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Next Generation Cytotoxics
OSI-211
OSI-7904L
OSI-7836
Our core discovery technologies and capabilities
Since their introduction in the 1950s, the development and use of
cytotoxic drugs has helped to successfully treat many people with
cancer. In fact, some cancers can now be cured routinely with chemotherapy
and others can be controlled for long periods of time. These products
are effective in killing rapidly dividing cancer cells, but because
they usually interfere directly and non-selectively with normal
processes in the cell, they are frequently associated with severe
toxicities.
In addition to our targeted programs, we are also developing next-generation
cytotoxics that are designed to improve the activity and reduce
the undesired side effects associated with chemotherapy. We feel
that our ability to develop both novel targeted drugs and next-generation
therapies is a necessary approach to becoming a successful oncology
franchise.
Our next-generation cytotoxic chemotherapy candidates are designed
to improve upon currently marketed products that belong to the same
class of drugs. As part of our acquisition of the Gilead oncology
division in November of 2001, we acquired a portfolio of three promising
next-generation cytotoxic agents. These include two compounds incorporating
novel liposomal formulations—OSI-211, a topoisomerase I inhibitor,
and OSI-7904L, a thymidylate synthase inhibitor. Non-liposomal formulations
of these product classes are currently marketed for cancer indications.
The third compound, OSI-7836, is being developed as an alternative
to Gemzar® (gemcitabine) for multiple solid tumors.
OSI-211 is a proprietary liposomal formulation of the active topoisomerase
I inhibitor lurtotecan. It is a member of the camptothecin class
of cytotoxics. Topoisomerase I is an enzyme critical to cellular
replication. An example of a currently marketed non-liposomal topoisomerase
inhibitor is Hycamtin® which is used to treat relapsed ovarian
cancer and relapsed small cell lung cancer.
Initial Phase II studies of OSI-211 revealed comparable anti-tumor
activity to Hycamtin® in ovarian cancer. However, in order to
develop this agent we believe it is essential that we clearly differentiate
it and we have therefore initiated a comparative Phase II trial
versus Hycamtin® in refractory ovarian cancer and a Phase II
trial in refractory small cell lung cancer.
OSI-7904L is a member of the class of drugs known as thymidylate
synthase inhibitors (TSI), a well-established group of agents with
a validated mechanism of action. The most frequently prescribed
drug in the treatment of colorectal cancer is 5-Fluorouracil (5-FU).
5-FU, and more recently Xeloda®, are examples of TSIs that play
a prominent role in the treatment of cancer. OSI-7904L is a liposomal
formulation of a potent TSI (GW1843), which is designed to improve
activity by maintaining active concentrations of drug in the tumor
for extended periods of time. Phase I studies for this product are
ongoing.
OSI-7836 is a member of the nucleoside class of cytotoxic drugs
of which gemcitabine is the market leader. We are developing OSI-7836
as an alternative to gemcitabine and the candidate has clearly demonstrated
anti-tumor activity in a variety of solid tumor xenograft models.
This product is currently in Phase I development.
At OSI, our efforts have focused on applying the discovery technology
platforms we have developed over the last decade to the cancer setting.
With the Gilead oncology acquisition, we have added important in
vivo pharmacology and toxicology capabilities, and the British
Biotech acquisition significantly expanded our medicinal and process
chemistry capabilities. Our research teams target the genetic, molecular
and cellular basis of cancer. Both internally and through a range
of collaborations with leading academic research institutions, we
are working hard to translate basic research knowledge into effective
treatments for cancer. Our drug discovery platforms constitute an
integrated set of technologies and capabilities covering every major
aspect of pre-clinical and clinical development.
This fully integrated drug discovery platform is built to advance
the process of identifying and optimizing high-quality, small molecule
drug candidates.
- gene transcription, signal
transduction, protein kinases and other assay systems
- automated high-throughput screening
systems and automated lead compound profiling systems (assessing,
for example, metabolism and pharmacokinetic characteristics)
- a library of over 350,000 proprietary
small molecule compounds
- medicinal, computational, molecular
modeling and automated combinatorial chemistry approaches
- in vivo pharmacology,
pharmacokinetics and pharmaceutical development capabilities
With the successful integration of the Gilead
and British Biotech acquisitions, we now possess an extensive pipeline
of oncology product candidates, a strong core of discovery research
and top-tier oncology clinical development and regulatory affairs
capabilities that we feel differentiate our company and will provide
us with the ability to excel in our goal of becoming a global leader
in oncology.
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