Exten Industries (fka BB: EXTI)

[Patricia_1]

Upcoming Conference 2/23/04 to 2/24/04

http://www.isciencex.com/ETS-2004program.htm

4th INTERNATIONAL CONFERENCE ON EARLY TOXICITY SCREENING:
In Silico, In Vitro and High Throughput Screening Approaches
February 23-25, 2004

San Diego, CA, USA

Symposium Venue: San Diego Mission Valley Marriott

Featuring experts from the following institutions: AstraZeneca; Bayer Crop Science; Charles River Laboratories; Chiron Corp; GlaxoSmithKline; HemoGenix; Institute for In Vitro Sciences Inc.; Johnson & Johnson PRD; Lexicon Genetics; Millennium Pharmaceuticals; National Cancer Institute; NIEHS; Novartis Pharmaceuticals; Partek Incorporated; Pfizer, Inc.; Advanced Pharmaceutical Sciences, Inc.; Promega Corp.; University of Toronto.

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http://www.isciencex.com/ETS-2004program.htm

Look at these presentation topics and note that Pfizer
is one of the represented institutions...

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9:00 AM – 9:30 AM

Overview: Challenges Towards Accurate Prediction of Human Drug
Toxicity (Albert P. Li; Advanced Pharmaceutical Sciences, Inc.;
Baltimore, MD) It has been estimated that the cost of drug
development is $800 million per new drug. One of the reasons for
the high cost is failure in clinical trials due to drug toxicity.
Furthermore, there are examples of marketed drugs that were
withdrawn due to unexpected drug toxicity, not predicted by
preclinical and clinical safety trials. An overview of the past
problems, present limitations and promising new technologies for the
prediction of human drug toxicity will be presented.

9:30 AM – 10:00 AM

Species Differences in Xenobiotic Toxicity (Joe Tomaszewski,
National Cancer Institute; Bethesda, MD) One of the constant
struggles that faces the toxicologist when evaluating toxicity data
on a potential new drug, is how much data is enough to ensure that
the Phase I clinical trial in man will be safe. Another is whether
the accumulated data is sufficient to predict toxicities in man.
One of the confounding issues that must be dealt with in this
regard, is the disparity in response that often times occurs in the
different animal species used to generate this data. Differences
in metabolic rate, size, clearance, body weight, surface area, etc.
are major contributors to the toxicological difficulties we face.
If one attempts to deal with this conundrum as a regulatory box that
must be checked prior to entering the clinic, the outcome often
results in failure. One of the keys to dealing with species
differences is to utilize all of what is known to explain those
differences and to draw upon past experience to help guide the way.
This talk will attempt to draw upon past experiences to help
understand some of these differences and shed some light on how they
can be used to design appropriate studies that produce interpretable
data. However, despite our best efforts, toxicities do occur and
occur frequently in man that is never predicted by even the most
carefully designed studies. This is perhaps one of the reasons
that the toxicologist needs newer tools in his armamentarium other
than the whole animal to predict human sensitivity.

10:00 AM – 10:30 AM

Nonclinical Testing Predictive for Idiosyncratic Liver Injury (Carl
L. Alden; Millennium Pharmaceuticals; Cambridge, MA) Preclinical
toxicology and metabolism functions must play a pivotal role in
improving speed and decreasing attrition attributable to toxicity,
side effects, or DMPK attributes. These functions must provide a
clear view of any drug development limiting barriers before
committing the enormous resources to develop the fundamental data to
gain market access. The technology now exists that enables the near
elimination of development failures because of DMPK attributes as
well as reduction of attrition attributable to toxicity or side
effects from the current benchmark level of 40% to less than 20%.
However, the dominant paradigm states that predicting for
idiosyncratic liver injury cannot be achieved in nonclinical
testing. Idiosyncratic responses can cause withdrawal from the
market (e.g. bromfenac, troglitazone) or prevent business success
(e.g. zileuton) potentially creating negative impact beyond the lost
cost of development. Idiosyncratic liver injury is also generally
considered to be non-dose responsive and of low/sporadic incidence
requiring sample size for detection that often exceeds the number of
patients tested in development. Review of the summary basis of
approval for three drugs causing idiosyncratic injury indicates the
dominant belief that preclinical testing does not predict for
idiosyncratic responses may not be true, at least in these cases. A
preclinical testing strategy to avoid idiosyncratic liver injury
will be described.

Toxicity Screening in Drug Development

Chair: Jim Xu

11:15 PM – 11:45 PM

The Design and Interpretation of In Vitro Safety Assays in Discovery
(Jim (Jinghai) Xu; Pfizer - Groton Labs; Groton, CT) It is now well-
accepted that the identification of safer drug candidates for
further development relies on a panel of in vitro safety assays in
Discovery. However, key elements in the design of such an in vitro
safety panel, and the proper interpretation of these in vitro
results, have not been fully addressed. This presentation will
focus on the strategies in designing an "optimal" in vitro safety
panel. Emphasis will be placed on the use of "optimal" in vitro
models, concordance with GLP tests, in vitro in vivo correlations,
and proper interpretation of the in vitro results.

11:45 PM – 12:15 PM

The Role of Early Toxicity Screening in Drug Safety Evaluation
(Jessica E. Sutherland, Charles River Laboratories Discovery and
Development Services; Worcester, MA) Early toxicity screens are an
extremely important component of pharmaceutical safety assessment.
A properly designing toxicity screening program can be used to
optimize lead compounds in an attempt to identify which should move
from discovery into development. Early toxicity screening is also
useful during pilot and dose range-finding studies or when
formulation decisions are needed. Early toxicity screening is also
helpful in identifying unusually toxic agents, target organs, and
estimating lethality. Selection of the proper animal model(s),
sample size, route of administration, and toxicological end points
is vital to the success of these early nonclinical programs.

In Silico Toxicology

Chair: Alan G. Wilson

2:15 PM – 2:45 PM

Predictive In Silico Technologies – Strategic Role in Drug Discovery
(Alan G.E. Wilson, Lexicon Genetics; The Woodlands, TX) ADME/PK and
toxicity issues remain significant hurdles to drug success and
productivity. Of increasing interest is the application of
predictive in silico ADME and toxicity modeling. Linkage of in
silico models with other emerging technologies, and biomarkers,
could substantially facilitate the reliability of PK/PD and safety
extrapolations. This presentation will discuss the current status
and opportunities of in silico ADME and toxicity modeling in drug
discovery.

2:45 PM – 3:15 PM

Predictive Toxicity Screening – Future Directions for In Silico
Applications (Dale E. Johnson, Chiron Corp.; Emeryville, CA)
Predicting potential human toxicity during the early phases of
pharmaceutical R&D continues to be only partially successful. The
application of new technologies such as toxicogenomics, proteomics
and metabonomics continue to be in the validation stage; whereas
high-content screening using human cell-based systems and transgenic
animal models may emerge as reasonable alternatives to current
approaches. Since In silico applications require the generation of
new data involving large sets of chem-tox correlations, cell-based
assays may become a preferred approach if reasonable validation
programs can be established.

3:30 PM – 4:00 PM

Toxicity Evaluation Using Statistical Analysis and Visualization
(Tom Downey, Partek Incorporated; St. Charles, MO) Statistical
analysis is useful for finding correlations and patterns in
screening data. After the patterns are identified, they can be
presented using informative interactive visualization of the data.
The result is that the data may be used to create in-silico models
to predict toxicity of new compounds prior to selecting which
compounds to test in-vitro. This talk will demonstrate the
application of statistical methods such as statistical tests,
principal components analysis of structure-activity relationships,
and identification of patterns and trends in high throughput
screening data.