DP-b99: A Phase II Product for Treatment of Patients with Ischemic Stroke-Inhibiting the Spread of Neurological DamageEnhancer product line.

Released on = May 5, 2005, 4:21 am

Press Release Author = Addi Amirav

Industry = Healthcare

Press Release Summary = Background The only FDA approved treatment for ischemic stroke is thrombolytic therapy which aims to restore blood circulation to the ischemic region. This therapy is, however, limited to a small number of eligible stroke patients, <5%, and can only be administered within 3 hours of stroke onset...

Press Release Body = DP-b99: A Phase II Product for Treatment of Patients with Ischemic Stroke-Inhibiting the Spread of Neurological Damage

Background
The only FDA approved treatment for ischemic stroke is thrombolytic therapy which aims to restore blood circulation to the ischemic region. This therapy is, however, limited to a small number of eligible stroke patients, <5%, and can only be administered within 3 hours of stroke onset. There is no approved treatment in the US aimed at prevention or rescue of the neurological tissue damage following stroke. Hence, there's currently a great unmet need for alternative treatment strategies aimed at limiting neurological damage following stroke within a realistic time
window.

The Concept
DP-b99 is a discovery product rationally designed using D-Pharm’s proprietary MAC technology. There is considerable evidence to suggest that redistribution of metal ions and disturbances in metal ion homeostasis are key components in the cascade of
events that accompany stroke. In the first hours post-stroke, these disturbances cause excitatory cell damage and in the days and weeks following they contribute to edema, inflammation and programmed cell death or apoptosis. D-Pharm is developing
the revolutionary concept of neuroprotection based on selective modulation of calcium, zinc, copper and iron homeostasis within cell membranes. DP-b99 attenuates activity of metal-dependent proteins associated with cell membranes and protects
ischemic brain tissue. The Aim DP-b99, a selective modulator of calcium and zinc homeostasis, is being developed as a novel neuroprotective agent for treatment of acute stroke and traumatic brain injury, as well as for prophylactic treatment of neurological damage associated with
coronary artery bypass graft (CABG).

Mechanism of action
DP-b99 is a multi-target drug that moderates key damaging processes characteristic of both early and late periods following the onset of ischemia. For example, DP-b99 reduces toxic zinc levels and generation of reactive oxygen species (ROS) that occur during ischemia in affected cells and attenuates both the effects of tumor necrosis factor &#945; (TNF-&#945;), an early component in neuro-inflammatory processes, and matrix metalloproteinase-9 (MMP-9) an enzyme partly responsible for brain damage and edema. We expect that these characteristics will endow DP-b99 with a wide therapeutic window, consistent with the 1-12 therapeutic window successfully employed in our Phase II study.

Human Experience
In the clinical setting, DP-b99 has been found to be exceptionally safe. A dose-escalating Phase I clinical trial of DP-b99 was completed in a total of 60
young and elderly male volunteers. No side effects, except for local injection site irritation, were observed. This remarkable Phase I safety profile remained even when DP-b99 was administered at 100 times the expected effective dose.

There have been numerous failures in stroke drug development, mainly owing to safety issues, hence it was a major achievement to find from our first Phase II clinical trial that DP-b99 can be used safely in stroke patients. No outstanding pattern of either serious or non-serious adverse events related to DP-b99 was observed compared to placebo. The Phase II study demonstrated that DP-b99 is safe and potentially effective when administered up to 12-hours post-stroke. Notably, that even though
this study was performed on relatively small number of patients (26), statistically significant improvements were observed in the clinical neurological scale scores 2, 7 and 30 days after the stroke.

An international, multi-center efficacy Phase IIb trial has commenced with first patient enrolment expected in February, 2005.

Summary
DP-b99 exhibits the auspicious combination of an excellent safety profile coupled with an innovative and effective mechanism of action. These drug characteristics hold great promise for the treatment of neurological damage following stroke and provide a solid foundation for our intensive DP-b99 clinical development program. For more information please link to: http://www.biomedahead.com

From: Ahead Business Solutions Ltd.
On Behalf of:
D-Pharm
Email: tami@dpharm.com

Web Site = http://www.biomedahead.com

Contact Details = Ahead Business Solutions Ltd.
25 Manchester Square London
addia@ahead-bs.com