Avalon Pharmaceuticals, Inc. (AVRX)

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AVN944 Shows Potent Antiproliferative Activity in Human Endothelial Cells
Wednesday April 18, 6:30 am ET

GERMANTOWN, Md., April 18 /PRNewswire-FirstCall/ -- Avalon Pharmaceuticals, Inc. (Nasdaq: AVRX - News), today described the potent antiproliferative activity of AVN944 in human endothelial cells (HUVEC), and showed that the compound prevents blood vessel formation in a mouse model. The newly elucidated antiangiogenic properties of the compound were examined in a study poster entitled, "Antiangiogenic Properties of AVN944, A Potent Inhibitor of IMPDH," presented at the American Association for Cancer Research Annual Meeting held April 14-18, 2007, in Los Angeles.

"Results of this study provide new insight into the mechanism of action of AVN944," stated Zoe Weaver, Ph.D., staff scientist at Avalon and lead investigator in the study. "The suppression of blood vessel growth, without any adverse effects to the mice, gives us a strong rationale to include solid tumors, especially those that may be more sensitive to agents that inhibit tumor angiogenesis, in our Phase II trials."

AVN944 is an orally available inhibitor of inosine monophosphate dehydrogenase (IMPDH) 1 and 2. IMPDH2 is highly upregulated in many malignancies, including hematologic cancers, and is required for the de novo production of guanine nucleotides. AVN944 is a potent inhibitor of cancer cell proliferation and elicits a specific set of cellular responses directly related to depletion of cellular guanosine triphosphate (GTP) pools. Recent studies of IMPDH inhibitors suggest that they may elicit antiangiogenic effects and could provide added benefit as a cancer therapy through blockade of tumor angiogenesis. To investigate this approach, scientists at Avalon evaluated AVN944 in a series of angiogenesis assays to determine the potential utility of this drug as an antiangiogenic agent for cancer treatment.

As a result, AVN944 was found to potently inhibit proliferation of HUVECs. This antiproliferative activity was reversed by the addition of guanine, indicating that AVN944 is inhibiting IMPDH activity and depleting GTP pools in endothelial cells. Other in vitro assessments of AVN944 activity in endothelial cells included a comprehensive analysis of global gene expression changes resulting from IMPDH inhibition in these cells. The gene expression signature induced by AVN944 in endothelial cells was indicative of GTP metabolism and cell cycle inhibition, similar to gene expression profiles exhibited by cancer cell lines. Additionally, treatment of Matrigel plug- bearing mice with AVN944 inhibited the growth of new blood vessels to a similar or greater degree than mycophenolate mofetil, an FDA-approved immunosuppressant drug.

Avalon investigators next plan to expand the AVN944 preclinical program to include rodent solid tumor models. Avalon's results, detailing the potent inhibition of endothelial cells in vitro combined with inhibition of angiogenesis in an in vivo model, could position this drug for rapid development as a novel antiangiogenic agent for cancer therapy.

About AVN944

AVN944 is an oral small molecule drug candidate that inhibits inosine monosphospate dehydrogenase (IMPDH), an enzyme that is critical for cells to be able to synthesize guanosine triphosphate (GTP), a molecule required for DNA synthesis and cellular signaling. IMPDH is over expressed in some cancer cells, especially in the case of hematological malignancies. In laboratory experiments, AVN944 has been shown to inhibit IMPDH activity in cells, and suppress pools of GTP. Anticancer activities of IMPDH inhibitors correlate with sustained depletion of GTP pools both in cellular models and in human subjects. AVN944 appears to have a selective effect on cancer cells in that deprivation of GTP in normal cells results in a temporary slowing of cell growth, while GTP deprivation in cancer cells induces cell death, or apoptosis.

Results from preclinical studies of AVN944 indicate that AVN944 inhibited the proliferation of lymphoid and myeloid cells, the principal cells involved in the most common types of human leukemias. In a single-dose, dose- escalation Phase I clinical trial of AVN944 conducted in the United Kingdom in healthy volunteers, AVN944: (1) was well tolerated at all tested doses with no notable side effects; (2) demonstrated good pharmacokinetic properties; and (3) had a significant inhibitory effect on IMPDH enzyme activity. Avalon filed an IND with the FDA in August 2005 and initiated U.S. Phase I clinical trials in January 2006 for the treatment of hematological cancers.

About Avalon Pharmaceuticals

Avalon Pharmaceuticals is a biopharmaceutical company using its proprietary technology, AvalonRx®, to discover and develop cancer therapeutics. Avalon has a lead product in Phase I clinical development (AVN944 - IMPDH inhibitor), as well as preclinical programs to discover inhibitors for the beta-catenin and aurora pathways now in late stage lead candidate optimization. Avalon also has discovery programs on modulators of survivin function and a drug discovery program targeting the MYC oncoprotein, one of the most important and previously intractable cancer targets. The company has value generating partnerships with Merck, MedImmune, Medarex, and Novartis. Avalon Pharmaceuticals was established in 1999 and is headquartered in Germantown, Md.

Safe Harbor Statement

This announcement contains, in addition to historical information, certain forward-looking statements that involve risks and uncertainties, in particular, related to progress in our drug discovery programs and our collaborations, and clinical progress in the development of AVN944. Such statements reflect the current views of Avalon management and are based on certain assumptions. Actual results could differ materially from those currently anticipated as a result of a number of factors, risks and uncertainties including the risk that the discovery programs and collaborations may not be successful and that AVN944 will not progress successfully in its clinical trials, and other risks described in our SEC filings. There can be no assurance that our development efforts will succeed, that AVN944 will receive required regulatory clearance or, even if such regulatory clearance is received, that any subsequent products will ultimately achieve commercial success. The information in this Release should be read in conjunction with the Risk Factors set forth in our 2005 Annual Report on Form 10-K and updates contained in subsequent filings we make with the SEC.

Contacts:
Avalon Pharmaceuticals, Inc. Noonan Russo
David Muth Greg Geisman
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& Chief Business Officer
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Fax: [phone] The Trout Group LLC
Email: [e-mail] Chad Rubin (Investors)
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