GERMANTOWN, Md., June 19, 2007 /PRNewswire-FirstCall/ -- Avalon Pharmaceuticals, Inc. , today announced continued positive interim results from its Phase I study of AVN944, for the treatment of hematologic malignancies in elderly and refractory patients. Interim data indicate AVN944 is well tolerated, has dose-dependent pharmacokinetics, induces biomarkers of programmed cell death in cancer cells from patients, and demonstrates stabilized disease in almost half of the patients after one-month of treatment.
"We continue to be encouraged by the positive interim results from the AVN944 trial," stated Michael Hamilton, M.D., Avalon Pharmaceuticals' Chief Medical Officer. "We have observed important indications of biological drug effect and disease stabilization in a significant number of patients. We continue to believe the Phase I trial will provide sufficient information to initiate multiple Phase II studies."
Background: AVN944 is an oral small molecule drug that inhibits inosine monosphospate dehydrogenase (IMPDH), a critical enzyme for synthesis of guanosine triphosphate (GTP), a molecule required for DNA synthesis and cellular signaling. IMPDH is over expressed in many cancer cells. Pre-clinical studies showed that AVN944 is a highly specific inhibitor of IMPDH, suppresses pools of GTP, and in cultured cells has a selective growth inhibition effect on cancer cells vs. normal cells.
An earlier single-dose, dose-escalation, healthy volunteer clinical trial conducted in the United Kingdom showed that AVN944 was well tolerated at all tested doses with no notable side effects; had good pharmacokinetic properties; and had a significant inhibitory effect on IMPDH enzyme activity.
Study Design: The current U.S. Phase I study is a repeat-dos e dose escalation trial in patients with advanced hematologic malignancies. Patients are dosed for 21 days on a 28-day cycle. A minimum of three patients are treated at each dose level. The study is divided into two arms, one for treatment of leukemia patients and the other for treatment of patients with lymphoma and myeloma. For the leukemia arm of the study, patients are currently being treated at the tenth dose level, 250 mg twice daily. For the lymphoma and myeloma arm, patients are currently being treated at the sixth dose level, 150 mg twice daily.
Positive Safety and Tolerability Data: The goal of the Phase I study is to establish the safety, tolerability and pharmacokinetics of the drug. Thus far, 104 one-month cycles of AVN944 have been initiated in 46 patients and the compound is well tolerated. Pharmacokinetics measurements indicate dose proportional plasma levels of AVN944 during treatment and sustained plasma concentrations at the dose levels tested thus far.
Early Activity Indicators: This Phase I study is designed to evaluate several pharmacodynamic and efficacy-related endpoints. Upon entering the trial, all patients have refractory, progressive disease and have failed all prior therapies. Thus far, 18 of 39 evaluable patients (46%) showed stabilized disease after one cycle of treatment with AVN944. These include patients with both leukemia and multiple myeloma. Patients who have achieved stable disease following completion of a one-month treatment cycle with AVN944, as determined by the clinical investigator, may be advanced to a subsequent cycle.
In the multiple myeloma cohort 60% of the patients have achieved stabilized disease after one month. Two of these patients completed five months of treatment and two others completed one full year of treatment. One AML patient has completed 8 monthly cycles of treatment.
Positive Dose Dependent Biomarker Data: The AvalonRx(R) platform has identified selected biomarkers from pati ent samples which show a correlation of changes in gene expression in a dose dependent manner. Importantly, several of these markers display a durable, sustained stress response indicative of cancer cell death, particularly in cancer cells from AML patients. As dose levels increase the biomarkers reflect an even greater impact of AVN944 on the cancer cells. Direct markers of apoptosis are induced at these higher levels, including members of the Bcl2 gene family which play a critical role in programmed cell death. Additionally, the IMPDH enzyme is inhibited and GTP pools are also depleted for more sustained time periods in treated patients.
Potential Study Stratification Biomarker Data: Additionally we have identified a genetic signature, existing prior to drug exposure, which correlates strongly with disease stabilization in the first cycle of therapy. While still preliminary, based on a small patient sampling, this signature could be the foundation for future patient stratification strategies in phase II and III clinical trials.
Teleconference and Webcast: The company will host a conference call on Wednesday, June 20, 2007 at 8 a.m. Eastern Daylight Time to discuss the interim results of the AVN944 Phase I clinical trial. Interested investors, analysts, members of the media and the general public can listen to the call live over the Internet from the investor section of the company's Web site or by dialing the numbers listed below. A detailed PowerPoint presentation will accompany the webcast.
Conference Call Details: Dial-In: (800) 291-5365 (U.S.) (617) 614-3922 (International) Pass code: 74005634 Webcast: Please go to www.avalonrx.com, Investor Relations, within 15 minutes prior to the call and select the webcast link. If listening by phone and viewing the slides, please choose the 'listen via phone' option to view the slides in real time as there is a 30 second delay otherwise. The conference call replay will be available through August 15, 2007 on Avalon's website (www.avalonrx.com).
About Avalon Pharmaceuticals
Avalon Pharmaceuticals is a biopharmaceutical company focused on the discovery and development of potential first-in-class cancer therapeutics. Avalon has a lead product in Phase I clinical development (AVN944), preclinical programs to develop inhibitors for the Beta-catenin and Aurora pathways, discovery programs for Survivin and Myc pathway inhibitors, and value generating partnerships with Merck, MedImmune, Medarex, and Novartis. By utilizing AvalonRx(R) our platform technology, based upon the proprietary use of large-scale gene expressions, we are uniquely positioned to develop therapeutics focused on pathways that have historically been characterized as "undruggable". Avalon was established in 1999 and is headquartered in Germantown, Md.
AvalonRx(R) is a comprehensive, innovative and proprietary suite of technologies based upon large-scale gene expression analysis. This platform facilitates drug discovery by expanding the range of therapeutic targets for drug intervention, including targets and target pathways frequently considered intractable using conventional HTS approaches, allows more informed decisions about which compounds to advance towards clinical trials, and facilitates drug development through identification of biomarkers of efficacy that can stratify patients or provide early indicators of response.
Safe Harbor Statement
This announcement contains, in addition to historical information, certain forward-looking statements that involve risks and uncerta inties, in particular, related to 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 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 2006 Annual Report on Form 10-K and updates contained in subsequent filings we make with the SEC.
Contacts: Avalon Pharmaceuticals, Inc. Russo Partners, LLC David D. Muth Wendy Lau (Media) Executive Vice President Tel: (212) 845-4272 Chief Business Officer Tel: (301) 556-9900 The Trout Group LLC Fax: (301) 556-9910 Chad Rubin (Investors) Email: Tel: (646) email@example.com
CONTACT: David D. Muth, Executive Vice President of AvalonPharmaceuticals, Inc., +1-301-556-9900, or fax, +1-301-556-9910,; or media, Wendy Lau of Russo Partners, LLC,+1-212-845-4272, for Avalon Pharmaceuticals, Inc.; or investors, ChadRubin, Chief Business Officer of The Trout Group LLC, +1-646-378-2947 firstname.lastname@example.org
Web site: http://www.avalonrx.com/
Ticker Symbol: (NASDAQ-NMS:AVRX)
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