Anavex Reports Animal Study Results as Lead Alzheimer's Compound Approaches Phase 1 Clinical Trials
Anavex Life Sciences Corp. ("ANAVEX") (OTCBB: AVXL) reports promising results from animal studies with ANAVEX 2-73, the company's lead compound for the treatment and modification of Alzheimer's disease. ANAVEX 2-73 is the first of a new class of drugs that target mitochondrial dysfunction thought to be caused by oxidative stress to modify Alzheimer's disease. This novel mechanism acts primarily via sigma receptors and is not a direct amyloid, nor tau, nor mitochondrial pore blockade mechanism. ANAVEX is developing non-amyloid focused approaches to disease modification in Alzheimer's disease and believes mitochondrial dysfunction caused by oxidative stress to be an underlying cause of Alzheimer's disease. By modulating ion channel signaling at a mitochondrial level, the company believes this class of patent-protected compounds may offer a new, disease-modifying approach in several neurological and neurodegenerative disorders.
Validated and standard animal models used to assess effects typically seen in Alzheimer's disease have been completed with excellent results. These studies were conducted in partnership with a leading Contract Research Organization, FORENAP Pharma EURL, which specializes in neuroscience and Alzheimer's disease research. The studies included oral and IV dosing and 28-day animal toxicity studies. Extensive studies were conducted in three species: rats, mice and dogs.
The company expects to submit the IND (Investigational New Drug) package to regulatory authorities in the near term.
"ANAVEX is delighted with the evidence generated in these extensive studies, including a favorable toxicology profile," said Dr. Cameron Durrant, Executive Chairman of ANAVEX. "The highly selective binding properties of ANAVEX 2-73 has led to beneficial effects at very low doses, which may ultimately lead to a favorable tolerability profile and offer a wide therapeutic index. This may mean many patients could benefit from low doses, although going to higher doses may be possible in some patients to offer greater efficacy without compromising on the tolerability profile. ANAVEX is confident in the emerging profile of ANAVEX 2-73 as it prepares for Phase 1 clinical trials. We have established that sigma receptors are druggable targets and we have worked to shape ANAVEX 2-73 as our optimized lead compound, which may prove to be neuroprotective."
When administered prior to amyloid-beta 25-35 peptide, ANAVEX 2-73 protected against the amyloid peptide-induced learning deficits, hippocampal lipid peroxidation and cell loss in the CA1 pyramidal layer and showed potent neuroprotective activity. Extensive in-vitro receptor binding and electrophysiology studies, sigma receptor binding studies and electrophysiological effects on sodium and calcium currents have been completed.
The binding affinities of ANAVEX 2-73 for more than 50 receptors were studied. The potency of ANAVEX 2-73, inhibiting enzyme activities was also studied on enzyme assays including calpain, nitric oxide synthase (constitutive and inducible form), protein kinase (PKCα and PKCβ), EGF receptor kinase and calcineurin.
"On average in the industry, it takes six and a half years for discovery and preclinical testing to yield a potentially viable lead compound. Over 80% of compounds fail in preclinical stages, before arriving at this stage of research. ANAVEX 2-73 is a novel oral disease modification agent that is believed to act at several levels, including the mitochondria, and may offer a therapy that could be used as a standalone or in combination with other agents if development proves successful," said Dr. Durrant. "Currently available therapies primarily treat the symptoms, as opposed to modifying the disease, and can fade in terms of effectiveness over time. Several experimental therapies being developed will have to be administered as injections or intravenous infusions. ANAVEX 2-73, and the follow-on compounds the company has in its pipeline, may prove to be novel disease-modifying agents that could impact the natural history of Alzheimer's disease, and which may be administered orally."
About Anavex Life Sciences Corp. Anavex Life Sciences Corp. (www.anavex.com) is a publicly traded biopharmaceutical company engaged in the discovery and development of novel drug candidates for the treatment of neurological diseases such as Alzheimer's, epilepsy, depression and pain, as well as cancer. The company's proprietary SIGMACEPTOR™ Discovery Platform involves the rational design of drug compounds that fulfill specific criteria to target specific receptors involved in the modulation of multiple cellular biochemical signaling pathways.
ANAVEX's SIGMACEPTOR™-N program involves the development of novel and original drug candidates that target neurological and neurodegenerative diseases (Alzheimer's disease, epilepsy, depression, pain). The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors, which have been extensively documented as potentially valuable drug targets and have demonstrated evidence for anti-amnesic and neuroprotective properties. The company is developing non-amyloid focused approaches to disease modification in Alzheimer's disease. ANAVEX 2-73 and the company’s several back up compounds modulate sigma receptors and may guard against oxidative stress and mitochondrial dysfunction via ion signaling modulation. So far the compounds have performed extremely well in well-recognized animal models of Alzheimer's disease, underscoring the promise of the company’s new alternative approach to the disease.
ANAVEX's SIGMACEPTOR™-C program involves the development of novel and original drug candidates targeting cancer. The company's lead drug candidates exhibit high, non-exclusive affinity for sigma receptors with strong evidence for selective pro-apoptotic, anti-metastatic and low toxicity properties in various types of solid cancers. Several of the company's compounds have demonstrated an ability to significantly delay the growth of cancerous tumors in patient-derived xenografts in advanced preclinical studies.