I am an Alzheimer's Caregiver: August 2008

“This positive aMCI clinical trial makes AL-108 the first drug to validate in humans the potential of the ‘tangle’ pathway in memory disorders present in Alzheimer’s disease,” Dr. Schmechel said.

Allon Therapeutics presents AL-108 human efficacy data at world’s leading Alzheimer’s disease conference

A potential new treatment for Alzheimer’s disease that reduces the classic Alzheimer’s “tangle” pathology in mice has also improved specific memory function in humans with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s disease, according to a presentation today at a news conference hosted by the Alzheimer’s Association at their International Conference on Alzheimer’s Disease and Related Disorders (ICAD 2008).

Dr. Donald E. Schmechel, a Duke University geriatrics professor and the principal investigator of the clinical trial that evaluated drug candidate AL-108 in 144 aMCI patients, said the trial’s results increase the importance of “tangles” in the search for treatments that modify the course of Alzheimer’s disease.

“The cause and effect of classic Alzheimer’s hallmarks, beta amyloid ‘plaques’ and neurofibrillary ‘tangles’, is the subject of much investigation, but the preponderance of drug development has so far focused on ‘plaques’, ” said Dr. Schmechel. “This new data suggests that ‘tangles’ may be as important — or perhaps more important — than ‘plaques’.”

“This positive aMCI clinical trial makes AL-108 the first drug to validate in humans the potential of the ‘tangle’ pathway in memory disorders present in Alzheimer’s disease,” Dr. Schmechel said.

In addition to today’s briefing to the news conference, perspectives of AL-108 are being presented to four scientific sessions at ICAD 2008. Dr. Schmechel is presenting additional details of the aMCI clinical trial data at a poster session today featuring new therapies and at Wednesday’s Hot Topics session. Additional data examining AL-108’s mechanism of action that halts and reverses “tangles” pathology and increases cognition in animals will also be presented at two sessions on Wednesday.

AL-108 is being developed by Allon Therapeutics (TSX: NPC), a Canadian biotechnology company located in Vancouver. The drug was discovered by Professor Illana Gozes of the Sackler Faculty of Medicine at Tel Aviv University.

Prof. Gozes also heads up research activities at Allon Therapeutics. Collaborative research led by Prof. Gozes has been supported by Tel Aviv University and the U.S. National Institutes of Health.

Clinical trial in aMCI patients
The Phase IIa trial was a double-blind, randomized, placebo-controlled, multiple-dose study to evaluate the safety, tolerability and effect on cognitive function of AL-108 after 12 weeks of intranasal administration in patients with aMCI. Clinically, patients with aMCI demonstrate memory impairment with otherwise normal cognition. Several aspects of cognitive function were evaluated. The trial was conducted at 17 sites in the United States in 144 patients aged 55 to 85 years and evenly divided between genders.

The trial demonstrated statistically significant, dose-dependent and durable improvements on key endpoints that measure short-term recall and working memory — two types of memory that are clinically relevant in Alzheimer’s disease. Successfully impacting these specific memory domains indicates AL-108 is active in the regions of the brain responsible for their function — primarily the medial temporal lobe, hippocampus and prefrontal cortex. AL-108 did not affect measures of cognitive functions that are not clinically impaired in patients with aMCI.

In this trial AL-108 was safe and well tolerated by patients. The most commonly reported side effects in subjects treated with AL-108 were headache and nasal congestion or irritation.

Trial results
Cognitive function was measured in the aMCI patients by tests that are widely-used and validated in clinical trials evaluating patients with mild cognitive impairment and Alzheimer’s disease.

Prior to receiving drug or placebo, the cognitive function of each patient was measured with these tests. These results became the baseline for each patient’s performance during the trial.

Patients were treated for 12 weeks and tested at weeks four, eight, 12 and 16. Each patient’s test results were compared with his or her baseline performance and to other treatment groups.

A significant, dose-dependent and durable improvement was seen in two tests that measure short-term recall and working memory — delayed-match-to-sample and digit span. The high dose (15 mg twice daily) group showed a 62.4% improvement from baseline (p=0.038, versus placebo) in the delayed-match- to-sample 12-second delay test by the end of the trial.
Similarly, the high dose group showed a 17.2% increase from baseline (p=0.028, versus placebo) in the digit span forward test.

The primary end-point for the trial was a composite of several cognitive tests (composite cognitive memory score, or CCMS) that measured memory and executive function. Patients treated with AL-108 showed statistically significant improvement on tests that measured short-term recall and working memory, but no improvement on tests that involved executive functions, such as planning, cognitive flexibility and abstract thinking.

This divergence in results explains why the composite primary endpoint was trending toward, but did not achieve, statistical significance.

This data suggests that patients with aMCI have significant memory impairment but no significant impairment of executive function. Thus, AL-108 appears to have an impact on regions of the brain that are impaired in aMCI such as those that are known to control memory (medial temporal lobe, hippocampus and prefrontal cortex). However, no measurable effect of AL-108 on executive function was seen in this population since they were not impaired on tests that involve executive function such as Paired Associates Learning, Spatial Working Memory and One-Touch Stockings of Cambridge.

AL-108 was safe and well tolerated in this study. Overall, the incidence of adverse events between the placebo group and the AL-108 group was similar with most adverse events being mild to moderate. Headache (13%), nasopharyngitis (8%), and nasal discomfort (4%) were the most common adverse events reported in subjects receiving AL-108 and were more frequent in subjects receiving AL-108 than those receiving placebo. The rates of discontinuations for adverse events were low and similar between the placebo and AL-109 groups.

About aMCI and Alzheimer’s Hallmarks
There is increasing evidence that some forms of cognitive impairment are precursors to Alzheimer’s disease. Amnestic mild cognitive impairment (aMCI) is a subset of MCI in which only the memory components of an individual’s function are affected.

Scientists agree that the brains of Alzheimer’s patients are characterized by two classic hallmarks of the disease: amyloid beta plaque accumulation outside neurons and neurofibrillary tangles inside neurons. No drug on the market today has any impact on these plaques and tangles.

Scientific studies have shown that the pathology of aMCI and Alzheimer’s is similar. For example, amyloid beta plaques and neurofibrillary tangles occur in both. Allon’s extensive animal data show that AL-108 dramatically reduces neurofibrillary tangles, reduces plaques, and that treated animals have significantly improved cognition. AL-108 is the first drug in development to have shown reduction of both neurofibrillary tangles and amyloid beta plaques in animal studies.

Neurofibrillary tangles are the result of degeneration of microtubules, key components of the communication and transport pathways inside brain cells. Tangles occur when tau protein, which normally acts to hold microtubules together, converts from a soluble to an insoluble form, a process known as hyperphosphorylation.

AL-108 is derived from an eight amino acid peptide (NAPVSIPQ: “NAP”) synthesized from a naturally occurring neuroprotective brain protein known as activity dependent neuroprotective protein (ADNP).

About ICAD 2008
The International Conference on Alzheimer’s Disease and Related Disorders (ICAD 2008) is being held in Chicago July 26-30. ICAD 2008 is organized by the Alzheimer’s Association, the leading U.S. voluntary health organization in Alzheimer’s care, support and research. The conference is bringing together more than 5,000 researchers, physicians and care providers from 60 countries – the largest group of international leaders in Alzheimer research and care ever convened.

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 CompanyTM) and based in Vancouver. For additional information please visit the Company's website: www.allontherapeutics.com.

Forward Looking Statements
Statements contained herein, other than those which are strictly statements of historical fact may include forward-looking information. Such statements will typically contain words such as "believes", "may", "plans", "will", "estimate", "continue", "anticipates", "intends", "expects", and similar expressions. While forward-looking statements represent management’s outlook based on assumptions that management believes are reasonable, forward-looking statements by their nature are subject to known and unknown risks, uncertainties and other factors that may cause the actual results, events or developments to be materially different from any future results, events or developments expressed or implied by them. Such factors include, among others, the inherent uncertainty involved in scientific research and drug development, Allon's early stage of development, lack of
product revenues, its additional capital requirements, the risks associated with successful completion of clinical trials and the long lead-times and high costs associated with obtaining regulatory approval to market any product which Allon may eventually develop.

Other risk factors include the limited protections afforded by intellectual property rights, rapid technology and product obsolescence in a highly competitive environment and Allon’s dependence on collaborative partners and contract research organizations. These factors can be reviewed in Allon’s public filings at www. SEDAR.com and should be considered carefully. Readers are cautioned not to place undue reliance on such forward-looking statements and Allon disclaims any obligation to update or announce changes in any such factors except in its periodic filings.

FOR FURTHER INFORMATION PLEASE CONTACT:

Allon Therapeutics Inc. - Investor and Media Contact
Aaron Keay
Director, Investor Relations
(604) 742-2540 or Cell: (604) 323-6911
Email: akeay@allontherapeutics.com
Website: www.allontherapeutics.com

The Alzheimer's Action Plan: The Experts' Guide to the Best Diagnosis and Treatment for Memory Problems

Researchers Identify Promising Indicators and Targets for Drug Development

Researchers from the University of Pennsylvania School of Medicine have identified a technique to detect the progression of Alzheimer’s disease earlier. By catching Alzheimer’s disease before symptoms are apparent, physicians can prescribe treatments to slow down the disease progression.

“With the development of this technique, we hope clinicians will be able to detect structural brain changes that are typical of Alzheimer’s disease earlier, before individuals present cognitive decline, by measuring levels of brain deterioration,” said Dr. Davatzikos. “We plan to integrate MRI with other biomarkers and especially with imaging of amyloid plaques, the protein deposits in the brain associated with Alzheimer’s disease.”

Results of the study demonstrated:

* Significant brain deterioration was evident a number of individuals who had no apparent symptoms when compared to cognitively healthy elderly.
* An increase of changes or abnormalities in brain structure was accompanied by a decrease in cognitive performance.
* There was an increase in Alzheimer’s-like brain deterioration as people aged.

In addition, researchers uncovered a connection between two risk factors for dementia. Alzheimer’s-like structural changes were accompanied by diseases of small blood vessels in the brain.

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