Preclinical Pipeline
Aminoglycoside Program
Resistance among hospital acquired infections
represents a global challenge for medicine and the treatment of
infectious disease. Antibiotic resistance has become a
major cause of morbidity and mortality in the hospital setting
resulting in escalating healthcare costs. Hospital acquired
infections alone, with approximately 2 million cases annually,
contribute to over $5 billion in US healthcare costs.
Bacteria continue to become more resistant to
nearly all of the currently available antibiotics through a variety
of resistant mechanisms. As a result, many key opinion leaders
and experts in the field of infectious diseases have expressed
concerns as to where the next generation of drugs to combat such
pathogens will come from. This is an especially urgent concern
for gram-negative pathogens because nearly all new antibiotic
development over the past decade has focused on agents used to treat
gram-positive infections. Thus, there is a dearth of
gram-negative agents and consequent urgent unmet need.
SelectX's most advanced program is a very
promising preclinical
aminoglycoside antibiotic that addresses the rapidly emerging gram-negative hospital infection market.
This new antibiotic has
demonstrated superior potency and spectrum of activity in vitro
as
well as in animal models against resistant clinical isolates of the most
relevant gram-negative pathogens. MIC90s are generally 10 to 100
times better than currently marketed comparator antibiotics.
SelectX's aminoglycoside has also demonstrated a very favorable
safety profile and, consequently, a significantly improved
therapeutic index compared to marketed aminoglycosides. The
company expects to file an IND in 2008.
Additional applications for aminoglycosides are
also being explored, addressing potential indications of
inflammation, cancer, and other diseases for which there is a
significant unmet medical need.
Genetic Chemistry Platform
Strategy
SelectX's technical strategy is the application of its Genetic Chemistry platform to
efficiently discover and develop natural product derived small
molecules.
This proprietary platform forms the foundation for the Company's in-house drug discovery program.
In addition, owing to its broad applicability, SelectX's Genetic
Chemistry platform is also the basis for partnered programs and is
being applied in a variety of areas.
SelectX has innovated two highly complementary
technologies in order to facilitate its Genetic Chemistry platform.
Directed Discovery™:
Small Molecule Discovery
Directed Discovery™
enables the selective isolation, cloning, and expression of entire natural product biosynthetic pathways or individual genes from unculturable environmental microorganisms.
A significant advantage of this platform
approach is the inherent linkage between compound discovery,
synthesis, optimization and scale-up. Compounds cannot
be discovered unless they are successfully produced, also meaning
complete access to the biosynthetic chemistry. This
permits the rapid progression from hit to optimized lead, typically
in about six months.
ComGene™:
Combinatorial Genetics
ComGene™ is a combinatorial genetics based molecular diversity engine,
enabling the rapid analoging and optimization of natural product
lead compounds, as well as the production of
novel scaffolds. The
biosynthetic production of natural product small molecules typically involves the concerted activities of several enzymes – a biosynthetic
pathway. It is known that the substitution of one or more similar enzymes into a given
pathway can result in the production of novel compounds (including novel backbone), often with novel
and improved activities and/or pharmacologic properties. Thus, the potential of this generalized approach for drug discovery is tremendous,
owing to the power of biosynthetic enzymes that is unmatched by
synthetic or medicinal chemistry. However, until the development of ComGene™, a high-throughput platform for exploiting this strategy and realizing its potential did not exist.
DART™: Drug and Antibiotic Resistance Technology
In addition to its Genetic Chemistry
platform, SelectX has also innovated DART, a platform technology
that permits the rapid characterization of antibiotic resistance prior to
its emergence in the clinic. This is especially useful for
generating more durable antibiotics as well as second generation
therapeutics. In essence, DART allows antibiotic
development to stay a step ahead of resistance development.
Drug resistance to antibiotics is a serious and increasingly prevalent problem to the world medical community.
The World Health Organization, the Centers for Disease Control and Prevention,
and the Infectious Diseases Society of American (IDSA) have all declared the current problem a "crisis". The rate at which antibiotics become ineffective due to resistance, is also increasing at an alarming rate. For example, it has been found that the onset of resistance to new antibiotics by target bacteria may occur in as little as only a few months after the drug has been widely used in a clinical setting.
DART™ was developed to allow for the prediction of both the time and the molecular mechanism of drug resistance by target organisms prior to the widespread clinical use of the drug. Subsequently, this allows pharmaceutical developers to pre-plan second generation drugs and/or re-engineer primary compounds prior to clinical use in order to increase
their time of efficacy. This has significant economic importance to the global pharmaceutical industry, as well as the world health at large, by
delaying or eliminating the onset of resistance.
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