Investors
Company Profile
Avalon is a biopharmaceutical company focused on the discovery, development and commercialization of first-in-class cancer therapeutics. Our lead product candidate, AVN944, an IMPDH inhibitor, is in Phase II clinical development. We have late stage preclinical programs to develop inhibitors of the Beta-catenin and PLK3 (Aurora/Centrosome) pathways, discovery programs for inhibitors of the Survivin and Myc pathways and partnerships with Merck, AstraZeneca/MedImmune, ChemDiv, Medarex, and Novartis. We use AvalonRx®, our proprietary platform which is based on large-scale biomarker identification and monitoring, to discover and develop therapeutics for pathways that have historically been characterized as "undruggable." We are headquartered in Germantown, Maryland.

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Company Pipeline

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Partnerships

Company	Collaboration Type	Field
	Discovery, Development & Commercialization	Oncology
	Discovery	Undisclosed
	Discovery, Development & Commercialization	Oncology
	Discovery, Development & Commercialization	Oncology (Large Molecule)
	Discovery, Development & Commercialization	Inflammation

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Pipeline
AVN944
AVN944 is an oral small molecule inhibitor of Inosine Monophosphate Dehydrogenase (IMPDH), an enzyme, which is required for cancer cell growth. AVN944 is a highly specific inhibitor of IMPDH, it suppresses pools of GTP, and in cultured cells has a selective growth inhibition effect on cancer cells vs. normal cells. AVN944 is currently in late Phase I studies in hematological malignancies and in Phase II studies in solid tumors.

In June 2007, we announced positive interim results from the ongoing AVN944 Phase I trial in adult Acute Myelogenous Leukemia (AML) patients, indicating that AVN944 is well tolerated, has dose-dependent pharmacokinetics, induces biomarkers of programmed cell death in cancer cells from patients, and demonstrates a stabilized disease in almost half of the patients after one month of treatment. We also reported on the discovery of a set of AVN944 biomarkers to monitor the activity of the drug in patients.

In 2007 we announced the initiation of a Phase II clinical trial in pancreatic cancer patients. The advancement of AVN944 into a Phase II trial in solid tumors represents a significant milestone, since we believe AVN944 has the potential to provide patient


Beta-catenin Pathway Inhibitor
The Beta-catenin pathway plays a key role in the initiation and progression of cancer. It is activated in a large number of different cancer types, in particular colon cancer, where it has been estimated to be abnormally activated in the majority of cases.

AvalonRx® is particularly well suited for the identification and optimization of drugs targeting the Beta-catenin pathway. The biological complexity and the classically intractable nature of the Beta-catenin protein have prevented this pathway from being effectively targeted by conventional drug discovery techniques.

Using AvalonRx® we have identified structurally distinct chemical compounds that affect the Beta-catenin pathway, and advanced one of the compound series into lead optimization and preclinical studies. This lead compound series causes the death of many different types of cancer cells, decreases the Beta-catenin protein levels in cancer cells and xenograft tumors, induces biomarkers of Beta-catenin pathway inhibition, and exhibits antitumor growth properties. We plan to nominate a lead candidate in this program in 2008.

PLK3 (Aurora/Centrosome) Pathway Inhibitor
The Aurora/Centrosome pathway is a key regulator of cancer cell survival and contains many proteins known to be involved in the initiation and survival of cancer cells. Inhibition of the centrosome pathway is known to slow the uncontrolled cell growth that characterizes cancer, and to induce cell death preferentially in cancer cells.

Proteins that regulate centrosome function are increasingly considered to be promising therapeutic cancer targets. Several proteins in the Centrosome pathway have been targeted for drug development activities using conventional techniques, however, the critical druggable nodes in the pathway are not yet fully understood.

Application of AvalonRx® has enabled us to develop a drug discovery program that can identify the key druggable nodes in this important pathway. Notably, we have used our drug discovery series that disrupts the Centrosome pathway activity, potently induces apoptosis in cancer cells, and has a novel chemical structure.

Survivin Pathway Inhibitor
The Survivin protein is part of an important and undruggable cancer pathway. The protein is recognized as critical to the survival of many different cancer types, but remains an elusive target for cancer therapeutics. The lack of enzymatic function or a druggable motif in the protein makes Survivin an attractive pathway for the AvalonRx® discovery platform.

The Survivin pathway is critical for cancer cell functions including cell death, cell growth, and drug and radiation resistance. The Survivin protein is over-expressed in multiple tumor types including breast, lung, prostate, pancreatic and colon. While broadly expressed, the protein is undetectable in most normal adult cells. High levels of Survivin expression have been associated with cancer progression, drug resistance, poor prognosis and short patient survival.

We have carried out a screen to identify small molecule inhibitors of the Survivin pathway that induce apoptosis in cancer cells. We have identified a set of structurally distinct hit compounds and are advancing them through further hit characterization studies.

Myc Pathway Inhibitor
The Myc pathway is one of the most important but intractable cancer targets known and is associated with many types of aggressive tumors. The pathway has been known for years to be central to cancer cell proliferation and survival, but it has not been amenable to conventional approaches used in drug discovery. Even though the Myc pathway genes are some of the most frequently misregulated in human cancer and known to be required for cancer cell survival, the lack of a druggable motif and the complexity of the protein's biology have led to no successful drug development programs that specifically inhibit this important pathway. We have used our AvalonRx® technology to identify hits from a high throughput screen that appear to specifically inhibit the pathway associated with Myc function. Several hits are currently being validated an analyzed.

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AvalonRx® Proprietary Drug Discovery & Development Platform
AvalonRx® is our proprietary suite of technologies, which facilitates discovery and development of novel therapeutics through the systematic use of large-scale gene expression biomarker analysis. We identify key signatures of pathway activities and use them to screen and develop small molecule inhibitors of critical (often undruggable) pathways. 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.

We believe AvalonRx® can revolutionize the drug discovery process by expanding the range of therapeutic targets for drug intervention, including targets and pathways frequently considered undruggable. It also allows us to make informed decisions about which compounds to advance into clinical trials, based on novel comparisons of compound activity across thousands of genes during lead selection and optimization. We believe AvalonRx® has potential to expedite drug development and commercialization through the identification of biomarkers, which can guide patient selection and provide early indicators of drug response.