Pharmacokinetics Study Confirms Therapeutic-Enabling Quantities of Allon's Drugs AL-108 and AL-208 in Human Cerebrospinal Fluid

Aug 12, 2008 09:15 ET

VANCOUVER, BRITISH COLUMBIA and BOSTON, MASSACHUSETTS--(Marketwire - Aug. 12, 2008) - Allon Therapeutics Inc. (TSX:NPC) announced today that a pharmacokinetics study has confirmed that the Company's clinical stage drugs AL-108 and AL-208 penetrate the blood brain barrier of healthy adults and Alzheimer's disease patients in sufficient quantities to enable a therapeutic effect on Alzheimer's and other neurodegenerative diseases.

Gordon McCauley, President and CEO of Allon, said the results support the Company's ongoing clinical development programs for AL-108 and AL-208 and will help determine appropriate dosages for future clinical trials.

"Our results confirmed that therapeutic-enabling quantities of AL-108 or AL-208 were found in the cerebrospinal fluid (CSF) of the healthy adults and the Alzheimer's patients," said McCauley. "The amounts of AL-108 and Al-208 in the CSF were dose proportional and both drugs were safe and well-tolerated by the test subjects."

McCauley announced the pharmacokinetic results during his presentation to the Canaccord Adams Inc. 28th Annual Global Growth Conference in Boston, MA. The conference brings together institutional investors, venture capital investors and small to mid-cap growth-oriented companies.

Allon is developing AL-108 as a treatment for Alzheimer's disease and for schizophrenia-related cognitive impairment. Allon is developing AL-208 as a treatment for the ischemic damage resulting from a variety of acute brain injuries.

- Earlier this year, Allon announced that a Phase IIa clinical trial evaluating AL-108 in 144 patients with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer's disease, demonstrated that specific memory function improved in patients who were given twice daily dosages of 15 milligrams (mgs) of AL-108 intranasally over 12 weeks. Later this year, the Company will begin enrolment in a Phase IIb clinical trial evaluating AL-108 in Alzheimer's patients.

- The Company expects to complete patient enrolment during the Third Quarter and report top-line results during the Fourth Quarter from a Phase II clinical trial evaluating AL-108 as a treatment for schizophrenia-related cognitive impairment.

- The Company expects to release top-line results during the Third Quarter from the randomized portion of a Phase II clinical trial evaluating the safety, tolerability and effect of AL-208 as a prevention for the mild cognitive impairment resulting from ischemic damage during coronary artery bypass graft surgery.

Pharmacokinetic study results

Test subjects were given a single 15 mg intranasal dose of AL-108 or a single intravenous dose of 50 mg or 300 mg of AL-208. These doses were found to be safe and well-tolerated by the healthy volunteers and mild-to-moderate AD patients.

The pharmacokinetic profile of AL-108 and AL-208 in healthy volunteers confirm results obtained in Allon's previous Phase 1 trials. These conclusions are based on measures of peak concentrations, overall exposure to drug and rate of clearance. The concentration of AL-108 and AL-208 in CSF indicate that the drug crosses the blood-brain barrier in quantities that have conferred protection in prior experimental models.

McCauley said the pharmacokinetic profile of 15 mg AL-108 in mild-to-moderate Alzheimer's patients provides sufficient information to design dose-range components of the Company's proposed Phase IIb Alzheimer's trial. "The modest intra-individual variability observed in the Alzheimer's patients validates the intranasal route of administration for this therapeutic indication and provides us with added confidence in moving this program forward," said McCauley.

About Allon's neuroprotective platforms

Allon's two neuroprotective technology platforms are based on two naturally occurring proteins secreted by the brain in response to a range of insults. The platforms are activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF). Because the two platforms are based on different proteins, the drugs from each are different molecules with different therapeutic mechanisms and distinct commercial opportunities. Clinical-stage drugs AL-108 and AL-208 are derived from ADNP, while preclinical stage drug AL-309 is derived from ADNF.

About Allon

Allon Therapeutics Inc. is a clinical-stage biotechnology company developing treatments for major neurodegenerative conditions. In Q1 2008, Allon's drug AL-108 demonstrated human efficacy in amnestic mild cognitive impairment, a precursor to Alzheimer's disease. Allon has Phase II human efficacy programs pursuing three large underserved markets: Alzheimer's disease, stroke and schizophrenia-related cognitive impairment. The Company is listed on the Toronto Stock Exchange under the trading symbol "NPC" (Neuro Protection Company^TM) and based in Vancouver. For additional information please visit the Company's website: www.allontherapeutics.com.

Hydrocephalus

From Hydrocephalus Association:

Hydrocephalus comes from Greek words: hydro means water, cephalus means head. Hydrocephalus is an abnormal accumulation of fluid—cerebrospinal fluid, or CSF—within cavities called ventricles inside the brain. This condition may occur at any age. CSF is produced in the ventricles, circulates through the ventricular system in the brain and is absorbed into the bloodstream. CSF is in constant circulation and has many functions. It surrounds the brain and spinal cord and acts as a protective cushion against injury. CSF contains nutrients and proteins that are needed for the nourishment and normal function of the brain. It carries waste products away from surrounding tissues. Hydrocephalus occurs when there is an imbalance between the amount of CSF that is produced and the rate at which it is absorbed. As the CSF builds up, it causes the ventricles to enlarge and the pressure inside the head to increase.

While there's no known cure for hydrocephalus, the future holds promise. Recent research gives great hope that we may one day find a cure. In the meantime, gradual advances in technology as well as diagnostic and treatment protocols are helping more and more people with hydrocephalus to lead full and active lives.

Although hydrocephalus (hi-dro-sef-a-lus) is not yet a household word, it is NOT uncommon and you are not alone. Over a million people of all ages currently live with hydrocephalus in the United States, though it occurs all over the world. Hydrocephalus knows no socioeconomic, gender or ethnic boundaries. Of every 1,000 babies born in this country, one or two will have hydrocephalus. It is the most common reason for brain surgery in children, but it can also be diagnosed in any decade of life. Experts estimate that hundreds of thousands of older adults have normal pressure hydrocephalus (NPH), which often goes undetected or is misdiagnosed as untreatable dementia, Alzheimer’s or Parkinson’s.

How is Hydrocephalus treated?
There is no known way to prevent or cure hydrocephalus. To date, the most common treatment is surgical insertion of a shunt. A shunt is a flexible tube placed into the ventricular system of the brain which diverts the flow of CSF into another region of the body, most often the abdominal cavity, where it can be absorbed. A valve within the shunt regulates the flow of CSF.

The shunt procedure is performed by a neurosurgeon. Shunts can become clogged or malfunction and surgical revisions are often required. Endoscopic Third Ventriculostomy (ETV) is a procedure in which a small perforation is made in the thinned floor of the third ventricle, allowing movement of CSF out of the blocked ventricular system. It is a promising technique that can treat hydrocephalus without a shunt. ETV is not a cure for hydrocephalus and it is not an appropriate choice of treatment for many types of hydrocephalus. Each case must be evaluated individually by experienced medical professionals.


The association provides a family book about Hydrocephalus. You can get it here.


Useful Links

Hydrocephalus Association

Pediatric Neurosurgery - Hydrocephalus

Hydrocephalus Fact Sheets