AvalonRx®

AvalonRx® is a drug discovery platform that integrates well-defined biomarkers and molecular profiling in all stages of drug discovery and development. AvalonRx® uses biomarkers for identification of compounds from high throughput screens, for revealing a compound's mechanism of action, for directing drug optimization efforts, and for identification of pharmacodynamic markers used for clinical development. AvalonRx® provides a much broader and fundamental understanding of the biological activity of drugs before they enter human clinical trials.

AvalonRx® can identify biomarkers that specifically report on the activity of well validated disease pathways 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 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.

The AvalonRx® platform is composed of a comprehensive, innovative and proprietary suite of technologies which is supported by a combination of state-of-the-art robotics and computational analysis capabilities.

The components of the AvalonRx® platform include:

1. High-throughput Integrated Transcriptional Screen (HITS®) - proprietary systems for identification of specific and selective biomarker signatures for critical disease related pathways using transcriptional profiling, and the use of these signatures in gene expression-based high-throughput screening using a economical, robust and fully automated process
2. Compound profiling – An integrated toolkit for characterizing a compound’s mechanism of action using Avalon's gene expression databases and gene signature. This is critical for exploring functional characteristics, pathway information, or adverse effect data of compounds. This system consists of custom and standard microarray platforms for chemical genomic analysis, an extensive database of transcriptional response profiles for several hundred reference agents, 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 microarray based system to monitor compound activity termed RACETraCK(Rapid Assessment of Compound Efficacy, Transcriptional Change and Kinetics). This is a unique method for determining changes in gene expression using murine xenograft models which tracks the activity of the compounds in the target tissue of interest.
5. Pharmaceutical Development and Clinical Biomarkers - The identification and use of biomarkers of drug exposure and effects in the clinical setting is becoming an integral part of drug development. We have developed systems for monitoring the activity of biomarkers in clinical samples to further optimize patient selection and direct clinical development.

Avalon’s internal drug discovery efforts are focused in oncology. The Company's emerging drug pipeline includes novel small molecule drug candidates for the treatment of a variety of different cancer types. Many other diseases are also amenable to this approach, so in collaboration with pharmaceutical partners, we are utilizing AvalonRx® to identify candidate therapeutics for other disease areas such as immunology, inflammation and cardiovascular. Avalon has also entered a collaboration to develop antibody therapeutics (large molecules).

The AvalonRx® platform allows our 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.

References:

K. Carter. The Genome as a Tool for Drug Discovery and Development - The Case for Embracing Complexity (as PDF file). Drug Discovery World, Fall 2006.

David Bol and Reinhard Ebner. Gene expression profiling in the discovery, optimization and development of novel drugs – One screening platform for all drugs and diseases (as PDF file). Pharmacogenomics, Mar;7(2):227-35 (2006).

D.K. Bol, D.R. Soppet, A. Glodek. The Changing Landscape of Drug Discovery Screening. Current Drug Discovery, 17-21, July 2003.

P.E. Young, D.K. Bol. High-Throughput Transcriptional Profiling for Drug Discovery and Lead Development (as PDF file). Genetic Engineering News, Vol. 23. January 2003.