Preclinical Pipeline

Novel 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 the first half of 2010.

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.

Novel Carbapenem Program

Currently marketed carbapenems are less than optimal and suffer from several liabilities including lack of metabolic stability (DHP-1), short half-life, and/or reduced spectrum toward serious nosocomial pathogens including Pseudomonas.  SelectX is addressing these liabilities through its genetic chemistry platform to drive the discovery and optimization of a superior, best-in-class carbapenem with the following key characteristics:

• broad spectrum coverage, including multi-drug resistant Pseudomonas

• resistant to all β-lactamases, including extended spectrum and AmpC

• cidal, minimization of emergence of resistance

• superior pharmacokinetics with extended half-life permitting once daily dosing

• metabolically stable

Platform Power: Genetic Chemistry

SelectX's technical strategy is the application of its Genetic Chemistry platform to drive the efficient discovery and development of 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.

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.

SelectX Pharmaceuticals, Inc.
One Innovation Drive
Worcester, MA  01605
Phone: (508) 798-0216
Fax: (508) 798-0217