Avalon's AVN944 Inhibits IMPDH And Induces Apoptosis-Related Biomarkers In Patients With Hematological Cancers

[Guest guest]

BlankAvalon's AVN944 Inhibits IMPDH And Induces Apoptosis-Related Biomarkers In

Patients With Hematological Cancers

26 Dec 2006

Avalon Pharmaceuticals, Inc. (Nasdaq and NYSE Arca: AVRX), presented a poster

detailing the effect of AVN944 on a comprehensive set of genetic and biochemical

biomarkers at the American Society of Hematology 48th Annual Meeting. AVN944

demonstrated a statistically meaningful impact on IMPDH and other proteins that

are critical to activities in cancer cells, including nucleotide biosynthesis,

energy and metabolism, DNA replication, apoptosis and cell cycle control. The

data were collected in an ongoing Phase I open-label, repeat dose-escalation

study designed to evaluate the safety and tolerability of AVN944 in patients

with advanced hematologic malignancies and to determine the optimal dose for

Phase II efficacy trials. Further data from an interim analysis of the trial is

expected to be available shortly.

" IMPDH is highly upregulated in most hematological cancers and in many solid

tumors, " said Beverly S. , M.D., Deputy Director of the Stanford

Comprehensive Cancer Center and E. Becker Professor of Medicine at

Stanford University. " IMPDH plays an essential role in cancer cell synthesis of

DNA and RNA, and the inhibition of IMPDH represents a new and potentially

important approach to the treatment of cancer. "

Analysis of the selected markers in patient samples from the Phase I trial

showed a correlation of changes in the expression of these genes to dose level

and duration of exposure. Importantly, several of these markers have been shown

to reflect a durable, sustained stress response indicative of cancer cell death,

particularly in cancer cells from AML patients. Specifically, it was found that

the gene HspA1A, a marker of stress response found to correlate with depleted

GTP pools in cancer cell lines, is induced within hours upon the first treatment

of the drug in patients, even at the trial's lowest doses. Following continued

dosing of AVN944, this marker of disease cell stress was elevated even in the

absence of circulating levels of the drug between doses. Other genes directly

related to IMPDH inhibition showed similar response characteristics.

" AvalonRx®, our proprietary gene expression platform, enabled us to identify a

set of 34 genes that reflect the mechanism-based activity of AVN944, " said

Bol, Ph.D., Senior Vice President of Product and Pharmaceutical Development at

Avalon. " These gene markers correlate with the biochemical effects of AVN944 on

protein function, which we believe will result in tumor cell apoptosis at the

right doses. Our goal for the current Phase I study is to achieve those dose

levels in patients. It is very encouraging that we have not seen any drug

related adverse events even though we are already seeing biomarker movements

consistent with significant inhibition of the IMPDH enzyme. This indicates the

potential for a good therapeutic window. Additionally, these data showcase the

power of the AvalonRx® technology in understanding the pharmacologic,

pharmacodynamic and biologic activity of a drug on patients in early clinical

studies. "

This analysis of the trial data was intended to describe how these biomarkers

correlate with biologic activity of the drug in patients as the doses escalate.

When comparing patients with different hematologic cancers, examination of the

complete set of markers clearly demonstrated the utility of comprehensive gene

expression analysis in clinical trials by distinguishing individuals with

similar diseases, as well as patients with different malignancies, based on the

makeup of their disease prior to drug administration as well as the different

nature of the cellular response following drug administration.

An abstract of the Presentation, entitled, " Genetic and Biochemical Biomarkers

of IMPDH Inhibition in Phase I Dose Escalation of AVN944 for Hematological

Malignancies, " is now available on the ASH website, http://www.hematology.org.