TAU Therapeutics LLC

A New Way of Treating Cancer

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NAVIGATE:
Changing the Way We Think About Treating Cancer:
Discovery of the Universal Pathway to Cellular Proliferation

In little more than 100 years, treating cancer has made its greatest advancements. After the discovery of the X-Ray in the 1890’s a dramatic change in how cancer was treated – a world transformed from surgery to a strategy of killing the cancerous tumors. In fact, the first therapeutic use of X-ray therapy is reported to have occurred on January 29, 1896 for breast cancer. After the conclusion of World I, soldiers began to return home from the battlefield when doctors recognized that those soldiers exposed to mustard gas had significantly lower white blood counts. Since leukemia patients have elevated white blood counts, the simple remedy was to use a version of mustard gas to help control the cancer. Fast forward again nearly fifty years and researchers have unraveled human genome. Today, doctors have a much better understanding of how cells work and have developed lower dose chemotherapies that target specific areas of the cells growth factors. In all instances, cancer is conventionally treated by killing cancer cells in some way. Cancer cells are cut out, poisoned, or bombarded with radiation.

These methods of treating cancer are very much aligned with the image of a "War on Cancer," which was declared in 1971 by President Richard Nixon. While the great advances in treatments have taken place in the last thirty years, this war is a continuing stalemate with the age-adjusted incidence of death from cancer remaining unchanged since 1970. In fact, cancer is poised to overtake heart disease as the number one killer in America. Among the problems is that the current cytotoxic treatments need to be 100% effective—even a single remaining cancer cell can regenerate the tumor and all too often the surviving cells are those that are more resistant to cytotoxic drugs, producing tumors that are increasingly difficult to eradicate.

Most conventional cytotoxic therapies kill cancer cells by targeting proliferating cells in a patient's body, because uncontrolled growth is a hallmark of cancer. But some normal cells also proliferate in their routine job of keeping people healthy and most conventional cytotoxic agents do not discriminate between cancerously dividing and normally dividing cells. Collateral damage to these normal cells is what produces the serious and debilitating side effects of cancer therapy. The consequences of cytotoxic chemotherapy and radiation are often tragically amplified because these therapies are themselves carcinogenic and secondary cancers caused by treatment are a well-recognized side effect of cytotoxic cancer therapies.

The Development of Cytotoxic Targeted Therapies – An Evolution in the War on Cancer

Despite the difficulties and drawbacks, researchers continue to devise new cytotoxic therapies. One approach has been to ratchet up the toxicity of new agents in an attempt to kill more cancer cells--to increase the enemy's body count. Other approaches have attempted to engineer selectivity for cancer cells into the cytotoxic agent. These targeted therapeutics are based on the identification of proteins that are highly localized, if not specific, to the targeted tumor. Targeted therapeutics leverage the differential levels of the target to enhance tumor selective toxicity. Alternative approaches include cancer immunotherapy, such as tumor vaccines, that attempt to activate the body’s immune system to attack and destroy tumor tissue. These new cytotoxic modalities have provided increasingly selective tumor targeting and have raised considerable optimism for the treatment of cancer. However, they have not yet translated into dramatically different outcomes for patients. Despite the innovation exemplified by these new cytotoxic approaches, they clearly represent an evolution rather than a revolution in the War on Cancer and have not resulted in improved quality or quantity of life for people with cancer.

Cytostatics: Anti-Angiogencisis – A New Way of Thinking

Dr. Judah Folkman, of Harvard Medical School, has envisioned a new way to combat the war on cancer.(see attached WSJ article) The first, and so far only, indication of a change in conventional wisdom was the discovery in Dr. Folkman’s laboratory of anti-angiogenic agents—inhibitors of new blood vessel growth. In experimental cancer models, anti-angiogenic agents were shown to “starve” the cancer by inhibiting the development of blood vessels essential for nourishing tumor growth and maintenance and thus act cytostatically. Anti-angiogenic therapies differed from traditional cytotoxic strategies in two fundamental ways. First, anti-angiogenic agents target normal tissue required by the tumor for growth—that is, anti-angiogenic agents retard the growth of new blood vessels feeding the tumor, not the cancer itself. Second, the anti-angiogenic strategy does not seek to eradicate the tumor, but simply to keep it from growing. This strategy reasons that tumor growth kills by eroding the anatomic and physiologic integrity of the body leading ultimately to death. The logic of cytostatic chemotherapy is simple: stop tumor growth, stop its erosive power, and a person with cancer will not succumb to it. Moreover, the collateral damage to normal tissues from conventional cytotoxic drugs is minimized or eliminated. If cytostatic therapy can be realized, cancer treatment will no longer be crisis management and instead will become analogous to the treatment for other chronic diseases.

However, anti-angiogenic therapy (Genetech’s Feb. 2004, launch of Avastin), while promising, has serious limitations. It must be administered by intravenous injection requiring a person with cancer to regularly visit a doctor's office or medical clinic and it is extremely expensive. Most importantly, the target is secondary; anti-angiogenic therapies do nothing to the cancer itself but instead target a single component of the cancer's "infrastructure." Recent clinical observations indicate that this focus on a single component of the cancer's infrastructure can be unproductive because cancer cells can "find" or evolve a way around this single point blockade.

The ability of cancer to “find” its way around a single point blockade has doctors now prescribing combinations and even “cocktails” of drugs to close off multiple paths or points. The problem is there are simply too many points for the cancer to evolve and continue to grow.

Tau’s approach represents an entirely new modality for treating cancer – a true disruptive technology. Cytostatic chemotherapy aims to reduce the proliferative rate of cancer to that of healthy tissue. The rationale behind this strategy is that tumor growth kills by eroding the anatomic and physiologic integrity of the body leading ultimately to death. The logic of cytostatic chemotherapy is simple: stop tumor growth, stop its erosive power, and a person with cancer will not succumb to it. Moreover, the collateral damage to normal tissues from conventional cytotoxic drugs is minimized. If cytostatic therapy can be realized, cancer treatment will no longer be crisis management and instead will become analogous to the treatments for other chronic diseases.

Tau will develop a spectrum of products using our platform technology. Each agent will be an orally available small molecule intended for chronic administration and optimized to treat a different form of cancer. Ultimately, these compounds may realize the true potential of cytostatic chemotherapy --they may be the leading edge of a revolution in cancer chemotherapy. Tau’s approach to cancer therapy, like Copernicus’ solution to planetary motion, will change the way we think about a fundamental tenet of our lives.