Competitive Advantage

The AngioGenex technology has important competitive advantages that can be summarized as follows:

Innovation/novel application of Id technology. The Id genes have been shown to be a key component for the growth and spread of tumors. When the actions of the Id genes or Id proteins are blocked, there is a significant inhibition of tumor growth and metastasis. The Id proteins are either absent or present in very low concentration in normal, adult tissues since their primary function is in the developing embryo. Therefore, drugs that block their action are expected to be useful anti-cancer agents while causing few side effects or problems since they will not interfere with a key body function. Also, the problem of resistance that occurs with many anti-cancer treatments and is a major cause of the recurrence of tumors, will not occur. Diagnostics and prognostics for cancer are based on the measurement of the Id proteins in blood and are expected to be more sensitive, selective and predictive than currently used tests.
Compelling scientiifc data. The Id genes have been validated as essential for the growth of tumors in multiple animal models. Some of these are highly representative of the actual initiation and course of human disease and are, therefore, likely to identify potential anti-tumor drugs. Tumor growth is inhibited significantly in these models in the absence or even a partial reduction the Id proteins. Based on these results, the Company is pursuing the discovery and development of anti-cancer drugs as it first priority. The mechanism of Id action is well understood allowing for high-throughput screening and rational design of drugs that are anti-cancer candidates. This has resulted in the discovery of two highly active anti-Id drugs, AGX51 and AGX8.
Development of a companion diagnostic that will provide personalized therapy. In collaboration with BioCheck, Inc., the Company has developed a highly sensitive diagnostic test for the detection of Id proteins in blood and tumor tissue. Preliminary results suggest that its high sensitivity allows the detection of a tumor in the body at a very early stage by virtue of appearance of Id proteins in blood. Such a finding would result in treatment of the patient with an anti-Id drug such as AGX51. This diagnostic is also expected to be useful to detect the effectiveness of anti-Id therapy and recurrence of disease by detecting the appearance of Id proteins in blood following anti-cancer treatment.
Strategies for the clinical use of anti-angiogenic products. A key clinical strategy of the Company is to couple an anti-Id drug with an existing treatment (eg., a chemotherapeutic). A variety of solid tumors have been show to contain the Id proteins suggesting that they are likely to be responsive to an anti-Id drug. The combination of an anti-Id drug with one of the widely-used cytotoxic agents to treat Id-containing tumors is expected to be at least additive and possibly synergistic since the mechanism of action of these agents is very different.
Application of Id technology to other therapeutic areas. The Id technology is being applied in non-oncologic diseases or conditions in which the overgrowth of blood vessels contributes to the underlying pathology. Anti-angiogenic marketed drugs such as Lucentis have been shown clinically to be useful to treat diabetic retinopathy and age related macular degeneration. This agent blocks the growth of new blood vessels into the retina of the eye preventing further loss of vision. The Company is testing the anti-Id approach in animal models of ocular disease and hopes to obtain sufficient preclinical data to approach potential partners.

Competition

Unlike standard chemotherapy, anti-angiogenesis drugs don't attack cancer cells directly. Instead, they target and block the formation of new blood vessels these cells need to survive and grow. By doing so, they can prevent new tumors from growing and cause large tumors to shrink by cutting-off their blood supply.

A large number of anti-angiogenic drugs of differing chemical types and mechanisms are in various stages of clinical testing for cancer. Most of these drugs are directed at inhibiting growth factors such as vascular endothelial growth factor (VEGF), the target of bevacizumab (Avastin). VEGF is a very important protein in causing new blood vessel growth. This protein is not made in large amounts by normal cells, but some cancer cells secrete it into their surrounding area. VEGF attaches to a protein (called the VEGF receptor, or VEGFR) on the surface of nearby endothelial cells. This sends a signal to the control centers of these cells causing them to start growing and forming new blood vessels. Most of the current anti-angiogenesis drugs attack the VEGF pathway. Avastin was the first drug targeted at new blood vessel formation to be approved for use against cancer. It is a monoclonal antibody-a man made version of an immune system protein-that binds to VEGF, and blocks VEGF from reaching the VEGF receptor. Sales of Avastin in 2010 in the US are expected to be over $6 Billion despite relatively modest efficacy. Other antiangiogenic drugs, such as sunitinib (Sutent) and sorafenib (Nexavar), are small molecules that attach to the VEGF receptor itself, preventing it from being turned on.

However, inhibiting normal cell functions while blocking angiogenesis has, in some instances, caused severe side-effects (hypertension, stroke, heart attack) as has occurred with Avastin. These side effects are a direct consequence of targeting a growth factor involved in new blood vessel formation that is also required for the normal activity of cells involved in important functions such as the maintenance of large blood vessels. This same concern must also be considered for any factors involved in the angiogenic process that are also required for normal function, such as integrins and metalloproteinases. In addition, safety must also be a concern for some drugs already in use against cancer that have been found to affect blood vessel growth as part of a broad general anti-growth activity. Examples of this type of drug drugs are thalidomide (Thalomid) and lenalidomide (Revlimid) which are known to affect blood vessel growth while acting as an anti-cancer drug in other ways.

The anti-Id drugs are not expected to have these drawbacks primarily because the Id-genes are not active in the adult and are only active when a tumor signals the need for new blood vessels so that it can grow and metastasize. Unlike other growth factors that are being targeted for the purpose of blocking angiogenesis, the Id proteins are not required for normal cell function. Therefore, an anti-Id drug is much more likely to inhibit angiogenesis in a selective and non-toxic manner.

Besides the above mentioned marketed drugs, a number of candidate anti-angiogenic drugs are undergoing evaluation in clinical trial.

Market Potential of AngioGenex Products

Pharmaceutical companies often form collaborations with biotechnology companies to access drugs, diagnostics or new technologies in the pursuit of novel products. Competitive pressures have made pharmaceutical companies more willing to pay premium prices for these if they have undergone optimization and proven activity. Pricing for Id-type products will be at a high level for these reasons and because this target is unique and acknowledged to have great potential.

Oncology drugs. The oncology market has had remarkable growth during the past five years and is poised for even greater growth during the next three years. The total oncology market is expected to reach over $100 billion worldwide in 2012. Factors contributing to this growth include a trend towards aggressive chemotherapy, an increasing patient population that demands access to the newest therapy and a favorable pricing environment. It is also common practice to use several drugs in combination and this leads to an expansion of drug use. It is expected that the anti-Id drugs will be used, at least initially, in combination with standard chemotherapy.
Diagnostic/prognostic products for oncology. There is an increasing focus on diagnostics and prognostics by healthcare providers and payers since early detection of disease means a better chance for the success of treatment and potentially lower treatment costs. Accurate diagnostic tests and prognostic monitoring are recognized as essential for cost-effective disease management. The use of anti-Id drugs to treat Id containing tumors in combination with an Id diagnostic/prognostic is likely to offer the most promising therapy.
The current worldwide market for serum in vitro diagnostics alone is over $1000 MM and oncology is the fastest growing segment. Advances in molecular testing technology are expected to spur the current modest annual growth rate (7%) to greater than 25 percent. Experts predict that molecular tests such as Id measurements will make the greatest gains in the coming years and should play a major role in cancer diagnosis before the end of this decade. Like the PSA test that represents 40% of the current cancer diagnostic market, an Id test would also be used routinely to detect cancer, to follow progress of therapy and to monitor of the recurrence of disease. Therefore, an Id diagnostic/prognostic is expected to be a highly useful medical tool and a commercially successful product.
Drugs for non-oncology indications. The current market for ARMD and diabetic retinopathy is more than $3.0 billion. In the U.S., there are more than five million cases of diabetic retinopathy and over 1.5 million who suffer from the wet form of ARMD, a type that causes blindness in 90% of those afflicted. Worldwide, there are over 0.5 million new cases of the wet form of ARMD each year. The importance of these markets has been demonstrated by the medical and commercial success of anti-angiogenic drugs such as Macugen and the clinical success of Lucentis. A number of anti-angiogenic drugs are being tested for the treatment of these diseases.