AvalonRx®
Lead Development
In the lead development stage of AvalonRx®, pharmacokinetic behavior, activity in disease models, bioavailability and stability of candidate therapeutic compounds are examined and improved.

With our internal focus on oncology, one of Avalon's most valuable discovery platforms is Rapid Assessment of Compound Efficacy, Transcriptional Change and Kinetics (RACETraCK). This is a unique method for determining changes in gene expression using murine xenograft models. Gene expression changes, observed earlier in our cell-based model systems, are examined in tumor bearing mice exposed to the same compound. The information from these in vivo models is correlated with the data from our in vitro testing through use of our databases.

RACETraCK allows Avalon scientists to compare the pharmacodynamics of compounds using gene transcriptional profiles generated by identical compound treatments both in vitro and in vivo. Because the platform does not depend on measurable tumor growth, which can take several weeks or more to observe, such in vivo pharmacodynamic experiments dramatically accelerate discovery and maximize the efficiency of our lead optimization program. Further improvements in terms of speed and data content come from collecting information on appropriate dose levels and various potential dosing schedules as well as early monitoring of genes that are candidate markers of exposure and efficacy.

Information on likely off-target effects and potential in vivo toxicity is also collected at this stage. In combination with in vitro results and data from reference agents, RACETraCK contributes useful observations on possibly adverse effects or systemic or localized toxicity. Along with estimates of achievable, tolerated and beneficial dose ranges, these results allow for rational toxicity binning of lead candidates.

Avalon's RACETraCK platform provides many advantages - more compounds can be tested in a shorter period of time and on fewer animals, and dozens of compounds can be tested exhaustively within weeks. A single RACETraCK experiment provides a wealth of information on:

• tumor exposure (markers of exposure / markers of efficacy),
• mechanism of action,
• indications of toxic effects,
• in vivo biomarkers / predictors, and
• dose/ dose schedule information.

Avalon takes full advantage of this information in guiding the development of lead compounds to clinical candidates.