no longer a probability,
but is now a reality with several ongoing clinical trials. Most trials use
synthetic siRNAs, which are transient in effect. Since our goal is the treatment
of HIV infection, we have initiated a clinical trial using an expressed shRNA
targeting HIV in combination with two other RNA based therapeutic agents. The
status of this clinical trial along with proposed new approaches for using
multiplexed RNAi to treat HIV will be discussed.
3:15 Development of Bevasiranib
Nathan R.F. Beeley, PhD, Senior Project Manager, Pharmaceutical Product Development, Opko
Ophthalmologies, LLC
3:45 The DNAi Company PNT2258 - To the Clinic or Bust!
Dr Richard D Gill, BSc, Ph.D., President & CEO, ProNAi
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DNAi Differentiated Approach DNAi vs RNAi
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Lead Drug Candidate PNT2258 Pre IND Efficacy & Safety Data will be reviewed
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Delivery Technology Novosom Smarticles
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Manufacturing Specifications cGMP Supply Chain/Drug Product/Manufacturing/Particle Size
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Clinical Development Complete Phase I Design for IND Submission
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Discovery Strategy MOA/DNAi-HiT Platform/PNT200
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Why are we all investing in ProNAi?
4:15 Networking Refreshment Break in the Exhibit Hall
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4:50 Technology Watch
The Quest for Improving siRNA Performance
David Dorris,
Ph.D., Senior Director & GM, Cell Biology & RNAi,
Applied Biosystems
Critical to siRNA experimental success is use of effective,
potent, and specific siRNAs for silencing their respective
targets. In the past year, we have embarked on a comprehensive
program to improve siRNA performance using a combination of
all new siRNA design parameters, updated bioinformatic
filtering criteria, and novel chemical modifications. We will
describe these efforts, as well as their impact on cell-based
assay derived phenotypic data. |
Sponsored by
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5:15 RNAi Nanoplex™ Technology for Systemic Delivery of siRNA Therapeutics in Oncology
Xiaodong Yang, M.D., Ph.D., Vice President Research and Preclinical Development, IntradigmCorporation
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Challenges of systemic delivery of siRNA
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Target selection for siRNA therapeutics in oncology
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Overview of RNAi Nanoplex™ technology
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Preclinical development of ICS-283
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Panel Discussion
5:45 Is the Drug Development Paradigm the Same for siRNAs and RNAi’s as
compared to Other Drugs - What is the Same and What is Different?
Panelist:
Richard D. Gill, BSc, Ph.D., President & CEO, ProNAi
Xiaodong Yang, M.D., Ph.D., Vice President Research and Preclinical Development, Intradigm Corporation
Nathan R. F. Beeley, Ph.D., Senior Project Manager, Pharmaceutical Product Development,
Opko Ophthalmologies, LLC
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6:15 End of Conference Day
Thursday, October 18
7:30 – 8:35 am Registration & Morning Coffee
ANTI-SENSE THERAPEUTICS IN CLINICAL DEVELOPMENT: LESSONS
LEARNED
8:35 Chairperson’s Remarks
Arthur Levin, Ph.D., Senior Consultant, Levin Biotechnology Services
8:40 Lessons Learned with First Generation Oligonucleotides
Arthur Levin, Ph.D., Senior Consultant, Levin Biotechnology Services
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Initial strategies: Antisense as local therapy
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Vitravene the first approved antisense drug
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Systemic administration in life threatening diseases
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Crohn’s disease: trials and tribulations
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First generation anti-sense drugs in oncology
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Overview of first generation successes and disappointments
9:10 Progress on Second Generation Antisense
Oligonucleotides
Brenda F. Baker, Ph.D., Clinical Research &
Development, Isis Pharmaceuticals
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Second generation antisense oligonucleotides have
improved potency, safety and convenience
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Improved preclinical profiles
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Translating Improvements in drug profile into clinical
designs
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Antisense oligonucleotides for cardiovascular disease
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Antisense oligonucleotides in metabolic disease
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Overview of second generation success and prospects for
improvements for the technology
9:40 TPI ASM8 for the Treatment of Asthma
Mark Parry-Billings, Ph.D., Chief Development Officer Topigen
Pharmaceuticals, Inc. Canad
TPI ASM8 has been designed for the therapy of asthma and
contains two modified phosphorothioate antisense oligonucleotides (ODNs),
directed against human CCR3 and the common beta chain (βc) of IL-3, IL-5,
and GM-CSF receptors, thereby down-regulating expression of CCR3 and βc.
This presentation will discuss the challenges when employing oligonucleotides in
a multitarget approach, focusing on:
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Preclinical
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Toxicology
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CMC and Clinical results
10:10 Networking Coffee Break in the Exhibit Hall
10:55 Therapeutic
Possibilities of Catalytic DNA
Levon M. Khachigian, Ph.D., D.Sc., Professor and Head
Transcription and Gene Targeting Laboratory, Centre for Vascular Research,
University of New South Wales
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DNAzymes as tools to
provide insights into biological functions of targeted genes –
Suppressing "master regulators"
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Demonstration of
DNAzymes as potential therapeutic agents in a variety of preclinical
models
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Interactive Panel Discussion
11:55 This is Your Chance! Interactive Panel Discussion with Questions from
the Floor Regarding Lessons Learned.
To what degree have
various companies and the FDA been able to capitalize on the
similarities between anti-sense oligonucleotides of different
sequences? Under what circumstances are these generalizations
permissible?
Under what
circumstances is it inappropriate to generalize?
What are the
challenges in anti-sense oligonucleotide development for the coming
decade?
How do the lessons of
the past decade help with those challenges?
Where are those
lessons not going to applicable?
Moderator: Arthur Levin, Ph.D., Senior Consultant, Levin Biotechnology
Services
Panelist:
Brenda F. Baker, Ph.D., Clinical Research & Development, Isis
Pharmaceuticals
Mark Parry-Billings, Ph.D., Chief Development Officer Topigen Pharmaceuticals,
Inc. Canad
Levon M. Khachigian, Ph.D., D.Sc., Professor and Head Transcription and
Gene Targeting Laboratory, Centre for Vascular Research, University of New South
Wales
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12:25 pm Luncheon Workshop
(Sponsorship Available) or Lunch on Your Own
12:55 Session Break
Update on Aptamers and
Immunostimulatory Oligonucleotides in
Clinical Development
1:55 Chairperson’s Remarks
Page Bouchard, D.V.M., D.A.C.V., Senior Vice President, Nonclinical Research
& Development, Archemix Corporation
2:00 Development of the REG1 Anticoagulation System
Christopher P. Rusconi, Ph.D., Chief Scientific Officer, Regado Biosciences,
Inc.
REG1 is an anticoagulation system consisting of the aptamer-based
coagulation factor IXa inhibitor, RB006, and its specific antidote, RB007. This
presentation will include the following:
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Overview of the Regado drug-antidote technology
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Overview of the REG1 System
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Nonclinical development of the REG1 System
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Summary of phase 1 findings
2:30 The Regulatory Development of HEPLISAV ™
William Turner, Vice President of Regulatory Affairs, Dynavax Technologies
HEPLISAV™ is a hepatitis B vaccine in Phase 3 development
that uses 1018 Immunostimulatory Sequence (ISS), a TLR9 agonist, as an adjuvant
to recombinant hepatitis B surface antigen (HBsAg). ISS are DNA sequences
containing unmethylated cytosines in CpG motifs. The talk will focus on the
development of HEPLISAV from the regulatory perspective and include:
3:00 Networking Refreshment Break in the Exhibit Hall
PROBLEMS/ISSUES ACROSS ALL OGN PLATFORMS
3:40 Delivery Challenges
Mark A. Tracy, Ph.D., Senior Director, Alnylam Pharmaceuticals, Inc
- Overview of delivery barriers in-vivo
- Formulation challenges
- Requirements for delivery systems for local and systemic administration
- Overview of delivery approaches
- Strategies for overcoming delivery challenges
4:10 Metabolism, Metabolic Profiling, and Bioanalysis of Aptamer
Therapeutics
Renta Hutabarat, Ph.D., Director, DMPK, Archemix Corporation
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Methods for bioanalysis of PEGylated and un-PEGylated
oligonucleotides
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Methods for studying in vitro and in vivo
metabolism of aptamers and use in metabolic optimization
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Methods for studying ADME properties in vivo and
general observations as examples
4:40 The Chemistry Behind Oligonucleoitde Therapeutics
Muthiah Manoharan, Ph.D., Vice President, Drug Discovery, Alnylam
Pharmaceuticals
This presentation will address the following points
concerning the chemistry behind oligonucleotide therapeutics:
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Different types of oligonucleotide therapeutics
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Chemistry needs based on site of action: Intracellular
Mechanisms and Extracellular mechanisms
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RNAse H chemistries: DNA/P=S and Gapmers
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Tolerance of RISC for chemical modifications: Constructs
for siRNAs and Antagomirs
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Virtues and limitations of phosphorothioates
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Successful sugar-phosphate modifications: 2’-OMe, 2’-F,
2’-MOE, LNA, Morpholinos, Amidates
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Successful nucleobase modifications
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Conjugates: their role in altering PK and achieving
Delivery
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Panel Discussion
5:10 Interactive Panel Discussion
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Under what circumstance
is it possible to generalize among the entire family tree of
oligonucleotide therapeutics? What similarities are there among the
classes?
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How can the lessons
learned from anti-sense oligonucleotides, the most mature technology, be
applied to the younger technologies?
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Are oligonucleotides
drugs or biologics?
- RNAi versus antisense - is this a truly
new paradigm?
Moderator: Arthur Levin, Ph.D.,
Senior Consultant, Levin Biotechnology Services
Panelist:
Renta Hutabarat, Ph.D., Director, DMPK,
Archemix Corporation
Muthiah Manoharan, Ph.D., Vice
President, Drug Discovery, Alnylam Pharmaceuticals
Dmitry Samarsky, Ph.D., Vice President,
Technology Development, RXI Pharmaceuticals Corporation
Mark A. Tracy, Ph.D., Senior Director,
Alnylam Pharmaceuticals, Inc.
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5:40 Close of Oligonucleotide-Based Therapeutics Conference
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