Company Overview
Development of Building Blocks for In-Silico
Simulation Technology Based Approach to Drug Discovery
Mission Statement
The business objective is to shorten the time to successful drug
discovery, reduce costs, increase efficiency and improve success rate
of the pharma drug discovery process. This is achieved by the
development of “in silico” computational simulation models of basic and
complex systems using industry standard representation formats based on
commercial simulation platforms.
About Cellworks Group Inc.
Cellworks Group Inc. is an angel-funded company incorporated in June
2005 out of California. The R&D team of the company is based in
Bangalore, India – Cellworks Research India Limited (CRIL) with
established growing collaborations with global research teams in
academia and Pharma. CRIL is the fully owned subsidiary of Cellworks
Group and is a “Software Technology Park India” (STPI) unit.
Three different vectors are playing out in the Pharma space – First is
that the R&D budgets are increasing on a year to year basis (~13%
increase per year). Second is the number of New Molecular Entities
approval by FDA is almost flat or slightly reducing from year to year
(~20 per year). Finally the R&D budgets as percentage of sales is
one of the highest of any industry and growing every year (Average
being 18% of sales). In addition detection of serious side-effects in
late stages of clinical trials and post drug roll out are causing
withdrawal of blockbuster drugs. The benefits of predicting and
detecting problems early on in the discovery process is huge as the
drug discovery costs reach almost $2B/- from Discovery to Launch. The
company business objective is productivity improvement, reduction of
drug discovery costs, increase efficiency, improve success rate of
Pharma drug discovery process and enable “fast-failing” methodology by
identifying potential side-effects earlier in the process.
Cellworks develops and provides technology based solutions to enable
drug discovery research and development (R&D). This approach is
based on Systems Biology and involves development of a disease
physiology aligned “virtual experimental system”. This system is a
representation of all the different cellular processes relevant to the
disease and associated assayable endpoints at the cell signaling and
biochemical pathways level. The development is bottom-up methodology
based in which the relevant proteins, enzyme, receptor, adaptors and
chaperones; functionality and interaction are modeled and the
relationships represented computationally using mathematics. The
complete disease specific platform is an integrated transparent view of
human cellular physiology available as a virtual experimental system.
Technology WHY/Motivation
Despite all cells of multi-cellular organisms having the same genome,
there exists a wide diversity of cell types with distinct functions,
shapes and sizes. There are different sets of proteins in every cell
type and it is the interaction of the networks within each cell and
between different cell types that is the basis of life. There are some
basic metabolic processes such as respiration which are common to all
cell types while certain other processes are unique to specialized
cells. For instance a skeletal muscle cell has contractile machinery,
while a cholinergic neuron has the capability of secreting
acetylcholine neurotransmitter upon appropriate stimulus.
“Complexity and emergent properties in
biology derive
from several features: first, complex inputs that stimulate multiple
pathways; second, multiple outputs that are integrated network
responses to the inputs; third, interactions between multiple cell
types; and fourth, multiple contexts and environments for each cell
type or combination of cell types.” (Butcher, E.C. et al; Nature
Biotechnology, 2004).
To understand the effects of a drug
designed to a
specific target/(s), data must be derived from cell responses in
multiple environments. With the complexity and the large diversity in
cell types, it is essential to create models of each specific cell
type, which will eventually integrate into models of complex systems.
Cellworks is pioneering this new multi-disciplinary approach to create
accurate models.
Business WHY/Motivation
The drug industry spends nearly 25% of its revenues on R&D which is
about twice that of other high-tech industries like semiconductor chip
design and automotive design. Developing a drug typically costs $900M
and takes 15 years. Only one in 1,000 compounds tested makes it into
human trials, and only one in five of those emerges as a drug. Having
access to and simulating in-silico models easily will be the key to
eliminating false-positives quickly and focusing on the right compounds.
Here are few recent references of drugs that have been recalled at
different stages of development and clinical trial which could have
been avoided if in-silico simulation approach was used in the
development process.
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Biogen, Elan voluntarily withdrew
MS drug –
Washington post – Associated Press, Tuesday, March 1, 2005. The drug
Tysabri, used to treat multiple sclerosis was withdrawn after some
adverse affects on 2 patients. Stocks of both Biogen Idec. Inc. crashed
40% and Elan Corp. tumbled 70%. (Investor’s Business Daily, Mon. Feb
28, 2005). Tysabri sales were forecast to $3 billion.
-
Amgen halted phase II clinical
trail of GDNF for
Parkinson’s disease – News Release – www.amgen.com.
Feb 11, 2005. Patient safety concerns were cited as the reason. Roger M
Perlmutter, executive vice president, Research and Development, Amgen
said – “After careful review, we stand behind our decision to stop
providing GDNF to patients due to potential safety risks observed in
preclinical studies, including irreversible brain damage, and the
absence of any demonstrated medical benefit.”
-
Merck withdrew Vioxx – Sept., 30,
2004 – Product
news – www.merck.com.
Merck announced a voluntary worldwide withdrawal of VIOXX (rofecoxib),
its arthritis and acute pain medication. There was an increased risk of
cardiovascular events such as heart attacks and stroke, beginning 18
months after treatment in patients taking VIOXX. VIOXX was launched in
the US in 1999 and has been marketed in more than 80 countries.
Worldwide sale of VIOXX in 2003 were $2.5 billion.
Technology Background and Solutions
Systems biology is the study of the mechanisms underlying complex
biological processes as integrated systems of many, diverse,
interacting components. It involves the integration of large sets of
experimental data from various ‘omics’ (genomics, transcriptomics,
proteomics, metabolomics) sources, and the proposal of mathematical
models that account for significant aspects of this data set. Accurate
fitting of this data to experimental data and subsequent simulation
would ultimately aid in developing predictive models of human disease.
Such models would help both to identify promising targets and to
determine the degree to which a drug can affect them.
Data-driven computer simulations at the level of molecular pathways and
regulatory networks within and between cells and cell types would
explain and predict how basic components of the cell interact and
underlie the physiology of the cell, of tissues, of organs, and
ultimately of the whole organism. “The goal of modeling in system
biology is to provide a framework for hypothesis generation and
prediction based on in silico simulation of human disease biology, from
molecular reactions, to organism homeostasis and disease response.”
(Butcher, E.C. et al; Nature Biotechnology, 2004).
In the April 2005 issue of Drug Discovery and Development, an industry
journal, several drug companies including Roche, Pfizer, and Johnson
& Johnson, offered high praise for the systems biology approach.
Roche said that biosimulations had helped it to find additional uses
for Pegasys, its hepatitis-C drug. Pfizer noted that FDA had
specifically mentioned that computer models “provided confirmatory
evidence of efficacy” of Neurontin, a drug that treats the pain after a
bout of shingles.
Cellworks Group Inc. adopts a multi-disciplinary and analytical
approach to solving intricate biological problems and is part of a new
technology wave that will change our perceptions of the diagnosis and
treatment of human disease.
Unique Strengths of Cellworks Group Inc.
-
The innovative team of Cellworks
personnel is
highly inter-disciplinary, with skills in biology, semiconductor
implementation/modeling, medicine, mathematics, software engineering
and chemistry to tackle the challenge of modeling complex biological
systems.
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The computational biological
models generated by
the Cellworks Group are dynamic and are customized to suit a
scientist's/company's specific needs. They come packaged with design
methodology and can be tweaked at various levels for in-depth analysis
and research.
-
The company has partnerships with
institutions and
leading researchers in the US and India that help with the unique
challenges of modeling complex systems.
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Cellworks' business model is to
supply computational biological models of cell systems that can be used
to analyze pathways in disease vs. normal conditions. This
would enable an understanding of the effects of probable drugs on
pathways within a cell and on cell systems.
#303 A Block, 3rd
Floor, 60 feet road, AECS Layaout, Marathahalli Post, Bangalore
-560037, India. Ph: 91-80-4115 8733, Fax-091-08-4115 8734, e-mail:
info@cellworksgroup.com
