Investment Highlights
Fast Facts
Stock exchange listing > Toronto Stock Exchange (TSX)
Stock symbol > NPC
Shares outstanding > 78-mm
Cash > $13 M
(Sept 30, 2009)
2009 Milestones
- Announce top-line results from the Phase II study in schizophrenia-related cognitive impairment
- Execute a partnership agreement
- Initiate a Phase II study in frontotemporal dementia
- Commence a Phase IIb study in AD with a partner
- Initiate a Phase II PET study in AD patients
Highlights
Human Efficacy
Allon has released positive results from a Phase IIa clinical trial that showed two daily 15 mg doses of davunetide delivered intranasally over 12 weeks of treatment resulted in 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 – in patients diagnosed with amnestic mild cognitive impairment (aMCI), a precursor to Alzheimer’s disease.
Allon’s Phase IIa human clinical data and animal study results, presented to the International Conference on Alzheimer’s Disease and Related Disorders (ICAD 2008), demonstrate that Allon’s lead drug davunetide is the first drug in development to reduce the classic Alzheimer’s “tangles” pathology and also increase memory function.
Allon has also released positive top line results from a Phase IIa clinical trial showing that davunetide, has a positive impact on
the capacity of schizophrenia patients to carry out important activities in their daily lives. The study showed statistically significant
efficacy was achieved on the UCSD (University of California at San Diego) Performance-based Skills Assessment (UPSA). The
UPSA scale assesses the functional capacity of skills for daily living. In total, six domains were tested in staged tasks: medication
management, comprehension/planning, financial, communication, transportation, and household skills.
The UPSA scale has been recognised by drug regulators as an important co-primary endpoint in patients suffering from
schizophrenia-related cognitive impairment.
Technology 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 drug davunetide is derived from ADNP, while preclinical stage drug AL-309 is derived from ADNF.
Products
Davunetide
Allon’s lead product davunetide is being evaluated in human clinical trials as a treatment for Alzheimer’s disease, for schizophrenia cognitive impairment, and frontotemporal dementia (FTD). The Company has robust Phase IIa human efficacy data for davunetide in patients with aMCI and will commence a Phase IIb trial in Alzheimer’s patients with a partner.
In addition, the Company will initiate a Phase II study to examine the effect of davunetide on human brain metabolism, which declines with progression of AD. Positron emission tomography (PET) scans will be used to image glucose metabolism in the brains of patients with AD, providing a method for evaluating the short-term treatment effects of davunetide.
In Q3 2009, positive top-line results from a Phase IIa clinical trial showed that davunetide has a positive impact on the ability of schizophrenia patients to carry out important activities in their daily lives. The trial was funded largely by TURNS (Treatment Units for Research on Neurocognition and Schizophrenia), which is supported by the U.S. National Institute of Mental Health.
The Company will initiate in 2009 a Phase II clinical trial in frontotemporal dementia (FTD). FTD describes several cognitive disorders, such as Pick’s disease, for which no treatment is currently available, including several that are fatal within three to five years of diagnosis. In addition, about 50% of the FTD disorders are tauopathies, or tau-related diseases. Allon’s technology is recognized as the most clinically advanced tau-related therapy.
Davunetide
A second generation davunetide is also being developed for Alzheimer’s disease. Allon has previously reported that a Phase
IIa clinical trial in patients who had undergone coronary artery bypass surgery demonstrated that davunetide delivered intravenously was safe and well-tolerated by patients at a dose 20 times greater than the dose used intranasally.
AL-309
AL-309 is in preclinical development and has demonstrated efficacy in animal models related to neuropathy, Alzheimer’s disease and fetal alcohol syndrome. The most likely human clinical application for this product candidate is peripheral neuropathy, a group of debilitating and painful conditions suffered by millions of people and resulting from nerve damage for which there is currently no effective treatment available. Among the major causes of neuropathy are diabetes and cancer chemotherapy.
Partnering
Allon expects to execute a development
and commercialization partnership with a
major pharmaceutical company in 2009
around its Alzheimer’s program.
Clinical Stage Compounds:
Davunetide
Davunetide is the eight amino acid peptide (NAPVSIPQ) derived from ADNP being developed for the treatment of chronic neurodegenerative diseases.
Davunetide has demonstrated neuroprotective activity in a variety of animal models such as Alzheimer’s disease, stroke, traumatic brain injury, dementia, ocular neuropathy and multiple sclerosis. Specifically, davunetide has demonstrated neuroprotective effects on Amyloid beta (Ab) and tau pathology using the triple transgenic mouse, a model that recapitulates both of the classic hallmarks of AD. Intranasally administered davunetide significantly lowered levels of Ab in the brain and significantly reduced levels of hyperphosphorylated tau.
Pre-clinical Compounds
AL-309
AL-309 is a D-amino acid derivative of AL-209 (SAL) that has shown oral bioavailability, a property that is unusual for a peptide drug that may provide alternative opportunities for chronic daily dosing. It has demonstrated efficacy in animal models related to AD and fetal alcohol syndrome. AL-309 is in pre-clinical development, with IND-enabling studies ongoing.
The company’s compounds have demonstrated the following desirable features for drug development:
Penetrate blood brain barrier: Allon has completed several
studies confirming blood brain barrier access. In particular, Allon
completed cerebrospinal fluid (CSF) pharmacokinetic studies
to determine the bioavailability of davunetide intranasal and davunetide intravenous. We have
shown that following both intranasal and intravenous administration,
davunetide intranasal and davunetide intravenous rapidly appeared in the plasma and the CSF.
These data confirm the bioavailability of davunetide intranasal and davunetide intravenous in
the targeted therapeutic compartment, the brain.
Broad bioavailability: Pharmacokinetics studies demonstrated that davunetide intranasal and davunetide intravenous have bioavailability suitable for daily administration and sufficient to show clinical efficacy.
Multiple routes of administration: Davunetide is formulated for intranasal delivery via a metered spray device. In addition, the drug substance of davunetide has also been delivered intraperitoneally and subcuta-neously in animal studies.
Benign Toxicology: In more than 324 human subjects the dosing for davunetide has been safe and well tolerated. The no observed effect levels of (NOEL) davunetide is 1000 fold the effective dose seen in animal models.
Effective: Davunetide has demonstrated neuroprotective effects in 15 different models of 10 neurodegenerative disease animal models.
Market
Drugs to treat the symptoms and effects of neurodegenerative diseases represent a rapidly growing global pharma market, at approximately $37 billion in 2005 and are forecasted to reach $41.7 billion in 2009.
In the United States alone, direct and indirect annual costs of caring for individuals with AD are at least $100 billion, according to estimates used by the Alzheimer’s Association and the National
Institute on Aging. Sales for Alzheimer’s therapies is estimated to increase to more than $7.8 billion by 2010 in the seven major markets.
Additional Markets
Chronic
> Schizophrenia Antipsychotics: $18B market opportunity
> Neuropathy: $2.5B market opportunity
> Frontotemporal dementia: $1B market opportunity
External validation
(TURNS) Treatment Units for Research on Neurocognition
and Schizophrenia: Selected Allon from from more than 50 companies
for funding in a Phase II efficacy trial in schizophrenia-related cognitive
impairment.
(MJFF) The Michael J. Fox Foundation for Parkinson’s
Research: Selected Allon amongst 9 others from over 300 applicants for
preclinical funding in Parkinson’s research
