AvalonRx®
Biomarker based High Throughput Screening
The AvalonRx® screening process starts with the selection of highly specific sets of disease biomarkers (screen signature) in key disease pathways. This biomarker signature is then used in a process we termed High-throughput Integrated Transcriptional Screen (HITS®), to identify compounds that specifically affect the disease pathway. Libraries of small molecule compounds are screened against this signature, and molecules that elicit desirable response profiles are rapidly identified as hits.

Most conventional drug discovery efforts center on finding target proteins and on deciphering their role in disease. The process involves a significant amount of target validation work and development of an assay to measure functional changes in the target.

HITS® screening has many advantages over the conventional methods including:

• Identification of inhibitors directed at important pathway activities
• One screen identifies many druggable nodes in each pathway
• Screen against ‘intractable’ targets and proteins with unknown function
• Screening within the correct cellular context including the use of primary cell types

The HITS® screening process consists of two basic parts, identification of a specific gene signature and the use of this signature in high-throughput screening using our HITS® platform.

Gene signatures can be derived by a variety of means including RNA interference, gene targeting, treatments with reference agents, or combinations of these methods. Avalon’s novel screening approach is exceptionally powerful when combined with the RNA interference technology which is amenable to a wide variety of target types, in particular ones that are considered undruggable using conventional technologies.

Avalon’s custom built HITS® platform monitors the expression of the signature gene set using an optimized quantitative PCR (qPCR) technology. The HITS® screening system allows for rapid and economical screening of small molecule compound libraries against target profiles, and is supported by state-of-the-art robotics and computational analysis. This system allows us to screen our internal collection of hundreds of thousands of small molecule compounds to rapidly identify compounds which specifically affect important pathways.