STRATEGIC FOCUS ON ONCOLOGY

Diffusion Pharmaceuticals is a clinical-stage biotechnology company developing first-in-class drugs to treat hypoxia.  Hypoxia – lack of oxygen in tissue – is a primary underlying cause for failure of cancerous tumors to fully respond to radiation and chemo-therapy, as well as for morbidity and death in life-threatening conditions ranging from stroke to peripheral artery disease (PAD).

The Company’s lead drug candidate, trans sodium crocetinate (TSC), is a proprietary, first-in-class oxygen diffusion enhancing compound formulated for IV delivery.  Based on a novel mechanism of action, TSC safely re-oxygenates hypoxic tissue without causing hyper-oxygenation of normal tissue. 

Following the successful completion of preclinical and early stage clinical work, the Company is now focused on obtaining statistically significant proof-of-principle of TSC’s safety and efficacy in controlling tumor growth and enhancing survival in newly diagnosed primary brain cancer patients (glioblastoma multiforme, or GBM).

Published studies demonstrate superior tumor control and a tripling of survival when TSC is combined with radiation and chemotherapy in animal models of cancer.  Based on this work, the Company has initiated a Phase II clinical trial of TSC in GBM patients. 

In collaboration with some of the most distinguished Principal Investigators in the field of oncology, this Phase 2 trial is enrolling patients at 15 major cancer centers around the country.  The study’s FDA-approvable endpoints include overall survival at one and two years, as well as progression free survival at six months.  TSC’s ease of use (small bolus iv injection), proven safety profile in humans and the possibility of real therapeutic benefit have attracted the favorable attention of these oncology experts and should help drive timely patient enrollment.  The study, which is statistically powered to show significant benefit, could potentially serve as a pivotal trial.

The trial is registered on the www.ClinicalTrials.gov  as NCT 01465347 at http://www.clinicaltrials.gov/ct2/show/NCT01465347?term=NCT01465347&rank=1 .

COMPLETED SAFETY STUDIES

Phase I/II Clinical Study of TSC

In 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 objectives of the study, designated NCT00725881 on the clinicaltrials.gov website, 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.

This was a randomized, double-blinded, placebo-controlled study of TSC in patients with intermittent claudication symptoms from PAD enrolling a total of 48 patients.  TSC or placebo was dosed intravenously as a bolus injection once daily for 5 consecutive days.  Forty patients received TSC and 8 received placebo.

Efficacy was evaluated using exercise treadmill tests and measuring the change from baseline in claudication onset time and peak walking time using a modified Gardner graded protocol after treatment with TSC.  Quality of life was measured using a modified Walking Impairment Questionnaire.  PK samples were collected after dose three.  Follow-up safety assessments were done at 14- and 30-days after completion of dosing.

The positive results of this proof-of-concept study were clinically meaningful, suggesting that TSC could benefit PAD patients’ daily functioning, such as walking ability, onset of leg pain and overall quality of life. 

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.

Study results were presented orally at the American Heart Association Annual Meeting Scientific Sessions in Chicago on 15-November, 2010.

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 much higher than the doses that were ultimately used in clinical trials in patients.

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