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 delayed injury 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

threatening (meningitis).

- Viruses and bacteria can cause serious and life diseases of the brain (encephalitis) and meninges

Contact:

Dr. Adrian Harel Tel:+972-54-472-7696 [email protected]

www.medicortex.com