TECHNOLOGY
The current status and use of anti-cancer drugs. AngioGenex is a biopharmaceutical company formed for the discovery and development of proprietary products for the treatment, diagnosis and prognosis of cancer. While there are numerous companies that have the same objective, none have the unique technology that is being exploited by AngioGenex. Most companies focus on the discovery and development of drugs that kill cancer cells directly; these are quite toxic to the patient causing serious side effects and not infrequently, death. These are the so-called chemotherapeutic drugs that are used widely today, often in combination with radiation therapy. Many companies support a major effort to discover drugs that act through known targets of marketed drugs. An example of the latter is the enormous investment being made in an attempt to discover drugs like AvastinTM that inhibit vascular endothelial growth factor (VEGF), the multi-billion dollar drug sold by Genentech. Avastin has been shown to be marginally effective in extending life of patients with colon cancer and is being tested in other tumors as well. Recently, the FDA concluded that Avastin is ineffective in the treatment of breast cancer and have withdrawn aproval for its use in this indication.
Avastin does not cure cancer and the FDA has warned that it can cause life threatening side effects such as stroke and heart attacks. While it is recognized that Avastin is the first new type of anti-cancer drug in many years, its limitations in effectiveness, in particular, have been disappointing. The medical community has concluded that Avastin constitutes only a modest advance in the treatment of cancer and that new approaches are urgently needed to find more effective and safer drugs. These two approaches have produced drugs that have changed the cancer survival rate only marginally over the years of the declared war on cancer.
Innovative research is the basis for the discovery of new and more effective anti-cancer drugs. What is needed to find more effective and safer anti-cancer drugs is new knowledge that leads to an understanding of how to kill cancer cells without seriously compromising the cancer patient. New drugs can then be developed to exploit this information to provide a totally new and better way of treating cancer. There have been numerous examples of this type of information emerging from small biotech companies and academic institutions that has been the basis for discovery and development of drugs for different diseases. This has been a major source of new drugs for the large companies in the pharmaceutical industry. Over a period of ten years and continuing today, this type of information has emerged from one of the most famous cancer laboratories in the world [Memorial Sloan Kettering Cancer Center (MSKCC), NYC]. This research is conducted under the direction of a distinguished member of this institute, Dr. Robert Benezra. Dr. Benezra has received world-wide acclaim for demonstrating the importance of a previously unknown cause of the growth and spread of tumors. His findings have been published in highly respected scientific journals and have received media attention both within and outside of the U.S. He discovered that certain genes (Id genes) that are actively involved in the formation of the embryo can be, for reasons that are not clear, inappropriately activated in the adult in the presence of even a very small tumor. And, as a result of their activation, these genes promote tumor growth and metastasis. He was able to demonstrate that if these genes or the proteins they produce are even partially inactivated, tumor growth is markedly inhibited in animals. The AngioGenex team recognized the importance and potential of this research and in 2001 obtained an agreement with MSKCC for exclusive rights to all existing and future patents related to the Id technology. Dr. Benezra has since collaborated solely with the Company to advance the discovery and development of anti-Id drugs.
The discovery of new anti-cancer drugs by AngioGenex. AngioGenex has pursued this new information and has discovered and developed drugs that have the ability to block the action of these Id genes. The AngioGenex team continues to study the role of the Id genes in tumor formation and have uncovered additional ways in which anti-Id drugs act to kill cancer cells. These findings continue to be consistent with the interpretation that the Id genes are the master genes in a unique and previously unknown process that supports the growth and spread of tumors. It has also been shown that the amount of Id in tumors reflects their potential lethality. AngioGenex has developed a test suitable to quantitate the amount of Id in blood or tumor tissue. This test is expected to be used as a diagnostic to detect the presence of a tumor in the body early in its formation and a predictor of the needs to treat a tumor with an anti-Id drug. Virtually all human tumors examined to date have been shown to contain the Id proteins. AngioGenex is in the unique position of being the sole patent holder of all technology related to the use of anti-Id drugs for the treatment of cancer.
Validation of the Id genes and proteins as new targets for anti-cancer drugs. The proprietary technology of AngioGenex offers a unique opportunity to develop new types of anti-cancer drugs based on new knowledge of factors controlling the growth and spread of tumors. This is the result of painstaking efforts by Dr. Benezra and his team over many years of research in an outstanding cancer research laboratory. This technology has been validated in animals with tumors by reducing the amount of Id genes present in the animal through genetic manipulation, or through the use of drugs that prevent either the Id genes or the Id proteins from acting to support tumor growth. Using either approach, there is a profound inhibition of fast-growing tumors in animals causing them to survive while tumor bearing animals die (See Figure below). The Id genes are found in humans as well as animals with only minor differences in their composition. Therefore, based on past medical experience, it is expected that these same drugs will be effective in cancer patients. Besides suppressing tumor growth, they are also expected to eliminate existing tumors and prevent the spread of tumors while having few side effects.
AngioGenex has a long-term commitment to bring anti-Id drugs into clinical use for the treatment of cancer. The investment community is wary of new technology that has not been previously proven to be useful in man. Most new drugs reaching the market mimic existing products and offer little in improved therapy for the cancer patient. As a result, emergence and clinical application of new technology is delayed for many years despite overwhelming evidence of its potential usefulness. In this environment, many promising approaches are never pursued for lack of resources eliminating the possibility that promising, new therapies reach the marketplace. The continued existence of AngioGenex is a result of the commitment of a small dedicated group who persist in their belief that the Id technology constitutes a scientific breakthrough and provides a new and unique approach to treating cancer. While operating partly with their own funds, AngioGenex scientists have added significantly to experimental evidence that supports and extends Dr. Benezra’s research findings. Over a period of ten years, the AngioGenex team has become increasingly committed to make this technology available to cancer patients. The AngioGenex team consists of scientists who have many years of experience conducting research and managing the discovery and development of drugs in pharmaceutical and biotechnology companies. They are supported by a respected Scientific Advisory Board under its head, Dr. Benezra.
A Novel Strategy for the development of anti-cancer drugs. Dr. Benezra of MSKCC demonstrated that the Id genes function early in the developing embryo to promote the growth of normal cells and blood vessels but cease functioning prior to birth and are usually inactive in adult life. In their absence the embryo dies. He further proved that the Id genes are active in many tumor cells in the early stages of disease causing growth of the tumor, and are involved in the formation of the blood vessels that infiltrate tumors. Through genetic manipulations in mice, he demonstrated that a partial loss of Id function leads to a profound inhibition of the growth and metastasis (spread) of tumors. This inhibition can be attributed to the failure of the animals to develop an intact vasculature (network of blood vessels) within the tumor mass causing the tumor cells to die due to the lack of nutrients. Importantly, non-tumor bearing animals with reduced Id levels are healthy and normal in every respect. Thus, the Id genes and proteins become attractive drug targets for the following reasons:
· The normal function of the Id proteins is to participate in the formation of normal cells and blood vessels in the growing embryo. Their inappropriate activation in the adult causes the growth of new blood vessels into tumors (angiogenesis) but they are not required for any other essential body function. Therefore, it is possible to design anti-tumor drugs that do not interfere with some essential body function and, as a result, these drugs would not be expected to cause untoward side effects. AngioGenex has discovered, and is testing testing, proprietary drugs of this type in animals.
· Only a partial reduction in Id activity in mice causes a significant inhibition of tumor angiogenesis and tumor growth. It is not necessary to completely inhibit the genes or proteins. This suggests that since small doses of an anti-Id drug will be effective, it is less likely to cause side effects.
· Inactivation of Id genes before or after tumor formation is effective in either preventing or limiting tumor growth in animal models. These data are accepted by the FDA as supporting the proposal that it predicts similar results in humans.
· The research of Dr. Benezra clearly describes some of the key steps by which Id genes and related proteins causes tumor growth. As a result, it has been possible for the Company to identify small molecule inhibitors of the Id proteins, and inhibitors of Id genes that are viable anti-cancer drug candidates.
While there are many companies that are attempting to develop anti-angiogenic drugs, none are pursuing the Id genes and proteins as targets in this process. AngioGenex has its own patents as well as exclusive access to Id-related technology from Dr. Benezra’s laboratory.
