PATIENT POPULATIONS AND MARKETS

Diffusion Pharmaceuticals’ novel lead drug candidate TSC has potential clinical applications in millions of patients for whom the re-oxygenation of hypoxic tissue is vital, including oncology, cardiovascular and respiratory diseases.  TSC’s proven human safety profile and solid preclinical and clinical results have allowed the Company to choose an optimal development pathway from among the many possibilities.  Based on factors such as unmet need, competitive position, accessible market, regulatory environment and reimbursement potential, the Company has focused its TSC development activities on a unique set of opportunities within the oncology space. 

FIRST USES

Cancerous Tumors in Conjunction with Radiation Therapy

Radiation therapy is the mainstay of treatment for the approximately two million patients per year (750,000 in the US) who are diagnosed with solid cancerous tumors.  However, there is a fundamental problem.  The presence of oxygen in tumors is an essential element for the effectiveness of radiation therapy, with poorly oxygenated cancerous tumor cells being two to three times less susceptible to radiation than normally oxygenated tumor cells.  Many types of cancerous tumors are well known to contain these hypoxic regions that are less sensitive to treatment.  TSC combined with radiation therapy in animal models of cancer triples survival and provides superior tumor control, as demonstrated by numerous recently published peer-reviewed studies.  Thus, administration of TSC before radiation represents an exciting new treatment possibility to improve tumor control and overall patient survival. 

Diffusion Pharmaceuticals has been granted an Orphan Drug designation by the U.S. FDA for such use of TSC in newly diagnosed primary brain cancer (GBM) patients.  Over 18,000 US patients (30,000 world wide) are diagnosed with GBM every year.  Even a modest improvement in the survival of these patients would lead to a timely acceptance of TSC into the established high-margin $450 million U.S. ($900 million world wide) annual GBM treatment market.  The only drug currently approved for newly diagnosed GBM is temozolomide, which improves median survival by only two months and goes off patent in 2013.  

Follow-on programs include the use of TSC as a radiation sensitizer in any cancerous tumor for which radiation therapy is used.  Prominent among these is the improved treatment of brain metastases, an unmet medical need afflicting about 18o,000 U.S. patients annually, with an accessible market over $1 billion.  Other potential targets include use in head and neck, breast, lung and cervical cancers.  The Company’s goal is to move TSC to approval for use in all solid tumors treated with radiation, comprising an unmet medical need approaching two million patients and an overall annual market over $4 billion dollars.

Future competitive advancements in areas such as targeted therapies or vaccines should not displace TSC’s use so long as radiation therapy continues as part of the standard-of-care for cancer treatment. 

OTHER USES

Peripheral Artery Disease (PAD)

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 rests. 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 medical condition with treatment options that are often considered inadequate by patients and their clinicians. The only approved drug treatment for claudication may take as much as three months for its effect to be evident and has numerous precautions and warnings associated with its use, especially in patients with congestive heart failure. 

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 and reported positive study results at the American Heart Association Annual Meeting for a Phase I/II clinical trial in patients suffering from PAD.

Stroke, Cardiovascular and Respiratory Disease

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

Trauma and Hemorrhagic Shock

Published preclinical data show TSC acts as a resuscitative agent in models with severe blood loss or other trauma and resulted in improved oxygenation preventing tissue damage and increasing survival