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.

Brain Aerobics Could be Key to Famous Heart Doctor’s Longevity, Says Alzheimer’s Expert

The late pioneer heart surgeon Michael DeBakey attributed his longevity to genetics and not smoking. However, Alzheimer’s disease and brain longevity expert Dharma Singh Khalsa, M.D. believes that mental exercise and brain aerobics played a big role.

Tucson, AZ, August 06, 2008 --(PR.com)-- Dr. Michael E. DeBakey, one of the United States’ most eminent heart doctors, died recently at the ripe old age of 99 years.

Being the first to develop and perform surgical heart bypass surgery, as well as many other medical innovations, Dr. DeBakey worked and performed surgeries well into his 80’s.

Before his death, he was asked about the secret to his longevity. He gave credit to good family genes and having never smoked.

Dharma Singh Khalsa, M.D., president and medical director of the Alzheimer’s Research and Prevention Foundation (http://www.AlzheimersPrevention.org) — and America’s #1 brain longevity specialist — believes other factors may have also contributed to Dr. DeBakey’s long and active life.

“Just as your body needs strength building activities to keep fit, so does your brain.” Dr. Khalsa explains, “You need to carefully nurture your brain with vigorous mental exercise, what I call ‘brain aerobics’.”

According to Dr. Khalsa, Dr. DeBakey’s ritual of starting his day early in the morning, writing for two hours before leaving his house, working at the hospital until early evening, reading or writing again before bed was key in keeping his brain fit and active.


A diligent course of brain exercises, such as reading and writing everyday, is paramount to staving off age-related memory loss and Alzheimer’s disease.

Numerous studies have shown that memory loss and mental decline do not have to be an inevitable part of the aging process. In fact, Dr. Khalsa says, brain degeneration can be prevented or even reversed through an integrated health program consisting of what he calls the Four Pillars to Building a Better Memory: proper diet and vitamins, stress management, exercise, and medication.

Brain aerobics is an important element of the Four Pillars because it is the key to maintaining a sharp memory. Just like physical exercise increases blood flow and oxygen to the muscles, mental exercise increases blood and oxygen to the brain, thereby improving neural cell growth.

As reported by the non-profit organization Alzheimer’s Research and Prevention Foundation (http://www.AlzheimersPrevention.org) (ARPF), regular participation in brain aerobics has shown to reduce the chances of developing Alzheimer’s disease by up to 70%.

The ARPF, founded by Dr. Khalsa, believes an integrative medical approach utilizing the best of conventional, as well as alternative medical practices such as diet, brain specific nutrients, stress management, physical, and mental exercise, offers the best chance of preventing Alzheimer’s disease.

The Alzheimer’s Research and Prevention Foundation is the leading non-profit organization in the country dedicated to the prevention of memory loss and Alzheimer’s disease. Its mission is to reduce the overall incidence of Alzheimer’s disease through clinical research and to provide public information in the form of educational outreach.

Scientists Identify Major Risk Gene for Alzheimer’s Disease

A team of scientists has identified a novel gene that puts people at risk for Alzheimer’s disease and the gene’s surprising identity – it is a calcium channel modulator – suggests a potentially new way to treat or even prevent the mind-robbing disorder.

Manhasset, NY (Vocus/PRWEB ) June 25, 2008 -- A team of scientists has identified a novel gene that puts people at risk for Alzheimer’s disease and the gene’s surprising identity – it is a calcium channel modulator – suggests a potentially new way to treat or even prevent the mind-robbing disorder.

Philippe Marambaud, PhD, an assistant investigator at The Feinstein Institute for Medical Research, and Fabien Campagne, PhD, of The Weill Medical College of Cornell University, began focusing their search for genes expressed in the hippocampus, an area that is hit early in the disease process. They identified several polymorphisms – or gene variants – in DNA samples from Alzheimer’s patients and controls, and one stood out preferentially in the Alzheimer’s brains in a previously uncharacterized gene. The authors found a new calcium channel modulator strongly expressed in the hippocampus, a brain region necessary for learning and memory.

Normally, channels work like a bridge to open up and allow boats to pass. In this case, the channel opens and allows calcium into the neuron, a mechanism that controls important signals inside the cells, such as memory formation. The study was published in the journal Cell. The risk gene, called CALHM1, leads to a partial loss of function, which means that less calcium gets into the cell and it weakens the signals normally regulated by calcium. The authors determined that one of these signals controls the levels of amyloid peptides, the building blocks of the characteristic senile plaques.

The researchers conducted the study using DNA from American deceased Alzheimer’s and age-matched controls with no pathological signs of the disease. They also collaborated with French researcher Jean Charles Lambert, PhD, who had access to DNA samples from patients in France, Italy and the United Kingdom. In total, they ran tests on 3,404 samples. The gene variant showed up more often in the Alzheimer’s samples. People who have the genetic variant have 1.5 times higher risk of developing Alzheimer’s.

The strongest risk gene identified for late-onset Alzheimer’s is Apo-E4. Just one copy of this gene variant triples the risk of the disease. No one knows precisely why or how it works to increase the risk for the disease. Dr. Marambaud and his colleagues are excited by their discovery, because there are medicines that block calcium channels and it would be easier to develop targeted therapies.
“It is a lot easier to figure out how to alter this effect of this gene compared to Apo-E4,” said Peter Davies, PhD, head of the Litwin-Zucker Research Center for the Study of Alzheimer’s Disease and Memory Disorders. "This is the kind of target that pharmaceutical companies are familiar with. Calcium channel drugs have been well studied for decades.”

He added that a lot more basic science work is needed before such drugs are developed. They want to figure out what this newly identified modulator of calcium channel does in the normal brain, and then how it precisely works to increase the risk for Alzheimer’s.

"This is a robust genetic risk factor that was identified now in four different populations,” said Dr. Marambaud. “Having this risk gene can cause a functional problem. It may not only affect the balance of calcium in the brain, which is key to normal cellular processing in memory formation, but also increases the formation of the amyloid peptide, a key player in the pathogenic process of the disease”. He said that the gene, located on chromosome 10, is restricted primarily to the brain. This new work not only provides a better understanding of the pathogenic mechanisms leading to the disease but also identifies CALHM1 as a potentially important new target for therapy.


About The Feinstein Institute for Medical Research
Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in Parkinson's disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease, diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. Feinstein researchers are developing new drugs and drug targets, and producing results where science meets the patient. For more information, please visit www.FeinsteinInstitute.org or www.feinsteininstitute.typepad.com. The institute also publishes the scientific journal Molecular Medicine and a monthly podcast of the latest findings in the journal at www.molmed.org.