Initial Phase I Study of trans sodium crocetinate (TSC)

In September 2007, Diffusion Pharmaceuticals announced the results of its initial safety study – a randomized double-blind, placebo-controlled, dose-escalation study designed to evaluate the tolerability and pharmacokinetics of a single intravenous bolus injection of TSC in healthy human subjects. The study demonstrated that TSC is well-tolerated, raising no significant clinical issues in humans at doses significantly higher than the doses to be used in upcoming clinical trials in patients.

Phase I/II Clinical Study of TSC in Patients with Peripheral Artery Disease (PAD)

In the first quarter of 2010, the Company successfully completed a positive Phase I/II clinical trial of its lead drug candidate, TSC, in 48 patients suffering from walking impairment due to peripheral artery disease (PAD). The study, designated NCT00725881 on the clinicaltrials.gov website, assessed whether an immediate improvements in patients’ walking ability could be measured upon intravenous administration of TSC. Early analysis of the data indicates that the trial met its intended goals.

The study randomized 48 patients in four cohorts of 12 patients each at various research sites in the U.S. Patients were enrolled sequentially over an escalating range of TSC dosages. Subjects in the study received injections of either TSC or placebo intravenously once daily for five consecutive days. Safety and tolerability were evaluated in a safety review of each cohort before any patients were enrolled into the next cohort. Patients were evaluated during the study for safety parameters and for clinical endpoints using a treadmill test at prescribed time points. Follow-up assessments occurred at 5, 14 and 30 days after the last dose.

The objectives of the study were to evaluate the safety and pharmacokinetics of multiple doses of TSC; establish a dose-response relationship and effect of TSC on peak walking time and claudication onset time in intermittent claudication patients; determine the effect of TSC on potential hypoxia biomarkers; and evaluate the impact of TSC on quality-of-life parameters using the assessments measured in the Walking Impairment Questionnaire routinely used in PAD research.

The trial was sponsored and funded by Diffusion Pharmaceuticals and conducted in collaboration with CPC Clinical Research, a not-for-profit academic research organization specializing in the clinical testing of new approaches to the treatment of PAD. CPC is headed by William Hiatt, MD, professor of cardiovascular research in the Department of Medicine, University of Colorado Denver School of Medicine and chairman of the American Heart Association’s Peripheral Vascular Disease Council.

Investigator sites which participated in this randomized, double-blinded, placebo-controlled study included the University of Pennsylvania, Stanford University, the University of Oklahoma and four private clinics.

Detailed study results have been submitted for presentation at a major medical association meeting in the fall at which time more information will be forthcoming.

Clinical Development: Strategy

The Company chose PAD as its initial clinical indication because it has clearly measurable clinical end-points: increased treadmill walking time, and time to onset of claudication in PAD patients. Data from these clinical end-points will help demonstrate whether TSC’s remarkable effects in hypoxia animal models can be translated into effective treatments for humans. These data, combined with pharmacokinetic results, will provide invaluable dose response information to aid in designs for follow-on trials.

We believe that positive results from this study show the applicability of our technology to the entire range of
indications characterized by hypoxia.

Clinical Development: Planning

The company is currently designing the following clinical trials and protocols:

Peripheral Artery Disease (PAD):
A Phase II PAD clinical trial to build upon the positive results seen in the Phase I/II study. This will be a larger study, powered for statistical significance, focused on firmly establishing best dose, over a longer testing period, in an expanded patient population.

Cancer:
A Phase II study of TSC for its use as a radiation sensitizer in the treatment of newly diagnosed primary brain cancer patients for potential collaboration with the National Cancer Institute’s Adult Brain Tumor Consortium (ABTC), with enhanced patient survival as the primary endpoint.

Stroke:
An initial protocol for a stroke clinical trial to treat both hemorrhagic and ischemic stroke patients.

For more information on the Company’s clinical development plans, please contact Dr. Kim Mays Whitten, PharmD, RAC.