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Avalon Pharmaceuticals is a fully integrated drug discovery organization, with novel approaches to the screening, characterization and optimization of new drugs .
Most conventional drug discovery efforts center on finding target proteins and discovering their role in disease . Once candidates for drug intervention have been identified, high-throughput assays are developed measuring functional changes in the target triggered by ligand binding, followed by the screening of libraries of chemical compounds .
In contrast, Avalon starts with a systems biology approach that measures alterations in key disease pathways. We select highly specific sets of molecular disease biomarkers to monitor effects in the Company's primary screens that combine novel transcriptional assay technology with state-of-the-art robotics. Libraries of compounds are screened against such signature sets of expressed genes, and molecules that elicit desirable response profiles are rapidly identified. This approach permits the evaluation of compounds against many different targets - both known and unknown - in parallel within a single assay.
| "We focus on outcomes - global and specific changes in cellular gene expression - not just on single targets." |
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A key advantage of Avalon's approach is that it addresses a major need for an alternative to traditional HTS (high-throughput screening) programs. Traditional HTS suffers from long lead times and high costs to validate targets, screens that are often hard to design, little confidence regarding the efficacy or toxicity of hits, and many targets that are considered "intractable" or "undruggable." Further, focusing on single protein targets ignores the complexity of interactions between proteins in various cellular pathways. In contrast, Avalon's approach provides precise information about a compound's actions across multiple pathways within a cell.
Avalon's rapid, information-rich screening strategy also allows for quicker decision-making regarding the progression of hits from screening into optimization. The process is enriched by subsequent microarray analysis of compound effects across thousands of genes simultaneously, and comparison of the 'activity' of compounds to a large transcription database derived from cellular treatments with many known reference compounds. Additionally, microarray analysis enables the identification of gene signatures specific to a given compound that are used to guide the chemical synthesis of analogs and to accelerate the drug optimization process.
| "Characterization and profiling of hits allows better and faster decisions on selection of compounds for optimization and development." |
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Avalon's innovative discovery systems provide multiple product opportunities including biomarkers, novel targets, diagnostics and new drugs. Importantly, this approach also facilitates the identification of pharmacodynamic markers for use for patient stratification and response prediction in clinical trials, adding to the acceleration of the drug discovery and development process.
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| "Multiple product opportunities: novel targets, biomarkers, diagnostics and drugs." |
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Currently, Avalon has chosen to focus its drug discovery engine on medicine for the treatment of cancer, however, many diseases are amenable to this approach. The Company's emerging drug pipeline includes novel small molecule drug candidates for the treatment of a variety of cancers. Avalon is also partnering with other companies to develop antibody therapeutics.
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