- Iconix Pharmaceutics (Mountain View, CA;
www.iconixpharm.com) is a privately held pharmaceutical
company focusing in the area of chemogenomics.
- Chemogenomics integrates tools and technologies of
chemistry and genomics to profile drug candidates for their
mechanisms of action and safe advancement for therapeutic
development. Iconix's chemogenomic capabilities enable
pharmaceutical companies to increase the odds of advancing the
right compounds to the clinic, reducing attrition rates and
the costs of drug discovery.
Introduction
The process of drug discovery and development takes
approximately 10 years and over $800 million. In the past
decade, several drugs have been taken out of the pipeline either
early in the discovery process, during clinical trials, or
post-marketing. In the majority of these cases, these drugs had
some adverse effects or toxicity associated with them. This has
resulted in the loss of millions of dollars for pharmaceutical
companies. Such huge capital loss can be avoided, and successful
drugs with minimal or no toxic effects can be developed, if the
mechanism of drug action is well-defined early in the discovery
or development process. Chemogenomics is a discipline that is
determined to address this question in a robust fashion.
Chemogenomics leverages advancements that have been made in the
areas of genomics (especially gene expression and
bioinformatics) and chemistry to study, evaluate, and
potentially predict the effects of a candidate compound on all
pathways in a complete biological system. Iconix Pharmaceuticals
has made tremendous advances in the areas of chemogenomics to
qualify drug candidates and predict their potential mechanisms
early in the drug development progress.
Corporate Information
Iconix Pharmaceutics was founded in 1998 as a spin-off from
Microside Pharmaceuticals under the directorship of Keith A.
Bostian, Ph.D. Dr. Bostian is the company's original founder and
was formerly President and Chief Executive Officer. Dr. Bostian
was also founder, Chief Operating Officer, and Director of
Microside Pharmaceuticals and now Essential Therapeutics
(Waltham, MA). He was Executive Director of Microbiology and
Molecular Genetics at Merck Research Laboratories, from
1987-1992. Mr. Jim Neal joined Iconix Pharmaceuticals in June
2002 as Chief Executive Officer. Prior to joining Iconix, Mr.
Neal was Executive Vice President responsible for Sales,
Marketing, and Business Development and a member of the
Executive Team at Incyte Genomics (Palo Alto, CA). Mr. Neal led
a group of over 100 people responsible for Incyte's global
commercial activities with clients and collaborators. David J.
O'Reilly is the Chief Business Officer for Iconix Pharmaceutics.
Mr. O'Reilly joined Iconix as Vice President of Corporate
Development during the founding of the company in 1998. Prior to
this, he was an executive at ARIAD Pharmaceuticals (Cambridge,
MA), where he was responsible for partnerships and licenses with
pharmaceutical, biotechnology, and academic organizations.
Leslie J. Browne, Ph.D., is the Chief Operating Officer for
Iconix. Previously, Dr. Browne was the Chief Operating Officer
at GeneTrace, a functional genomics company developing products
and services in drug discovery research. Before that, he spent
over a decade at Berlex/Schering AG, most recently as Corporate
Vice President, Berlex Laboratories, and President of Schering
Berlin Venture Corporation. Additional distinguished members
include Kurt Jarnagin, Ph.D., Vice President, Biological
Sciences and Chemical Genomics; Alan H. Roter, Ph.D., Vice
President of Informatics; and Alan Engelberg,Vice President,
Product Management.
The scientific advisory board of Iconix consists
distinguished scientists including Patrick O. Brown, Ph.D.,
Professor, Department of Biochemistry, and Investigator, Howard
Hughes Medical Institute, Stanford University School of
Medicine; John C. Chabala, Ph.D., Formerly President, Chief
Scientific Officer and Director, Pharmacopeia; Frank McCormick,
Ph.D., F.R.S., Director, UCSF Cancer Center; Roy G. Smith,
Ph.D., formerly Vice President of Basic Research, Merck Research
Laboratories; and Kenneth S. Zaret, Ph.D., Senior Member, Cell
and Developmental Biology Program, Fox Chase Cancer Center,
Philadelphia, PA.
Iconix currently has approximately 60 employees with the
majority of them holding a Ph.D. in the areas of Pharmacology,
Biology, and Chemistry.
Financial Analysis
Iconix is a privately held company that has been financed by the
venture capital firms Abingworth Management, Institutional
Venture Partners, and Kleiner Perkins Caufield and Byers. In
addition, the company has received equity financing from its
strategic partners, Motorola, Incyte Genomics, and MDS Pharma
Services. To date, Iconix has raised approximately $100 million
U.S. dollars.
Research and Development Activities
Iconix is pioneering the new field of chemogenomics.
Chemogenomics integrates tools and technologies of chemistry and
genomics to profile a drug candidate's mechanisms of action.
Previously, drug compounds were advanced through the pipeline
based on a few tests that were performed in standard
pharmacology. Standard pharmacological approaches provided very
little information on the mechanisms that are set forth by the
compound at the molecular level in vivo. Additionally, it
has not been possible, to date, to predict the mechanisms of
unknown drugs based on their structure. Iconix's chemogenomic
capabilities enable pharmaceutical companies to study and
predict the mechanisms of drug action early enough in the
process to make critical decisions on drug candidates.
The approach that Iconix has taken is quite simple but does
provide incredible in-depth information and predicting power
regarding the activity of a compound in an intact in vivo
environment. To date, the company has selected 600 environment.
To date, the company has selected 600 compounds that are
toxicological standards or drugs that are well-known and are
either going through clinical trials, approved by the Food and
Drug Administration (FDA), or currently being marketed. These
represent structural and mechanistic diversity of 2000
compounds, including approved drugs, failed drugs, standard
toxicants, and biological standards. The company is studying the
effect of these drugs in different organs by generating highly
enriched gene expression profiles. The gene expression is
further classified by generation of chemogenomic signatures
unique for each compound. Thus, in a typical experiment, rats
were given a compound orally at a concentration that was
selected based on the literature. In a majority of the cases, a
maximum tolerated dose is selected to generate expression
profiles and signatures. The drug is given daily for 5 days, and
animals are watched for weight loss. Twelve different tissues
are then harvested, and RNA from selected tissues is isolated
for labeling to hybridize to a microarray slide. Using a
CodeLinkTM ing CodeLink array system (Amersham Biosciences,
Piscataway, NJ) that contains 10,000 genes (3500
well-characterized genes and 6500 expressed sequence tags [ESTs]),
a gene expression profile is generated. After performing
sophisticated informatics, Iconix has generated specific gene
expression profiles termed as signatures. These signatures
represent a collection or families of clusters of genes
expressed (up- or down-regulated) in a unique manner. These
signatures are stored in a database and serve as a reference and
learning set to profile future drug candidates.
Iconix provides reference systems and know-how to predict
toxic liabilities and side effects of drug candidates and to
determine if they are on or off target. In addition to
generating gene signatures, pharmacology and blood chemistry
tests are performed on these rats, and then the tissues are
frozen. Changes in blood chemistry, the histopathology, the
relevant literature on the drug candidates, and biochemical
assays are all critical components in generating a reference
learning set. All this enriched data is then organized into an
integrated database architecture to bridge genomics and drug
design, novel bio- and chemoinformatics software, and advanced
expression array and cellular assay development capabilities.
This searchable database is termed DrugMatrix™. DrugMatrix
provides drug designers with a uniform source of chemogenomic
information on benchmark drugs and toxicants and analytical
tools and data mining algorithms to optimize drug candidates and
predict their potential efficacy and toxicity before they
advance to expensive preclinical and clinical development
studies. All benchmark drugs in DrugMatrix are profiled in an
extensive series of large-scale gene expression microarray,
in vivo histopathology, molecular pharmacology, and
literature curation studies performed by Iconix. Based on the
data in DrugMatrix, the company has mined out a library of Drug
Signatures™, which are genomic patterns that are predictive of
specific forms of toxicity and mechanisms of action.
With so many drugs entering into the drug development steps,
it is critical to understand the potential toxicity and adverse
pharmacological effects that they may have sooner rather than
later. There also lies the possibility of refining the structure
of the compound to reduce or eliminate adverse effects.
DrugMatrix provides a collection of signatures that can predict
the potential chemogenomic effects of unknown and new chemical
entities. The company has reported that, based on the analysis
of drug signatures, they have been able to correctly call the
mechanism of unknown drug action and potential toxicological
liabilities. It has to be pointed out that it is not solely the
gene expression patterns that are driving chemogenomics to
define the mechanism of action, but also the enriched
pharmacological and pathological information generated as part
of DrugMatrix. Iconix has recently initiated collaborations with
the FDA to provide them access to DrugMatrix and the company's
expertise in the area of chemogenomics, thus enabling the FDA to
prepare guidelines for sponsors in the use of genomic data.
Additional Literature on Chemogenomics
- Huang Y, Sadee W. Drug sensitivity and resistance genes in
cancer chemotherapy: a chemogenomics approach. Drug Discov
Today 2003;8:356-363. 2003;8:356-363.
- Schuffenhauer A, Floersheim P, Acklin P, Jacoby E.
Similarity metrics for ligands reflecting the similarity of
the target proteins. J Chem Inf Comput Sci
2003;43:391-405.
- Nislow C, Giaever G. Chemogenomics: tools for protein
families, and chemical genomics: chemical and biological
integration. Pharmacogenomics 2003;4:15-18.
- Nguyen C, Teo JL, Matsuda A, et al. Chemogenomic
identification of Ref-1/AP-1 as a therapeutic target for
asthma. Proc Natl Acad Sci USA 2003;100:1169-1173.
2003;100:1169-1173.
- Shokat K, Velleca M. Novel chemical genetic approaches to
the discovery of signal transduction inhibitors. Drug
Discov Today 2002;7:872-879.
- Ashton GH, McGrath JA, South AP. Strategies to identify
disease genes [review]. Drugs Today (Barc)
2002;38:235-244. 2002;38:235-244.
- Bleicher KH. Chemogenomics: bridging a drug discovery gap.
Curr Med Chem 2002;9:2077-2084.
