About AvalonRx®
AvalonRx® is a drug discovery platform developed originally at Avalon Pharmaceuticals, Inc. that integrates well-defined biomarkers and molecular profiling throughout all stages of a drug discovery and development pipeline. It is a comprehensive, innovative and proprietary suite of technologies supported by a combination of state-of-the-art robotics and computational analysis capabilities.

AvalonRx uses biomarkers for identification of hit compounds from high throughput screens, for revealing compound's mechanism of action, for directing drug optimization efforts, and for identification of pharmacodynamic markers used for clinical development. It can identify biomarkers that specifically report on the activity of well validated disease pathways thus overcoming many of the problems encountered in current high-throughput screening systems. Importantly, AvalonRx expands the range of therapeutic targets for drug intervention, including targets and pathways frequently considered intractable by conventional high-throughput screening approaches.

AvalonRx provides a fundamental and much broader understanding of the biological activity of drugs before they enter human clinical trials. It provides the data to make more informed decisions about which compounds to advance toward clinical trials, and facilitates clinical drug development through identification of pharmacodynamic markers for efficacy, patient stratification or response.

For information on partnering opportunities or to use the AvalonRx platform, contact busdevavalonrx@pgxhealth.com.

The components of the AvalonRx platform include:

1. High-throughput Integrated Transcriptional Screen (HITS®) – a robust, proprietary platform for the application of transcriptional profiling to gene expression-based high-throughput screening. Allows for identification of specific and selective biomarker signatures for critical disease-related pathways and screening compound libraries against them.
2. Compound profiling - an integrated system for characterizing compounds using transcriptional databases and gene-expression signatures. Allows for exploration of compound functional characteristics, molecular pathway information or adverse effects. This system consists of standard and custom-built gene-expression microarray platforms, an extensive reference database of transcriptional response profiles for several hundred known drugs, and proprietary informatics tools for data analysis.
3. Biomarker based lead optimization - a unique platform for elucidating structure-activity-relationships based on transcriptional changes (Transcriptional SAR, TSAR) along with phenotypic and biochemical assays. This includes the synthetic and analytical chemistry capabilities for lead explosion that enable the rapid optimization of hits to leads.
4. Lead development - a method for optimizing the activity of drugs in disease models using pharmacodynamic markers. We utilize a proprietary method termed RACETraCK for Rapid Assessment of Compound Efficacy, Transcriptional Change and Kinetics. It tracks compound activity in the target tissue of interest using murine xenograft models and gene-expression microarrays.
5. Pharmaceutical development and clinical biomarkers - systems for monitoring the activity of biomarkers in clinical samples to further optimize patient selection and to direct clinical development.

The AvalonRx platform allows scientists to make informed decisions about which compounds to develop and advance into clinical trials, and can expedite clinical drug development and commercialization through the identification of biomarkers which stratify patient populations and provide early indicators of drug response.

AvalonRx in Action
The Beta-catenin pathway plays a key role in the initiation and progression of many types of cancer, in particular colon cancer, where it has been estimated that the pathway is abnormally activated in more than 85% of cases. The Beta-catenin pathway is activated in a large number of different cancer types, frequently by mutation of pathway members, and presents one of the premier targets in oncology.

Unfortunately, biological complexity and classically intractable nature of the Beta-catenin protein itself have prevented this pathway from being effectively targeted by conventional drug discovery techniques. AvalonRx® is particularly well suited for the identification and optimization of drugs targeting the Beta-catenin pathway as it is able to select and optimize drug candidates based on inhibition of the pathways activity.

Using AvalonRx, we have identified a set of structurally distinct chemical compounds that appear to affect the Beta-catenin pathway, and advanced one of the compound series into lead optimization and preclinical studies. We nominated one of these compounds, AVN316, as a lead candidate for preclinical development. It inhibits the Beta-catenin pathway and is a potent inducer of cell cycle arrest and apoptosis. We are currently advancing this compound to IND.