Potential Markets for Diffusion Pharmaceuticals’ Technology

Diffusion Pharmaceuticals’ novel treatment for tissue oxygen deprivation could have wide clinical application across a variety of indications that have tissue hypoxia (oxygen deprivation) contributing to their disease states, including:

Peripheral Artery Disease (PAD)

• Affects 10 million Americans (including 12-20 percent of Americans age 65 and older)
• The annual U.S. market potential for PAD with intermittent claudication (IC) exceeds $1 billion

PAD is a circulation problem characterized by hypoxia, or oxygen deprivation at the cellular level. Arteries that carry blood to the legs or arms become narrowed or clogged, interfering with the normal flow of blood. The most common cause of PAD is atherosclerosis, often called “hardening of the arteries.” In atherosclerosis, the blood flow is restricted by the buildup of plaque, preventing blood from passing through narrowed or blocked vessels, and restricting oxygen and other nutrients from getting to normal muscle tissue.

The most common symptom of PAD is called intermittent claudication, which is leg pain that occurs when walking and disappears when the person stops. In more severe cases of PAD, the patient may experience continuous pain – called rest pain – and open sores which will not heal. In the most severe cases, insufficient blood flow leads to limb amputation.

PAD is a debilitating condition with treatment options that are often considered inadequate. The only approved drug treatment for claudication may take as much as three months for its effects to be evident and is a member of a pharmacologic class that is dangerous to people with weakened hearts.

Development of TSC as a treatment for PAD is premised on enhancing the diffusion of oxygen through blood plasma to alleviate the claudication pain caused by hypoxia in the tissues of the legs. TSC may improve oxygenation of muscle tissue and relieve the pain of PAD in both acute and chronic situations. In 2010, the Company successfully completed a Phase I/II clinical trial in patients suffering from PAD.

Cancerous Tumors in Conjunction with Radiation Therapy

• Hypoxic regions within a tumor cell makes cells less sensitive to radiation therapy (Gray et al., 1953)
• Hypoxic cancerous tumor cells are 2 to 3 times less susceptible to radiation than oxygenated tumor cells (Hall and Giaccia, 2006)
• The presence of oxygen in tumors is an essential element for the effectiveness of radiation therapy in the treatment of cancer (Hall and Giaccia, 2006)
• Improving tumor oxygenation in conjunction with radiation therapy could provide for enhanced tumor radiosensitivity and allow for a better clinical outcome (Harrison and Blackwell, 2004)
• The non-responsiveness of cancerous tumors to radiation therapy is directly linked to this oxygen deficiency within the cells of the tumor
• Annual estimated U.S. market for glioblastama is over $100 million and for Brain Metastases is over $1 billion

Published preclinical data show TSC improves oxygenation of the tumor, increasing the effectiveness of radiation therapy and thus increasing survival.

Stroke, Cardiovascular and Respiratory Disease

• Ischemic conditions caused by stroke, myocardial infarction or respiratory disease:
• Strokes affect 600,000 to 750,000 Americans each year
• Cardiovascular disease affects approximately 22 million Americans and is the leading cause of death in the U.S.
• Respiratory disease covers a wide range of conditions, ranging from asthma to emphysema

Published preclinical data indicate TSC improves oxygenation in each of these conditions.

Trauma and Hemorrhagic Shock

• Hemorrhagic shock occurs when blood loss exceeds the body’s ability to compensate and provide adequate tissue oxygenation
• Death due to blood loss is the major cause of death on the battlefield

Published preclinical data show TSC acts as a resuscitation agent in cases entailing severe blood loss or other trauma, improving oxygenation, preventing tissue damage and increasing survival.