2007年8月9日 木曜日
Workshop A
LifeCycle Management and Drug Repositioning Strategies
With the coming expiration of the patent life of many drugs in the market, and the high cost of
abandoned programs, pharmaceutical companies are anxious to find new indications for existing drugs
to extend their patent life; and to find new uses for failed compounds and discontinued programs.
This session features some of the leading companies who are bringing unique solutions to revive
drugs with new uses.
1:00
Chairperson's Opening Remarks
Alexis Borisy, Ph.D., President
and CEO, CombinatoRx, Inc.
1:05
Melior Discovery: Pioneering a High-Throughput Pharmacology Approach to
Drug Repositioning
Melior Discovery has developed a unique platform of multiplexed in
vivo assays that systematically uncovers new therapeutic indications for development stage
pharmaceuticals. Melior balances proprietary and partnered programs, developing its own internal
pipeline of acquired compounds as well as performing collaborative research for pharmaceutical
partners. This presentation will discuss highlights of the technology and Melior's internal drug
candidates.
Andrew Reaume, Ph.D., President
& CEO, Melior Discovery, Inc
1:35
Challenge of Identifying New Biological Target for Stalled Drug
Candidates
Abstract not available at time of print.
Takashi Ono, Ph.D., Director,
Business Development, Sosei Co. Ltd.
2:05
Novel Synergistic Combinations Provide New Mechanisms, New Uses, and New
Life to Elite Molecules
Synergy between molecular pathways enables new and selective
action, enabling synergistic combinations to provide new and novel opportunities for the elite
molecules in our industry. The selective action of these special synergies can improve the main
activity of the existing molecules, widen the therapeutic window, or provide completely new
therapeutic avenues. Case examples will include expanding a dislipidemia agent to diabetes, a
cardiovascular drug to arthritis, creating a dissociated steroid, widening an anti-depressant to
immuno-inflammatory diseases, and creating new opportunities for some of the new molecular targets.
Alexis Borisy, President
& CEO, CombinatoRx, Inc.
3:00
Drug Repositioning: Connecting Discovery Pharmacology with Commercial
Opportunity
Specialty pharmaceutical companies, like their big pharmaceutical
brethren, are under increasing pressure to expand their product pipelines. In order to address the
demand for new and innovative specialty medicines, developers of such products need to establish
sound strategies that integrate clinical discovery pharmacology, drug repositioning and enhanced
drug delivery technology.
Thomas Logan, Vice
President Life Sciences, BTG International Inc.
3:30
A Repositioning Strategy to Discover Value in Failed Development
Compounds
The productivity of the pharma industry is not only determined by
the number of new drugs for which novel applications have been discovered. Additional significant
value is frequently generated through the (serendipitous) finding of other therapeutic
possibilities. Strategies will be discussed in which the technological advances of modern drug
discovery are exploited to maximize the output of research towards new drug candidates.
Marcel van Duin, Ph.D., Executive Director, Head Department of Pharmacology, NV
Organon
4:00
Application of Enhanced Pro-Drug Technology to Rescue or Reposition
Failed Compounds
Critical properties of drugs that can be addressed by application
of EPD Technology are: Unacceptable toxicity and insufficient tolerability, in particular,
myelosuppression; insufficient ADME properties, such as too short plasma half-life, extensive first
pass metabolism, plasma instability, insufficient distribution to intracellular targets as well as
certain physicochemical properties. The evaluation process for identifying appropriate drug
candidates and examples of promising drugs in development based on EPD-technology will be presented.
Hans-Georg Opitz, Ph.D., Chief Scientific Officer, Preclinical Research, Heidelberg
Pharma AG
4:30
Innovative Life Cycle Management and Line-Extension of a Biologic
Arubor is developing proprietary line-extensions of an existing
biologic. Reformulation and localized dosing provides major advantages over parenteral dosing.
Inhalation therapy optimizes drug distribution to affected tissues while dramatically reducing drug
exposures. With innovative lifecycle management of an aging biologic Arubor is addressing serious
unmet needs and major new markets.
Roy Clifford Levitt, M.D., Chairman and Chief Executive Officer, Arubor
Corporation
Workshop B
RNAi Technologies and Therapeutics: From Basic Research to Products
It is an exciting time for the RNAi market with the recent awarding of the Nobel Prize to Craig
C. Mello and Andrew Fire for their discovery of RNA interference and heightened M&A activity in
the RNAi space. RNAi applications both as a discovery tool and as a therapeutic are rapidly
advancing. This workshop will discuss the recent trends and progress of RNAi technologies and
therapeutics from basic research to products.
1:00
Workshop Chairperson's Opening Remarks
Tod Woolf, Ph.D., President
and CEO, RXi Pharmaceuticals
1:05
Delivery of Intact RNAi to Target Tissues in vivo
Delivery of intact RNAi to target tissues is the main challenge in
obtaining RNAi activity in vivo. We will present examples employing nanotransporters to deliver RNAi
systemically in mouse models.
Tod Woolf, Ph.D., President
and CEO, RXi Pharmaceuticals
1:35
Advancing RNAi Technology for Novel Targeted Therapeutics
Using siRNA as a therapeutic modality allows us to specifically
inhibit expression of a disease gene target. Clinical success of drugs with multi-target property
and knowledge learned from System Biology promote us to take a novel approach using siRNA
oligo-cocktail for treatment of human diseases. We are currently advancing technologies for
multi-targeted RNAi therapeutics.
Patrick Y. Lu, Ph.D., President
and CEO, Sirnaomics
2:05
Potential Treatment for Seasonal or Pandemic Influenza Using siRNAs
Targeting Conserved Regions of Influenza A
Alternative influenza therapies are urgently needed; short
interfering RNAs (siRNAs) to highly conserved regions are a potential treatment. In models, siRNAs
reduced virus production by 10-fold and up to 200-fold when formulated. Highly active sequences and
optimized formulations will permit lower doses, reduced dosing frequency, and longer duration of
effect.
Michael V. Templin, Ph.D., Director, Pharmacology & Toxicology, Nastech
Pharmaceutical Company
3:00
Preclinical and Clinical Development of NUCB1000 - An Expressed
Interfering RNA-Based Hepatitis B Antiviral
The presentation will provide a brief overview of Nucleonics' RNA
interference technology and preclinical development of its eiRNA-based anti-HBV therapeutic,
NUCB1000. Unlike current small molecule HBV therapies, NUCB1000 has been shown to suppress viral
antigen expression in addition to inhibiting viral replication. NUCB1000 has been designed to be
effective against all HBV genotypes and has demonstrated activity against known drug resistant
mutants. The presentation will detail product development, including delivery, efficacy and safety
in preclinical models. NUCB1000 is anticipated to enter the clinic early in the second quarter of
2007.
Catherine J. Pachuk, Ph.D., Vice President, Preclinical Research, Nucleonics
3:30
RTP801: From Gene Discovery to Clinical Trials
RTP801 is a gene identified and patented by Quark Biotech. The gene
is strongly overexpressed in pathological conditions associated with oxidative tissue injury.
Inhibition of RTP801 by specific siRNA in vivo leads to suppression of such pathogenic features as
apoptosis of parenchymal cells, inflammatory cell infiltration, microvasculature leakage and
proliferation.
Elena Feinstein, M.D., Ph.D., Senior Vice President, Research and CSO, Quark Biotech
Inc., Israel
4:00
Panel Discussion
Moderator: Tod Woolf,
Ph.D., President and CEO, RXi
Pharmaceuticals
- Overcoming delivery issues/challenges of RNAi
- Current and future landscape of RNAi technologies
- Strategies for developing RNAi IP to build an RNAi business
- Status of RNAi drugs in development
Workshop C
Novel In Vivo Disease Models for Earlier Safety and Efficacy Prediction
This workshop will address the potential value of earlier in vivo safety and efficacy data
including approaches and techniques for gathering this information. It will also address where and
when in the discovery process these data are most useful and highlight examples of various in vivo
disease models. A discussion of the advantages of each approach, costs, throughput and challenges to
integration will also be provided.
1:00
Workshop Moderator's Opening Remarks
Nina U. Sawczuk, Co-Founder
and CEO, Zygogen LLC
1:05
Strategic Applications of Model Organisms in Drug Discovery
Novel target identification and subsequent validation are potential
applications of zebrafish and C. elegans in drug discovery and development. With the ability to
manipulate and measure multiple biological and genomic processes quickly, these models may be used
in screening for both efficacy and safety endpoints. As with any model system, technical and
biological limitations abound, but creative applications that leverage the strengths of each model
allow in vivo assessment and decision making early in the drug discovery process.
Shawn Estrem, Ph.D., Senior
Research Scientist, Eli Lilly & Co.
1:35
Drug Screening with Model Organisms for Efficacy and Toxicity
Zebrafish and Drosophila models can be manipulated to allow
high-volume, high-content screening of small molecule drug candidates. This approach generates data
which is both highly predictive of efficacy and toxicity in humans, while having the potential to
decrease the time and cost of drug discovery and development.
Jon Tinsley, Ph.D., Director
of Therapeutic Programs, Vastox, United
Kingdom
2:05
Automated Zebrafish Assays: The In Vivo answer to Cell-based Phenotyping
and Compound Screening
Automated fluorescent zebrafish assays accelerate drug discovery by
providing early and rapid analysis of target function, compound efficacy and toxicity in a live
vertebrate organism. The immediate advantage of performing zebrafish screens is to increase the
success rate of the requisite mammalian pre-clinical models while diversifying model-specific risk.
Nina U. Sawczuk, Co-Founder
and CEO, Zygogen LLC
3:00
A Moderate Throughtput Zebrafish Screen for Angiogenesis Modifiers
We optimized a medium-scale angiogenesis screen in a transgenic
zebrafish that expresses a green fluorescent protein under the control of the VEGFR2 promoter.
Careful attention to statistical needs and developmental parameters results in a reliable,
cost-effective assay with Z'>0.5. We then screened the LOPAC1280 compound library for
anti-angiogenic compounds and identified several expected and several unexpected compounds.
Ray Dingledine, Ph.D., Professor
and Chair, Department of Pharmacology, Emory University School of
Medicine
3:30
High-throughput in vivo Screening in Zebrafish: Modeling 'Complex'
Disease
The development of high resolution and high-throughput physiologic
assays for the zebrafish will be described. The utility of such assays in phenotype-driven genetic
or chemical screens and forward genetics will be discussed with specific focus on the validation of
human genome wide association studies, disease modeling, drug discovery and toxicology.
Calum A. MacRae M.D., Ph.D., Assistant Professor of Medicine, MGH and Harvard
Medical School
4:00
Panel Discussion
Moderator: Nina U. Sawczuk,
Co-Founder and CEO, Zygogen LLC
- Value of earlier, high throughput in vivo compound screening
- Zebrafish as an emerging in vivo tool for rapid target validation and compound screening
- Getting to a decision point with data from in vivo models
- Validation criteria for non-mammalian models in efficacy and safety
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