Traumatic Brain Injury
Complex problem - Creative solution
Copyright © MediCortex USA Ltd.
MediCortex USA
• MediCortex is registered as an American company.
• At present, the company is being funded using personal capital.
•Currently, the company is looking for investment of
US$4,000,000. Minimum seed investment: US$300,000
•The proceeds raised will be used for:
1. Chemical synthesis
2. In-vitro toxicology
3. In-vivo efficacy
Proof of concept (PoC) as lucrative investment
• Once the key PoC milestone is reached, MediCortex’s value
would easily exceed US$20M
• Particularly strong pre-clinical efficacy combined with a solid
safety profile would justify a multiple of the above figure.
“Throughout my career at Aventis, Hoffmann-La Roche
and Alcon (a Novartis company), we focused on proof of
concept as the critical milestone when considering when
to partner with or purchase a compound from a small
biotech.”
- Dr. Jean Michel Gries, Covance Inc.
Traumatic Brain Injury (TBI)
•
TBI is a highly complex disorder that includes varying
degrees of contusion, diffuse axonal injury, hemorrhage
and hypoxia.
• Collectively, these effects induce biochemical and metabolic
changes that lead to progressive tissue damage and
associated cell death.
• Both the early primary events and the delayed secondary
alterations contribute to the resulting neurological deficits.
• TBI is a major cause of morbidity and mortality, with an incidence of
235 per 100,000 people and a worldwide mortality of more than 1.5
million per year.
• The public health impact of TBI is expected to increase, since the
most common cause of TBI is road traffic accidents. It is projected to
become the fourth leading cause of disability by 2030.
• In addition, TBI is a major problem in combat areas/war zones. The
New England Journal of Medicine published a study showing that
over 15% of soldiers in Iraq are suffering from TBI.
• “The Pentagon estimates up to 360,000 cases of brain injury suffered
by veterans of the wars in Iraq and Afghanistan (as of 2009)”.
Organizations that have sprouted up in reaction to TBI awareness:
The need:
• Traumatic Brain Injury (TBI) is a major worldwide cause of mortality
and morbidity, with a substantial predicted increase in incidence.
• Although preclinical studies have suggested many promising
pharmacological agents, more than 30 phase III prospective clinical
trials have failed to show significance for their primary endpoint.
• Despite an obvious need, there are currently no pharmacological
treatment options for TBI.
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention
TBI market:
Currently, TBI patients are treated with a combination of surgery, rehabilitation and
pharmacological agents used for managing post-trauma conditions. Consequently, the
estimates for global market value for TBI therapy is in the region of US$10 billion, the
majority of which is accounted for by the demand in Europe and the United States.
Forecast Value of the TBI market in the United States 2015-2020
(Assuming first products launched within the next 3 years. Source: Arrowhead Publishers)
MediCortex’s Innovation
• Most of the agents tested in the clinical studies to treat
TBI have targeted only single factors proposed to
mediate secondary injury.
• The complexity and diversity of the secondary injury
mechanisms warrant targeting of multiple delayedinjury factors, either by combining agents that have
complementary effects or by using multi-potential drugs
that modulate multiple injury mechanisms.
• MediCortex develops molecules that
have a unique combination of activities
targeting multiple pathways mediating
secondary injury.
MediCortex’s New Chemical Entities (NCEs):
Medicortex has designed a bank of chemically verified molecules
that can cross the blood-brain barrier (BBB), each possessing an
innovative chemical spacer with two or more of the following
properties for preventing secondary brain deterioration in TBI
patients:
• Binding of free metal ions
• Anti-oxidation,
• Anti-inflammation
• Anti-bacterial activity
Work plan: Chemistry
•Optimization of synthesis
•Improving yields
•Setting up an analytical method (HPLC)
•Providing solubility and stability in solution and in plasma
•Setting membrane permeability
•Calculating Kd’s (dissociation constant) and LogD
•Formulating the optimization of the treatment method
Work plan: In-Vitro studies
• Preliminary information of toxicity to cells will be tested (XTT, LDH).
The efficiency of an innovative method for neuronal growth and
monitoring single cell response to stimuli will be demonstrated.
• The LCA (liveCell array, Nunc) modified for neurons and glial cells will
be utilized to demonstrate neuro-protection.
The LCA (liveCell array™) innovative system
Work plan: In-Vivo studies
• Compounds in the appropriate formulation will be tested for their
efficacy in a TBI animal model of percussion injury.
• Behavioral, memory and function tests will be used to evaluate
the outcome of the treatment.
• ELISA tests will be utilized to measure and follow up a marker,
specific to the prediction of outcome in TBI in rats.
Brain Injury Terminology
Open Head Injury - Results most often from bullets and shrapnel.
Closed Head Injury - Results from slips, falls, and motor vehicle crashes.
When severe enough, closed head injuries are termed “concussions”.
Deceleration Injury – Results from the differential movement of the skull
and the brain when the head is shaken severely. Diffuse axonal shearing
occurs as it is slammed back and forth inside the skull. The brain is
alternately compressed and stretched because of its gelatinous
consistency.
Metabolic disorders – Result most often from exposure to chemical
toxins, including insecticides, solvents, carbon monoxide, and lead, all of
which can damage the neurons, creating a condition wherein the brain
releases the wrong chemicals or the wrong amounts of normally occurring
chemicals.
Hypoxia (Lack of Oxygen) – Results typically from heart attacks, stroke,
internal bleeding, respiratory failure, drops in blood pressure and
exposure to a low-oxygen environment. Reduced blow flow and low
blood-oxygen levels can cause irreversible brain damage in minutes.
Brain Tumors - Tumors can cause brain injury by invading the spaces of
the brain, leading to direct neuronal damage. Damage can also result
from pressure effects around an enlarged tumor. Surgical procedures
aimed at removing the tumor may also contribute to brain injury.
Brain Infections - Viruses and bacteria can cause serious and lifethreatening diseases of the brain (encephalitis) and meninges
(meningitis).
Contact:
Dr. Adrian Harel
Tel:+972-54-472-7696
onomatop@netvision.net.il
www.medicortex.com